diff --git "a/Text_summarization/task110_rct_text_summurization.json" "b/Text_summarization/task110_rct_text_summurization.json" new file mode 100644--- /dev/null +++ "b/Text_summarization/task110_rct_text_summurization.json" @@ -0,0 +1,1533 @@ +{ + "Contributors": "RCT", + "Source": "RCT", + "URL": "https://huggingface.co/datasets/allenai/mslr2022", + "Categories": [ + "Text Summurization" + ], + "Definition": [ + "You will be given some study titles and abstracts. Your task is to summarize the main conclusions of the studies." + ], + "Reasoning": [], + "Input_language": [ + "English" + ], + "Output_language": [ + "English" + ], + "Instruction_language": [ + "English" + ], + "Domains": [ + "Public Health", + "Heathcare" + ], + "Positive Examples": [], + "Negative Examples": [], + "Instances": [ + { + "input": "Study1: Therapy in type 2 diabetes: insulin glargine vs. NPH insulin both in combination with glimepiride. Type 2 diabetes (T2DM) patients often fail to achieve adequate glycemic control with oral antidiabetic drugs (OADs). Insulin has been shown to improve glycemic control in these patients but with increased risk of hypoglycemia. This study compared the efficacy and safety of insulin glargine and NPH insulin, both in combination with a once-daily fixed dose of glimepiride, in terms of glycemic control and incidence of hypoglycemia. In this open-label, 24-week randomized trial in ten Latin American countries, T2DM patients poorly controlled on OADs (HbA1c > or = 7.5 and < or = 10.5%) received glimepiride plus insulin glargine (n = 231) or NPH insulin (n = 250) using a forced titration algorithm. The primary endpoint was the equivalence of 24-week mean changes in HbA1c. Insulin glargine and NPH insulin achieved similar HbA1c reductions (adjusted mean difference -0.047; 90% CI -0.232, 0.138; per-protocol analysis). Confirmed nocturnal hypoglycemia was significantly lower with insulin glargine vs. NPH insulin (16.9 vs. 30.0%; p <0.01; safety analysis). Patients receiving insulin glargine were significantly more likely to achieve HbA1c levels < 7.0% without hypoglycemia (27 vs. 17%; p = 0.014; per-protocol analysis). There was a more pronounced treatment satisfaction improvement with insulin glargine vs. NPH insulin (p <0.02; full analysis). The proportion of patients who lost time from work or normal activities due to diabetes was lower with insulin glargine vs. NPH (1.8 vs. 3.3%; full analysis). In patients with T2DM, inadequately controlled on OADs, once-daily insulin glargine plus glimepiride is effective in improving metabolic control with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin.\nStudy2: Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia. In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups. During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01). Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.\nStudy3: Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes. The aim of this study was to compare the efficacy and safety of a basal-bolus insulin regimen comprising either insulin detemir or neural protamine hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 2 diabetes. This was a 26-week, multinational, open-label, parallel group trial with 505 patients with type 2 diabetes (mean age, 60.4 +/- 8.6 years; mean BMI, 30.4 +/- 5.3 kg/m(2); mean HbA(1c), 7.9 +/- 1.3%). Patients, randomized 2:1 to insulin detemir or NPH insulin, received basal insulin either once or twice daily according to their pretrial insulin treatment and insulin aspart at mealtimes. After 26 weeks of treatment, significant reductions in HbA(1c) were observed for insulin detemir (0.2%-points, p = 0.004) and NPH insulin (0.4%-points; p = 0.0001); HbA(1c) levels were comparable at study end (insulin detemir, 7.6%; NPH insulin, 7.5%). The number of basal insulin injections administered per day had no effect on HbA(1c) levels (p = 0.50). Nine-point self-measured blood glucose (SMBG) profiles were similar for the two treatment groups (p = 0.58), as were reductions in fasting plasma glucose (FPG) (insulin detemir, 0.5 mmol/l; NPH insulin, 0.6 mmol/l). At study end, FPG concentrations were similar for the two treatment groups (p = 0.66). By contrast, within-subject day-to-day variation in fasting SMBG was significantly lower with insulin detemir (p = 0.021). Moreover, patients receiving insulin detemir gained significantly less body weight than those who were administered NPH insulin (1.0 and 1.8 kg, respectively, p = 0.017). The frequency of adverse events and the risk of hypoglycaemia were comparable for the two treatment groups. Patients with type 2 diabetes, treated for 26 weeks with insulin detemir plus insulin aspart at mealtimes, experienced comparable glycaemic control but significantly lower within-subject variability and less weight gain compared to patients treated with NPH insulin and insulin aspart. Insulin detemir was well tolerated and had a similar safety profile to NPH insulin.\n", + "output": "Conclusions: Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with \"basal\" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir." + }, + { + "input": "Study1: Auricular acupuncture for dental anxiety: a randomized controlled trial. Auricular acupuncture can be an effective treatment for acute anxiety, but there is a lack of direct comparisons of acupuncture to proven standard drug treatments. In this study we compared the efficacy of auricular acupuncture with intranasal midazolam, placebo acupuncture, and no treatment for reducing dental anxiety. Patients having dental extractions (n = 67) were randomized to (i) auricular acupuncture, (ii) placebo acupuncture, and (iii) intranasal midazolam and compared with a no treatment group. Anxiety was assessed before the interventions, at 30 min, and after the dental extraction. Physiological variables were assessed continuously. With the no treatment group as control, the auricular acupuncture group, and the midazolam group were significantly less anxious at 30 min as compared with patients in the placebo acupuncture group (Spielberger Stait-Trait Anxiety Inventory X1, P = 0.012 and <0.001, respectively). In addition, patient compliance assessed by the dentist was significantly improved if auricular acupuncture or application of intranasal midazolam had been performed (P = 0.032 and 0.049, respectively). In conclusion, both, auricular acupuncture and intranasal midazolam were similarly effective for the treatment of dental anxiety.\nStudy2: The effects of applied tension on symptoms in French-speaking blood donors: a randomized trial. Blood-donation-related symptoms such as dizziness and weakness discourage people from participating in this important health-related activity. Four hundred sixty-seven young adult, French-speaking blood donors were randomly assigned to (a) a condition in which they learned a possible preventive technique called applied tension and were asked to practice it from the time they got on the donation chair until they were just about to get up, (b) a placebo condition in which they learned applied tension and were asked to practice it from the time they got on the chair until the insertion of the donation needle, or (c) a no-treatment control condition. Donors assigned to the treatment condition reported significantly fewer blood-donation-related symptoms than did donors assigned to the other conditions and rated their likelihood of returning to give blood again as greater than did those in the no treatment condition. Among donors whose chairs were not reclined, participants in the treatment condition had significantly smaller heart rate reactions to blood donation than did those in the other conditions. 2006 APA, all rights reserved\nStudy3: The effect of high and low frequency electroacupuncture in pain after lower abdominal surgery. In the present study, we examined the effects of preoperative electroacupuncture (EA) at classical bilateral acupuncture points (Zusanli, also known as ST-36) on postoperative pain and opioid-related side effects. One hundred healthy consenting women undergoing lower abdominal surgery were randomly assigned to four treatment regimens: Group I (n=25), control; Group II (n=25), sham-EA (needle insertion without electrical stimulation); Group III (n=25), low-EA (2 Hz of electrical stimulation); and Group IV (n=25), high-EA (100 Hz of electrical stimulation). EA groups received needle insertion with or without electrical stimulation 20 min prior to anesthesia. All patients received patient-controlled analgesia (PCA) of morphine postoperation. Postoperative pain was evaluated by recording (1). the time of the first required analgesic, (2). the number of PCA demands, (3). the total amount of morphine required by PCA, and (4) patients' VAS pain score. We found that the time of first analgesic requested was 10, 18, 28, and 28 min in the control, sham-, low-, and high-EA groups, respectively. During the first 24h, the total amount of morphine required was decreased by 21, 43 and 61% in the sham-, low- and high-EA groups, respectively. The incidence of nausea and dizziness during the first 24h after surgery was significantly reduced in both the low-EA and high-EA groups compared with the control and sham-EA groups. We also found that sham-EA exerts a beneficial effect with respect to its pain relieving quality but not the side effect profiles. Our findings demonstrates that preoperative treatment with low-EA and high-EA can reduce postoperative analgesic requirements and associated side effects in patients undergoing lower abdominal surgery.\nStudy4: Expectancy, false galvanic skin response feedback, and systematic desensitization in the modification of phobic behavior. nan\nStudy5: Stress management training for hypertensives: cognitive and physiological effects. The contribution of training procedures designed to alter individuals' psychological responses to stressful life stimuli to the reduction of blood-pressure levels of hypertensives was evaluated. The treatment consisted of a set of coping skill-building experiences. Forty-one black males, mildly to moderately hypertensive and under medical supervision in an outpatient cardiovascular unit of a veterans' hospital, participated. Subjects were randomly assigned to one of three groups: Cognitive Self-Management Training (CSM), Attention Placebo Control, and Current Clinic Conditions Control. The dependent measures were the State Anxiety Scale, Trait Anxiety Scale, Coping Strategic Inventory, systolic blood pressure, and diastolic blood pressure. Subjects in the CSM group reported significant increases in the use of cognitive coping strategies in their lives and demonstrated significant decreases in measured levels of state anxiety and systolic blood pressure. Promising reductions of diastolic blood pressure ratings were obtained as well.\nStudy6: A controlled study of reserpine on chronically disturbed patients. nan\nStudy7: Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial. To determine whether a home based exercise programme can improve outcomes in patients with knee pain. Pragmatic, factorial randomised controlled trial of two years' duration. Two general practices in Nottingham. 786 men and women aged >/=45 years with self reported knee pain. Interventions: Participants were randomised to four groups to receive exercise therapy, monthly telephone contact, exercise therapy plus telephone contact, or no intervention. Patients in the no intervention and combined exercise and telephone groups were randomised to receive or not receive a placebo health food tablet. Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities (WOMAC) osteoarthritis index at two years. Secondary outcomes included knee specific physical function and stiffness (scored on WOMAC index), general physical function (scored on SF-36 questionnaire), psychological outlook (scored on hospital anxiety and depression scale), and isometric muscle strength. 600 (76.3%) participants completed the study. At 24 months, highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups (mean difference -0.82, 95% confidence interval -1.3 to -0.3). Similar improvements were observed at 6, 12, and 18 months. Regular telephone contact alone did not reduce pain. The reduction in pain was greater the closer patients adhered to the exercise plan. A simple home based exercise programme can significantly reduce knee pain. The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist.\nStudy8: Paradoxical intention and insomnia: an experimental investigation. nan\nStudy9: Cognitive-behavior therapy with adult patients with epilepsy: a controlled outcome study. The present study evaluated the efficacy of group cognitive-behavior therapy for the alleviation of psychosocial problems and reduction of seizures with adult epileptic patients. Twenty-seven outpatients were randomly assigned to one of three groups: Cognitive-Behavior Therapy, Supportive Counseling (attention-placebo control), and Waiting list (no treatment control). The major outcome measures used were: patient's, neurologist's, and therapist's global ratings of psychological adjustment, patient's target complaints and weekly seizure frequency, patient's and neurologist's ratings of seizure control, the Minnesota Multiphasic Personality Inventory, the Washington Psychosocial Seizure Inventory, and the Beck Depression Inventory. No significant differences were found among the three groups on these measures except for therapist's global ratings of psychological adjustment, on which both the Cognitive-Behavior Therapy and Supportive Counseling groups improved significantly after therapy, but the Waiting List control group did not. Overall, little support was found for the efficacy of group cognitive behavior therapy (eight 2-h weekly sessions) for the reduction of psychosocial difficulties or seizures. Implications of the present findings are discussed, with the need for further controlled outcome research stressed.\nStudy10: Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates. To assess and compare the analgesic effects of orally administered glucose and sucrose and pacifiers. To determine the synergistic analgesic effect of sucrose and pacifiers. Randomised prospective study with validated behavioural acute pain rating scale. Maternity ward. 150 term newborns undergoing venepuncture randomly assigned to one of six treatment groups: no treatment; placebo (2 ml sterile water); 2 ml 30% glucose; 2 ml 30% sucrose; a pacifier; and 2 ml 30% sucrose followed by a pacifier. Median (interquartile) pain scores during venepuncture were 7 (5-10) for no treatment; 7 (6-10) for placebo (sterile water); 5 (3-7) for 30% glucose; 5 (2-8) for 30% sucrose; 2 (1-4) for pacifier; and 1 (1-2) for 30% sucrose plus pacifier. Mann-Whitney U test P values for comparisons of 30% glucose, 30% sucrose, pacifier, and 30% sucrose plus pacifier versus placebo (sterile water) were 0.005, 0.01, <0.0001, and <0.0001, respectively. Differences between group median pain scores for these comparisons were 2 (95% confidence interval 1 to 4), 2 (0 to 4), 5 (4 to 7), and 6 (5 to 8), respectively. P values for comparisons of 30% glucose, 30% sucrose, and 30% sucrose plus pacifier versus pacifier were 0.0001, 0.001, and 0.06, respectively. Differences between group medians for these comparisons were 3 (2 to 5), 3 (1 to 5), and 1 (0 to 2), respectively. The analgesic effects of concentrated sucrose and glucose and pacifiers are clinically apparent in newborns, pacifiers being more effective than sweet solutions. The association of sucrose and pacifier showed a trend towards lower scores compared with pacifiers alone. These simple and safe interventions should be widely used for minor procedures in neonates.\n", + "output": "Conclusions: We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed." + }, + { + "input": "Study: Outpatient vs hospital methadone detoxification: an experimental comparison. This study compares the effectiveness and cost of hospital narcotic detoxificationand outpatient narcotic detoxification using methadone. Forty heroin addicts seeking narcotic withdrawal were randomly assigned to treatment groups. Methadone treatment was planned for no longer than 10 days while psychiatric supportive services were made available to continue as needed. The results suggest little benefit from either treatment approach and there was no significant differences between the treatments. Only a few patients achieved a drug-free state, and of those who did, all but one had returned to use of narcotics within 2 months. The data indicate that detoxification using methadone is a palliative procedure. The cost of outpatient detoxification can be accomplished for approximately one-tenth the cost of inhospital treatment without significantlyaltering the effectiveness of treatment.\n", + "output": "Conclusions: This review demonstrates that there is no good available research to guide the clinician about the outcomes or cost-effectiveness of inpatient or outpatient approaches to opioid detoxification." + }, + { + "input": "Study1: Nutritional support and neurotrauma: a critical review of early nutrition in forty-five acute head injury patients. Forty-five acute head trauma patients were randomized into a neurotrauma nutritional study to compare the efficacy of two forms of standard nutritional supplementation; namely total parenteral nutrition (TPN) versus enteral nutrition (NG). Forty patients were male, 5 were female, with a median age of 28 years. The mean admitting Glasgow coma scale score was 5.8. Patients were given high calorie and nitrogen feedings for the 14 days of the study period in an attempt to achieve positive calorie and nitrogen balance. TPN patients had significantly higher mean daily nitrogen intakes (P less than 0.01) and mean daily nitrogen losses (P less than 0.001) than the NG fed patients; however, no significant differences were discovered with respect to maintenance of serum albumin levels, weight loss, the incidence of infection, nitrogen balance, and final outcome. The exaggerated nitrogen excretion experienced by patients fed large nitrogen loads illustrates a problem in achieving nitrogen equilibrium in acute head injured patients.\nStudy2: Early nutrition support modifies immune function in patients sustaining severe head injury. Immunosuppression after severe head injury has been characterized by a depressed CD4 (T-helper/inducer)-CD8 (T-suppressor/cytotoxic) ratio and decreased T-lymphocyte responsiveness. Some investigators propose that this immunocompromized state is the result of an injury-associated hypermetabolic response and inadequate nutrient delivery during the immediate postinjury recovery phase. Previous observations from our institution demonstrated a preserved CD4-CD8 ratio in severe closed-head injury (CHI) patients receiving early parenteral nutrition (PN). It was unclear whether early PN or other aspects of patient care eliminated the characteristic depression in cellular immunity. The purpose of this study was to further investigate the effect of early PN on the immune function of CHI patients. Nine patients sustaining severe CHI were prospectively randomized to either early PN (n = 4) at day 1 or delayed PN (n = 5) at day 5. Total nutrient administration was delivered at 2 g of protein/kg per day and 40 nonprotein kcal/kg per day for at least the first 14 days of hospitalization. Analysis for T-lymphocyte expression of CD4 and CD8 cell surface antigens and interleukin-6 was performed on days 1, 3, 7, and 14 of hospitalization. T-lymphocyte activation in response to stimulation by concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogens (PWM) was also assessed on these days. Significant increases in total CD4 cell counts (2048 +/- 194 to 2809 +/- 129 vs 1728 +/- 347 to 1825 +/- 563, p < .05) and CD4% (42.6 +/- 4.4% to 56.2 +/- 2.6% vs 36.6 +/- 6.6% to 36.6 +/- 11.3%, p < .05) were observed at day 14 in patients receiving early vs delayed PN. An improved lymphocyte response from baseline to day 14 after Con A stimulation was demonstrated in the early PN group (3850 +/- 1596 to 16144 +/- 5024 cpm, p < .05). A significant rise in the CD4-CD8 ratio over baseline to day 14 was also noted in the early PN group (1.43 +/- 0.17 to 2.38 +/- 0.54, p < .05). The early aggressive nutrition support of CHI patients appears to modify immunologic function by increasing CD4 cells, CD4-CD8 ratios, and T-lymphocyte responsiveness to Con A.\nStudy3: The favorable effect of early parenteral feeding on survival in head-injured patients. This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p less than 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p less than 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury.\nStudy4: Nutritional assessment in head injured patients through the study of rapid turnover visceral proteins. Nutritional monitoring of rapid turnover visceral protein is important in the recognition of malnutrition in patients admitted to the Intensive Care Unit (ICU). We studied prealbumin and retinol-binding protein in patients who received three different kinds of artificial nutrition in order to evaluate the appropriateness of artificial nutrition. 45 consecutive head injury patients received enteral (Group A), parenteral (Group B) or both enteral and parenteral nutrition (Group C) at random. We considered these parameters: prealbumin, retinol binding protein and nitrogen balance before (T1), after 3 (T2), 7 (T3) and 11 (T4) days after the beginning of study. Statistical analysis was performed with Kruskal-Wallis test and Bonferroni's t -test. Plasma prealbumin and Retinol binding protein (RBP) showed an increasing of basal values during the study period in all groups (< 0.0001) and more significantly in group A (Enteral nutrition P < 0. 001 vs Total parenteral nutrition (TPN) and Enteral P< 0.01 vs Enteral and parenteral nutrition). Data obtained in the present study indicate that a laboratory is essential for monitoring nutritional assessment and for checking the appropriateness of nutritional therapy. We found prealbumin to be the most sensitive measure and found it to be the test of choice for early assessment and intervention. Copyright 1999 Harcourt Publishers Ltd.\nStudy5: Enteral versus parenteral nutrition: effects on gastrointestinal function and metabolism. The effects of total parenteral nutrition (TPN) versus enteral nutrition (TEN) were studied in 34 patients following major neurosurgery. Measurements were made of resting energy expenditure (REE), urea production rate (UPR), visceral proteins, parameters of liver and pancreas function, as well as gastrointestinal absorption. To predict nutritional status, nutritional index (NI) was calculated. UPR revealed no significant differences between the groups. After 12 days of TEN, however, synthesis of visceral proteins increased significantly. In addition, NI improved after TEN (p < 0.05), whereas it remained unchanged after TPN. Thrombocyte and lymphocyte counts rose predominately during enteral nutrition. Only in the TEN group was REE increased by 18% and Glasgow Coma Scale (GCS) enhanced from Day 6 on. Exogenous insulin demand was enhanced in the parenterally fed group, and bilirubin (p < 0.05), amylase (p < 0.05), and lipase (p < 0.01) rose significantly, as did gamma-glutamyl-transferase (p < 0.0005) and alkaline phosphatase (p < 0.0005). After 12 d of TPN, vitamin A absorption was significantly attenuated, indicating reduced fat absorption compared to TEN. Carbohydrate absorption did not show significant changes between the groups. Only during TPN did mean values of xylose absorption remain below the normal range. Therefore, enteral nutrition following neurosurgical procedures is associated with an accelerated normalization of nutritional status and an improved substrate tolerance. TEN opposes early postoperative absorption disturbances of the small intestine.\nStudy6: The benefits of early jejunal hyperalimentation in the head-injured patient. To determine the efficacy of early jejunal hyperalimentation as nutritional support in the head-injured patient, 32 head-injured patients with Glasgow Coma Scale scores less than 10 were studied for the first 7 days after injury. The experimental (E) group had nasojejunal feeding tubes placed fluoroscopically. Within 36 hours of injury, they received nutritional support equal to their measured resting energy expenditure. The control (C) group was fed gastrically when bowel sounds returned. There were no significant differences (P greater than 0.05) in age, Glasgow Coma Scale score, type of neurological injury, or associated injuries between the two groups. The mean resting energy expenditure, serum albumin, glucose, lymphocyte count, body weight, and total nitrogen loss were nearly identical for both groups. With the jejunal feedings, daily caloric (E = 2102 kcal versus C = 1100 kcal) and nitrogen intake (E = 11.1 g versus C = 5.6 g) and daily nitrogen balance (E = -4.3 g versus C = -11.8 g) improved. The incidence of bacterial infections (E = 3 versus C = 14) and days of intensive care unit hospitalization (E = 6 versus C = 10) were significantly reduced (P less than .05). Head-injured patients will tolerate early jejunal hyperalimentation despite the presence of a clinically silent abdomen, and the cost and complications of total parenteral nutrition are avoided. The increased caloric and nitrogen intake and improved nitrogen retention markedly reduced infections and days of stay in the intensive care unit.\nStudy7: Enteral versus parenteral nutrition after severe closed head injury. We measured energy expenditure (MREE) and nitrogen excretion (UUN) in patients with severe head injury randomized to early parenteral (TPN, n = 21) or jejunal (ENT, n = 27) feeding with identical formulations. The MREE rose to 2400 +/- 531 kcal/day in both groups and remained at 135% +/- 26% to 146% +/- 42% of predicted energy expenditure over 4 weeks. Nitrogen excretion peaked the second week at 33.4 +/- 10 (TPN) and 31.2 +/- 7.5 (ENT) g N/day. Both routes were equally effective at meeting nutritional goals (1.2 x MREE, 2.5 g protein/kg/day intake, stabilized albumin and transferrin levels). Infections were equally frequent: 1.86 episodes/TPN patient versus 1.89 episodes/ENT patient. While patient charges were much greater for TPN, the hospital costs were similar for TPN and ENT support regimens. These findings show that patients with head injuries are hypermetabolic for weeks, that only 27% are capable of spontaneously eating nutritional requirements by discharge, and that either TPN or ENT support is equally effective when prescribed according to individual measurements of MREE and nitrogen excretion.\n", + "output": "Conclusions: This review suggests that early feeding may be associated with a trend towards better outcomes in terms of survival and disability. Further trials are required. These trials should report not only nutritional outcomes but also the effect on death and disability." + }, + { + "input": "Study1: Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study. To assess and compare the efficacy and safety of three triple combination antiretroviral therapies in HIV-1-infected treatment-naive patients. Seventy treatment-naive HIV-infected adults with CD4+ T-cell counts >50/microL were randomized to receive either zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP), stavudine + didanosine + nevirapine (d4T+ddI+NVP), or stavudine + lamivudine + nevirapine (d4T+3TC+NVP) for 52 weeks. Patient assessments were conducted monthly and included measurement of plasma HIV RNA levels and CD4+ T-cell counts and evaluations for drug toxicity. The mean time-weighted reductions in plasma HIV RNA in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 1.29, 2.13, and 1.78 log(10) copies/mL, respectively (p =.389). The proportions of patients with HIV RNA <50 copies/mL in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 73%, 68%, and 80%, respectively (p =.71). The mean time-weighted increases in CD4+ T-cell counts in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 139, 113, and 174 cells/microL, respectively (p =.30). Three patients ceased assigned treatment due to rash (one from each treatment arm), and 5 of the 45 patients on d4T (3 from the d4T+3TC+NVP arm and 2 from the d4T+ddI+NVP arm) ceased assigned treatment due to neuropathy. All three-drug combinations were equally effective at suppressing viral load and increasing CD4+ T-cell counts. No significant differences were detected between the treatment groups in virological or immunological response or cessation of study drugs due to adverse events, although it is possible that the study was underpowered to detect differences. NVP was safe and efficacious in this setting, and efficacy was not influenced by nucleoside reverse transcriptase inhibitor backbone.\nStudy2: A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: selection of thymidine analog regimen therapy (START I). No clinical trial results directly comparing two nucleoside analog pairs in a drug regimen for HIV that includes a protease inhibitor are available. To compare the safety and efficacy of stavudine (d4T) + lamivudine (3TC) with zidovudine (ZDV) + 3TC, each in combination with indinavir (IDV). Randomized, open-label, multi-center. Fifteen HIV clinical research centers. Two-hundred and four antiretroviral-naive HIV-1-infected-patients with CD4 cell counts > or = 200 x 10(6)/l and HIV-1 RNA > or = 10,000 copies/ml (bDNA assay), modified to 5000 copies/ml. d4T 40 mg twice a day, 3TC 150 mg twice a day plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h (modified to 300 mg every 12 h) plus 3TC and IDV. Primary endpoint: plasma HIV-1 RNA < 500 copies/ml. Additional endpoints: HIV-1 RNA < or = 50 copies/ml; change from baseline in HIV-1 RNA and CD4 cell counts; safety and adverse events. For HIV-1 RNA, 62% of patients on d4T + 3TC + IDV and 54% of patients on ZDV + 3TC + IDV had < 500 copies/ml HIV RNA at weeks 40 through 48 [90% confidence interval, -0.204 to 0.036; P= 0.213], with 49% and 47% respectively achieving < or = 50 copies/ml at 48 weeks (90% CI, -0.134 to 0.096; P = 0.834). Median change in CD4 cell counts at 48 weeks was +227 x 10(6)/l and +198 x 10(6)/l for the d4T- and ZDV-containing arms, respectively. The median time-weighted average change from baseline in CD4 cell counts was significantly greater at 48 weeks in the d4T-containing arm (142 x 10(6)/l versus 110 x 10(6)/l; P = 0.033). Serious adverse events were not significantly different between treatment arms, but there were significant differences for frequency of adverse events of all severity with increased nausea and vomiting in the ZDV-containing arm, and increased diarrhea and rash in the d4T-containing arm. These results support the choice of d4T + 3TC as a nucleoside analog pair in combination with a protease inhibitor in an initial HIV treatment regimen.\n", + "output": "Conclusions: While ideally future research would focus on direct comparison of standard therapeutic combinations of d4T+3TC+an NNRTI and AZT+3TC+an NNRTI to compare these regimens more directly, it is unlikely that additional trials will be mounted. Observational studies should focus on understanding outcomes, including toxicity and tolerability, in low- and middle-income countries." + }, + { + "input": "Study1: Warming of insufflation gas during laparoscopic hysterectomy: effect on body temperature and the autonomic nervous system. Hypothermia is a known side effect of laparoscopic operations. It may increase the sympathetic activity of the autonomic nervous system (ANS), which can be evaluated noninvasively by heart rate variability (HRV). We tested the hypothesis that warming of the delivered CO2 insufflation gas helps to maintain the normal body temperature. Thirty-seven healthy women undergoing laparoscopic hysterectomy were randomized into heated (37 degrees C, n=18) or unheated (24 degrees C, n = 19) gas insufflation groups. Anesthesia was induced with propofol and maintained with sevoflurane in O2-air. Tympanic (ttymp) temperature was recorded before, during and after the operation. Nasopharyngeal (tnaso) temperature was recorded only during operation. Electrocardiograms were recorded and stored to evaluate changes in HRV. The individual changes in HRV were compared after decibel (dB) transformation. A median decrease in tympanic temperatures during the operation was 0.7 degrees C in the heated and 0.3 degrees C in the unheated group (P = 0.01 between groups), and in nasopharyngeal 0.3 degrees C and 0.1 degrees C (P = 0.03), respectively. Preanesthetic tympanic values were reached within 90 min after anesthesia. After dB transformation, HRV high frequency power differed between the groups. It was better preserved in the patients receiving unheated gas. The heating of insufflation gas does not prevent a decrease in body temperature and is thus unnecessary during laparoscopic hysterectomy.\nStudy2: Effect of CO(2) gas warming on pain after laparoscopic surgery: a randomized double-blind controlled trial. Previous studies have suggested that gas temperature has an influence on postlaparoscopy pain. This trial therefore was conducted to study the effect of gas warming on pain after upper abdominal laparoscopic surgery. Patients who underwent laparoscopic cholecystectomy, fundoplication, or Heller's myotomy were included and randomly allocated to receive either warm or cold gas. Primary end point was shoulder tip pain, and secondary end points were subcostal, trocar wound, and visceral pains, as well as other postoperative events. Criteria of pain assessment were the visual analog scale, verbal rating scale, and amount of analgesics. A total of 100 patients were suitable for postoperative evaluation. The groups were well matched. Shoulder tip and subcostal pains were significantly more intense after gas warming (p < 0.05). The three assessment criteria showed the same differences. No difference was observed concerning trocar wound and visceral pains and the other secondary end points. Subdiaphragmatic temperature was not significantly different (34.4 degrees with warming vs. 34 degrees without warming). Gas warming does not reduce, and probably increases, postoperative shoulder tip and subcostal pains.\nStudy3: Comparison of immunologic and physiologic effects of CO2 pneumoperitoneum at room and body temperatures. Prolonged and complex laparoscopic procedures expose patients to large volumes of cool insufflation gas. The aim of this study was to compare the effects of a conventional room temperature carbon dioxide (CO2) pneumoperitoneum with those of a body temperature pneumoperitoneum. Patients were randomized to undergo laparoscopic cholecystectomy with a CO2 pneumoperitoneum warmed to either body temperature (n = 15) or room temperature (n = 15). The physiologic and immunologic effects of warming the gas were examined by measuring peroperative core and intraperitoneal temperatures, peritoneal fluid cytokine concentrations, and postoperative pain. The mean duration of surgery was 32 min in both groups. Core temperature was reduced in the room temperature group (mean, 0.42 degrees C; p < 0.05). No reduction in temperature occurred when the gas was warmed. Greater levels of cytokines were detected in peritoneal fluid from the room temperature insufflation group tumor necrosis factor alpha (TNF-alpha): mean, 10.9 pg/ml vs. 0.42, p < 0.05; interleukin 1 beta (IL-1beta): mean, 44.8 pg/ml vs. 15.5, p < 0.05; and IL-6: mean, 60.4 ng/ml vs. 47.2. There was no difference in postoperative pain scores or analgesia consumption between the two groups. The authors conclude that intraoperative cooling can be prevented by warming the insufflation gas, even in short laparoscopic procedures. In addition, warming the insufflation gas leads to a reduced postoperative intraperitoneal cytokine response.\nStudy4: The clinical impact of warmed insufflation carbon dioxide gas for laparoscopic cholecystectomy. Reports suggest that the insufflation of cold gas to produce a pneumoperitoneum for laparoscopic surgery can lead to an intraoperative decrease in core body temperature and increased postoperative pain. In a randomized controlled trial with 20 patients undergoing laparoscopic cholecystectomy, the effect of insufflation using carbon dioxide gas warmed to 37 degrees C (group W) was compared with insufflation using room-temperature cold (21 degrees C) gas (group C). Intraoperative body core and intra-abdominal temperatures were determined at the beginning and end of surgery. Postoperative pain intensity was evaluated using a visual analog scale and recording the consumption of analgesics. There were no significant group-specific differences during the operation, neither in body temperature (group W: 36.1 +/- 0.4 degrees C vs group C: 35.7 +/- 0.6 degrees C) nor in intra-abdominal temperature (group W: 35.9 +/- 0.3 degrees C vs group C: 35.6 +/- 0. 6 degrees C). Postoperatively, the two groups did not differ in pain susceptibility and need of analgesics. The use of carbon dioxide gas warmed to body temperature to produce a pneumoperitoneum during short-term laparoscopic surgery has no clinically important effect.\nStudy5: Heated and humidified insufflation during laparoscopic gastric bypass surgery: effect on temperature, postoperative pain, and recovery outcomes. Controversy exists regarding the efficacy of heated and humidified intraperitoneal gases in maintaining core body temperature. We performed a sham-controlled study to test the hypothesis that active warming and humidification of the insufflation gas reduces intraoperative heat loss and improves recovery outcomes. Fifty morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass procedures using a standardized anesthetic technique were randomly assigned to either a control (sham) group receiving room temperature insufflation gases with an inactive Insuflow (Lexion Medical, St. Paul, MN) device, or an active (Insuflow) group receiving warmed and humidified intraperitoneal gases. Esophageal and/or tympanic membrane temperature was measured perioperatively. Postoperative pain was assessed at 15 minute intervals using an 11-point verbal rating scale, with 0 = none to 10 = maximal. In addition, postoperative opioid requirements, incidence of nausea and vomiting, as well as the quality of recovery, were recorded. Use of the active Insuflow device was associated with significantly higher mean +/- standard deviation (SD) intraoperative core body temperatures (35.5 +/- 0.5 vs. 35.0 +/- 0.4 degrees C). Postoperative shivering (0 vs. 19%) and the requirement for morphine in the postanesthesia care unit (5 +/- 4 vs. 10 +/- 5 mg) were both significantly lower in the Insuflow vs. control groups. Patients in the Insuflow group also reported a higher quality of recovery 48 hours after surgery (15 vs. 13, P < 0.05). The Insuflow device modestly reduced shivering and heat loss, as well as the need for opioid analgesics in the early postoperative period. However, it failed to improve laparoscopic visualization due to fogging, and provided improvement in the quality of recovery only on postoperative day 2.\nStudy6: Double-blind, prospective, randomized study of warmed, humidified carbon dioxide insufflation vs standard carbon dioxide for patients undergoing laparoscopic cholecystectomy. Patients undergoing warmed, humidified carbon dioxide (CO2) insufflation for laparoscopic cholecystectomy will (1) maintain a warmer intraoperative core temperature, (2) have their surgeon experience less fogging of the camera lens, and (3) have less postoperative pain than patients undergoing laparoscopic cholecystectomy with standard CO2 insufflation. A double-blind, prospective, randomized study comparing patients undergoing laparoscopic cholecystectomy with standard CO2 insufflation vs those receiving warmed, humidified CO2 (Insuflow Filter Heater Hydrator; Lexion Medical, St Paul, Minn) was performed. Main variables included patient core temperature, postoperative pain, analgesic requirements, and camera lens fogging. One hundred one blinded patients (69 women, 32 men) undergoing laparoscopic cholecystectomy were randomized into 2 groups-52 receiving standard CO2 insufflation (group A) and 49 receiving warmed, humidified CO2 (group B). Mean patient intraoperative core temperature change (group A decreased by 0.03 degrees C, group B increased by 0.29 degrees C, P =.01) and mean abdominal pain (Likert scale, 0-10) at 14 days postoperatively (group A, 1.0; group B, 0.3; P =.02) were different. Other variables (camera lens fogging, early postoperative pain, narcotic requirements, recovery room stay, and return to normal activities) between groups were similar. While patients undergoing laparoscopic cholecystectomy with warmed, humidified CO2 had several advantages that were statistically significant, no major clinically relevant differences between groups A and B were evident.\nStudy7: Heating and humidifying of carbon dioxide during pneumoperitoneum is not indicated: a prospective randomized trial. Carbon dioxide (CO2) pneumoperitoneum usually is created by a compressed gas source. This exposes the patient to cool dry gas delivered at room temperature (21 degrees C) with 0% relative humidity. Various delivery methods are available for humidifying and heating CO2 gas. This study was designed to determine the effects of heating and humidifying gas for the intraabdominal environment. For this study, 44 patients undergoing laparoscopic Roux-en-Y gastric bypass were randomly assigned to one of four arms in a prospective, randomized, single-blinded fashion: raw CO2 (group 1), heated CO2 (group 2), humidified CO2 (group 3), and heated and humidified CO2 (group 4). A commercially available CO2 heater-humidifier was used. Core temperatures, intraabdominal humidity, perioperative data, and postoperative outcomes were monitored. Peritoneal biopsies were taken in each group at the beginning and end of the case. Biopsies were subjected staining protocols designed to identify structural damage and macrophage activity. Postoperative narcotic use, pain scale scores, recovery room time, and length of hospital stay were recorded. One-way analysis of variance (ANOVA) and the nonparametric Kruskal-Wallis test were used to compare the groups. Demographics, volume of CO2 used, intraabdominal humidity, bladder temperatures, lens fogging, and operative times were not significantly different between the groups. Core temperatures were stable, and intraabdominal humidity measurements approached 100% for all the patients over the entire procedure. Total narcotic dosage and pain scale scores were not statistically different. Recovery room times and length of hospital stay were similar in all the groups. Only one biopsy in the heated-humidified group showed an increase in macrophage activity. The intraabdominal environment in terms of temperature and humidity was similar in all the groups. There was no significant difference in the intraoperative body temperatures or the postoperative variable measured. No histologic changes were identified. Heating or humidifying of CO2 is not justified for patients undergoing laparoscopic bariatric surgery.\nStudy8: A randomized controlled trial assessing the benefit of humidified insufflation gas during laparoscopic surgery. We conducted a randomized controlled trial during laparoscopic cholecystectomy to determine the extent of heat preservation and postoperative pain reduction using humidified carbon dioxide (CO2) gas insufflation instead of standard dry insufflation gas. Forty consecutive patients were randomized. Twenty patients received humidified CO2, and 20 control patients received standard CO2 insufflation. A sample of 16 patients from each group was evaluated for postoperative pain levels. No adverse effects from the humidification of insufflated gas were observed. There was no significant difference in core body temperature between the two groups for this brief operation. Pain, as assessed by the Analogue Pain Score (APS) was significantly less for the group with humidified gas insufflation than for the control group at 6 h postoperatively as well as on the 1st, 2nd, and 3rd postoperative day and at follow-up 10 days after the operation. In the humidified group, the mean time to return to normal activities was significantly less-5.9 days, as compared to 10.9 days in the control group. The use of humidified insufflation gas reduces postoperative pain following laparoscopic cholecystectomy, but except for these relatively brief procedures, the heat-preserving effect of humidified gas insufflation is not significant.\nStudy9: Beneficial effects of humidified, warmed carbon dioxide insufflation during laparoscopic bariatric surgery: a randomized clinical trial. Recent data has shown that the use of warmed, humidified carbon dioxide (CO2) insufflation during laparoscopic surgery may be associated with better outcomes. We performed a randomized, doubleblind, prospective controlled clinical trial of 30 patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP). Patients were randomized into 2 groups. The first group (group 1, n=15) received standard (dry, room temperature) CO2 for insufflation during the surgery, while the second group (group 2, n=15) received warmed (35 degrees C) and humidified (95%) CO2. Patients received postoperative analgesia from morphine delivered via a patient-controlled analgesia (PCA) pump. Pain scores (on a scale of 0 to 10, 0 being no pain and 10 being the worst pain) were measured postoperatively at 3 h, 6 h, 1 day and 2 days. The amount of morphine that was delivered through the PCA was also measured at the same time intervals. Operating-room (OR) time, core temperature, and total hospital length of stay were documented. Postoperative pain as documented by pain scores and narcotic usage were not statistically different in the 2 groups. We demonstrated a statistically significant difference (mean+/-SD) in OR time (76+/-16 min vs 101+/-34 min, P=0.02), total hospital length of stay (3.2+/-.4 days vs 4.0+/-.9 days, P=0.01) and end-of-case core temperature (36.2+/-.5 degrees C vs 35.7+/-.6 degrees C, P=0.02) in group 2 compared with group 1. The use of warmed, humidified CO2 insufflation in bariatric patients undergoing LRYGBP was not associated with any significant benefit with regards to postoperative pain.\nStudy10: Effect of heated and humidified carbon dioxide gas on core temperature and postoperative pain: a randomized trial. Intraoperative hypothermia is a common event during laparoscopic operations. An external warming blanket has been shown to be effective in preventing hypothermia. It has now been proposed that using heated and humidified insufflation gas can prevent hypothermia and decrease postoperative pain. Therefore, we examined the extent of intraoperative hypothermia in patients undergoing laparoscopic Nissen fundoplication using an upper body warming blanket. We also attempted to determine whether using heated and humidified insufflation gas in addition to an external warming blanket would help to maintain intraoperative core temperature or decrease postoperative pain. Twenty patients were randomized to receive either standard carbon dioxide (CO2) gas (control, n = 10) or heated and humidified gas (heated and humidified, n = 10). After the induction of anesthesia, an external warming blanket was placed on all patients in both groups. Intraoperative core temperature and intraabdominal temperature were measured at 15-min intervals. Postoperative pain intensity was assessed using a visual analogue pain scale, and the amount of analgesic consumption was recorded. Volume of gas delivered, number of lens-fogging episodes, intraoperative urine output, and hemodynamic data were also recorded. There was no significant difference between the two groups in age, length of operation, or volume of CO2 gas delivered. Compared with baseline value, mean core temperature increased by 0.4 degrees C in the heated and humidified group and by 0.3 degrees C in the control group at 1.5 h after surgical incision. Intraabdominal temperature increased by 0.2 degrees C in the heated and humidified group but decreased by 0.5 degrees C in the control group at 1.5 h after abdominal insufflation. There was no significant difference between the two groups in visual analog pain scale (5.4 +/- 1.6 control vs 4.5 +/- 2.8 heated and humidified), morphine consumed (27 +/- 26 mg control vs 32 +/- 19 mg heated and humidified), urine output, lens-fogging episodes, or hemodynamic parameters. Heated and humidified gas, when used in addition to an external warming blanket, minimized the reduction of intraabdominal temperature but did not alter core temperature or reduce postoperative pain.\n", + "output": "Conclusions: The study offers evidence that during laparoscopic abdominal surgery, heated gas insufflation, with or without humidification, has minimal benefit on patient outcomes." + }, + { + "input": "Study1: Pragmatic, cluster randomized trial of a policy to introduce low-low beds to hospital wards for the prevention of falls and fall injuries. To evaluate the efficacy of a policy to introduce low-low beds for the prevention of falls and fall injuries on wards that had not previously accessed low-low beds. This was a pragmatic, matched, cluster randomized trial with wards paired according to rate of falls. Intervention and control wards were observed for a 6-month period after implementation of the low-low beds on the intervention wards. Data from a 6-month period before this were also collected and included in analyses to ensure comparability between intervention and control group wards. Public hospitals located in Queensland, Australia. Patients of 18 public hospital wards. Provision of one low-low bed for every 12 on a hospital ward, with written guidance for identifying patients at greatest risk of falls. Falls and fall injuries in the hospital measured using a computerized incident reporting system. There were 10,937 admissions to control and intervention wards combined during the pre-intervention period. There was no significant difference in the rate of falls per 1,000 occupied bed days between intervention and control group wards after the introduction of the low-low beds (generalized estimating equation coefficient=0.23, 95% confidence interval=-0.18-0.65, P=.28). The rate of bed falls, falls resulting in injury, and falls resulting in fracture also did not differ between groups. Some difficulties were encountered in intervention group wards in using the low-low beds as directed. A policy for the introduction of low-low beds did not appear to reduce falls or falls with injury, although larger studies would be required to determine their effect on fall-related fractures.\nStudy2: Falls prevention: the efficacy of a bed alarm system in an acute-care setting. The present study examined the clinical efficacy of a bed alarm system in reducing falls from bed on a geriatric evaluation and treatment unit. A nine-month case-controlled study was designed, in which 70 patients (60 women, 10 men; mean age 84 years, range 67-97 years) at increased risk for bed falls were randomly assigned to either an experimental or a control group. Subjects in the experimental group (n = 35) received a bed alarm system and those in the control group (n = 35) did not. Outcome measures included bed falls, performance of the bed alarm system, and staff attitudes toward the use of the system. Although results failed to demonstrate a statistical difference in bed falls between the experimental (n = 1) and control (n = 4) groups (p = 1.00), there was a clinical trend toward reduced falls in the experimental group. The system functioned properly, activating an alarm in all instances when patients were transferring from bed, and with the exception of one case, nurses could respond in a timely fashion to assist patients and prevent bed falls. The system did not produce any adverse effects in patients, nor did the device interfere with the rendering of medical care. The system was well accepted by patients, families, and nurses. These data suggest that bed alarm systems are beneficial in guarding against bed falls and are an acceptable method of preventing falls.\n", + "output": "Conclusions: The effectiveness of interventions designed to prevent patient injuries from their beds (including bed rails, low height beds and bed exit alarms) remains uncertain. The available evidence shows no significant increase or decrease in the rate of injuries with the use of low height beds and bed exit alarms. Limitations of the two included studies include lack of blinding and insufficient power. No randomised controlled trials of bed rails were identified. Future reports should fully describe the standard care received by the control group." + }, + { + "input": "Study1: [A comparison of phosphorus-chelating effect of calcium carbonate versus calcium acetate before dialysis]. The hyperphosphatemia, hypocalcemia and low calcitriol levels are pathogenic factors for secondary hyperparathyroidism in chronic renal failure. The phosphorus control is essential to prevent secondary hyperparathyroidism. There are not comparatives studies to test the efficacy of control of phosphorus binders in predialysis patients. To compare the efficacy of calcium carbonate vs calcium acetate as phosphate binder in predialysis patients. The present study includes 28 patients with chronic renal failure (mean clearance of creatinine 21 ml/min). Patients were separated into two groups: Group 1: (n = 14) received calcium carbonate 2,500 mg/day (1,000 mg of calcium); Group 2: (n = 14) receives calcium acetate 1,000 mg (254 mg of calcium). Calcium and phosphorus were determined every 4 months; i-PTH, alkaline phosphatase and clearance of creatinine were determined every six months. Both groups were comparable regarding age, renal function, calcium, phosphorus, alkaline phosphatase and i-PTH on basal situation and the end of study were not different. The serum calcium increased, not significantly, in the calcium carbonate group (group 1) [from 9.2 to 9.8 mg/dl (p = 0.05)], however it was not modified in the calcium acetate group (group 2). The serum phosphorus decreased significantly (p < 0.05) in both groups, independently of the calcium levels. Alkaline phosphatase and i-PTH not was modified during the study period. 1) Both calcium carbonate and calcium acetate are similarly effective as phosphate binder. 2) The carbonate group required four fold greater doses of calcium that acetate group. 3) The calcium acetate has less hypercalcemic effect than calcium carbonate.\nStudy2: Multicenter prospective randomized, double-blind comparative study between lanthanum carbonate and calcium carbonate as phosphate binders in Japanese hemodialysis patients with hyperphosphatemia. The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported, but not from a double-blind, comparator-controlled comparative study. The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a randomized, double-blind, comparator-controlled, parallel group, multicenter study. This study is the first study using a randomized, double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders. In the double-blind phase, the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups. The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant. However, the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group. The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group. Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner. However, lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia.\nStudy3: Aluminum hydroxide, calcium carbonate and calcium acetate in chronic intermittent hemodialysis patients. Prevention of secondary hyperparathyroidism in uremia necessitates correction of hyperphosphatemia and hypocalcemia. In order to avoid aluminum toxicity, calcium containing phosphate binders are used increasingly, instead of aluminium hydroxide. Recent studies have shown that calcium acetate has many characteristics of an ideal phosphate binder. It is, for instance, a more readily soluble salt compared with calcium carbonate. This advantage might, however, disappear if calcium carbonate is taken on an empty stomach, a few minutes before meals. We examined the efficacy of three different phosphate binding agents in a randomized prospective study of 53 patients on regular hemodialysis. Bicarbonate dialyses were performed with a dialysate calcium concentration of 1.75 mmol/l. After a three-week wash-out period, patients received either aluminum hydroxide (control group), calcium acetate, or calcium carbonate as their phosphate binder. Patients were instructed to take the calcium salts a few minutes before meals on an empty stomach, and aluminum hydroxide during meals. Serum calcium, phosphate, intact parathormone, and alkaline phosphatase levels were determined every month. Patient compliance was estimated every month by asking the patients which phosphate binder and what daily dose they had used. Aluminum hydroxide tended to be the most effective phosphate binder. The mean +/- SEM required daily dose of calcium acetate at 12 months was 5.04 +/- 0.60 g, corresponding to 10.1 +/- 1.20 tablets of 500 mg. Co-medication with aluminum hydroxide, however, was needed (1.29 +/- 0.54 g per day, corresponding to 2.6 +/- 1.08 tablets of 500 mg). The required daily calcium carbonate dose appeared to be 2.71 +/- 0.48 g, corresponding to 5.4 +/- 0.95 capsules of 500 mg, with an adjuvant daily aluminum hydroxide dose of 0.69 +/- 0.27 g, corresponding to 1.4 +/- 0.55 tablets of 500 mg (p = 0.0055). Thus, the mean daily doses of elemental calcium were comparable between the calcium acetate and calcium carbonate-treated patients (1.28 +/- 0.15 g versus 1.09 +/- 0.19 g; n.s.). The incidence of hypercalcemic episodes (albumin-corrected serum calcium levels above 2.80 mmol/l) in the calcium acetate-treated group was 18% versus 31% in the calcium carbonate-treated group (p < 0.005). None of the aluminum hydroxide-treated patients experienced hypercalcemic episodes. Mean serum concentrations of alkaline phosphatase, intact parathormone, and aluminum did not differ between the groups. In chronic intermittent hemodialysis patients, per gram administered elemental calcium phosphate binding with either calcium acetate or calcium carbonate is equivalent, provided that calcium carbonate is taken on an empty stomach a few minutes before meals. The number of capsules calcium carbonate, but also the total amount in grams, necessary to keep serum phosphate and intact parathormone levels into an acceptable range then is significantly less. This might improve patient compliance.\nStudy4: Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate. Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients. In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks. Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group. This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750-3,000 mg/day) is similar to that seen with calcium carbonate (1,500-9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate.\nStudy5: Calcium acetate versus calcium carbonate for the control of serum phosphorus in hemodialysis patients. Recent in vitro and in vivo studies have shown that calcium acetate (CaAC) is a more effective phosphorus binder than, among other calcium salts, calcium carbonate (CaCO3). More efficient binding allows serum phosphorus to be controlled with a lower dose; moreover, less calcium seems to be absorbed when CaAC is used. These properties could reduce the incidence of hypercalcemia; however, in clinical practice few reports have compared these two calcium salts, and results disagree. We evaluated in a 24-week prospective cross-over study the clinical efficiency of CaCO3 and CaAC in 10 selected chronic hemodialysis patients. Only 7 patients completed the study period. The patients were randomly assigned to start treatment with one of the two calcium salts; after 12 weeks they shifted to the other treatment. Serum analytical tests included weekly control of calcium, phosphorus, and alkaline phosphatase. PTH values (intact molecule) were obtained initially and at the end of every study period. The same good control of the phosphorus level (4.79 +/- 0.6 vs. 4.94 +/- 0.8 mg/dl) was obtained with CaAC (mean doses 4.1 +/- 0.3 g/day) as with CaCO3 (mean doses 4.01 +/- 0.8 g/day). The mean serum calcium levels were similar (10.36 +/- 0.5 vs. 10.20 +/- 0.5 mg/dl). The dose of elemental calcium administered was significantly less with CaAC (957 +/- 83 mg/day) than with CaCO3 (1,590 +/- 317 mg/day). However, the incidence of hypercalcemia (Ca > 11 mg/dl) was similar during the two treatment periods (13% with CaAC vs. 14% with CaCO3). Also the incidence of Ca x P products 765 was comparable (9.5 vs. 11.9%).(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy6: Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis. The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum-aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients.\nStudy7: Higher strength lanthanum carbonate provides serum phosphorus control with a low tablet burden and is preferred by patients and physicians: a multicenter study. Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d. This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with or = 2. According to the TNM classification, the tumor distribution was as follows: 11 T1, 153 T2, 175 T3, and 42 T4. The mediastinum was involved in 174 patients. All patients were treated by external radiation therapy with a total dose of 60-65 Gy. Classical fractionation of the irradiation dose was done in 217 patients and hypofractionation was used for 164 patients. After treatment, improvement of the superior vena and Pancoast's syndromes was observed in 90% of the patients. Radiological complete response was obtained in 177 patients (47%). The 5-year overall survival rate was 6.2%. No significant differences in survival according to the initial tumor size, the mediastinum status or the fractionation scheme were noted. The 5-year survival rate was 13% in patients with a tumor that completely responded to irradiation. Death was mainly due to local failure (231 patients, 69%) and metastatic disease (107 patients, 32%). The radiotherapy tolerance was acceptable. Although irradiation provides good palliation and a 10%-survival rate at 3 years, the results relating to radiation therapy were disappointing.\nStudy8: Superior vena caval obstruction syndrome in small cell lung cancer. In a series of 643 patients with small cell lung cancer (SCLC), 55 patients (8.6%) had signs or symptoms of superior vena caval obstruction syndrome (SVCO). Relatively long intervals from the onset of the first symptoms of SVCO to the start of therapy were observed, and invasive diagnostic procedures were safely performed in most patients. The pretreatment characteristics of patients with SVCO were not significantly different from those of patients without signs of the syndrome, and survival was similar in both groups. Patients with SVCO were usually treated first with induction chemotherapy, and prompt resolution of signs and symptoms occurred in the majority. Radiation was effective in controlling SVCO at relapse or after failure of initial chemotherapy. It was concluded that SVCO in patients with SCLC should be treated initially with systemic chemotherapy, as for other presentations of this disease. The current data do not support the commonly held view that SVCO in SCLC should be approached as an oncologic emergency.\nStudy9: Combination chemotherapy in the management of superior vena caval obstruction in small-cell anaplastic carcinoma of the lung. Among 225 consecutive patients with small-cell anaplastic bronchogenic carcinoma, 26 (11.5%) had superior vena caval obstruction when the malignancy was diagnosed. Of these 26 patients, a consecutive series of 22 were treated initially with combination chemotherapy (cyclophosphamide, methotrexate and CCNU, in some cases combined with vincristine) alone, and in all these cases resolution of the syndrome was prompt within a median of 7 days. In no case were symptoms increased transiently by the treatment. No difference in response rate was observed between the histologic subtypes of small-cell anaplastic bronchogenic carcinoma according to the WHO classification. Combination chemotherapy alone is an effective treatment of superior vena caval obstruction in patients with small-cell anaplastic bronchogenic carcinoma.\nStudy10: Case report: migration and shortening of a self-expanding metallic stent complicating the treatment of malignant superior vena cava stenosis. nan\n", + "output": "Conclusions: Chemotherapy and radiotherapy are effective in relieving SVCO in a proportion of patients whereas stent insertion appears to provide relief in a higher proportion and more rapidly. The optimal timing of stent insertion (whether at diagnosis or following failure of other modalities) and the effectiveness of steroids remain uncertain." + }, + { + "input": "Study1: The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. The range of human milk docosahexaenoic acid (DHA) concentrations worldwide is much broader than the range explored in randomized clinical trials to date. The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age. Secondary objectives were to evaluate visual acuity maturation, red blood cell fatty acids, tolerance, anthropometric measures, and adverse events. This double-masked, randomized trial was conducted at 2 sites (Dallas and Kansas City). Three hundred forty-three healthy, term, formula-fed infants were enrolled at 1-9 d of age and were randomly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts, except for long-chain polyunsaturated fatty acids: control (0% DHA), 0.32% DHA, 0.64% DHA, or 0.96% DHA; DHA-supplemented formulas also provided 0.64% arachidonic acid. Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination. Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas (P < 0.001). There were no significant differences in visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested. DHA supplementation of infant formula at 0.32% of total fatty acids improves visual acuity. Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity. This trial was registered at clinicaltrials.gov as NCT00753818.\nStudy2: Long-chain polyunsaturated fatty acids and infant formula. nan\nStudy3: Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study. To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development. A double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at or =2 third molars were randomized according to pain severity (moderate vs severe) to receive a single dose of placebo (n = 45), rofecoxib 50 mg (n = 90), celecoxib 200 mg (n = 91), or ibuprofen 400 mg (n = 46). Using a patient diary, patients recorded pain intensity, pain relief, and global evaluations throughout the 24-hour period after dosing. The overall analgesic effect, onset of action, peak effect, and duration of effect were evaluated, with the primary end point being total pain relief over 8 hours (TOPAR8). The safety profile was assessed on the basis of physical findings, laboratory results, and spontaneous reports of adverse experiences. The results showed that compared with celecoxib, rofecoxib had superior analgesic effects on all measures of analgesic efficacy, including overall analgesic effect (TOPAR8, 18.3 vs. 12.5; P<0.001), time to onset of effect (30 vs. 60 minutes; P = 0.003), peak pain relief (score, 2.8 vs 2.3; P<0.05), and duration of effect (>24 vs. 5.1 hours; P<0.001). In addition, rofecoxib's analgesic efficacy was similar to that of ibuprofen (TOPAR8, 18.3 vs. 17.0; P = 0.460), but the duration was longer (P<0.05); with ibuprofen, the time to on set was 24 minutes, peak pain relief score was 2.9, and duration of analgesic effect was 8.9 hours. The safety profile was similar across all treatment groups. Thus rofecoxib provided analgesic efficacy superior to that of celecoxib and comparable to that of ibuprofen in the treatment of patients with acute postoperative dental pain.\nStudy6: MK-0703 (a cyclooxygenase-2 inhibitor) in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. MK-0703 is a selective cyclooxygenase-2 inhibitor investigated for the treatment of acute pain and inflammation. The purpose of this single-dose, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was to compare MK-0703 12.5, 50, and 100 mg with ibuprofen 400 mg or placebo in patients who experienced moderate to severe pain after surgical removal of at least 2 third molars. Overall analgesic effect, duration of analgesic effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. The primary endpoint of this study was total pain relief over 8 hours postdose. The study included 121 patients (mean age, 23 yr); 16, 31, 28, 31, and 15 patients enrolled in the placebo, MK-0703 12.5 mg, MK-0703 50 mg, MK-0703 100 mg, and ibuprofen 400 mg groups, respectively. Both MK-0703 50 and 100 mg were significantly more effective than placebo for all endpoints (P < 0.01) and comparable with ibuprofen 400 mg. The onset of analgesic effect in the MK-0703 50 mg and 100 mg and ibuprofen 400 mg groups did not differ significantly from each other (P > 0.20). MK-0703 was generally well tolerated in single doses up to 100 mg. In summary, MK-0703 50 and 100 mg were efficacious in the treatment of postoperative dental pain and were indistinguishable from the active comparator, ibuprofen 400 mg.\nStudy7: Pregabalin in patients with postoperative dental pain. Pregabalin is an analogue of the inhibitory neurotransmitter gamma-aminobutyric acid. In preclinical models, it has shown activity as an analgesic agent. A randomized, double-blind, placebo-controlled, parallel-group trial was undertaken to compare pregabalin to placebo and 400 mg of ibuprofen using a dental pain model. Study medication was administered postoperatively to patients who had undergone elective surgery to remove one or two third molars, at least one of which was mandibular and fully or partially impacted in bone. The study was conducted in the UK at a single centre and evaluated pregabalin at doses of 50 and 300 mg. Primary efficacy parameters included pain relief (PR), pain intensity difference (PID), pain relief intensity difference (PRID), time to onset of analgesia, and duration of analgesia. The patient's global impression of the study medication was used as a secondary efficacy parameter. Efficacy data were evaluated for the intent-to-treat (ITT) population, defined as all randomized patients who took study medication. Results showed that there were statistically significant differences in PR, PID, and PRID between the 300-mg pregabalin group and placebo. In addition, the 300-mg pregabalin group had a significantly longer duration of analgesia than the ibuprofen group and had the highest score on the patient global impression of study medication. Adverse events were reported more frequently in the pregabalin 300-mg group. Pregabalin appears to have significant analgesic properties in the third molar extraction model. Further research is needed to confirm these findings. Copyright 2001 European Federation of Chapters of the International Association for the study of pain.\n", + "output": "Conclusions: The very substantial amount of high quality evidence demonstrates that ibuprofen is an effective analgesic in treating postoperative pain. NNTs for 200 mg and 400 mg ibuprofen did not change significantly from the previous review even when a substantial amount of new information was added. New information is provided on remedication." + }, + { + "input": "Study1: Ovarian function after cancer treatment in young women affected by Hodgkin disease (HD). We have evaluated the best method to assess the ovarian reserve and the ovarian protective effect of GnRH-analog (GnRH-a), in 29 women with Hodgkin's disease (HD) treated with chemotherapy (CHT). The ovarian reserve was studied by measuring the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, antimullerian hormone (AMH) and the ultrasound antral follicular count (AFC). The patients were randomly treated with or without GnRH-a. At the time of study menstrual function was normal in 21 cases (72.4%), but absent in 8 (27.5%). Mean basal values of FSH, LH, AMH, inhibin B and AFC were normal in patients less than 30 years old and in the group treated four years or less before observation. AFC appeared to be the best marker of reduced ovarian reserve and a combination of AFC-AMH or inhibin B appeared the best predictor. In the GnRH-a group, no women had amenorrhoea, although ovarian reserve assessment was not significantly different from those who were not treated. The time-interval from CHT was the only significant predictor of ovarian function in GnRH-a treated patients. In conclusion, ovarian reserve evaluation, in young patients treated by CHT, can be performed by AFC. GnRH-a treatment does not have a protective effect, but could delay the development of ovarian failure.\nStudy2: Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study. To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not. Prospective randomized controlled study. Department of Obstetrics and Gynecology, Mansura University Hospital, Mansura, Egypt. Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study. Patients were assigned randomly to receive combined GnRHa and chemotherapy or chemotherapy alone. One woman in each group dropped out. Return of spontaneous menstruation and ovulation. Hormonal changes (FSH, LH, E(2), P) during and after the course of treatment. In the study group, 89.6% resumed menses and 69.2% resumed spontaneous ovulation within 3-8 months of termination of the GnRHa/chemotherapy cotreatment; 11.4% experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment. In the control group (chemotherapy without GnRHa), 33.3% resumed menses and 25.6% resumed normal ovarian activity. The median FSH and LH concentrations, 6 months after completion of the GnRHa/chemotherapy cotreatment group, were significantly less than the control group. During the GnRHa/chemotherapy cotreatment the concentrations of FSH, LH, and P decreased to almost prepubertal levels. However, within 1-3 months after the last GnRHa injection, an increase in LH and FSH concentrations was detected, followed several weeks later in by an increase in P concentrations to within normal levels. GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women <40 years. Long-term studies are required.\n", + "output": "Conclusions: The use of GnRH agonists should be considered in women of reproductive age receiving chemotherapy. Intramuscular or subcutaneous GnRH analogues seem to be effective in protecting ovaries during chemotherapy and should be given before or during treatment, although no significant difference in pregnancy rates was seen." + }, + { + "input": "Study1: A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation. Normal saline (NS; 0.9% NaCl) is administered during kidney transplantation to avoid the risk of hyperkalemia associated with potassium-containing fluids. Recent evidence suggests that NS may be associated with adverse effects that are not seen with balanced-salt fluids, e.g., lactated Ringer's solution (LR). We hypothesized that NS is detrimental to renal function in kidney transplant recipients. Adults undergoing kidney transplantation were enrolled in a prospective, randomized, double-blind clinical trial of NS versus LR for intraoperative IV fluid therapy. The primary outcome measure was creatinine concentration on postoperative Day 3. The study was terminated for safety reasons after interim analysis of data from 51 patients. Forty-eight patients underwent living donor kidney transplants, and three patients underwent cadaveric donor transplants. Twenty-six patients received NS, and 25 patients received LR. There was no difference between groups in the primary outcome measure. Five (19%) patients in the NS group versus zero (0%) patients in the LR group had potassium concentrations >6 mEq/L and were treated for hyperkalemia (P = 0.05). Eight (31%) patients in the NS group versus zero (0%) patients in the LR group were treated for metabolic acidosis (P = 0.004). NS did not adversely affect renal function. LR was associated with less hyperkalemia and acidosis compared with NS. LR may be a safe choice for IV fluid therapy in patients undergoing kidney transplantation.\nStudy2: Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Metabolic acidosis and changes in serum osmolarity are consequences of 0.9% normal saline (NS) solution administration. We sought to determine if these physiologic changes influence patient outcome. Patients undergoing aortic reconstructive surgery were enrolled and were randomly assigned to receive lactated Ringer's (LR) solution (n = 33) or NS (n = 33) in a double-blinded fashion. Anesthetic and fluid management were standardized. Multiple measures of outcome were monitored. The NS patients developed a hyperchloremic acidosis and received more bicarbonate therapy (30 +/- 62 mL in the NS group versus 4 +/- 16 mL in the LR group; mean +/- SD), which was given if the base deficit was greater than -5 mEq/L. The NS patients also received a larger volume of platelet transfusion (478 +/- 302 mL in the NS group versus 223 +/- 24 mL in the LR group; mean +/- SD). When all blood products were summed, the NS group received significantly more blood products (P = 0.02). There were no differences in duration of mechanical ventilation, intensive care unit stay, hospital stay, and incidence of complications. When NS was used as the primary intraoperative solution, significantly more acidosis was seen on completion of surgery. This acidosis resulted in no apparent change in outcome but required larger amounts of bicarbonate to achieve predetermined measurements of base deficit and was associated with the use of larger amounts of blood products. These changes should be considered when choosing fluids for surgical procedures involving extensive blood loss and requiring extensive fluid administration. Predominant use of 0.9% saline solution in major surgery has little impact on outcome as assessed by duration of mechanical ventilation, intensive care unit stay, hospital stay, and postoperative complications, but it does appear to be associated with increased perioperative blood loss.\n", + "output": "Conclusions: The administration of buffered fluids to adult patients during surgery is equally safe and effective as the administration of non-buffered saline-based fluids. The use of buffered fluids is associated with less metabolic derangement, in particular hyperchloraemia and metabolic acidosis. Larger studies are needed to assess robust outcomes such as mortality." + }, + { + "input": "Study1: A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness. In a multicenter, placebo-controlled, clinical trial, the efficacy of Limbitrol was compared with that of its components, amitriptyline and chlordiazepoxide. All patients had a diagnosis of primary depression. Data from 279 patients were evaluated using the Hamilton depression scale, the Beck depression inventory, and physician and patient global change measures. Statistically significant differences favoring Limbitrol occurred after 1 week of treatment, and a trend in favor of Limbitrol continued throughout the remaining 3 weeks. In most efficacy comparisons, the combination was as good as, or better than, amitriptyline alone. It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment. Each component produced an independent contribution to the total therapeutic effect: the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks. A trend favoring amitriptyline over chlordiazepoxide was evident by week 4. The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups. Limbitrol-treated patients exhibited more sedation, but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects.\nStudy2: Hypnotics as concurrent medication in depression. A placebo-controlled, double-blind comparison of flunitrazepam and lormetazepam in patients with major depression, treated with a (tri)cyclic antidepressant. The addition of benzodiazepine hypnotics to a treatment with tricyclic antidepressants has received little systematic study. In a double-blind placebo-controlled design, the effects on mood and on sleep of two benzodiazepine hypnotics (lormetazepam and flunitrazepam) were studied in patients with major depression who were also treated with maprotiline or nortriptyline. After 4 weeks of combined treatment, lormetazepam resulted in a significantly greater decrease in the score on the Hamilton Depression Subscale than placebo, while there was a non-significant trend in favour of lormetazepam in comparison with flunitrazepam. With respect to sleep EEGs, lormetazepam resulted in a significantly greater suppression of REM sleep. The differences between lormetazepam and flunitrazepam may be partly explained by the shorter half-live of lormetazepam.\nStudy3: Comparative effects of limbitrol and amitriptyline on sleep efficiency and architecture. Chlordiazepoxide-amitriptyline (Limbitrol) has been shown to be more rapidly effective than amitriptyline alone for treating depression. A double-blind, randomized study was designed to compare the effects of Limbitrol and amitriptyline on insomnia, anxiety, and depression. The rate of improvement of symptoms was faster with Limbitrol. No differences were noted between groups in the degree or rate of improvement of the sleep laboratory parameters nor in sleep Stages 1 to 4. Percentages of rapid eye movement (REM) sleep and REM latency were similarly affected by the drugs, but REM density showed a significantly greater decrease with Limbitrol. Phasic REM factors may be crucial in the role of REM sleep and depression.\nStudy4: Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression? Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment. A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension. Fifty outpatient volunteers aged 18-65 from Seattle and Portland with moderate-marked depression received fluoxetine (20 mg) doubled at 6 weeks if needed; half took clonazepam (0.5 mg) and half took an identical placebo, 1 or 2 tablets adjusted during the first 2 weeks, until a 3-week taper at 3 months. No serious adverse events and no special problems with sedation or discontinuation were noted. Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D (t=2.03, df=48, P<0.05) and CGI-I (32 vs. 4% responders, P<0.03, Fisher Exact Test) but not otherwise. Cotherapy was effective in reducing insomnia but not anxiety or core symptoms (low mood, suicidality, reduced interest). The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76% after 8 weeks compared to 16 weeks for monotherapy. Small sample size (N=50) limited power and rendered conclusions tentative. Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed outpatients: it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase. Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated. Copright 2002 Elsevier Science BV.\nStudy5: Alprazolam: an antidepressant? Alprazolam, desipramine, and an alprazolam-desipramine combination in the treatment of adult depressed outpatients. The antidepressant efficacy of alprazolam (ALP) was tested in a double-blind controlled comparison with desipramine (DMI) and an ALP-DMI combination in outpatients diagnosed with major depressive disorder by Research Diagnostic Criteria (90% met criteria for endogenous subtype). Following a placebo period of at least 1 week, subjects who continued to meet severity criteria defined by Hamilton Depression Rating Scale (HDRS) scores were administered oral doses of the active medication (N = 79), in a dose ratio of 1 mg ALP:50 mg DMI:1 mg ALP + 50 mg DMI. Treatment continued for 6 weeks, and all subjects who completed at least 2 weeks (N = 69) were included in endpoint analyses. Following the placebo baseline, symptoms were rated again at day 5 and at the end of weeks 1, 2, 4, and 6. Final doses averaged 4.6 +/- 1.3 mg for the ALP group, 230 +/- 61 mg for the DMI group, and 4.6 +/- 1.2 mg ALP + 229.5 +/- 1.2 mg DMI for the combination group. The final outcome was a comparable degree of improvement at the endpoint among the three treatment groups on measures of depression (HDRS and Beck Depression Inventory), anxiety (Hamilton Anxiety Rating Scale), and global improvement (Global Assessment Scale, and Physician and Patient Global Impressions). A similar outcome was found for the subgroup of patients who completed all 6 weeks (N = 56). Endpoint analyses also showed that ALP-treated subjects responded sooner and continued to show improvement throughout the course of the study on measures of depression, anxiety, and global status. These results suggest that ALP alone is as effective as a standard tricyclic for the acute treatment of patients with major depressive disorder and that significant improvement may occur within the first week of medication. Side effect profiles were compared among treatment groups and are discussed, as are other clinical studies that have investigated ALP's potential antidepressant efficacy.\nStudy6: A double blind study in out-patients with primary non-agitated depression treated with imipramine in combination with placebo, diazepam or dixyrazine. Sixty-three out-patients suffering from primary non-agitated depression were included in a double-blind, between-patient randomized study. All patients were treated with imipramine (100-200 mg-day) combined with either placebo, diazepam (10 mg/day) or dixyrazine (50 mg/day) for 8 weeks. The clinical efficacy assessed with a subscale of CPRS was significantly (p1 less than or equal to 0.05) better for the imipramine-dixyrazine combination than for the imipramine-diazepam or imipramine-placebo combination. Serum concentration of imipramine was significantly higher (p1 less than or equal to 0.05) in the group treated with dixyrazine than in the other two groups. Further, serum concentration of imipramine in the diazepam group was significantly lower (p1 less than or equal to 0.05) than in the placebo group. At the end of the study, 67% in both the placebo and the diazepam group and 86% in the dixyrazine group were practically symptom-free.\n", + "output": "Conclusions: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harms including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop out, on the other." + }, + { + "input": "Study: Effects of pentoxifylline on coagulation profile and disseminated intravascular coagulation incidence in Egyptian septic neonates. Neonatal sepsis is frequently associated with pathological activation of the coagulation system, leading to microcirculatory derangement and multiple organ dysfunction syndrome (MODS). The key role in the pathogenesis of sepsis has been attributed to proinflammatory cytokines. These trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. Pentoxifylline (PTX), a methylxanthine derivative that is used in peripheral vascular disease, has the potential to modify inflammatory response. The current work was designed to evaluate the potential protective effects of PTX against sepsis-induced microcirculatory derangement in Egyptian neonates. A double-blind placebo-controlled quasi-randomized design was used. Thirty-seven neonates with sepsis were randomly allocated into two groups. Seventeen patients were given PTX (5 mg/kg/h for 6 h; for 6 successive days). Twenty patients received equivalent volume of normal saline and represented the placebo group. Prothrombin time (PT), Activated partial thromboplastin time (APTT), fibrinogen, d-dimer, C-reactive protein (CRP), complete blood count (CBC), also hemodynamic parameters comprising arterial blood pressure, heart rate, capillary refill and urinary output were assessed in both groups before and after treatment. Coagulation parameters in the two groups showed no significant differences. However, a higher incidence of DIC was observed in the placebo group neonates. PTX significantly lowered the percentage of bleeding (P = 0.0128) and less frequent use of FFP was observed in the PTX group (35.53% in PTX group vs. 80% in placebo group, P = 0.003). Incidence of MODS was significantly lower (P = 0.037) and hospital stay duration of survivors was significantly shorter (P = 0.044) in the PTX treated-infants. Pentoxifylline protects against sepsis-induced microcirculatory derangement in neonates. It significantly lowered the incidence of bleeding and MODS and shortened the length of hospital stay.\n", + "output": "Conclusions: Current evidence from four small studies suggests that the use of pentoxifylline as an adjunct to antibiotics in neonatal sepsis decreases mortality without any adverse effects. Researchers are encouraged to undertake large well-designed multicenter trials to confirm or refute the effectiveness of pentoxifylline in reducing mortality and adverse outcomes in neonates with suspected or confirmed neonatal sepsis and NEC." + }, + { + "input": "Study1: Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome. Danish-Swedish Multicenter Study Group. In southern Scandinavia most babies with respiratory distress syndrome are initially treated with nasal continuous positive airway pressure. We performed a multicenter trial to investigate whether the addition of a single dose of porcine surfactant administered during a short intubation before the occurrence of serious deterioration could reduce the subsequent need for mechanical ventilation. We randomly assigned 35 infants with moderate-to-severe respiratory distress syndrome to surfactant therapy (Curosurf, 200 mg per kilogram of body weight) plus nasal continuous positive airway pressure and 33 infants to nasal continuous positive airway pressure alone. The study was not blinded. The indications for mechanical ventilation were a ratio of arterial to alveolar oxygen tension of less than 0.15, severe apneic attacks, or both. Six hours after randomization, when the median age of the babies was 18 hours, the mean ratio of arterial to alveolar oxygen tension was 0.37 in the surfactant-treated babies, as compared with 0.25 in the controls (P < 0.001). The need for subsequent mechanical ventilation was reduced with surfactant therapy (to 43 percent of the surfactant-treated babies as compared with 85 percent of the controls; P = 0.003). When 17 infants with ratios of arterial-to-alveolar oxygen tension of less than 0.15 at randomization were excluded, the need for mechanical ventilation was still significantly reduced in the surfactant-treated group (to 33 percent [9 of 27 babies], as compared with 83 percent [20 of 24 babies] in the control group; (P < 0.001). After 28 days, two of the surfactant-treated babies had died, as compared with five of the control babies. In babies with moderate-to-severe respiratory distress syndrome treated with nasal continuous positive airway pressure, a single dose of surfactant reduced the need for subsequent mechanical ventilation.\nStudy2: Early extubation and nasal continuous positive airway pressure after surfactant treatment for respiratory distress syndrome among preterm infants <30 weeks' gestation. To test the hypothesis that preterm infants with infant respiratory distress syndrome who are treated with nasal continuous positive airway pressure (NCPAP) and surfactant administration followed by immediate extubation and NCPAP application (SURF-NCPAP group) demonstrate less need for mechanical ventilation (MV), compared with infants who receive MV after surfactant administration (SURF-MV group). A prospective randomized study was conducted, in which infants <30 weeks' gestation were randomized to the SURF-NCPAP group or the SURF-MV group. At 7 days of life, no patient in the SURF-NCPAP group but 6 patients (43%) in the SURF-MV group still were undergoing MV. The duration of oxygen therapy, NCPAP, and MV, the need for a second dose of surfactant, and the length of stay in the intensive care unit were significantly greater in the SURF-MV group. The immediate reinstitution of NCPAP after surfactant administration for infants with infant respiratory distress syndrome is safe and beneficial, as indicated by the lesser need for MV and the briefer requirement for respiratory supports, compared with the institution of MV after surfactant treatment. Moreover, this strategy contributed to reducing the need for surfactant treatment and reducing the time and costs involved in keeping the infants in the neonatal intensive care unit.\n", + "output": "Conclusions: Early surfactant replacement therapy with extubation to NCPAP compared with later selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with less need mechanical ventilation, lower incidence of BPD and fewer air leak syndromes. A lower treatment threshold (FIO2 < 0.45) confers greater advantage in reducing the incidences of airleak syndromes and BPD; moreover a higher treatment threshold (FIO2 at study > 0.45) was associated with increased risk of PDA. These data suggest that treatment with surfactant by transient intubation using a low treatment threshold (FIO2 < 0.45) is preferable to later, selective surfactant therapy by transient intubation using a higher threshold for study entry (FIO2 > 0.45) or at the time of respiratory failure and initiation of mechanical ventilation." + }, + { + "input": "Study: Cataract surgery in high-risk age-related macular degeneration: a randomized controlled trial. To investigate if cataract surgery causes progression, from high-risk early age-related macular degeneration (AMD) to choroidal neovascularization (CNV), in the postoperative period. Randomized controlled trial. Patients, with visually significant cataract and fundus features of early AMD at high risk of progression to CNV, were randomized into two groups and were evaluated at baseline and 6 months. The study patients (n = 27) underwent immediate cataract surgery. The control group (n = 29) comprised patients who had cataract surgery deferred until after the 6-month visit. Assessment included visual acuity, quality of life (QoL) and fundus fluorescein angiography (FFA). Of 68 eligible eyes, 60 participated and 56 completed the study. Three referred eyes (3.2%) were ineligible on the basis of a pre-existing, unsuspected occult CNV that was detected by baseline FFA. All three cases had end-stage exudative AMD in the fellow eye. Of the study eyes in the immediate surgery arm (n = 27), one (3.7%) developed CNV compared with none (0/29) in the deferred arm (chi(2); P = 1.0) at 6 months. In the operated group, there was a 2.8-line improvement in logMAR visual acuity and 2.1-fold average gain in QoL at 6 months. No increased short-term risk of progression of AMD to CNV in high-risk fundi following uncomplicated phacoemulsification surgery was found. A low threshold for performing preoperative imaging in patients with AMD, especially in those with exudative AMD in the fellow eye, to exclude undetected CNV is recommended. Provided there is no CNV, there are distinct benefits of cataract surgery in people with early AMD.\n", + "output": "Conclusions: At this time, it is not possible to draw reliable conclusions from the available data to determine whether cataract surgery is beneficial or harmful in people with AMD.\u00a0Physicians will have to make practice decisions based on best clinical judgment until controlled trials are conducted and their findings published.\nIt would be valuable for future research to investigate prospective RCTs comparing cataract surgery to no surgery in patients with AMD to better evaluate whether cataract surgery is beneficial or harmful in this group. However ethical considerations need to be addressed when delaying a potentially beneficial treatment and it may not be feasible to conduct a long-term study where surgery is withheld from the control group.\u00a0Utilization of pre-existing, standardized systems for grading cataract and AMD and measuring outcomes (visual acuity, change in visual acuity, worsening of AMD and quality of life measures) should be encouraged." + }, + { + "input": "Study1: Effect of visco-elastic foam mattresses on the development of pressure ulcers in patients with hip fractures. This study had three aims: to investigate if visco-elastic foam mattresses are more effective than standard hospital mattresses in reducing the incidence of pressure ulcers in patients with hip fractures; to compare pressure ulcer grade and location and documented nursing prevention and treatment interventions in patients using the two types of mattresses; to identify possible predictors of pressure ulcer development. Using a prospective randomised controlled trial design 101 patients (mean age: 84 years) were randomly allocated either a visco-elastic foam mattress or a standard mattress. There was no significant difference in the incidence of pressure ulcers between the two groups, but patients on standard mattresses tended to develop more severe pressure ulcers. Furthermore, according to the documentation, patients with grade I pressure ulcers who were allocated a standard mattress received more preventive interventions, which may have reduced the differences in outcomes between the two groups. The researchers concluded that the results support the use of the test mattress. Significant predictors of pressure ulcer development were long waiting times for surgery and low haemoglobin levels at hospital admission.\nStudy2: The role of alternating air and Silicore overlays in preventing decubitus ulcers. Patients with chronic neurological diseases who were at high risk of decubitus ulcers were randomly assigned to alternating air on silicore mattress overlays for a period of 3 months. Of 148 subjects who completed the trial, more than 50% in each group developed one or more ulcers. No statistically significant differences between groups were found in the incidence, severity, healing duration or the location of the ulcers; with the exception of a significant difference (p less than 0.001) in the categorical location of the trochanters.\nStudy3: Study results: prediction and prevention of pressure ulcers in surgical patients. nan\nStudy4: Profiling beds versus standard hospital beds: effects on pressure ulcer incidence outcomes. Most standard hospital beds are flat based with a pull-out backrest, resulting in a tendency for the patient to slide down the bed. This study aimed to compare the outcome for patients at high risk of developing pressure ulcers nursed on either this type of bed or an electrically operated, multi-sectioned profiling bed. A total of 100 patients were randomly assigned either to the profiling bed with a pressure-reducing foam mattress (experimental group) or a flat-based bed with an appropriate pressure-redistributing mattress (control group) for a maximum of 10 days. Risk status and pressure damage were assessed daily. Both a patient and a nurse questionnaire were completed. Data from 70 patients who participated in the study for five days or more were included in the analysis. Pressure ulcer incidence was 0% in both groups. All patients (35) in the experimental group were able to maintain a sitting position compared with only 12/35 in the control group (p = 0.0001). While the questionnaire results suggest there were significant differences in postural control and ease of transfer between patients in the two groups, it was not possible to map this to pressure ulcer formation. Poor recruitment into the study was due to the 'blocking' of electric beds by heavily dependent patients who did not meet the inclusion criteria, precluding a significant result in terms of pressure ulcer outcomes. This nurse-led use of the profiling beds was examined alongside the main study to investigate why they were allocated in this way.\nStudy5: Pressure-reducing mattresses. A clinical evaluation of eight base foam pressure-reducing mattresses was undertaken at Addenbrooke's NHS Trust, Cambridge. Data were collected on the medical and nutritional status, skin condition, medication, weight and Waterlow score for each patient, together with ratings on mattress comfort. At the beginning and end of the study, mattresses were assessed for interface pressures and the general condition of each mattress and its cover was evaluated.\nStudy6: Pressure relieving support surfaces: a randomised evaluation. To determine differences between alternating pressure overlays and alternating pressure replacement mattresses with respect to the development of new pressure ulcers, healing of existing pressure ulcers, patient acceptability and cost-effectiveness of the different pressure-relieving surfaces. Also to investigate the specific additional impact of pressure ulcers on patients' well-being. A multicentre, randomised, controlled, open, fixed sample, parallel-group trial with equal randomisation was undertaken. The trial used remote, concealed allocation and intention-to-treat (ITT) analysis. The main trial design was supplemented with a qualitative study involving a purposive sample of 20-30 patients who developed pressure ulcers, to assess the impact of the pressure ulcers on their well-being. In addition, a focus group interview was carried out with clinical research nurses, who participated in the PRESSURE (Pressure RElieving Support SUrfaces: a Randomised Evaluation) Trial, to explore the experiences of their role and observations of pressure area care. The study took place in 11 hospital-based research centres within six NHS trusts in England. Acute and elective patients aged 55 years or older and admitted to vascular, orthopaedic, medical or care of the elderly wards in the previous 24 hours were investigated. Patients were randomised to either an alternating pressure overlay or an alternating pressure mattress replacement, with mattress specifications clearly defined to enable the inclusion of centres using products from different manufacturers, and to exclude hybrid mattress systems (which either combine foam or constant low pressure with alternating pressure in one mattress, or can be used as either an overlay or a replacement mattress). Development of a new pressure ulcer (grade < or =2, i.e. partial-thickness wound involving epidermis/dermis only) on any skin site. Also healing of existing pressures ulcers, patient acceptability and cost-effectiveness. In total, 6155 patients were assessed for eligibility to the trial and 1972 were randomised: 990 to the alternating pressure overlay (989 after one postrandomisation exclusion) and 982 to the alternating pressure mattress replacement. ITT analysis found no statistically significant difference in the proportions of patients developing a new pressure ulcer of grade 2 or above [10.7% overlay patients, 10.3% mattress replacement patients, a difference of 0.4%, 95% confidence interval (CI) -2.3 to 3.1%, p = 0.75]. When logistic regression analysis was used to adjust for minimisation factors and prespecified baseline covariates, there was no difference between the mattresses with respect to the odds of ulceration (odds ratio 0.94, 95% CI 0.68 to 1.29). There was no evidence of a difference between the mattress groups with respect to time to healing (p = 0.86). The Kaplan-Meier estimate of the median time to healing was 20 days for each intervention. More patients allocated overlays requested mattress changes due to dissatisfaction (23.3%) than mattress replacement patients (18.9%, p = 0.02) and more than one-third of patients reporting difficulties associated with movement in bed and getting into or out of bed. There is a higher probability (64%) that alternating mattress replacements are cost-saving; they were associated with lower overall costs (74.50 pounds sterling per patient on average, mainly due to reduced length of stay) and greater benefits (a delay in time to ulceration of 10.64 days on average). Patients' accounts highlighted that the development of a pressure ulcer could be pivotal in the trajectory from illness to recovery, by preventing full recovery or causing varied impacts on their quality of life. There is no difference between alternating pressure mattress replacements and overlays in terms of the proportion of patients developing new pressure ulcers; however, alternating pressure mattress replacements are more likely to be cost-saving. The results suggest that when renewing alternating pressure surfaces or ordering equipment within a rental contract, mattress replacements should be specified; however, overlays are acceptable if no replacement mattress is available. Similarly, patient preferences can be supported, without any great increase in risk, if individual patients request an overlay rather than a replacement mattress. Further research could include a randomised controlled trial comparing alternating pressure mattress replacements and high-specification foam mattresses in patients at moderate to high risk; an accurate costing study to understand better how much pressure ulcers cost health and social services in the UK; and trials in higher risk groups of patients. Also future trials should measure time to ulceration as the primary end-point, since this is more informative economically and possibly also from a patient and clinical perspective.\nStudy7: Randomised controlled trial to evaluate a new double-layer air-cell overlay for elderly patients requiring head elevation. A clinical investigation was conducted concerning the effects of a newly designed double-layer air-cell overlay in preventing the onset of pressure ulcers for patients with a Braden scale score of < or = 16, and who require a head-elevated position of 45 degrees or higher. A randomised controlled trial was undertaken involving 82 patients from a general hospital ward using one of the following three support surfaces: a double-layer air-cell overlay, a single-layer air-cell overlay or a standard hospital mattress. A significantly lower percentage of patients using the double-layer air-cell overlay developed pressure ulcers (3.4%) compared to 19.2% and 37.0% for those patients using the single-layer air-cell overlay and standard mattress respectively. Based on these findings, a double-layer air-cell overlay should be more effective in preventing the onset of pressure ulcers than either a single-layer air-cell overlay or a standard hospital mattress for subjects requiring head elevation.\nStudy8: A comparison of two pressure-relieving devices on the prevention of heel pressure ulcers. The effectiveness of hospital pillows versus a commercial heel elevation device (the Foot Waffle [EHOB incorporated]) in preventing heel pressure ulcers was examined using an experimental balanced factorial design with repeated measures on 52 patients (ages 27 to 90) in randomized groups. Heel interface pressures were taken with patients in supine and right lateral tilt positions. Logistic regression demonstrated a statistically significant difference between interface pressures on left and right heels (p = .004) and a trend toward significance between the pillow and Foot Waffle (p = .069). The Generalized Estimating Equations (GEE) method revealed the Foot Waffle was four times more likely not to suspend the heel off the bed than the pillow, and the left heel was four-and-a-half times more likely to have higher interface pressures than the right. There was no significant difference between groups in incidence of lower-extremity pressure ulcers, but patients using the Foot Waffle developed pressure ulcers significantly sooner (10 days versus 13 days for the pillow). Heels require additional protection beyond the use of specially beds and mattress overlays. In order to provide continuous heel suspension, clinicians must consider proper fit, turning schedules, patient position, patient activity, and presence of additional equipment when selecting heel protection products. This study illustrates how difficult it is to control for all these factors when doing clinical research. Note: This study was done with a Foot Waffle model that has since been redesigned. No research is available on the new model.\nStudy9: Clinical effectiveness of a low-tech versus high-tech pressure-redistributing mattress. To compare the effectiveness of a high-specification foam mattress (control) with a high-tech (Duo2, Hill Rom) alternating/continuous low-pressure mattress (treatment) in the prevention of pressure ulceration. The study also evaluated if there is a difference in performance between the two working modalities (alternating and continuous low pressure) of the high-tech mattress in a comparable sample of patients. MethoD: Thirty-three patients were observed for two weeks in the control group. In the treatment group, 86 patients were randomised to receive alternating low pressure and 84 continuous low pressure. Incidence of pressure ulcers in both arms was recorded. Student's t-test was used to compare all Braden scores, and the chi-square test and Fisher's exact test to evaluate differences between groups. There was a high difference in the number of new pressure ulcers in the control group when compared with the treatment group. There was no difference in performance between the alternating and continuous low-pressure modes. However, the sample size is too small to prove or disprove a statistically significant difference between the two modalities. The high-tech mattress was markedly more effective than the high-specification foam mattress in preventing the onset of pressure ulcers. Initial data suggest that the use of alternating or continuous low pressure made little or no difference to the results.\nStudy10: Effects of position and mattress overlay on sacral and heel pressures in a clinical population. A comparison of pressure reducing properties of alternating air, static air, and water mattress overlays was conducted with 57 patients in a surgical intensive care unit. Sacral and heel pressures in both recumbent and semi-Fowler's positions were tested for each surface using a repeated measures design. Mean pressures for the alternating air mattress were significantly higher than pressures with other surfaces, regardless of position or site. There were significant main effects for position and site, with higher pressures in the semi-Fowler's position and at the sacral site. A significant interaction between surface, site, and position was found. Pressure sores developed in eight patients, but the incidence was not significantly different across groups. A pressure measuring device constructed from available clinical materials proved to be both sensitive and reliable. The findings suggest alternating air overlays should be avoided, and that positioning and periodic position change to reduce sacral pressures for patients requiring prolonged upper body elevation is important.\n", + "output": "Conclusions: People at high risk of developing pressure ulcers should use higher-specification foam mattresses rather than standard hospital foam mattresses. The relative merits of higher-specification constant low-pressure and alternating-pressure support surfaces for preventing pressure ulcers are unclear, but alternating-pressure mattresses may be more cost effective than alternating-pressure overlays in a UK context. Medical grade sheepskins are associated with a decrease in pressure ulcer development. Organisations might consider the use of some forms of pressure relief for high risk patients in the operating theatre." + }, + { + "input": "Study1: Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection. Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection. Minor side-effects requiring no specific medication were recorded in a small proportion of individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001). The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy.\nStudy2: Treatment of chronic Chagas' disease with itraconazole and allopurinol. Four hundred four patients with chronic Chagas' disease were treated with itraconazole (6 mg/kg of body weight/day for 120 days), allopurinol (8.5 mg/kg of body weight/day for 60 days), or with a placebo of pure starch. Patients were monitored over a period of four years by clinical examination, serology, xenodiagnosis, hemoculture, and electrocardiogram. Drug tolerance was good, with only four treatments discontinued due to side effects that subsided after suspension of treatment. Parasitologic cure was evident in 44% of the those treated with allopurinol and 53% of those treated with itraconazole, and the electrocardiographic evaluation showed normalization in 36.5% and 48.2%, respectively, of patients with chronic or recent cardiopathy.\n", + "output": "Conclusions: Despite major public health importance, trypanocidal\u00b7therapy for chronic asymptomatic T. cruzi infection has been tested in few, small size RCTs which were designed to assess parasitic-related, but not clinical outcomes. Therefore, the potential of trypanocidal therapy to prevent Chagas' disease among asymptomatic, chronically infected subjects is promising, but remains to be evaluated. Trypanocidal therapy, particularly nitroimidazolic derivatives given to children or adults with positive xenodiagnosis improve parasite-related outcomes. The large contrast between the burden of Chagas disease and the existing evidence on its prevention points the need to test these or newer agents in more and larger RCTs that include clinical endpoints." + }, + { + "input": "Study1: [Femoral nerve block as pain relief in hip fracture. A good alternative in perioperative treatment proved by a prospective study]. Almost 25% of all patients with hip fracture experience temporary confusion pre- and directly postoperatively due to trauma, advanced age, transport between units, and the use of analgesics, 35-50% of the patients suffer temporary or chronic decubitus. Analgesics often lead to nausea. A femoral nerve block can interrupt sensory impulses from the hip joint and provide complete pain relief without affecting the CNS, thus making preoperative care easier and postoperative rehabilitation can be started earlier. 80 consecutive patients with hip fracture were randomized to femoral nerve block or pharmacological treatment only. Paracetamol and tramadol were the standard analgesics used. All patients were followed up with regard to pain, duration of the block, number of analgesics doses, temporary confusion and time for postoperative mobilization. Pain was estimated by the patients using the visual analogue scale (VAS). A nerve block was performed to block the femoral nerve, the lateral femoral cutaneous nerve and the obturator nerve with 30 ml of ropivacaine 7.5 mg/ml. Mental status was evaluated with Pfeiffer-test. All patients experienced relatively intense pain on admission with an average VAS of 6. After nerve block the VAS was 2. Pain relief was the same in the control group. Pain relief was sustained for 15 hours. The time for mobilization after surgery was significantly lower, 23 hours compared to 36 for the control group. There was a lower number of patients temporarily confused in the block group compared to the control group, however no significant differences were seen. Femoral nerve block provides adequate pain relief, equivalent to pharmacological treatment in most patients. The time for postoperative mobilization was shorter and less temporary confusion was seen. There were no complications in this group, making nerve block a good alternative to traditional pharmacological preoperative treatment for patients with hip fractures.\nStudy2: Epidural infusion of bupivacaine and fentanyl reduces perioperative myocardial ischaemia in elderly patients with hip fracture--a randomized controlled trial. Perioperative myocardial ischaemia is an important risk factor for cardiac morbidity and mortality after noncardiac surgery. The impact of analgesic management on the incidence and severity of cardiac ischemia was studied in 77 elderly patients undergoing surgical treatment of traumatic hip fracture. After hospital admission and written consent, patients were randomised to conventional analgesic regimen (intramuscular oxycodone, OPI group) or continuous epidural infusion of bupivacaine/fentanyl (EPI group). The analgesic regimens were started preoperatively. Patients were operated under spinal anaesthesia and the treatments were continued three days postoperatively. ECG was continuously recorded. ST segment depression of > or = 0.1 mV or elevation of > or = 0.2 mV lasting > or = 1 min were considered as ischaemic episodes. Nocturnal arterial oxygen saturation (SaO2) was recorded perioperatively, and subjective pain was assessed every morning using a visual analogue scale (VAS). Fifty-nine (OPI 30, EPI 29) patients were evaluable for efficacy. Thirteen patients (43%) in the OPI and 12 patients (41%) in the EPI group had ischaemic episodes (NS). However, significantly more patients in the OPI group had ischaemic episodes during the surgery (8 vs. 0 in the EPI group, P=0.005). The median (quartal deviation) total ischaemic burden (i.e. integral of ST-change vs. time) in patients with ischaemic episodes was ten times larger in the OPI group (340 [342] mm x min) compared with the EPI group (30 [36] mm x min) (P=0.002). There were no significant differences between the groups in average heart rates or in heart rates at the start of ischaemic episodes or in maximal heart rates during the attacks. Average nocturnal SaO2 was similar in the two groups and there were no differences in the number of hypoxaemic (SaO2<90%) episodes. Preoperatively there were no differences in subjective pain, but postoperative and average perioperative VAS scores for pain were almost 40% lower in the EPI group (P=0.006). Perioperative myocardial infarctions were not detected. Continuous epidural bupivacaine/fentanyl analgesic regimen, started preoperatively, reduces the amount of myocardial ischaemia in elderly patients with hip fracture.\nStudy3: [Analgesia after hip fracture repair in elderly patients: the effect of a continuous femoral nerve block: a prospective and randomised study]. The usefulness of peripheral femoral nerve block for pain management after hip fracture has been established. This prospective and randomised study compared the analgesia effect of a continuous femoral nerve block (CF) versus two conventional analgesia procedures after hip fracture. Patients. (n=62) scheduled for surgery under spinal anaesthesia were prospectively included. After surgery, analgesia (48 hours) was randomised: group FC (femoral catheter, anterior paravascular approach, initial bolus followed by continuous infusion of ropivacaine 0.2%), group P (iv 2 g propacetamol/6 hours), group M (sc morphine, 0.05 mg/kg per 4 hour). Intravenous morphine titration was performed, followed by subcutaneous (sc) morphine every 4 hours according to the VAS score. The primary end-point was the morphine requirements. Secondary end-points were VAS score, side effects, and mortality. Demographic data and surgical procedures were similar between groups. After morphine titration, the VAS pain score did not differ between groups. All patients in-group M received additional morphine. Morphine mean consumption was increased in CF group: 26 mg (5-42) versus P: 8 mg (3-12) (p=0.0001) or M: 19 mg (8-33) (p<0.006) while constipation was decreased in P group vs CF. Percentage of patients requiring no morphine was similar between P (n=6; 28%) and CF (n=6; 28%) and greater than M (n=0; 0%). Hospital discharge, cardiovascular or pulmonary complications and mortality after 6 months showed no statistical difference. Continuous femoral nerve block provided limited pain relief after hip fracture did not reduced side effects and induced an expensive cost.\nStudy4: Preoperative cardiac events in elderly patients with hip fracture randomized to epidural or conventional analgesia. Perioperative myocardial ischemia occurs in 35% of unselected elderly patients undergoing hip fracture surgery. Perioperative epidural analgesia may reduce the incidence of adverse cardiac events. The effect of early administration of epidural analgesia during the stressful period, on cardiac events was evaluated in a prospective randomized study in 68 patients with hip fractures who either had known coronary artery disease or were at high risk for coronary artery disease. On admission to the emergency room, patients were assigned to receive a usual care analgesic regimen (intramuscular meperidine, control group, n = 34) or continuous epidural infusion of local anesthetic and opioid (epidural group, n = 34). Monitoring in the preoperative period included a preoperative history and physical examination, daily assessment of cardiac adverse events, serial electrocardiograms, cardiac enzymes, and pain scores. Preoperative adverse cardiac events were significantly more prevalent in the control group compared with the epidural group (7 of 34 0 of 34; = 0.01). Adverse cardiac events included fatal myocardial infarction in three, fatal congestive heart failure in one, nonfatal congestive heart failure in one, and new onset atrial fibrillation in two. The incidence of intraoperative and postoperative adverse cardiac events was similar for the two groups. The significant difference between groups in the incidence of preoperative cardiac events prompted interruption of the study after the planned interim analysis. The authors' data indicate that compared with conventional analgesia, early administration of continuous epidural analgesia is associated with a lower incidence of preoperative adverse cardiac events in elderly patients with hip fracture who have or are at risk for coronary artery disease. Preoperative epidural analgesia may be advantageous for this surgical population.\n", + "output": "Conclusions: Because of the small number of participants included in this review, limitations in the measurement and reporting of outcomes and the differing types of nerve blocks and timing of insertion, it is not possible to determine if nerve blocks confer any significant clinical benefit when compared with other analgesic methods as part of the treatment of a hip fracture. They do, however, reduce the degree of pain experienced by the patient from the hip fracture and subsequent surgery. Further randomised trials with larger numbers of participants and full reporting of clinical outcomes would be justified." + }, + { + "input": "Study1: A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto Study group. To report the results of a double-blind, placebo-controlled trial to evaluate Azuprostat, a beta-sitosterol, in patients with symptoms of outlet obstruction caused by benign prostatic hyperplasia (BPH). A randomized, double-blind and placebo-controlled clinical trial was conducted to assess the efficacy and safety of 130 mg free beta-sitosterol (phytosterol) daily, using the international prostate symptom score (IPSS) as the primary outcome variable. In total, 177 patients with BPH were recruited for 6 months of treatment in 13 study centres. In addition to the relative difference in the IPSS, changes in quality of life, peak urinary flow rate (Qmax) and post-void residual urinary volume (PVR) were recorded. The drug used in the trial consisted of a chemically defined extract of phytosterols, derived for example from species of Pinus, Picea or Hypoxis, with beta-sitosterol as the main component. There were significant (P < 0.01) improvements over placebo in those treated with beta-sitosterol; the mean difference in the IPSS between placebo and beta-sitosterol, adjusted for the initial values, was 5.4 and in the quality-of-life index was 0.9. There were also significant improvements in the secondary outcome variables, with an increase in Qmax (4.5 mL/s) and decrease in PVR (33.5 mL) in favour of beta-sitosterol when adjusted for the changes after placebo. These results show that beta-sitosterol is an effective option in the treatment of BPH.\nStudy2: A double-blind trial of the effect of beta-sitosteryl glucoside (WA184) in the treatment of benign prostatic hyperplasia. Cholesterol-lowering agents are still used in some countries for the treatment of benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled urodynamic study, carried out on 53 patients with proven outflow obstruction, has failed to prove that the drug, beta-sitosteryl beta-D-glucoside (WA184), is superior to placebo in the treatment of outflow obstruction due to BPH when administered at a dose of 0.3 mg/day. Possible reasons for this include an insufficient dose and duration of treatment (this drug is known to have a potent effect on cholesterol metabolism in the prostate) and the predominantly stromal pathological changes which characterize BPH and which may be unaffected by such agents.\nStudy3: Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multicentre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg beta-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6.7 (SD 4.0) points in the beta-sitosterol-treated group versus -2.1 (3.2) points in the placebo group p < 0.01. There was a decrease in IPSS (-7.4 [3.8] points in the beta-sitosterol-treated group vs -2.1 [3.8] points in the placebo group) and changes in urine flow parameters: beta-sitosterol treatment resulted in increasing peak flow (15.2 [5.7] mL/s from 9.9 [2.5] mL/s), and decrease of mean residual urinary volume (30.4 [39.9] mL from 65.8 [20.8] mL). These parameters did not change in the placebo group (p < 0.01). No relevant reduction of prostatic volume was observed in either group. Significant improvement in symptoms and urinary flow parameters show the effectiveness of beta-sitosterol in the treatment of benign prostatic hyperplasia.\n", + "output": "Conclusions: The evidence suggests non-glucosidic B-sitosterols improve urinary symptoms and flow measures. Their long term effectiveness, safety and ability to prevent BPH complications are not known." + }, + { + "input": "Study1: A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women. To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen. Randomised controlled trial. A tertiary teaching hospital. One hundred and thirteen women (66 premenopausal/47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy. Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen. De novo endometrial pathology at 1 year of tamoxifen. Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P= 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P= 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year. LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.\nStudy2: Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel-releasing intrauterine system: a randomised controlled trial. Tamoxifen is currently the most commonly used adjuvant treatment for breast cancer, however, it frequently causes episodes of unscheduled uterine bleeding, which could be associated with proliferative changes of the endometrium, or even endometrial cancer. We aimed to assess whether a levonorgestrel intrauterine system could modulate the uterine responses to tamoxifen. We also aimed to assess women's tolerance of the screening procedures, the insertion, removal, and potential side-effects of the device. We did a randomised controlled trial, in which postmenopausal women who had had at least 1 year of adjuvant tamoxifen treatment and who were undergoing regular follow-up for breast cancer were randomly assigned to either endometrial surveillance alone, or endometrial surveillance before and after insertion of the levonorgestrel intrauterine system for 12 months. We assessed tolerance of the surveillance procedures and the device with visual analogue scales. Baseline assessment showed only benign uterine changes in all women (n=122). Hysteroscopic assessment indicated a uniform decidual response (confirmed histologically in 40 of 41 cases) in all women fitted with the intrauterine system; there were no new polyps in these women and 13% had fewer fibroids than in controls. Both screening procedures and device were well tolerated. There was an excess of bleeding in the women fitted with intrauterine systems but this resolved to a baseline similar to those receiving surveillance only. The levonorgestrel-releasing intrauterine system had a protective action against the uterine effects of tamoxifen. The effectiveness of this device in preventing uterine changes in the endometrium needs to be assessed in the context of decreasing the need for repeated investigations of postmenopausal bleeding in women taking tamoxifen.\n", + "output": "Conclusions: The Mirena LNG-IUS appears to prevent the development of benign endometrial polyps in breast cancer patients taking tamoxifen, over a one-year period. There is no clear evidence from the available randomised controlled trials that LNG-IUS prevents endometrial hyperplasia or adenocarcinoma in these patients. Larger studies are necessary to assess the effects of LNG-IUS in preventing endometrial hyperplasia and endometrial cancer, and to determine whether LNG-IUS might have an impact on the risk of breast cancer recurrence." + }, + { + "input": "Study: A randomized controlled trial of intervention in fear of childbirth. To compare intensive and conventional therapy for severe fear of childbirth. In Finland, 176 women who had fear of childbirth were randomly assigned at the 26th gestational week to have either intensive therapy (mean 3.8 +/- 1.0 sessions with obstetrician and one with midwife) or conventional therapy (mean 2.0 +/- 0.6 sessions), with follow-up 3 months postpartum. Pregnancy-related anxiety and concerns, satisfaction with childbirth, and puerperal depression were assessed with specific questionnaires. Power analysis, based on previous studies, showed that 74 women per group were necessary to show a 50% reduction in cesarean rates. Birth-related concerns decreased in the intensive therapy group but increased in the conventional therapy group (linear interaction between the group and birth-concerns P =.022). Labor was shorter in the intensive therapy group (mean +/- standard deviation 6.8 +/- 3.8 hours) compared with the conventional group (8.5 +/- 4.8 hours, P =.039). After intervention, 62% of those originally requesting a cesarean (n = 117) chose to deliver vaginally, equally in both groups. Cesarean was more frequent for those who refused to fill in the questionnaires than for those who completed them (57% compared with 27%, P =.001). In the log-linear model, parous women who had conventional therapy and refused to fill in the questionnaires chose a cesarean more often than expected (standardized residual 2.54, P =.011). There were no differences between groups in satisfaction with childbirth or in puerperal depression. Both kinds of therapy reduced unnecessary cesareans, more so in nulliparous and well-motivated women. With intensive therapy, pregnancy- and birth-related anxiety and concerns were reduced, and labors were shorter.\n", + "output": "Conclusions: Implementation of guidelines with mandatory second opinion can lead to a small reduction in caesarean section rates, predominately in intrapartum sections. Peer review, including pre-caesarean consultation, mandatory secondary opinion and postcaesarean surveillance can lead to a reduction in repeat caesarean section rates. Guidelines disseminated with endorsement and support from local opinion leaders may increase the proportion of women with previous caesarean sections being offered a trial of labour in certain settings. Nurse-led relaxation classes and birth preparation classes may reduce caesarean section rates in low-risk pregnancies." + }, + { + "input": "Study: Clobazam in therapy-resistant patients with partial epilepsy: a double-blind placebo-controlled crossover study. Clobazam was compared with placebo as antiepileptic adjunct medication in 129 therapy-resistant epileptic patients who were mainly suffering from complex partial seizures. The study was performed in five European countries according to a double-blind crossover design lasting 7 months. Two treatment periods of 3 months (1 month adjustment and 2 months maintenance medication) were separated by one medication switch-over month. The difference in seizure reduction between clobazam and placebo was significant (p less than 0.05). Nineteen percent of patients receiving clobazam became seizure-free during the maintenance dose period. In contrast, freedom from seizures was not observed in any placebo patient. Electroencephalogram (EEG) signs, mood ratings, and global impressions also indicated therapeutic effects of clobazam in epilepsy. The most frequent adverse reactions to clobazam were drowsiness and dizziness. However, the sedative effects of clobazam seemed to be less pronounced in comparison with other benzodiazepines. The study gives evidence of the therapeutic value of clobazam as adjunct medication in therapy-resistant partial seizures. The use of clobazam as monotherapy and long-term treatment, as well as the particular seizure response pattern to clobazam, has to be further investigated.\n", + "output": "Conclusions: Clobazam as an add-on treatment may reduce seizure frequency and may be most effective in partial onset seizures. However, it is not clear who will best benefit and over what time-frame. A large scale, randomised controlled trial conducted over a greater period of time, incorporating subgroups with differing seizure types, is required to inform clinical practice." + }, + { + "input": "Study1: A prospective randomized trial comparing subatmospheric wound therapy with a sealed gauze dressing and the standard vacuum-assisted closure device. Two methods of subatmospheric pressure wound therapy--wall suction applied to a sealed gauze dressing (GSUC) and the vacuum-assisted closure device (VAC)--were compared in hospitalized patients at University of Chicago Medical Center. VAC therapy is widely used, but can be expensive and difficult to apply; it also fails in some patients. A randomized prospective study of 87 patients (N = 45 in the GSUC arm and N = 42 in the VAC arm) was undertaken between October 2006 and May 2008. The study comprised patients with acute wounds resulting from trauma, dehiscence, or surgery. Demographics and wound characteristics were similar in both groups. There were significant reductions in wound surface area and volume in each group. In the GSUC group, the reductions in wound surface area and volume were 4.5%/day and 8.4%/day, respectively (P < 0.001 for both), and in the VAC group, this was 4.9%/day and 9.8%/day, respectively (P < 0.001 for both). The reductions in wound surface area and volume were similar in both groups (P = 0.60 and 0.19, respectively, for the group-by-time interaction). The estimated difference (VAC - GSUC) was 0.4% (95% confidence interval: -1.0, 1.7) for wound surface area and 1.4% (95% confidence interval: -0.7, 3.5) for volume. The mean cost per day for GSUC therapy was $4.22 versus $96.51 for VAC therapy (P < 0.01) and the average time required for a GSUC dressing change was 19 minutes versus 31 minutes for a VAC dressing change (P < 0.01). The sum of pain intensity differences was 0.50 in the GSUC group compared with 1.73 for the VAC group (P = 0.02). GSUC is noninferior to VAC with respect to changes in wound volume and surface area in an acute care setting. In addition, GSUC dressings were easier to apply, less expensive, and less painful.\nStudy2: A randomized, prospective, controlled study of forearm donor site healing when using a vacuum dressing. 1) Compare skin graft healing of the radial forearm free flap (RFFF) donor site when using a negative pressure dressing (NPD) versus a static pressure dressing (SPD). 2) Examine the association of graft size and medical comorbidities with healing of RFFF donor site. Randomized, controlled trial. Tertiary care hospital. After the study was approved, consenting adults undergoing RFFF for head and neck reconstructions were randomized into two arms: SPD and NPD groups. Fifty-four patients were enrolled from March 2007 to August 2009. Pre- and postoperative data were collected, including medical comorbidities, graft size, and area of graft failure/tendon exposure. Data were collected at two postoperative time points. The overall wound complication rate was 38 percent (19/50). Wound complications at the first postoperative visit (44.4% [12/27] SPD and 30.4% [7/23] NPD) were not significantly different between groups (P = 0.816). Similarly, wound complications at the second visit (68.8% [11/16] SPD and 80% [12/15] NPD) were not significantly different (P = 0.55). Percentage of area of graft failure between the groups also showed no difference (4.5% SPD vs 7.2% NPD, P = 0.361). The association of graft size with wound complications was analyzed by dividing the data set into three groups (<50 cm(2), 51-100 cm(2), and >100 cm(2)). This difference was not found to be significant (P = 0.428). Finally, when evaluating comorbidities, 50 percent (8/16) of subjects with comorbidities experienced complications compared with 32.4 percent (11/34) without comorbidities, also not reaching significance (P = 0.203). Although an attractive option for wound care, the NPD does not appear to offer a significant improvement over an SPD in healing of the RFFF donor site. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.\nStudy3: Negative pressure wound therapy to prevent seromas and treat surgical incisions after total hip arthroplasty. The purpose of this study was to evaluate the use of negative pressure wound therapy (NPWT) to improve wound healing after total hip arthroplasty (THA) and its influence on the development of postoperative seromas in the wound area. The study is a prospective randomised evaluation of NPWT in patients with large surgical wounds after THA, randomising patients to either a standard dressing (group A) or a NPWT (group B) over the wound area. The wound area was examined with ultrasound to measure the postoperative seromas in both groups on the fifth and tenth postoperative days. There were 19 patients randomised in this study. Ten days after surgery, group A (ten patients, 70.5 \u00b1 11.01 years of age) developed seromas with an average size of 5.08 ml and group B (nine patients, 66.22 \u00b1 17.83 years of age) 1.97 ml. The difference was significant (p = 0.021). NPWT has been used on many different types of traumatic and non traumatic wounds. This prospective, randomised study has demonstrated decreased development of postoperative seromas in the wound and improved wound healing.\nStudy4: Effectiveness of negative pressure closure in the integration of split thickness skin grafts: a randomized, double-masked, controlled trial. To determine the effectiveness of the negative pressure closure (NPC) technique in the integration of split-thickness skin grafts (STSG) to the recipient site. Randomized, double-masked, controlled trial. Setting: A tertiary burn unit. Patient characteristics: Between May 2003 and October 2004, 60 patients having wounds with skin loss which hindered primary closure, were incorporated to this study. We excluded patients with > or =20% of total body surface burns, polytraumatized, surgical contraindications, those who were enlisted in other clinical trials, and those who rejected the informed consent. Interventions: In all the patients, surgical cleaning of the recipient site and STSG were performed after which they were randomly assigned between 2 groups: a group that received a NPC dressing and were connected to the central aspiration system at -80 mm Hg versus a control group with similar dressing but without connection to negative pressure. Loss of STSG area at the fourth postoperative day, days of hospital stay. Sixty patients were included. The median loss of the STSG in the NPC group was 0.0 cm versus 4.5 cm in the control group (P = 0.001). The median hospital stay was of 13.5 days in the NPC group versus 17 days in the control group (P < 0.001). The use of NPC significantly diminishes the loss of STSG area, as well as shortens the days of hospital stay. Therefore, it should be routinely used for these kinds of procedures.\n", + "output": "Conclusions: There is no evidence for the effectiveness of NPWT on complete healing of wounds expected to heal by primary intention. There are clear cost benefits when non-commercial systems are used to create the negative pressure required for wound therapy, with no apparent reduction in clinical outcome. Pain levels are also rated lower when hospital systems are compared with their commercial counterparts. The high incidence of blisters occurring when NPWT is used following orthopaedic surgery suggests that the therapy should be limited until safety in this population is established. Given the cost and widespread use of NPWT, there is an urgent need for suitably powered, high-quality trials to evaluate the effects of the newer NPWT products that are designed for use on clean, closed surgical incisions. Such trials should focus initially on wounds that may be difficult to heal, such as sternal wounds or surgeries for obese patients." + }, + { + "input": "Study1: Blood transfusion-modulated tumor recurrence: first results of a randomized study of autologous versus allogeneic blood transfusion in colorectal cancer surgery. Allogeneic blood transfusions have reportedly been associated with a poor prognosis in patients with curatively resected cancer. To control for immunosuppression induced by a speculatively causal allogeneic blood transfusion, we designed a randomized study in which the control group received autologous blood transfusions not related to any condition of immunosuppression. One hundred twenty patients with potentially curative resectable colorectal cancer and the capability to predeposit autologous blood were randomly selected to receive either standard allogeneic blood transfusion or predeposited autologous blood. In curatively resected cancer patients, the number who needed allogeneic blood transfusions was reduced from 60% in the allogeneic blood group to 33% in the autologous blood group (P = .009). After a median follow-up duration of 22 months (range, 8 to 48) tumor recurrence was observed in 28.9% of the allogeneic blood group and 16.7% of the autologous blood group. Life-table analysis established a tendency toward a shorter tumor-free survival for the allogeneic blood group (log-rank P = .11). The problem with this analysis was the strong association of allogeneic blood transfusions with tumor recurrence, which interfered in 33% of patients in the autologous blood group who required additional allogeneic blood transfusions. Multivariate analysis of established risk factors for tumor recurrence and surgery-related variables reflecting potential immunosuppressive conditions showed that only pT stage (relative risk, 6.61; 95% confidence interval [CI], 1.82 to 23.99; P = .004), pN stage (relative risk, 8.39; 95% CI, 3.15 to 22.33; P < .001), and the need for allogeneic blood (relative risk, 6.18; 95% CI, 2.20 to 17.37; P < .001) were independent predictors of tumor recurrence. Subgroup analysis of patients who received a transfusion of < or = 2 U blood found a significantly higher risk of tumor recurrence in the allogeneic blood group (relative risk, 5.16; 95% CI, 1.13 to 23.62; P = .034), which was reduced to borderline significance (relative risk, 3.54; 95% CI, 0.76 to 16.51; P = .107) by adjustment for tumor (T) and node (N) stage. As indicated by these first results, the blood transfusion modality has a significant effect on tumor recurrence after surgical treatment of colorectal cancer. A change in the practice of blood transfusion might thus potentially surpass the impact of any recent adjuvant treatment strategies.\nStudy2: Autologous blood transfusion for hepatectomy in patients with cirrhosis and hepatocellular carcinoma: use of recombinant human erythropoietin. We evaluated the benefit of autologous blood transfusion and the effect of recombinant human erythropoietin (rh-EPO) on preoperative autologous blood donation for hepatectomy in patients with cirrhosis. Forty-two patients with cirrhosis and hepatocellular carcinoma underwent hepatectomy, 21 of whom (group A) donated autologous blood before operation. Eleven of these patients (group A1) were administered rh-EPO before operation, and ten patients (group A2) were untreated. Twenty-one patients (group B) did not donate autologous blood. The frequency of homologous blood transfusion was 24% in group A and 62% in group B (p < 0.05). Preoperative erythropoiesis increased markedly in group A1, and postoperative erythropoietin production was not suppressed in this group. Postoperative hematocrits recovered significantly more rapidly in patients transfused with only autologous blood. Postoperative serum total bilirubin concentrations were significantly higher in patients with transfused homologous blood. Autologous blood transfusion yields clinically superior results for hepatectomy in patients with cirrhosis when compared with homologous transfusion. Preoperative rh-EPO administration minimizes presurgical decreases in hematocrit caused by autologous blood donation.\nStudy3: Blood transfusions and prognosis in colorectal cancer. Blood transfusions may adversely affect the prognosis of patients treated surgically for cancer, although definite proof of this adverse effect has not been reported. We carried out a randomized trial to investigate whether the prognosis in patients with colorectal cancer would be improved by a program of autologous blood transfusion as compared with the current practice of allogeneic transfusion. Patients in the autologous-transfusion group were required to donate two units of blood before surgery. A total of 475 patients were evaluated. We found no significant difference in prognosis between the allogeneic-transfusion group (236 patients) and the autologous-transfusion group (239 patients); colorectal cancer-specific survival rates at four years were 67 percent and 62 percent, respectively (P = 0.39). Among the 423 patients who underwent curative surgery, 66 percent of those in the allogeneic-transfusion group and 63 percent of those in the autologous-transfusion group had no recurrence of colorectal cancer at four years (P = 0.93). We also found that the risk of recurrence was significantly increased in patients who received blood transfusions, either allogeneic or autologous, as compared with patients who did not require transfusions; the relative rates of recurrence were 2.1 (P = 0.01) and 1.8 (P = 0.04), respectively; these rates did not differ significantly from each other. The use of autologous blood as compared with allogeneic blood for transfusion does not improve the prognosis in patients with colorectal cancer. Regardless of their type, transfusions are associated with poor prognosis, probably because of the circumstances that necessitate them.\nStudy4: Preoperative autologous blood donation reduces the need for allogeneic blood products: a prospective randomized study. We sought to assess the efficacy of preoperative autologous blood donation in reducing patient exposure to allogeneic blood products following elective cardiac surgery. We included 48 patients in a prospective study and randomly assigned them into the control or treatment group. We excluded patients with aortic stenosis, main trunk stenosis and unstable angina. Group A (n=23; coronary disease n=21 and valvular disease n=2) was the control group, and group B (n=25; coronary disease n=21, valvular disease n=4) received preoperative autologous blood donation. All patients had cardiopulmonary bypass surgery, and we processed mediastinal blood with a cell-saver device before reinfusion. All patients received aprotinin, and we reinfused blood shed from the mediastinum postoperatively. No major peri- or postoperative complications occurred. We interrupted preoperative blood donation in 2 patients (8%) because of worsened angina pectoris. The mean time between the first blood donation and surgery was 22.5 (standard deviation [SD] 9.4, range 12-50) days. In group A, 9 patients (39.1%) were exposed to allogeneic blood products. In group B, 11 patients (47.8%) were exposed to blood products (p=0.73), and 4 (16%) were exposed to allogeneic blood products (p=0.036). Preoperative blood donation was completed in 92% of the targeted low-risk population. The procedure significantly reduced exposure to perioperative allogeneic blood products.\nStudy5: Predonation autologous blood in hip arthroplasty. In a prospective randomized study of elderly patients, a total of 130 units of blood were donated by 45 patients prior to a total hip arthroplasty. Fifteen patients served as controls (no phlebotomy). The average age was 71 (60-82) years. No major complication occurred with phlebotomy. All the patients were able to maintain their hematologic and chemical parameters within the normal range throughout the donation period. The autologous blood covered all the peroperative transfusion needs and 97 percent of the total transfusion requirements. There was less postoperative blood loss, as well as total blood loss, in the autologous groups compared with the control group. There was no difference in the rate of postoperative complications between the groups. The use of predeposited autologous blood in elective orthopedics, regardless of patient age, is feasible, cost effective, and avoids the risks associated with homologous blood transfusion.\nStudy6: [A comparison of autologous transfusion procedures in hip surgery]. The risks associated with transfusion can be minimized with autologous blood. The efficiency of preoperative deposit, preoperative hemodilution and intra- and postoperative autotransfusion in reducing homologous transfusions has been demonstrated. There seem to be few studies, however, that compared the different methods of autologous transfusion. This study was designed to evaluate the comparative efficiency of these methods. PATIENTS AND METHODS. Sixty-four patients scheduled for total hip arthroplasty were randomly divided into four groups: group I--preoperative autologous deposit: group II--preoperative hemodilution; group III--intra- and postoperative autotransfusion; group IV--control. Preoperative autologous donations were stored in CPDA-1 buffer. Three units of 450 ml were requested. A predonation hemoglobin (Hb) concentration of 11 g dl was required. Surgery was carried out in the 5th week after the first donation. Preoperative hemodilution to Hb 9 g/dl was carried out after induction of anesthesia and initial circulatory stabilization. A cell separator was used for intra- and postoperative autotransfusion. Postoperative autotransfusion of drainage blood was continued until 6 h after the beginning of the operation. Polygeline was used for volume resuscitation. If the Hb concentration fell below 9 g/dl in the operating room and intensive care unit or below 10 g/dl in the general ward, autologous blood or homologous packed red cells were transfused. Autologous blood collected with the cell separator was retransfused at the end of the operation and after the autotransfusion period irrespective of the actual Hb concentration. RESULTS. The general data of the patients, blood loss, and Hb concentration at the beginning of the study and postoperatively were comparable in the four groups. Homologous transfusion requirements amounted to 0 (0-1250) ml (median, range) packed red cells in group I (preoperative deposit). 500 (0-2000) ml in group II (hemodilution), 125 (0-1000) ml in group III (autotransfusion) and to 500 (0-1500) ml in group IV (control). In group I 14 of 16 patients, in group II 1 of 16, in group III 8 of 16 patients, in group IV 5 of 15 patients did not require homologous transfusion. The difference between group I and IV was significant (p = 0.004 and p = 0.003). Global coagulation tests, antithrombin III, and total serum protein were comparable in the four groups. DISCUSSION. The efficiency of preoperative hemodilution to reduce homologous transfusion requirements is limited]. In the present study, as in two other recent studies, hemodilution did not reduce homologous transfusion requirements. Autotransfusion with a cell separator can save approximately 50% of the erythrocytes lost during hip arthroplasty and 70% of the drainage loss. The homologous transfusion requirements for the autotransfused group reported here were less than in the control group; the difference, however, was not statistically significant. Patients participating in preoperative autologous deposit did not require homologous blood for hip arthroplasty in 62%-70% of cases in other investigations; in the present study 88% of the patients did not require homologous blood. CONCLUSION. Under the conditions studied, preoperative autologous deposit was the most efficient method of autologous transfusion for hip arthroplasty. It should be employed primarily.\nStudy7: A prospective, randomized study of preoperative autologous donation for hip replacement surgery. Preoperative autologous blood donation is commonly performed to meet potential perioperative transfusion needs and is a common practice prior to total hip arthroplasty. Using standardized transfusion guidelines, we prospectively analyzed the effectiveness of preoperative autologous donation as a method for decreasing allogeneic transfusion among patients undergoing unilateral primary total hip replacement who were eligible to donate autologous blood. Patients who were scheduled for primary total hip replacement surgery and who had a preoperative baseline hemoglobin level >or=120 g/L were randomized either to donate two units of blood (autologous donors) or not to donate any blood (nondonors). The donors and nondonors were compared with regard to demographic data, blood-loss volumes, hemoglobin measurements, and transfusion rates. Randomization continued until data were obtained from at least forty patients per treatment group. Of the ninety-six patients who completed the study, forty-two were autologous donors and fifty-four were nondonors. There were no significant differences between the donors and nondonors with regard to age, male:female ratio, estimated blood volume, baseline physical condition, or operative blood loss. The hemoglobin values at the time of enrollment (baseline), at the time of hospital discharge, and six weeks postoperatively were not significantly different between the two groups, although values at the time of admission (129 +/- 13 g/L versus 138 +/- 12 g/L) and in the recovery room (104 +/- 12 g/L versus 115 +/- 13 g/L) were significantly lower in the autologous donor group (p < 0.05). No patient in either group required an allogeneic transfusion. Twenty-nine (69%) of the forty-two donors received an autologous transfusion. Thirty-four (41%) of eighty-two autologous units were wasted. At a charge of $379 per autologous unit, there was an additional cost of $758 for each patient in the donor group. Preoperative autologous donation provided no benefit for nonanemic patients undergoing primary total hip replacement surgery. Preoperative autologous donation increased the likelihood of autologous transfusion, wastage of predonated units, and costs.\nStudy8: Preoperative use of recombinant human erythropoietin before total joint arthroplasty. Previous reports have suggested that the use of recombinant human erythropoietin is effective for decreasing the need for perioperative allogeneic blood transfusion. The purpose of this study was to evaluate the efficacy of erythropoietin in combination with, and compared with, preoperative autologous donation for reducing allogeneic blood requirements for total joint arthroplasty. Two hundred and forty patients undergoing primary and revision total hip or knee arthroplasty were enrolled into three groups with different treatment regimens: (1) erythropoietin and preoperative autologous donation (Group 1), (2) erythropoietin alone (Group 2), and (3) preoperative autologous donation alone (Group 3). Patients were evaluated with regard to requirements for allogeneic transfusion, change from the baseline to the lowest postoperative hemoglobin value, postoperative complications, and adverse reactions. The rate of allogeneic transfusion was 11% in Group 1 (erythropoietin and preoperative autologous donation) compared with 28% in Group 2 (erythropoietin alone) and 33% in Group 3 (preoperative autologous donation alone). Within Group 1, patients who had a unilateral primary arthroplasty had an allogeneic transfusion rate of 4% and those who had a bilateral or revision arthroplasty had an allogeneic transfusion rate of 17%. In Groups 2 and 3, the allogeneic transfusion rates were 14% and 15%, respectively, for the patients who had a unilateral primary arthroplasty and 35% and 47%, respectively, for those who had a bilateral or revision arthroplasty. Preoperative use of erythropoietin in conjunction with preoperative autologous donation reduces the need for allogeneic blood transfusion associated with total joint arthroplasty more effectively than does either erythropoietin or preoperative autologous donation alone.\nStudy9: Autologous blood transfusion in oral and maxillofacial surgery patients with the use of erythropoietin. Autologous blood transfusion presents few infectious or immunologic side effects. The aim of the present study was to determine the impact of autologous blood transfusion with or without recombinant human erythropoietin (rHuEPO) in patients who underwent elective maxillofacial operations. Seventy eight consecutive patients (29 men and 49 women) underwent elective maxillofacial operations during the years 1990-95. The patients were randomly assigned to three groups: In group 1, 30 patients preoperatively underwent autologous blood predonation with intravenous injection of erythropoietin 600 lU/kg after each blood predonation and autologous blood transfusion intraoperatively; in group 2, 28 patients underwent the same procedure without erythropoietin and in group 3, 20 patients underwent homologous transfusion serving as control group. All patients received ferrous sulphate daily by mouth, preoperatively until one week postoperatively. Group 1 patients showed higher levels of haematocrit, haemoglobin and red blood cell count pre- and postoperatively than the group 2 patients. It was also shown that the use of rHuEPO contributed to an improvement of the blood parameters of the patients in the group 1 compared with those of the patients in groups 2 and 3.\nStudy10: Feasibility of a predeposit autologous blood donation program in colorectal cancer patients: results from a randomized clinical study. The hematologic and transfusion data of a multicenter randomized trial investigating the effect of blood transfusions on the 5-year survival were used to study the feasibility of an autologous blood donation program in colorectal cancer patients. Three hundred and ten patients were randomized for autologous blood transfusions (predeposition of 2 units) or homologous blood transfusions, and transfusion rules were standardized. The Hb level in the patients who donated blood decreased by 20.1 +/- 1.3 g/l (mean +/- SEM) preoperatively and 4.5 +/- 1.8 g/l postoperatively, and in controls 3.7 +/- 1.1 g/l and 16.5 +/- 1.9 g/l (significantly different between the two groups, both pre- and postoperatively: p less than 0.01). Because blood loss and number of transfusions were similar in both groups, this indicated that either preoperative or postoperative erythropoiesis is stronger in patients who had donated blood. Twenty-three percent of the autologous patients and 61% of the homologous patients were exposed to homologous blood. The effectiveness of the procedure differed per tumor localization. In patients with a right-sided colon carcinoma, 22% of the control patients needed homologous blood, compared to 10% of the autologous patients. In patients with other colon carcinomas, this was 52 and 16%, respectively, and in patients with a rectal carcinoma 85 and 41%. We conclude that predeposition of 2 units of blood for colorectal cancer surgery is feasible and useful to prevent homologous blood usage in a significant number of patients with left colon carcinoma or rectal carcinoma.\n", + "output": "Conclusions: Although the trials of PAD showed a reduction in the need for allogeneic blood, the methodological quality of the trials was poor and the overall transfusion rates (allogeneic and/or autologous) in these trials were high, and were increased by recruitment into the PAD arms of the trials. This raises questions about the true benefit of PAD. In the absence of large, high quality trials using clinical endpoints, it is not possible to say whether the benefits of PAD outweigh the harms." + }, + { + "input": "Study1: Repeated prevalence surveys for monitoring effectiveness of hospital infection control. In a 1400-bedded teaching hospital single-day prevalence surveys of hospital infection were done every six months for 3 years. The prevalence of community-acquired infection remained constant; but, after the introduction of a general infection-control policy, the prevalence of hospital-acquired infection (HAI) fell linearly from 10.5% in the second survey to 5.6% in the last. After the introduction of a specific urinary catheter care policy, the prevalence of hospital-acquired urinary tract infection (HAUTI) fell from 3.2% in the first four surveys to 2.0% in the last three. These differences persisted when the results were adjusted by logistic regression for patient risk factors, which varied between surveys: the declines for HAI and HAUTI were then 9.9% to 6.0% and 2.9% to 2.2% respectively. Infection control policies, therefore, can have substantial impact on the prevalence of HAI, and their effectiveness can readily be measured by repeated prevalence surveys.\nStudy2: Comprehensive discharge planning for hospitalized elderly: a pilot study. The purpose of this randomized clinical trial was to examine the effects of a comprehensive discharge planning protocol implemented by a gerontological nurse specialist as compared to the hospital's general discharge planning procedure. There were no statistically significant differences between groups in length of initial patient hospitalization or in rates of posthospital infections. A statistically significant difference was found when groups were compared on the number of subjects rehospitalized during the study period. The findings of this pilot study reinforce the need for continued study of the impact of comprehensive discharge planning for hospitalized elderly.\nStudy3: Comprehensive discharge planning for the hospitalized elderly. A randomized clinical trial. To study the effects of a comprehensive discharge planning protocol, designed specifically for the elderly and implemented by nurse specialists, on patient and caregiver outcomes and cost of care. Randomized clinical trial. Hospital of the University of Pennsylvania. 276 patients and 125 caregivers. Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups. Group differences in patient outcomes (length of initial hospital stay, length of time between initial hospital discharge and readmission, and rehospitalization rates) and charges for care (charges for initial hospitalization, rehospitalizations, health services after discharge, and nurse specialist services) were measured 2, 6, and 12 weeks after discharge. From the initial hospital discharge to 6 weeks after discharge, patients in the medical intervention group had fewer readmissions, fewer total days rehospitalized, lower readmission charges, and lower charges for health care services after discharge. No differences in these outcomes were found between the surgical intervention and control groups during this period. Study findings support the need for comprehensive discharge planning designed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings. The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge.\nStudy4: Striving to prevent falls in an acute care setting--action to enhance quality. Although most falls do not result in serious physical injury, they can contribute to a loss of confidence and mobility which can culminate in a significant reduction in quality of life. Furthermore, the potential to fall is often increased when an individual is institutionalized because of frailty or confusion. The purpose of the study was, therefore, to establish whether a structured intervention would assist in preventing falls in an acute setting. This pre-test/post-test study was carried out over a 12-month period. Interventions included risk assessment, an alert system, reinforcing preventive actions, staff education and ongoing audits and feedback. Initial analysis of the data and comparison of fall rates indicated a significant reduction in the rate of falls between the pre- and post-intervention phases, although subsequent statistical analysis did not identify any significant relationships. It must be noted that no controls existed for extraneous variables, although patient profiles varied minimally during the period of the study. Outcomes include: a reduction in fall numbers and rates, enhanced staff morale with ownership of the programme, provision of a learning experience for staff (on which to build), and the fostering of a professional approach to improving the quality of patient care.\nStudy5: The employment of ward opinion leaders for continuing education in the hospital. Opinion leaders (OLs) are members within a social group with significant social influence over others. A guideline on urinary catheter care was introduced in three groups (A, B and C) of two randomly allocated wards. Two OLs per ward were identified by nurses in groups A and B, using a sociometric method. For education, inservice lectures for 30% of nurses and OLs tutorials for all nurses were used in group A; OLs tutorials in B, lectures in C and ward nurses were in turn responsible for educating new arrivals of student nurses. Before and after the education programme, the guideline's frequency of practice was assessed by surveying 30% of randomly selected nurses and by direct observation for incorrect practices. A student's quiz on the guideline was also conducted. For all three methods of measurement, the best results were in group A followed by B and C; and the differences for the three groups were significant (p less than 0.05). This indicates that continuing education in the hospital can be effectively conducted by the enlistment of ward OLs.\nStudy6: Effectiveness of nursing involvement in bedside monitoring and control of coagulation status after cardiac surgery. This study explores: (1) the feasibility of involvement of nursing staff in routine bedside testing of activated clotting time and (2) joint implementation with resident medical staff of a preformulated plan for management of mediastinal bleeding after cardiac surgery. Patients were divided randomly into two groups, an experimental group (n = 108) subjected to ACT testing and management by protocol, and a control group (n = 146) treated by independent medical decisions. Bleeding, volume of blood replaced, abnormal coagulation profiles and reoperations to control bleeding and its consequences were all reduced in the study group. We concluded that bedside measurement of activated clotting time by nursing staff, associated with therapy based on a flow diagram, enhanced the overall management of early mediastinal bleeding after cardiac surgery as compared with independent management decisions by resident medical staff. In addition, the method provided a sensitive and reliable means of detecting and correcting rebound heparinization in the early postoperative period.\nStudy7: Increasing the rate of identification of battered women in an emergency department: use of a nursing protocol. In recognition of the increasing problem of family violence, the authors developed and tested an interview protocol focused on female victims of family violence. The purpose of the protocol was to increase nurses' identification of battered women receiving care in the emergency department. Using a time-series design, data were collected from patient records during four months prior to introduction of the protocol. These data were compared to comparable post-protocol data. There was a significant increase in nursing staff identification of female domestic violence victims following introduction of the protocol.\nStudy8: Improving compliance with immunization in the older adult: results of a randomized cohort study. To compare three approaches for improving compliance with influenza and pneumococcal vaccination of elderly patients. Randomized controlled trial using three parallel group practices at a public urban teaching hospital. Public teaching hospital. All patients 65 years of age and older (n = 1202) seen by resident physicians (n = 66) attending three ambulatory medical practices from October 1, 1989 to March 31, 1990. All three provider groups received intensive education in immunization standards. The control group received no further intervention. Staff in the second group offered education to patients at their visits. In the third group, the prevention team, a flowsheet was used, patient education offered, and staff had their tasks redefined to facilitate compliance; for vaccinations, eg, nurses could vaccinate independent of MD initiative. Medical records were reviewed for the 1202 patients seen, including 756 patients seen during both the 1988-89 and 1989-90 influenza seasons, to determine documented offering and receipt of vaccinations. During the intervention period (1989-90), influenza vaccinations were offered significantly more frequently to prevention team patients (68.3%) than to patients in either the patient education (50.4%) or control (47.6%) groups (P = 0.006), even after adjusting for the patients' prior vaccination status, age, gender, race, and high-risk co-morbidity and for physicians' level of training. Likewise, pneumococcal vaccinations were offered more frequently to previously unvaccinated prevention team patients (28.3%) than to patient education (6.5%) or control (5.4%) group patients (P = 0.001), even after adjusting for the factors using multivariate analysis. Compliance rates did not differ between patient education and control subjects for either vaccine. Pre-intervention physician surveys documented higher perceived than actual compliance for both vaccines, with 89.0% and 52.8% of physicians believing that they complied with influenza and pneumococcal vaccination guidelines, respectively. The results of this trial provide strong support for organizational changes that involve non-physician personnel to enhance vaccination rates among older adults.\nStudy9: Protocol management of dysuria, urinary frequency, and vaginal discharge. A proctocol to be administered by nurses for the management of dysuria, frequent urination, and vaginal discharge was validated. In a randomized, controlled trial, 146 women were seen by both nurse and physician and then assigned to either the nurse-proctocol treatment plan or the physician treatment plan. The clinical data collected by the nurse showed no important differences from the physicians' data. The protocol recommended that 89 percent of the patients be sent home without seeing the physician. The physicians agreed with the protocol-recommended disposition in all but two cases. All patients with complications were appropriately referred to the physician. In follow-up, more than 95 percent of both groups reported symptomatic improvement, and repeat urine cultures were negative. We conclude that the protocol can be accurately administered, makes sound recommendations, is safe, and efficiently saves physician time.\nStudy10: A decentralized approach to maintenance of intravenous therapy. A prospective experiment was conducted in a university-affiliated hospital to evaluate the effectiveness of a core of specially trained staff nurses in the maintenance of IV therapy. Five staff nurses for each of two experimental units were trained for 1 month by an IV nurse educator and were expected to perform venipuncture and monitor peripheral IV care on their units. On three control units, IV therapy continued to be a shared function of all medical house staff and nurses. During this study, 876 IV infusions on 707 patients were studied. There was a decrease in the phlebitis rate on experimental units from baseline to study periods of from 33.5% to 20.9% (relative risk, controlled for duration of the use of an IV device, 0.53, p = 0.05), whereas the rate on control units increased slightly (23.8% to 26.7%, p = greater than 0.5). Regardless of duration of use, steel needles were associated with lower phlebitis rates than were plastic catheters. The mean duration that each infusion device was in place was significantly shorter on experimental units than on control units (2.4 vs. 3.3 days, p = less than 0.001). However, bacterial colonization of IV devices occurred more often on experimental units than on control units both at baseline (12.7% vs. 7.1%; p = 0.25) and during the study phase (19.4% vs. 5.9%; p = less than 0.01). This increased colonization occurred with IV infusions started by both physicians and nurses. There were no septic complications of IV therapy in the patients studied. Patient comfort, measured by number of sticks for each venipuncture and patient interview, was significantly improved (p = less than 0.001) on experimental units during the study phase. Costs to start such a decentralized IV program on 10 clinical units was calculated to be about +10,000. This study provides information useful to those making administrative decisions regarding the value of IV teams or other methods for IV therapy maintenance. We concluded that a decentralized program can be successful with commitment of time and money resources and with a system of monitoring to ensure compliance with written IV guidelines.\n", + "output": "Conclusions: There is some evidence that guideline-driven care is effective in changing the process and outcome of care provided by professions allied to medicine. However, caution is needed in generalising findings to other professions and settings." + }, + { + "input": "Study: The impact of an integrated treatment on HIV risk behavior among homeless youth: a randomized controlled trial. While many studies provide useful information on the risk behaviors in which homeless youth engage, few prior studies evaluate Human Immunodeficiency Virus (HIV) risk related reduction strategies. In this study, homeless youth (n = 180) were recruited from a drop-in center and randomly assigned to one of two conditions, either an integrated individual cognitive-behavioral treatment and HIV prevention intervention that focused on skills building and education or to treatment as usual. All youth were assessed at entry into the program and at 3 and 6 month follow-up points. Findings showed an interaction between treatment condition, age and time. In the interaction, youth assigned to the integrated treatment reported greater condom usage than youth assigned to treatment as usual, with younger youth assigned to treatment as usual showing no change in condom use. The number of sexual partners reported by youth in both treatment conditions was also reduced over time. However, youth in both conditions continued to engage in other high-risk behaviors. The integrated treatment findings are promising and suggest that interventions which target both HIV risk behavior in addition to other life areas (substance use, mental health and housing) among homeless youth may be necessary in order to significantly impact high-risk behaviors among this unique group.\n", + "output": "Conclusions: Analysis across the included studies found no consistently significant benefit for the 'new' interventions compared to standard services for street-connected children and young people. These latter interventions, however, have not been rigorously evaluated, especially in the context of LMICs. Robustly evaluating the interventions would enable better recommendations to be made for service delivery. There is a need for future research in LMICs that includes children who are on the streets due to urbanisation, war or migration and who may be vulnerable to risks such as trafficking." + }, + { + "input": "Study1: The prevention of early postmenopausal bone loss by cyclical etidronate therapy: a 2-year, double-blind, placebo-controlled study. To determine whether intermittent cyclical etidronate therapy can prevent early postmenopausal bone loss. This was a 2-year outpatient, randomized, double-blind, placebo-controlled clinical trial. The subjects were 152 women within 1 to 10 years of the onset of menopause and bone mineral density (BMD) between 0 and -2 SD of normal values for a 50 year old woman. The women were stratified according to years since the menopause (1 to 3 years: n = 43; 4 to 6 years: n = 53; 7 to 10 years: n = 56). Measurements of lumbar spine, proximal femur and total body BMD were performed at baseline, 12 and 24 months by dual x-ray absorptiometry. Biochemical markers of bone resorption and bone formation were measured on the same visits. One hundred thirty-five subjects completed the study. Mean percentage change in lumbar spine BMD (and SEM) at 2 years was +2.14 (0.47)% in the etidronate group and -1.72 (0.41)% in the placebo group. Results for lumbar spine BMD in the treated and control groups stratified according to years since the menopause were: 1 to 3 years: +1.73 (0.84)% and -3.30 (0.70)%; 4 to 6 years: +1.37 (0.88)% and -1.80 (0.61)%; 7 to 10 years: +3.42 (0.61)% and -0.38 (0.70)%. The effect of both treatment group and menopausal stratum were highly statistically significant for lumbar spine and total body BMD. Treatment group, but not stratum, was significant for BMD in the proximal femur. Markers of bone resorption and bone formation were significantly decreased by etidronate therapy. Cyclical etidronate prevents bone loss in the total skeleton and at the clinically relevant sites (spine and proximal femur) even in the early postmenopausal years. Hence, it appears to be an effective and safe nonhormonal therapy in postmenopausal women with normal or low BMD.\nStudy2: Effect of intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis. We evaluated intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis, with special reference to bone mineral density (BMD) and prevention of spinal fracture. The patients were 40 women, over 50 years of age, with lumbo-dorsal pain and low BMD (less than 0.70 g/cm(2)), measured by dual-energy X-ray absorptiometry (DXA). The patients were randomly assigned to two groups. The first group (HEBP) received 200 mg of HEBP per day for 2 weeks, followed by 2 g calcium lactate and 0.5 microg alphacalcidol per day for the next 10 weeks. This 12-week cycle was repeated eight times for 2 years. The second group (Ca. D) received 2 g calcium lactate and 0.5 microg alphacalcidol per day for 2 years. Lumbar BMD was measured before the treatment and every 6 months during the treatment until 24 months, and changes were evaluated. The number of fractured vertebrae was counted on X-ray films before treatment and at the final assessment. After 6 months of treatment, a significant and continuous increase in BMD was observed in the HEBP group. Moreover, the percentage of patients with new vertebral compression fractures in the HEBP group was one-tenth of that in the Ca. D group. These results suggest that intermittent cyclical treatment with HEBP and calcium plus alphacalcidol may be effective for increasing BMD and preventing fractures in postmenopausal osteoporosis.\nStudy3: Coherence therapy does not prevent axial bone loss in osteoporotic women: a preliminary comparative study. Coherence therapy, also known as ADFR (activate, depress, free, repeat) therapy, has been proposed as a new form of treatment for osteoporosis. We compared the effects of this therapy with those of gonadal steroid and calcium and of calcium alone in 93 osteoporotic women. Thirty women were treated for 1 yr with ADFR, in the form of K-phosphate (1.5 g/day), for 3 days followed by etidronate, (400 mg/day) for 14 days, followed by 8 weeks of neither drug, plus continuous calcium carbonate therapy (1 g/day). Thirty-six women received conjugated estrogens (0.625 mg/day) for 25 days/month plus medroxyprogesterone acetate (10 mg/day) for 10 days/month and calcium, while 27 women received calcium carbonate (500 mg, twice daily). Sixteen women in the ADFR group, 15 in the calcium group, and 19 in the hormone-calcium group completed 2 yrs of treatment. Spinal bone mineral density was measured by single energy quantitative computerized tomography (QCT) and in the proximal and distal radius by single energy photon absorptiometry. The 3 groups were similar in age, initial bone mass, years since menopause, and dietary calcium intake. After 2 yrs, the mean women in the ADFR therapy group had a mean reduction of 8.0% in spinal QCT (P less than 0.05), and no change in proximal radius mineral content/bone width (BMC), and distal radius BMC. The group treated with calcium only had a decrease of 3.8% in QCT (P less than 0.05), of 5.6% in proximal BMC (P less than 0.05), and of 4.9% in distal BMC (P less than 0.05). The group treated with hormonal replacement and calcium had no change in any of their measurements. The relative bone loss in the spine at the end of the study was greater in the ADFR group than in the hormone-calcium group (P less than 0.05). Bone loss in the calcium group was slightly but not significantly greater than that in the hormone group and lower than that in the ADFR group. In conclusion, these preliminary results indicate that the ADFR regimen using phosphate and etidronate in doses of 1.5 g/day for 3 days and 400 mg/day for 14 days, respectively, is not as effective as hormonal replacement in preventing trabecular bone loss in osteoporosis, nor it is any more effective than calcium supplementation alone.\nStudy4: The effect of a modified etidronate cyclical regimen on postmenopausal osteoporosis: a four-year study. To develop an improved treatment schedule for osteoporosis, a study was undertaken in 100 postmenopausal women using a modified ADFR 90-day cyclical regimen with etidronate. After one year of treatment, the etidronate-treated group showed a significant increase in bone density of the spine, which continued over the following 2 years of treatment and remained stable during the fourth year. In contrast, in the non-etidronate group, bone density decreased significantly after four years. In addition, the fracture rate was significantly lower in the etidronate group than in the non-etidronate group. Side effects were minimal in both groups and no serious adverse reactions were reported. In conclusion, it appears that a cyclical regimen using 1,25-dihydroxyvitamin D3, etidronate and calcium increases bone mass and reduces fractures with no significant side effects, thus making a useful contribution in the treatment of postmenopausal osteoporosis.\nStudy5: Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation. We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate, a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned in equal numbers to receive oral etidronate (400 mg per day) or placebo for 2 weeks, followed by a 13-week period in which no drugs were given. This sequence was repeated 10 times, for a total of 150 weeks. Daily oral supplementation with calcium and vitamin D was given throughout the study to both groups. Vertebral bone mineral content was measured by dual-photon absorptiometry; spinal radiographs were assessed to identify new vertebral fractures. Vertebral bone mineral content increased significantly (P less than 0.01) after 150 weeks of etidronate therapy (5.3 percent; 95 percent confidence interval, 2.0 to 8.6; n = 20) but decreased with placebo (-2.7 percent; 95 percent confidence interval, -7.3 to 1.9; n = 20). The difference between groups was 8.0 percentage points (P less than 0.01; 95 percent confidence interval, 2.4 to 13.6). The rates of fracture were significantly different for the period from week 60 to week 150 between the etidronate and placebo groups (6 vs. 54 fractures per 100 patient-years; P = 0.023). No adverse clinical, biochemical, or bone histomorphometric effects of treatment were observed. We conclude that at the end of nearly three years, etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content and, after approximately one year of treatment, a significant decrease in the rate of new vertebral fractures.\nStudy6: Prevention of early postmenopausal bone loss with cyclical etidronate therapy (a double-blind, placebo-controlled study and 1-year follow-up) The objective of the study was to evaluate the effects of cyclical therapy with etidronate and calcium on spinal and femoral bone loss in the early post menopausal period. Fifty-four women, 53 +/- 2.8 yr old (mean +/- SD) and 2.3 +/- 1.3 yr post menopause received oral doses of either 400 mg/day etidronate for 2 weeks followed by 500 mg/day elemental calcium for 11 weeks, or placebo for 14 days followed by calcium for 11 weeks, repeated over a total of 24 months. A statistically significant increase in spinal bone mineral density (BMD) was observed after 6 months in the etidronate group. At 2 yr, the mean treatment differences in spinal and femoral neck BMD were +2.93% (P < 0.02) and 2.02% (P < 0.03), respectively. Serum osteocalcin and urinary crossLaps/creatinine excretion were decreased significantly by etidronate. Etidronate was well tolerated with a safety profile similar to that of placebo. Thirty-seven women participated in a 1-yr open-label follow-up study. Twelve months after treatment withdrawal, spinal BMD in the former etidronate group decreased by 1.43% and serum osteocalcin and urinary crossLaps returned to pretreatment values. In conclusion, cyclical etidronate is an effective therapy for the prevention of both trabecular and cortical bone loss in the early menopause and has a good safety profile.\nStudy7: The use of etidronate and calcium versus calcium alone in the treatment of postmenopausal osteopenia: results of three years of treatment. The purpose of this open, prospective, controlled, randomized trial was to study the effect of intermittent, cyclic etidronate on the bone mass of osteoporotic postmenopausal women with or without fractures. Eligible subjects were asymptomatic women less than 75 years old who had been amenorrhoeic for at least 1 year. Those with secondary osteoporosis were excluded. Subjects also had to be ambulant with a bone mineral density (BMD) of the lumbar spine > 1 SD below that of age matched controls (Z-score < -1 SD). Eighty patients were enrolled, of whom 65 were recruited through a screening programme conducted in the practices of two general practitioners. The remaining patients were from other referrals. The subjects were randomized to two groups of 40 women. Treatment regimens were as follows. The etidronate group was treated with etidronate 400 mg once daily for 14 days followed by 76 days of 500 mg of elementary calcium once daily; this cycle was repeated every 3 months. The calcium group took 500 mg of elementary calcium once daily. The groups were not different in age, height, weight, time since menopause. BMD at baseline and prevalent vertebral fractures. In 50 patients (28 in the etidronate group and 22 in the calcium group) no vertebral fractures were present (67%). Sixty-four patients (35 in the etidronate group and 29 in the calcium group) completed the 3 years of the study. In the etidronate group the mean BMD of the lumbar spine, femoral neck, trochanter and Ward's triangle increased by 5.7%, 1.4%, 7.1% and 10.9% from baseline values respectively (p < 0.05 at all sites except for the femoral neck). In the calcium group no significant changes from baseline were found at any time point at any site after 3 years, except for the femoral neck, where BMD at 156 weeks decreased significantly by 3% (p < 0.003). In 3 patients, all in the calcium group, six new fractures were found. There were no serious adverse effects. We conclude that intermittent, cyclic treatment with etidronate causes a significant increase in the BMD of the lumbar spine and the proximal femur in osteopenic postmenopausal women, and that treatment is safe and has no serious adverse effects.\nStudy8: Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. To determine the effects of etidronate (a bisphosphonate that inhibits osteoclast-mediated bone resorption) in the treatment of postmenopausal osteoporosis, we conducted a prospective, two-year, double-blind, placebo-controlled, multicenter study in 429 women who had one to four vertebral compression fractures plus radiographic evidence of osteopenia. The patients were randomly assigned to treatment with phosphate (1.0 g) or placebo twice daily on days 1 through 3, etidronate (400 mg) or placebo daily on days 4 through 17, and supplemental calcium (500 mg) daily on days 18 through 91 (group 1, placebo and placebo; group 2, phosphate and placebo; group 3, placebo and etidronate; and group 4, phosphate and etidronate). The treatment cycles were repeated eight times. The bone density of the spine was measured by dual-photon absorptiometry, and the rates of new vertebral fractures were determined from sequential radiographs. After two years, the patients receiving etidronate (groups 3 and 4) had significant increases in their mean (+/- SE) spinal bone density (4.2 +/- 0.8 percent and 5.2 +/- 0.7 percent, respectively; P less than 0.017). The rate of new vertebral fractures was reduced by half in the etidronate-treated patients (groups 3 and 4 combined) as compared with the patients who did not receive etidronate (groups 1 and 2 combined) (29.5 vs. 62.9 fractures per 1000 patient-years; P = 0.043); the effect of treatment was most striking in the subgroup of patients with the lowest spinal bone mineral density at base line, in whom fracture rates were reduced by two thirds (42.3 vs. 132.7 fractures per 1000 patient-years; P = 0.004). The addition of phosphate provided no apparent benefit. There were no significant adverse effects of treatment. Intermittent cyclical therapy with etidronate for two years significantly increases spinal bone mass and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis.\n", + "output": "Conclusions: Etidronate, at 400 mg per day, demonstrated a statistically significant and clinically important benefit in the secondary prevention of vertebral fractures. No statistically significant reductions in vertebral fractures were observed when it was used for primary prevention. In addition, no statistically significant reductions in non-vertebral, hip, or wrist fractures were found, regardless of whether etidronate was used for primary or secondary prevention. The level of evidence for all outcomes is Silver (www.cochranemsk.org.)" + }, + { + "input": "Study1: A multicenter randomized controlled trial comparing patient-controlled epidural with intravenous analgesia for pain relief in labor. In this multicenter, randomized, controlled trial, we sought to determine whether patient-controlled epidural analgesia (PCEA) for labor affected the incidence of cesarean delivery when compared with patient-controlled IV opioid analgesia (PCIA). Healthy, term nulliparous patients in 4 Canadian institutions were randomly assigned to receive PCIA with fentanyl (n = 118) or PCEA with 0.08% bupivacaine and fentanyl 1.6 microg/mL (n = 124). There was no difference in the incidence of cesarean delivery-10.2% (12 of 118) versus 9.7% (12 of 124)-or instrumental vaginal delivery-21.2% (25 of 118) versus 29% (36 of 124)-between groups. The duration of the second stage of labor was increased in the PCEA group by a median of 23 min (P = 0.02). Fifty-one patients (43%) in the PCIA group received epidural analgesia: 39 (33%) because of inadequate pain relief and 12 (10%) to facilitate operative delivery. Patients in the PCIA group required more antiemetic therapy (17% versus 6.4%; P = 0.01) and had more sedation (39% versus 5%; P < 0.001). Maternal mean pain and satisfaction with analgesia scores were better in the PCEA group (P < 0.001 and P = 0.02, respectively). More neonates in the PCIA group required active resuscitation (52% versus 31%; P = 0.001) and naloxone (17% versus 3%; P < 0.001). These observations support the hypothesis that PCEA does not result in an increased incidence of obstetrical intervention compared with PCIA. PCEA provides superior analgesia and less maternal and neonatal sedation compared with PCIA.\nStudy2: Intravenous remifentanil vs. epidural levobupivacaine with fentanyl for pain relief in early labour: a randomised, controlled, double-blinded study. We hypothesised that intravenous patient-controlled analgesia (IV PCA) with remifentanil could provide as satisfactory pain relief for labour as epidural analgesia. Fifty-two parturients with singleton uncomplicated pregnancies were randomised to receive either IV PCA with remifentanil or epidural analgesia with 20 ml levobupivacaine 0.625 mg/ml and fentanyl 2 microg/ml in saline. The PCA dose of remifentanil was given over 1 min with a lockout time of 1 min. The dose was increased starting from the bolus of 0.1 microg/kg and following a dose escalation scheme up until the individual-effective dose was reached. The parturients assessed contraction pain (0-10), pain relief (0-4), sedation and nausea during 60 min. Forty-five parturients were included in the analysis. The median cervical opening was 4 cm before the study and 7 cm after the study. The median pain scores were 7.3 and 5.2 during remifentanil and epidural analgesia, respectively (P=0.009). The median pain relief scores were 2.5 and 2.8 (P=0.17). There was no difference between the groups in the proportion of parturients who discontinued due to ineffective analgesia, nor in the proportion of parturients who would have liked to continue the given medication at the end of the study. Sedation and low haemoglobin oxygen saturation were observed more often during remifentanil analgesia. Foetal heart rate tracing abnormalities were as common in both groups. In terms of pain scores, epidural analgesia is superior to that provided by IV remifentanil. However, there was no difference in the pain relief scores between the treatments.\nStudy3: Intravenous fentanyl PCA during labour. To evaluate the usefulness of intravenous patient-controlled analgesia (PCA) fentanyl for labour analgesia, its effectiveness for maternal pain and safety for the fetus and newborn. Twenty primigravidas were randomised to receive intravenous PCA fentanyl or epidural analgesia for labour pain. Maternal pain, heart rate and arterial oxyhaemoglobin saturation (SpO2) were monitored. Fetal and neonatal monitoring included cardiotocogram (CTG), APGAR, neurological scoring and static-charge-sensitive bed (SCSB) recording for 12 hr postnatally with ECG and SpO2. Fentanyl concentrations and pH of umbilical artery and vein were analysed. Initially, epidural analgesia was more effective (P = 0.01), and three patients in the fentanyl group were given epidural due to unsatisfactory pain relief. Overall satisfaction for analgesia did not differ between the groups. Maternal side-effects were more frequent in the fentanyl group (dizziness and tiredness most often, P = 0.0001). Severe side-effects were not reported. In CTG there were no differences between groups. All the newborns were healthy, APGAR and pH were normal. Naloxone was not used. Neurological scoring was similar in both groups. In 12 hr monitoring heart rate, breathing frequency and movement time were similar in both groups, but SpO2 was lower in the fentanyl group (P < 0.001). Umbilical cord fentanyl concentrations were low or beyond the detection limit. Intravenous fentanyl can be used for labour analgesia with the doses reported here as an alternative to epidural analgesia. However, the fetus and neonate must be appropriately monitored. Naloxone and oxygen should be available if neonatal distress occurs.\nStudy4: Effects of epidural lidocaine analgesia on labor and delivery: a randomized, prospective, controlled trial. Whether epidural analgesia for labor prolongs the active-first and second labor stages and increases the risk of vacuum-assisted delivery is a controversial topic. Our study was conducted to answer the question: does lumbar epidural analgesia with lidocaine affect the progress of labor in our obstetric population? 395 healthy, nulliparous women, at term, presented in spontaneous labor with a singleton vertex presentation. These patients were randomized to receive analgesia either, epidural with bolus doses of 1% lidocaine or intravenous, with meperidine 25 to 50 mg when their cervix was dilated to 4 centimeters. The duration of the active-first and second stages of labor and the neonatal apgar scores were recorded, in each patient. The total number of vacuum-assisted and cesarean deliveries were also measured. 197 women were randomized to the epidural group. 198 women were randomized to the single-dose intravenous meperidine group. There was no statistical difference in rates of vacuum-assisted delivery rate. Cesarean deliveries, as a consequence of fetal bradycardia or dystocia, did not differ significantly between the groups. Differences in the duration of the active-first and the second stages of labor were not statistically significant. The number of newborns with 1-min and 5-min Apgar scores less than 7, did not differ significantly between both analgesia groups. Epidural analgesia with 1% lidocaine does not prolong the active-first and second stages of labor and does not increase vacuum-assisted or cesarean delivery rate.\nStudy5: Can parturients distinguish between intravenous and epidural fentanyl? We tested the hypothesis that the sedative, euphoric, and analgesic effects of intravenous fentanyl would distinguish intravenous from epidural administration. One hundred ASA I and II labouring parturients received 100 micrograms fentanyl either iv or via an epidural catheter in a double-blind, randomized, cross-over fashion. Nineteen anaesthetists (8 staff and 11 residents) participated and correctly guessed the route of administration of the fentanyl in 61/66 intravenous doses and in 69/75 epidural doses yielding a sensitivity of 92.4%, a specificity of 92.0%, a positive predictive value of 91.0%, and a negative predictive value of 93.2%. Of the 41 patients that were crossed over, 38 (92.7%) were able to detect a difference between the routes of administration. Most patients experienced prompt, short-lived symptoms with iv fentanyl but no important differences in fetal heart rate pattern or in maternal desaturation were seen between the groups. This study suggests that subjective symptoms will accurately distinguish intravenous from epidural fentanyl administration in labouring parturients (P < 0.001), and should serve as a safe and reliable intravenous test dose for epidural anaesthesia in the obstetric population.\nStudy6: Randomized controlled comparison of epidural bupivacaine versus pethidine for analgesia in labour. We compared the incidence of Caesarean delivery in nulliparous women randomized to receive epidural analgesia with those randomized to intramuscular (i.m.) pethidine. On admission to the delivery suite in established labour, 802 nulliparae had already agreed to be randomized with respect to their first analgesia. One hundred and eighty-eight women required either no analgesia or 50% nitrous oxide in oxygen (Entonox) only. Of the remaining 614 women, 310 were randomly allocated to receive i.m. pethidine up to 300 mg and 304 to receive epidural bupivacaine. Labour management was standardized according to the criteria for active management of labour. The intention-to-treat analysis showed similar Caesarean section rates in those randomized to epidural (12%) or pethidine analgesia (13%). The difference in Caesarean rate was -1.1% with 95% confidence intervals from -6.3% to +4.1%. The normal vaginal delivery rates were similar (epidural, 59%; pethidine, 61%).\nStudy7: Cesarean delivery: a randomized trial of epidural versus patient-controlled meperidine analgesia during labor. Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries. However, only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery. The authors' primary purpose in this randomized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative: patient-controlled intravenous analgesia. Seven hundred fifteen women of mixed parity in spontaneous labor at full term were randomly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia. Epidural analgesia was maintained with a continuous epidural infusion of 0.125% bupivacaine with 2 microg/ml fentanyl. Patient-controlled analgesia was maintained with 10-15 mg meperidine given every 10 min as needed using a patient-controlled pump. Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman randomized in the study. A total of 358 women were randomized to receive epidural analgesia, and 243 (68%) of these women complied with the epidural analgesia protocol. Similarly, 357 women were randomized to receive patient-controlled intravenous meperidine analgesia, and 259 (73%) of these women complied with the patient-controlled intravenous analgesia protocol. Only five women who were randomized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief. There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original randomization (epidural analgesia, 4% [95% CI: 1.9-6.2%] compared with patient-controlled intravenous analgesia, 5% [95% CI: 2.6-7.2%]). Similar results were observed for the analysis of the protocol-compliant groups (epidural analgesia, 5% [95% CI: 2.6-8.5%] compared with patient-controlled intravenous analgesia, 6% [95% CI: 3-8.9%]). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia. Epidural analgesia was not associated with increased numbers of cesarean delivery when compared with a suitable alternative method of analgesia.\nStudy8: A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia. A number of recent studies have suggested that the analgesic effects of highly lipid-soluble opioids are similar when these agents are administered either epidurally or intravenously. We sought to test whether the lipid-soluble opioid sufentanil was more effective when administered intrathecally than when administered epidurally or intravenously. Twenty-four women during active labor received sufentanil 10 micrograms either intrathecally (n = 9), epidurally (n = 8), or intravenously (n = 7), using a combined spinal-epidural technique. The sufentanil was administered alone, without concomitant local anesthetics. Analgesia was assessed using the visual analogue score as well as the time elapsed from the administration of study drug to the patient's request for additional analgesia via the epidural catheter (bupivacaine 0.25%). The median duration of analgesia (median, interquartile range) was 84 (70-92) min in the intrathecal group, 30 (23-32) min in the epidural group, and 34 (17-30) min in the intravenous group (P < 0.001). The intrathecal group showed rapid and significant decrease in visual analogue scale scores, whereas visual analogue scale scores in the other two groups did not decrease and remained significantly elevated compared to those of the intrathecal group at all observation points. Side effects were limited to pruritus in 3 patients (2 moderate and 1 severe) in the intrathecal group. No patient developed post-dural puncture headache. We conclude that sufentanil 10 micrograms intrathecally provides rapid and effective analgesia of 1-2-h duration during labor. Epidural and intravenous use of this dose of sufentanil did not provide evidence of satisfactory analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy9: The impact of intrapartum analgesia on labour and delivery outcomes in nulliparous women. To determine if nulliparous women intending to have epidural analgesia have a similar labour profile and delivery outcome to women who intend to have their labour managed using alternative forms of pain relief. A prospective randomised controlled clinical trial conducted at a tertiary obstetric institution. Nulliparous women intending to deliver vaginally with a term singleton fetus were eligible for recruitment. 1159 women were recruited, of whom 992 were subsequently randomised to receive continuous midwifery support (CMS) or epidural analgesia (EPI) on presentation for delivery. The duration of labour was shorter in the CMS group compared with EPI (10.7 hours (inter quartile (IQ) 7.0,15.2) versus 11.4 hours (IQ 8.2,15.2), p = 0.039). The median duration of the first stage was 8.9 hours (IQ 6,12.5) versus 9.5 hours (IQ 7,12.7) (p = 0.069), and the median duration of the second stage was 1.33 hours (IQ 0.6,2.5) versus 1.48 hours (IQ 0.77,2.6) (p = 0.034). The requirement for oxytocin augmentation in spontaneous labour was 39.8% CMS versus 46.2% EPI (p = 0.129). There was no significant difference in the caesarean section rates. The need for any operative delivery was significantly lower in CMS (43.9% CMS versus 51.5% EPI, p = 0.019). Nulliparous women have a high usage of epidural analgesia, regardless of their prelabour intentions. In women who do not intend to use epidural analgesia, the temporal delay in insertion compared with those who use epidural analgesia as their primary analgesic modality is associated with a small but statistically significant reduction in overall labour duration and operative delivery rates.\nStudy10: A randomized trial of intrapartum analgesia in women with severe preeclampsia. To estimate whether the cesarean delivery rate differs between women with severe preeclampsia who receive intrapartum epidural analgesia versus patient-controlled intravenous opioid analgesia. Women with severe preeclampsia at at least 24 weeks' gestation were randomly assigned to receive either intrapartum epidural (n = 56) versus patient-controlled intravenous opioid analgesia (n = 60), and each was administered by a standardized protocol. The sample size was selected to have 80% power to detect at least a 50% difference in the predicted intergroup cesarean delivery rates. Data were analyzed by intent to treat. Selected maternal characteristics and neonatal outcomes were similar in the two groups. The cesarean delivery rates in the epidural group (18%) and the patient-controlled analgesia group (12%) were similar (P =.35). Women who received epidural analgesia were more likely to require ephedrine for the treatment of hypotension (9% versus 0%, P =.02), but their infants were less likely to require naloxone at delivery (9% versus 54%, P <.001). Epidural analgesia provided significantly better pain relief as determined by a visual analogue intrapartum pain score (P <.001) and a postpartum pain management survey (P =.002). Compared with patient-controlled intravenous opioid analgesia, intrapartum epidural analgesia did not significantly increase the cesarean delivery rate in women with severe preeclampsia at our level III center, and it provided superior pain relief.\n", + "output": "Conclusions: Epidural analgesia appears to be effective in reducing pain during labour. However, women who use this form of pain relief are at increased risk of having an instrumental delivery. Epidural analgesia had no statistically significant impact on the risk of caesarean section, maternal satisfaction with pain relief and long-term backache and did not appear to have an immediate effect on neonatal status as determined by Apgar scores. Further research may be helpful to evaluate rare but potentially severe adverse effects of epidural analgesia on women in labour and long-term neonatal outcomes." + }, + { + "input": "Study: Relaxation reduces disruption in mentally handicapped adults. To assess the effects of modified relaxation training on subsequent disruptive behaviour, two groups of six non-institutionalized mentally handicapped adults were compared. At the end of 3 weeks training, those given relaxation training showed 71% more relaxation after relaxation sessions and 74% less disruptive behaviour later in the day, whereas controls who were only told stories showed no decrease; aggression and verbal disruption showed the most consistent effects. This suggests that modified relaxation is rapidly effective in inducing relaxation and in reducing disruption.\n", + "output": "Conclusions: The existing evidence on the efficacy of cognitive behavioural and behavioural interventions on outwardly directed aggression in children and adults with learning disabilities is scant. There is a paucity of methodologically sound clinical trials. Given the impact of such behaviours on the affected individual, his or her carers and on service providers, effective interventions are essential. It is also important to investigate cost efficacy of treatment models against existing treatments. We recommend that randomised controlled trials of sufficient power are carried out using primary outcomes of reduction in outward directed aggression, improvement in quality of life and cost efficacy as measured by standardised scales." + }, + { + "input": "Study1: Benefits of continuous infusion epidural analgesia throughout vaginal delivery. Two groups of nulliparous women with fetuses in singleton vertex presentation received continuous infusion epidural analgesia (EDA) with bupivacaine: group A (90 parturients) without infusion analgesia in the second stage of labor and group B (90 parturients) with infusion analgesia throughout delivery. The groups were compared regarding pain relief, duration of the second stage, persistent malrotation of the fetal head, and rate of instrumental vaginal delivery. The continuous infusion EDA gave satisfactory pain relief in 93.3% of the parturients in group A and 97.8% in group B. The duration of second stage was the same in both groups. There were more persistent malrotations of the fetal head in group A, but the malrotation did not affect the mode of delivery. The rate of instrumental vaginal delivery was 25.5% in both groups. The main cause of operative intervention was delay in the second stage. When the continuous infusion technique is used, it seems unreasonable to discontinue the EDA and thereby deprive the parturient of analgesia during the second stage.\nStudy2: Effect of second-stage 0.25% epidural bupivacaine on the outcome of labor. To evaluate the effect of second-stage epidural bupivacaine on the outcome of labor. Two groups of 35 patients each were randomly allocated to receive continuous epidural bupivacaine throughout labor (group 1) or until an 8-cm dilatation of the cervix (group 2). There was no significant difference between the 2 groups in the rates of instrument deliveries and in their Apgar scores. The administration of continuous epidural bupivacaine (0.25%) throughout labor and delivery does not seem to affect the outcome of labor.\n", + "output": "Conclusions: There is insufficient evidence to support the hypothesis that discontinuing epidural analgesia late in labour reduces the rate of instrumental delivery. There is evidence that it increases the rate of inadequate pain relief in the second stage of labour. The practice of discontinuing epidurals is widespread and the size of the reduction in instrumental delivery rate could be clinically important; therefore, we recommend a larger study than those included in this review be undertaken to determine whether this effect is real or has occurred by chance, and to provide stronger evidence about the safety aspects." + }, + { + "input": "Study1: Effects of a partly self-administered exercise program before, during, and after allogeneic stem cell transplantation. Before, during, and after allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients experience considerable physical and psychologic distress. Besides graft-versus-host disease and infections, reduced physical performance and high levels of fatigue affect patients' quality of life. This multicenter randomized controlled trial examined the effects of a partly self-administered exercise intervention before, during, and after allo-HSCT on these side effects. After randomization to an exercise and a social contact control group 105 patients trained in a home-based setting before hospital admission, during inpatient treatment and a 6- to 8-week period after discharge. Fatigue, physical performance, quality of life, and physical/psychologic distress were measured by standardized instruments at baseline, admission to, and discharge from hospital and 6 to 8 weeks after discharge. The exercise group showed significantly improvement in fatigue scores (up to 15% improvement in exercise group vs up to 28% deterioration in control; P<.01-.03), physical fitness/functioning (P=.02-.03) and global distress (P=.03). All effects were at least detectable at one assessment time point after hospitalization or repeatedly. Physical fitness correlated significantly with all reported symptoms/variables. In conclusion, this partly supervised exercise intervention is beneficial for patients undergoing allo-HSCT. Because of low personnel requirements, it might be valuable to integrate such a program into standard medical care. \u00a9 2011 by The American Society of Hematology\nStudy2: Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer. PURPOSES/OBJECTIVES: To test the hypothesis that women participating in a walking exercise program during radiation therapy treatment for breast cancer would demonstrate more adaptive responses as evidenced by higher levels of physical functioning and lower levels of symptom intensity than women who did not participate. Experimental, two-group pretest, post-test. Two university teaching hospital outpatient radiation therapy departments. 46 women beginning a six-week program of radiation therapy for early stage breast cancer. Following random assignment, subjects in the exercise group maintained an individualized, self-paced, home-based walking exercise program throughout treatment. The control group received usual care. Dependent variables were measured prior to and at the end of radiation therapy. In addition, symptoms were assessed at the end of three weeks of treatment. Participation in the walking exercise program, physical functioning fatigue, emotional distress, and difficulty sleeping. Hypothesis testing by multivariate analysis of covariance, with pretest scores as covariates, indicated significant differences between groups on outcome measures (p < 0.001). The exercise group scored significantly higher than the usual care group on physical functioning (p = 0.003) and symptom intensity, particularly fatigue, anxiety, and difficulty sleeping. Fatigue was the most frequent and intense subjective symptom reported. A self-paced, home-based walking exercise program can help manage symptoms and improve physical functioning during radiation therapy. Nurse-prescribed and -monitored exercise is an effective, convenient, and low-cost self-care activity that reduces symptoms and facilitates adaptation to breast cancer diagnosis and treatment.\nStudy3: A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT. The aim of this randomized controlled trial was to investigate the effect of a 4- to 6-week multimodal program of exercise, relaxation and psychoeducation on physical capacity, functional performance and quality of life (QOL) in allogeneic hematopoietic cell transplantation (allo-HSCT) adult recipients. In all, 42 patients were randomized to a supervised multimodal intervention or to a control group receiving usual care. The primary end point was on aerobic capacity measured in VO(2) max. Secondary end points were muscle strength, functional performance, physical activity level, QOL, fatigue, psychological well-being and clinical outcomes. The multimodal intervention had a significant effect on physical capacity: VO(2) max (P<0.0001) and muscle strength: chest press (P<0.0001), leg extension (P=0.0003), right elbow flexor (P=0.0009), right knee extensor (P<0.0001) and functional performance (stair test) (0.0008). Moreover, the intervention group showed significantly better results for the severity of diarrhea (P=0.014) and fewer days of total parenteral nutrition (P=0.019). Longitudinal changes in QOL, fatigue and psychological well-being favored the intervention group, but did not reach statistical significance. Assignment of a multimodal intervention during allo-HSCT did not cause untoward events, sustained aerobic capacity and muscle strength and reduced loss of functional performance during hospitalization.\nStudy4: A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy. To examine the effects of a comprehensive rehabilitation program on facilitating physical and psychosocial adaptation of women with breast cancer who are receiving adjuvant chemotherapy. Experimental. Breast evaluation clinics of two New England medical centers with comprehensive cancer treatment programs. 14 women (mean age = 44 years) receiving adjuvant chemotherapy for breast cancer (86% stage II) following surgical treatment. Subjects were assigned randomly to the experimental group or the usual care group. Experimental group members began a structured exercise program of walking and attended support group meetings. All subjects were tested before beginning chemotherapy, during the course of chemotherapy, and one month following chemotherapy completion. Performance status, physical functioning, psychosocial adjustment, self-concept and body image, and 12 symptoms (e.g., fatigue, nausea, anxiety). Measures of physical performance, psychosocial adjustment, and symptom intensity revealed improved adaptation in subjects who completed the walking/support group program. Physical and psychosocial benefits from a modest walking exercise program and a support group are possible for patients receiving adjuvant chemotherapy. Although more detailed research is necessary to answer some of the questions raised by this study, implementing the walking program and forming a support group are achievable in an outpatient setting.\nStudy5: A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment. This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy. The study was designed as a randomised controlled trial (RCT). Physical functioning, fatigue and Quality of Life (QoL) outcomes were evaluated pre and post a 12-week intervention. The results showed that after 12 weeks the women who participated in the exercise programme (n = 12) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls (n = 10). Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance. These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe, well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer. Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women. Future studies need to address these issues and determine if these short-term benefits can be sustained.\nStudy6: Randomized controlled trial of yoga among a multiethnic sample of breast cancer patients: effects on quality of life. This study examines the impact of yoga, including physical poses, breathing, and meditation exercises, on quality of life (QOL), fatigue, distressed mood, and spiritual well-being among a multiethnic sample of breast cancer patients. One hundred twenty-eight patients (42% African American, 31% Hispanic) recruited from an urban cancer center were randomly assigned (2:1 ratio) to a 12-week yoga intervention (n = 84) or a 12-week waitlist control group (n = 44). Changes in QOL (eg, Functional Assessment of Cancer Therapy) from before random assignment (T1) to the 3-month follow-up (T3) were examined; predictors of adherence were also assessed. Nearly half of all patients were receiving medical treatment. Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates (P < .0001). Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL (P < .008), emotional well-being (P < .015), social well-being (P < .004), spiritual well-being (P < .009), and distressed mood (P < .031). Sixty-nine percent of intervention participants attended classes (mean number of classes attended by active class participants = 7.00 +/- 3.80), with lower adherence associated with increased fatigue (P < .001), radiotherapy (P < .0001), younger age (P < .008), and no antiestrogen therapy (P < .02). Despite limited adherence, this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors. Among patients not receiving chemotherapy, yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL.\nStudy7: Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects. We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema. The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem (P = .015), aerobic fitness (P = .006), and percent body fat (adjusted P = .076). Resistance exercise was superior to usual care for improving self-esteem (P = .018), muscular strength (P < .001), lean body mass (P = .015), and chemotherapy completion rate (P = .033). Changes in cancer-specific QOL, fatigue, depression, and anxiety favored the exercise groups but did not reach statistical significance. Exercise did not cause lymphedema or adverse events. Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy, but they did improve self-esteem, physical fitness, body composition, and chemotherapy completion rate without causing lymphedema or significant adverse events.\nStudy8: Benefits of supervised group exercise programme for women being treated for early stage breast cancer: pragmatic randomised controlled trial. To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer, with six month follow-up. Pragmatic randomised controlled prospective open trial. Three National Health Service oncology clinics in Scotland and community exercise facilities. 203 women entered the study; 177 completed the six month follow-up. Supervised 12 week group exercise programme in addition to usual care, compared with usual care. Functional assessment of cancer therapy (FACT) questionnaire, Beck depression inventory, positive and negative affect scale, body mass index, seven day recall of physical activity, 12 minute walk test, and assessment of shoulder mobility. Mixed effects models with adjustment for baseline values, study site, treatment at baseline, and age gave intervention effect estimates (intervention minus control) at 12 weeks of 129 (95% confidence interval 83 to 176) for metres walked in 12 minutes, 182 (75 to 289) for minutes of moderate intensity activity reported in a week, 2.6 (1.6 to 3.7) for shoulder mobility, 2.5 (1.0 to 3.9) for breast cancer specific subscale of quality of life, and 4.0 (1.8 to 6.3) for positive mood. No significant effect was seen for general quality of life (FACT-G), which was the primary outcome. At the six month follow-up, most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged. No adverse effects were noted. Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later. Clinicians should encourage activity for their patients. Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services. Trial registration Current controlled trials ISRCTN12587864 [controlled-trials.com].\nStudy9: Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. Lymphoma patients commonly experience declines in physical functioning and quality of life (QoL) that may be reversed with exercise training. We conducted a randomized controlled trial in Edmonton, Alberta, Canada, between 2005 and 2008 that stratified 122 lymphoma patients by major disease type and current treatment status and randomly assigned them to usual care (UC; n = 62) or 12 weeks of supervised aerobic exercise training (AET; n = 60). Our primary end point was patient-rated physical functioning assessed by the Trial Outcome Index-Anemia. Secondary end points were overall QoL, psychosocial functioning, cardiovascular fitness, and body composition. Follow-up assessment for our primary end point was 96% (117 of 122) at postintervention and 90% (110 of 122) at 6-month follow-up. Median adherence to the supervised exercise program was 92%. At postintervention, AET was superior to UC for patient-rated physical functioning (mean group difference, +9.0; 95% CI, 2.0 to 16.0; P = .012), overall QoL (P = .021), fatigue (P = .013), happiness (P = .004), depression (P = .005), general health (P < .001), cardiovascular fitness (P < .001), and lean body mass (P = .008). Change in peak cardiovascular fitness mediated the change in patient-rated physical functioning. AET did not interfere with chemotherapy completion rate or treatment response. At 6-month follow-up, AET was still borderline or significantly superior to UC for overall QoL (P = .054), happiness (P = .034), and depression (P = .009) without an increased risk of disease recurrence/progression. AET significantly improved important patient-rated outcomes and objective physical functioning in lymphoma patients without interfering with medical treatments or response. Exercise training to improve cardiovascular fitness should be considered in the management of lymphoma patients.\nStudy10: Effects of an integrated yoga programme on chemotherapy-induced nausea and emesis in breast cancer patients. This study examined the effect of an integrated yoga programme on chemotherapy-related nausea and emesis in early operable breast cancer outpatients. Sixty-two subjects were randomly allocated to receive yoga (n = 28) or supportive therapy intervention (n = 34) during the course of their chemotherapy. Both groups had similar socio-demographic and medical characteristics. Intervention consisted of both supervised and home practice of yoga sessions lasting for 60 min daily, while the control group received supportive therapy and coping preparation during their hospital visits over a complete course of chemotherapy. The primary outcome measure was the Morrow Assessment of Nausea and Emesis (MANE) assessed after the fourth cycle of chemotherapy. Secondary outcomes included measures for anxiety, depression, quality of life, distressful symptoms and treatment-related toxicity assessed before and during the course of chemotherapy. Following yoga, there was a significant decrease in post-chemotherapy-induced nausea frequency (P = 0.01) and nausea intensity (P = 0.01), and intensity of anticipatory nausea (P = 0.01) and anticipatory vomiting (P = 0.05) as compared with the control group. There was a significant positive correlation between MANE scores and anxiety, depression and distressful symptoms. In conclusion, the results suggest a possible use for stress reduction interventions such as yoga in complementing conventional antiemetics to manage chemotherapy-related nausea and emesis.\n", + "output": "Conclusions: This systematic review indicates that exercise may have beneficial effects at varying follow-up periods on HRQoL and certain HRQoL domains including physical functioning, role function, social functioning, and fatigue. Positive effects of exercise interventions are more pronounced with moderate- or vigorous-intensity versus mild-intensity exercise programs. The positive results must be interpreted cautiously because of the heterogeneity of exercise programs tested and measures used to assess HRQoL and HRQoL domains, and the risk of bias in many trials. Further research is required to investigate how to sustain positive effects of exercise over time and to determine essential attributes of exercise (mode, intensity, frequency, duration, timing) by cancer type and cancer treatment for optimal effects on HRQoL and its domains." + }, + { + "input": "Study1: Laser-assisted uvulopalatoplasty for snoring: does it meet the expectations? The high prevalence of habitual snoring (35% of the general population) and the increasing demand for an effective treatment have led, in the last decade, to the generalisation of laser-assisted uvulopalatoplasty (LAUP). However, acceptable studies on its effectiveness are lacking. The present randomised, placebo-controlled study included 25 nonapnoeic and mild obstructive sleep apnoea snorers to evaluate LAUP effectiveness for snoring. Group I received a one-stage LAUP treatment and group II a placebo (simulated snore surgery followed by an oral placebo). Before each treatment and 3 months after, the variables and procedures assessed were: body weight; sleepiness (Epworth sleepiness scale); quality of life (SF-36); subjective snoring intensity (0-10 analogue scale); objective snoring intensity (average decibel intensity); snoring index (number of snores per hour); and apnoea/hypopnea index. No differences were observed in body weight, sleepiness, quality of life, subjective and objective intensity, and frequency of snoring, and apnoea/hypopnea index between the groups before and 3 months after treatment. In conclusion, this study provides evidence of the lack of effectiveness of one-stage laser-assisted uvulopalatoplasty for snoring in nonapnoeic and mild obstructive sleep apnoea patients, with the result that it does not meet the expectations generated by the procedure.\nStudy2: [Multi-level treatment for obstructive sleep apnea syndrome: comparative study of four different surgical techniques of palate]. Palatopharyngeal surgery is a therapeutic option for Obstructive Sleep Apnea Syndrome. This surgery is based on the assumption that the soft palate is the principal apneogenic area of the upper airway. We report a comparison of four techniques of palatopharyneal surgery. In the other hand, the effectiveness of palatopharyngeal surgery for correcting other obstructions when present, was also evaluated.\nStudy3: Bipolar radiofrequency treatment for snoring with mild to moderate sleep apnea: a comparative study between the radiofrequency assisted uvulopalatoplasty technique and the channeling technique. We compared radiofrequency techniques used in the treatment of snoring and obstructive sleep apnea [radiofrequency assisted uvulopalatoplasty (RAUP) and channeling] as regard the efficacy and morbidity. A pilot, prospective randomized single blinded study was conducted on 40 patients in the ENT Department, Kasr Al-Aini Hospital, Cairo University during the period from April to December 2003. Patients were randomized into two groups each consisting of 20 patients. The first group was treated by submucosal channeling of the palate, while the second group was treated by radiofrequency assisted uvulopalatoplasty (RAUP). Patients were followed for 4 months, filling a questionnaire in a standard visual analogue score pattern. Assessment was done prior to the surgery and was repeated 3, 10 days and 3 weeks postoperatively. Visual analogue scores were done for the following parameters: pain, speech deficits, dysphagia, and snoring (by the bed partner). Polysomnography was done pre to intervention and was repeated 4 months postoperatively. This work confirms the favorable effects of radiofrequency in the treatment of patients with snoring and mild to moderate obstructive sleep apnea (OSA) particularly on snoring, confirming the results of the previous studies and highlighting the more rapid relief of snoring and apnea in RAUP group compared to channeling group but with more postoperative pain and morbidity.\nStudy4: Nasal-CPAP, surgery, and conservative management for treatment of obstructive sleep apnea syndrome. A randomized study. To assess separately the effectiveness and safety of nasal-continuous positive airway pressure (N-CPAP) and that of surgery in comparison to conservative management in patients with obstructive sleep apnea syndrome (OSAS). DESIGN. A randomized study with 1-year follow-up. A university hospital acting as a referral center for OSAS. Symptomatic patients with OSAS (72 male and 4 female patients aged 18 to 65 years), who had oxygen desaturations in the overnight recording. After the initial diagnostic workup, patients were considered to be candidates for either N-CPAP (44 patients) or surgical treatment (uvulopalatopharyngoplasty [UPPP] with or without mandibular osteotomy) (32 patients). Within the groups, the patients were then randomized to either the assigned treatment or conservative management. The number of nocturnal oxygen desaturation events of 4% or more per hour in bed (ODI4); daytime somnolence; side effects. N-CPAP Group: Compliance with N-CPAP therapy at 1 year was 13 of 21. The most common reason for noncompliance was general intolerance of CPAP. All compliant patients had a normal ODI4 ( < 10), whereas 1 of 20 of their control subjects had a normal finding. Patients receiving active treatment were significantly less somnolent than their control subjects at 1 year (p < 0.05). SURGERY GROUP: At 1 year, 7 of 18 of the surgically treated and 1 of 14 of the conservatively treated patients had a normal ODI4 (p < 0.001). Daytime somnolence was significantly less severe in the surgically treated patients compared with their control subjects (p < 0.001) both at 3 and 12 months. The overall postoperative complication rate was 22%. N-CPAP is an effective therapy for OSAS, but compliance is a problem. Surgical therapy (UPPP with or without mandibular osteotomy) needs further evaluation.\nStudy5: A randomized trial of temperature-controlled radiofrequency, continuous positive airway pressure, and placebo for obstructive sleep apnea syndrome. The study goal was to determine the effectiveness of (1) multilevel temperature-controlled radiofrequency tissue ablation (TCRFTA) or (2) continuous positive airway pressure (CPAP) for the treatment of mild to moderate obstructive sleep apnea syndrome (OSAS). We conducted a randomized, placebo-controlled, 2-site trial, comparing TCRFTA (n = 30) and CPAP (n = 30) with sham-placebo (n = 30) using intention-to-treat analysis. Compared with pretreatment baseline, TCRFTA improved reaction time, OSAS-specific quality of life (QOL), and subjective sleepiness (all P < 0.05). Compared with sham-placebo, TCRFTA improved QOL, airway volume, apnea index, and respiratory arousal index (all P < 0.05). TCRFTA side effects and complications were mild, temporary, and similar to sham-placebo. CPAP improved QOL and sleepiness compared with baseline and QOL when compared with sham-placebo (all P < 0.05). Significant differences were not seen between TCRFTA and CPAP outcomes. TCRFTA and CPAP each improve QOL for mild-moderate OSAS patients. TCRFTA improvements may result from changes in airway volume, apnea index, and respiratory arousal index.\nStudy6: Lateral pharyngoplasty versus uvulopalatopharyngoplasty: a clinical, polysomnographic and computed tomography measurement comparison. To compare the lateral pharyngoplasty procedure with uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS). Prospective randomized study. Academic tertiary center. Twenty-seven adults with OSAHS originally selected for treatment with UPPP. Patients were randomly assigned to 2 groups: in one group, we performed the lateral pharyngoplasty (15 cases), and in the other, we did the UPPP (12 cases). We compared treatment outcomes through the evaluation of OSAHS-related symptoms and the analysis of polysomnographic tests and computed tomography measurements of pharyngeal airway. The lateral pharyngoplasty group achieved a statistically greater reduction in body weight, excessive daytime sleepiness, and apnea-hypopnea index. In addition, only in this group did we observe a statistically significant increase in the amount of deep sleep stages and improvement in morning headaches. Patients from the UPPP group did not present significant changes in the polysomnographic parameters. Pharyngeal airway measurement outcomes were similar in both groups and did not reflect the clinical and polysomnographic differences we observed. Lateral pharyngoplasty produces better clinical and polysomnographic outcomes in the treatment of OSAHS than does UPPP, without resultant differences in the cross-sectional measurements of the pharyngeal airway between these treatments.\nStudy7: Preliminary findings from a prospective, randomized trial of two tongue-base surgeries for sleep-disordered breathing. This study compares the efficacy of 2 tongue-base surgical procedures in the treatment of patients with moderate to severe sleep-disordered breathing. We conducted a prospective, randomized crossover surgical trial at a university hospital. Seventeen patients with moderate to severe sleep-disordered breathing and Fujita type II upper airway collapse for whom conservative treatment failed were enrolled into an institutional review board-approved surgical protocol. They were randomly assigned to undergo palatopharyngoplasty combined with either tongue advancement (mandibular osteotomy) or tongue suspension. Parameters assessed included severity of sleep-disordered breathing (polysomnography), sleepiness (Epworth Sleepiness Scale), and anatomic changes (upper airway endoscopy), as well as demographic factors. Patients not achieving satisfactory improvement in their condition were offered nonsurgical management or additional surgical treatment that varied based on the postoperative assessment but included crossing over to the other tongue surgical procedure. Nine of the 17 patients were randomized to the tongue suspension group, and 8 to the tongue advancement group. In the 9 tongue suspension patients, Epworth Sleepiness Scale scores fell from 12.1 to 4.1 (P = 0.007). Airway collapse for all 9 patients measured on M\u00fcller maneuver improved, by a mean of 64% (P = 0.0006) at the palate and 83% (P = 0.0003) at the base of the tongue. In the 8 tongue advancement patients, Epworth Sleepiness Scale scores fell from a mean of 13.3 to 5.4 (P = 0.004). Airway collapse for 5 of 8 patients measured on M\u00fcller maneuver improved by a mean of 31% (P = 0.1) at the palate and 75% (P = 0.03) at the base of the tongue. Prospective, randomized trials of tongue-base surgery for sleep-disordered breathing are possible. Preliminary findings from the current protocol reveal a slight advantage of tongue suspension over tongue advancement.\nStudy8: Palatal implants for the treatment of snoring and obstructive sleep apnea/hypopnea syndrome. Randomized, double-blinded, placebo-controlled, clinical trial to determine the effectiveness of palatal implants for treatment of mild/moderate obstructive sleep apnea/hypopnea syndrome (OSAHS). Sixty-two non-obese adults with history of snoring, daytime sleepiness, and mild/moderate OSAHS, were randomized to receive palatal implants (n = 31) or placebo procedure (n = 31). Complete follow-up including quality of life (QOL, SF-36), snoring visual analog scale (VAS), and Epworth Sleepiness Scale (ESS) data were obtained in 62 patients. Seven patients refused follow-up polysomnography for a total of 55 patients (29 implant and 26 placebo). The treatment group (change in score of -7.9 +/- 7.7) was significantly improved compared with the placebo group (change in score of 0.9 +/- 4.3) for apnea/hypopnea index (AHI) (P < 0.0001), QOL, SF-36 (P < 0.0001), snoring VAS (P < 0.0001), and ESS (P = 0.0002). Palatal implants improve AHI, QOL, snoring intensity, and daytime sleepiness for selected patients with mild/moderate OSAHS.\nStudy9: Expansion sphincter pharyngoplasty: a new technique for the treatment of obstructive sleep apnea. In this study, we assessed the efficacy of a new method (expansion sphincter pharyngoplasty [ESP]) to treat obstructive sleep apnea. We conducted a prospective, randomized controlled trial. Forty-five adults with small tonsils, body mass index less than 30 kg/m2, of Friedman stage II or III, of type I Fujita, and with lateral pharyngeal wall collapse were selected for the study. The mean body mass index was 28.7 kg/m2. The apnea-hypopnea index improved from 44.2 +/- 10.2 to 12.0 +/- 6.6 (P < 0.005) following ESP and from 38.1 +/- 6.46 to 19.6 +/- 7.9 in the uvulopalatopharyngoplasty group (P < 0.005). Lowest oxygen saturation improved from 78.4 +/- 8.52% to 85.2 +/- 5.1% in the ESP group (P = 0.003) and from 75.1 +/- 5.9% to 86.6 +/- 2.2% in the uvulopalatopharyngoplasty group (P < 0.005). Selecting a threshold of a 50% reduction in apnea-hypopnea index and apnea-hypopnea index less than 20, success was 82.6% in ESP compared with 68.1% in uvulopalatopharyngoplasty (P < 0.05). The ESP may offer benefits in a selected group of OSA patients.\nStudy10: Radiofrequency vs laser in the management of mild to moderate obstructive sleep apnoea: does the number of treatment sessions matter? Obstructive sleep apnea (OSA) is a relatively common and serious problem with many medical and social consequences. Laser and radiofrequency are two recent techniques used to treat OSA and they can be carried out under local anaesthesia, but they need multiple sessions to achieve satisfactory outcome and are associated with better short-term than long-term outcomes. In this work we compare the two modalities as regards the optimal number of treatment sessions needed to achieve a favourable outcome in the short and long term. A total of 150 patients with apnoea hypopnoea index (AHI) between 5 and 30 events per hour, no morbid obesity and retropalatal site of obstruction were included in this prospective study. Patients were randomly and equally divided into two groups, each comprising 75 patients. The first group was treated with bipolar radiofrequency volumetric tissue reduction of the palate (BRVTR) and the second group was treated with laser-assisted uvulopalatoplasty (LAUP). Each group was further subdivided into five subgroups each consisting of 15 patients. The first group received one treatment session, the second received two sessions, the third received three sessions, the fourth received four sessions and the fifth group received five treatment sessions. Evaluation of efficiency of both techniques in treating OSA was assessed objectively by polysomnography. In those treated with BRVTR; at least three sessions were needed to achieve a favourable outcome in OSA in the short and long term. In those treated with LAUP, a single treatment session was enough to achieve a favourable outcome on OSA in the short term, while two sessions were needed to achieve the same long-term outcome. In OSA, fewer treatment sessions are needed with LAUP (one session) than with BRVTR (three sessions) to achieve a favourable outcome. In LAUP more treatment sessions (two) are needed to maintain a longer-term favourable outcome than those needed to achieve short-term favourable outcome (one session), which is not the case with BRVTR (three sessions are needed to achieve both short- and long-term favourable results).\n", + "output": "Conclusions: There are now a small number of trials assessing different surgical techniques with inactive and active control treatments. The studies assembled in the review have failed to demonstrate consistent effects in favour of surgery and do not provide convincing evidence to support its use in sleep apnoea/hypopnoea syndrome. Short-term outcomes are unlikely to consistently identify suitable candidates for surgery. Long-term follow-up of patients who undergo surgical correction of upper airway obstruction is required. This would help to determine whether surgery is a curative intervention, or whether there is a tendency for the signs and symptoms of sleep apnoea to re-assert themselves, prompting patients to seek further treatment for sleep apnoea." + }, + { + "input": "Study1: Double-blind study of the activity and tolerability of cabergoline versus placebo in parkinsonians with motor fluctuations. The use of a dopamine agonist with a long duration of action has theoretical advantages in attempting to reduce the motor fluctuations in Parkinson's disease. We report the results of a double-blind controlled study of adding cabergoline, an ergot derivative with potent long-lasting high affinity for the D2 receptor, to levodopa therapy in 37 patients with severe fluctuations in response to treatment. Increasing dosages of cabergoline (19 patients) or placebo (18 patients) were added to each patient's stable levodopa regime. The two patient groups were similar at baseline in terms of age, disease duration, duration of levodopa treatment, and average hours \"off\" per day. Following incremental dose titration, patients in the cabergoline group had a significant reduction in hours \"off\" per day from 5.0 (SD 2.1) to 3.0 (SD 2.5), but there was no change in this measure in the placebo group [4.0 (2.2) and 3.3 (2.3) respectively]. This was not at the expense of a significant increase in dyskinesia. However, there was no difference between the groups when comparing their average Hoehn and Yahr stage of disease, and Schwab and England activities of daily living index.\nStudy2: Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease. Cabergoline is a dopaminergic agonist relatively specific for the D2 receptor and much longer-acting than other dopamine agonists. We conducted a randomized, placebo-controlled, double-blind study of cabergoline in 188 levodopa/carbidopa-treated patients with suboptimally controlled Parkinson's disease (PD). The cabergoline patients had significantly better Activities of Daily Living (p = 0.032) and Motor Examination (p = 0.031) scores at the conclusion of the trial compared with the placebo group. The daily levodopa dose for the cabergoline patients decreased 18% compared with a 3% reduction for the placebo group (p < 0.001). The amount of time in the \"on\" state increased more in the cabergoline group (p = 0.022). The side-effect was similar to that seen with other dopamine agonists, and cabergoline was generally well tolerated. We conclude that cabergoline is an effective adjunct to levodopa for the treatment of PD.\n", + "output": "Conclusions: In the management of the motor complications seen in Parkinson's disease, cabergoline can be used to reduce levodopa dose and modestly improve motor impairment and disability with an acceptable adverse event profile. These conclusions are based on, at best, medium term evidence." + }, + { + "input": "Study1: Bezafibrate treatment: a new medical approach for PBC patients? A new medical approach to primary biliary cirrhosis (PBC) has been desired. We investigated the feasibility of using combination ursodeoxycholic acid (UDCA)-bezafibrate therapy in patients with PBC nonresponsive to UDCA monotherapy. During a 6-month period, 22 PBC patients with elevated serum alkaline phosphatase (ALP) despite UDCA monotherapy received either UDCA at 600 mg/day (control group) or UDCA at 600 mg/day plus bezafibrate at 400 mg/day (bezafibrate group). Each patient underwent detailed clinical and biochemical evaluation. During treatment, changes in ALP level were greater in the bezafibrate group than in the control group (P< 0.01). During and at the end of treatment, serum ALP levels were significantly lower than those before treatment in patients receiving UDCA plus bezafibrate (P< 0.05). At the end of the 6 months, normalization of serum ALP was observed in 5 of 11 (45.4%) patients given bezafibrate and in 2 of 11 (18.1%) patients not given bezafibrate (P< 0.16). Bile acid proportions during the combination therapy did not change. Pruritus disappeared in 1 of 7 bezafibrate-group patients with this symptom. UDCA at 600 mg/day plus bezafibrate at 400 mg/day may be considered as a new therapeutic option for patients with PBC.\nStudy2: Bezafibrate in the treatment of primary biliary cirrhosis: comparison with ursodeoxycholic acid. nan\nStudy3: Prospective randomized crossover trial of combination therapy with bezafibrate and UDCA for primary biliary cirrhosis. The aim of this study was to evaluate the effects of the combination therapy with bezafibrate and ursodeoxycholic acid (UDCA) for primary biliary cirrhosis (PBC), compared to UDCA monotherapy. Sixteen patients with compensated PBC were divided randomly into two groups. Group A received treatment with bezafibrate and UDCA for 6 months, while group B received UDCA alone, treatment protocols were then exchanged for another 6 months. The laboratory data was followed every month. The mean levels of alkaline phosphatase (ALP) decreased significantly more in group A than in group B in the first half of the study. Then serum ALP levels were elevated in group A after exchanged the therapy, but fell down in group B. Serum levels of gamma-glutamyl transferase (GGT), immunoglobulin M and triglycerides values were significantly lower in group B than in group A, after changing therapies from monotherapy to combination therapy with bezafibrate and UDCA. The mean levels of ALP, GGT and triglycerides were significantly lower at the end of the combination therapy than those at the end of the monotherapy. The combination therapy with bezafibrate and UDCA significantly improves the laboratory data that specific for PBC in comparison with UDCA monotherapy.\n", + "output": "Conclusions: This systematic review did not demonstrate any effect of bezafibrate versus no intervention on mortality, liver-related morbidity, adverse events, and pruritus in patients with primary biliary cirrhosis. Furthermore, we found no significant effects of bezafibrate on mortality, liver-related morbidity, or adverse events when compared with ursodeoxycholic acid, None of the trials assessed quality of life or fatigue. The data seem to indicate a possible positive intervention effect of bezafibrate on some liver biochemistry measures compared with the control group, but the observed effects could be due to systematic errors or random errors. We need more randomised clinical trials on the effects of bezafibrate on primary biliary cirrhosis with low risks of systematic errors and random errors." + }, + { + "input": "Study1: Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes. To determine if suppressive acyclovir therapy given to term gravidas experiencing a first episode of genital herpes simplex virus (HSV)-infection during pregnancy decreases the need for cesarean delivery for that indication. Forty-six pregnant women with first episodes of genital herpes during pregnancy were randomly assigned to receive oral acyclovir 400 mg or placebo, three times per day, from 36 weeks' gestation until delivery as part of a prospective, double-blind trial. Herpes simplex virus cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise, a cesarean was performed. Neonatal HSV cultures were obtained and infants were followed-up clinically. None of the 21 patients treated with acyclovir and nine of 25 (36%) treated with placebo had clinical evidence of recurrent genital herpes at delivery (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.002-0.745; P = .002). No woman treated with acyclovir had a cesarean for herpes, compared with nine of 25 (36%) of those treated with placebo (OR 0.04, CI 0.002-0.745; P = .002). No patient in either treatment group experienced asymptomatic genital viral shedding at delivery. No neonate had evidence of herpes infection or adverse effects from acyclovir. Suppressive acyclovir therapy reduced the need for cesarean for recurrent herpes in women whose first clinical episode of genital HSV occurred during pregnancy. Suppressive acyclovir treatment did not increase asymptomatic viral shedding and was not harmful to the term fetus.\nStudy2: Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding. Neonatal herpes affects about 1 in 15,000 newborns and the prognosis for disseminated disease with encephalitis is poor. We investigated whether acyclovir prophylaxis in late pregnancy effectively reduces the risk of viral shedding and, hence, of mother-to-child transmission at delivery. A prospective study was conducted. Pregnant women who had at least one episode of genital herpes during pregnancy were randomly assigned to two groups: group 1 (n=167) received oral acyclovir from 36 weeks of gestation to term; group 2 (n=121) received no treatment. Group 3 (n=201) comprised women not given prophylaxis who had a history of genital herpes, but no active episodes during pregnancy. No specific instruction were set up for obstetrical management except for cesarean section in case of a suspected herpes lesion at the time of labor. The rate of Cesarean section was 8.4% in group 1, 16.5% in group 2, and 9.9% in group 3 (p<0.001). 75% of cesareans in group 2 and 10% in group 3 were done for genital herpes. Percentage of viral shedding was, respectively, 0% (group1), 5% (group2), and 0.5%(group3) (p<0.05). These findings underline the value of antiviral prophylaxis in late pregnancy for women with a known history of genital herpes. Such prophylaxis only partly prevents neonatal herpes infection, because it is not applicable to patients with no known clinical history but may excrete the virus.\n", + "output": "Conclusions: Women with recurrent genital herpes simplex virus should be informed that the risk of neonatal herpes is low. There is insufficient evidence to determine if antiviral prophylaxis reduces the incidence of neonatal herpes. Antenatal antiviral prophylaxis reduces viral shedding and recurrences at delivery and reduces the need for cesarean delivery for genital herpes. Limited information exists regarding the neonatal safety of prophylaxis. The risks, benefits, and alternatives to antenatal prophylaxis should be discussed with women who have a history and prophylaxis initiated for women who desire intervention." + }, + { + "input": "Study1: Transjugular intrahepatic portosystemic shunts compared with endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. A randomized, controlled trial. Transjugular intrahepatic portosystemic shunts (TIPS) have widened the use of portal decompression as therapy for variceal hemorrhage. However, no controlled studies have examined the efficacy of TIPS compared with that of other treatments. To compare the efficacy and safety of TIPS with those of endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. Randomized, controlled trial. Tertiary-care academic medical center. 100 patients with cirrhosis were evaluated a mean of approximately 10 days after an episode of acute variceal bleeding; 20 patients were excluded because of portal venous thrombosis (n = 6), hepatoma (n = 3), florid alcoholic hepatitis (n = 6), and refusal to give consent (n = 5). TIPS (n = 41) or sclerotherapy (n = 39). The latter was performed by freehand injections of 5% Na morrhuate at 2- to 3-week intervals. Recurrent variceal hemorrhage was managed by sclerotherapy followed by angiographic assessment of TIPS and dilatation of the stents (TIPS group) or crossover to TIPS (sclerotherapy group). Rebleeding and survival were the primary end points. Complications and rates of rehospitalization were secondary end points. During a mean follow-up of approximately 1000 days, recurrent gastrointestinal bleeding resulted from variceal hemorrhage (9 patients in the TIPS group and 8 in the sclerotherapy group), portal gastropathy (1 patient in each group), and gastric lipoma (0 and 1 patients, respectively). A higher mortality rate was seen with TIPS (P = 0.03). Death resulted from variceal bleeding (5 patients in the TIPS group and 3 in the sclerotherapy group), sepsis (3 and 2 patients, respectively), liver failure (2 patients in each group), hepatoma (1 and 0 patients, respectively), and hemoperitoneum (1 and 0 patients, respectively). Encephalopathy was the most common complication in the TIPS group (n = 12), and pain developing after sclerotherapy was the most common in the sclerotherapy group (n = 10). The two groups had similar rates of rehospitalization. Endoscopic sclerotherapy and TIPS are equivalent with respect to rebleeding developing over the long term. However, sclerotherapy may be superior to TIPS with respect to survival.\nStudy2: Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage. Uncontrolled studies suggest that placement of a transjugular intrahepatic portosystemic shunt (TIPS) could be useful in the treatment of variceal bleeding. The aim of this study was to evaluate the efficacy and safety of TIPS in the elective treatment of hemorrhage from esophageal varices in a randomized controlled study that compared the effects of TIPS with those of endoscopic sclerotherapy (ES). Sixty-three consecutive cirrhotic patients with hemorrhage from esophageal varices were included. Thirty-two patients were randomly allocated to ES and 31 to TIPS groups. One patient in each group died before the therapeutic procedure could be performed. During a mean follow-up period of 15 months, variceal rebleeding occurred in 51.6% of the patients in the ES group and 23% of those in the TIPS group. Uncontrolled rebleeding occurred in 10 of 31 patients in the ES group, whereas rebleeding did not occur in any patient of the TIPS group. Hepatic encephalopathy was more frequent in TIPS patients (33.3%) than in those treated by ES (13%). However, mortality was similar in both treatment groups. These preliminary results suggest that TIPS is more effective than ES in the prevention of variceal rebleeding in cirrhotic patients, even though no difference in survival was observed.\nStudy3: Transjugular intrahepatic portosystemic stent shunt versus sclerotherapy plus propranolol for variceal rebleeding. In patients with cirrhosis of the liver, after the first variceal bleeding episode, transjugular intrahepatic portosystemic stent shunting (TIPS) and endoscopic sclerotherapy plus propranolol (ES) were compared regarding prevention of variceal rebleeding and mortality. Eighty-three patients with cirrhosis of the liver were randomized to undergo TIPS (n = 42) or ES (n = 41). Median observation time was in 1.6 years in the TIPS group and 1.45 years in the ES group. Cumulative rates of rebleeding were 23% in the TIPS group and 57% in the ES group (P = 0.0001). Hepatic encephalopathy was observed in 29% of the patients in the TIPS group and in 13% of those in the ES group (P = 0.041). Cumulative rates of survival were 69% in the TIPS group and 67% in the ES group (P = 0.62). Mortality rates in both groups were positively correlated with a higher Child's classification. Although TIPS significantly reduced the rate of rebleeding, survival rates were not improved. Because TIPS is associated with an increased risk of encephalopathy and high rates of shunt dysfunction, which requires reintervention, the procedure cannot be recommended for elective treatment after the first variceal bleeding episode, but it is an effective therapy in patients in whom endoscopic sclerotherapy fails to control bleeding.\nStudy4: Portacaval shunt versus endoscopic sclerotherapy in the elective treatment of variceal hemorrhage. Eighty-two consecutive Child-Campbell class A and B cirrhotic patients were included in a prospective controlled trial to assess the efficacy and safety of portacaval anastomosis vs. endoscopic sclerotherapy as elective treatment of variceal hemorrhage. Forty-one patients were randomized to portacaval anastomosis and 41 to sclerotherapy. After excluding dropouts, 34 patients were treated with portacaval anastomosis and 35 with sclerotherapy. The incidence of variceal rebleeding during follow-up (mean +/- SD, 20.6 +/- 14.2 months) was significantly higher in the sclerotherapy than in the portacaval groups, either considering the overall treated group or only patients completing sclerotherapy (40% and 25% vs. 2.9%; P = 0.0002 and P = 0.01, respectively). The 2-year probability of suffering from at least one episode of hepatic encephalopathy was significantly higher in patients submitted to portacaval anastomosis than in those treated with endoscopic sclerotherapy (40% vs. 12%; P = 0.04). However, disabling encephalopathy only appeared in 3 of 34 patients who underwent surgery (8.8%). Early and long-term mortality did not differ between the therapeutic groups; 2-year survival rates were 83% for portacaval anastomosis and 79% for sclerotherapy. It is concluded that portacaval anastomosis is more effective than endoscopic sclerotherapy in preventing variceal rebleeding in spite of the greater incidence of hepatic encephalopathy. The role of portacaval anastomosis in the elective treatment of variceal rebleeding should be reassessed.\nStudy5: Shunt surgery versus endoscopic sclerotherapy for variceal hemorrhage: late results of a randomized trial. Between September 1982 and April 1988, 60 cirrhotic patients with prior variceal hemorrhage were randomized to undergo the placement of an elective shunt (distal splenorenal: 26; nonselective: 4) or long-term endoscopic sclerotherapy (n = 30). Eighty-six percent of patients had alcoholic cirrhosis, and 33% were classified as Child's class C. After a mean follow-up of 87 months, 60% of patients undergoing sclerotherapy and 17% of shunt patients experienced rebleeding (p < 0.001). Shunt patients have survived longer than those who had sclerotherapy (6-year survival rates of 53% and 26%, respectively; p < 0.05). In part because of the wide geographic distribution of patients, only 4 of 13 patients in whom sclerotherapy failed (31%) could undergo salvage by shunt surgery. Although hepatic portal perfusion was better maintained after sclerotherapy, there were no major differences between the groups in terms of post-therapy hepatic or psychoneurologic function. In a predominantly alcoholic cirrhotic patient population (half non-urban), the results of elective shunt surgery were superior to those of chronic endoscopic sclerotherapy with respect to the prevention of recurrent variceal hemorrhage and survival.\nStudy6: A randomized clinical trial comparing transjugular intrahepatic portosystemic shunt with endoscopic sclerotherapy in the long-term management of patients with cirrhosis after recent variceal hemorrhage. The aim of this study was to compare the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with that of endoscopic sclerotherapy (ES) in the long-term management of patients with cirrhosis after variceal bleeding. Seventy-eight consecutive cirrhotic patients with recent variceal bleeding were randomly allocated to either TIPS (n=38) or ES (n=40). All patients were in good condition at randomization. The mean follow-up was 1116+/-92 days in the TIPS group and 1047+/-102 days in the ES group. Differences in rebleeding from any source (18.4% vs. 32.5%) and esophageal variceal rebleeding (15.7% vs. 27.5%) were not significantly different between the two groups (P>0.05). The mortality rates were similar in both treatment groups. Shunt dysfunction was noted in 27 patients (71%) in the TIPS group. There were more numbers of rehospitalization during follow-up in the TIPS group than in the ES group (2.6+/-0.4 vs. 1.1+/-0.2) (P<0.01). TIPS and ES are equally effective in the prevention of variceal rebleeding. However, TIPS is associated with high incidence of shunt dysfunction, which lead to more rehospitalization. Therefore, TIPS may not be a first-line treatment for the prevention of variceal rebleeding in cirrhotic patients who are in stable condition.\nStudy7: Distal splenorenal shunt versus endoscopic sclerotherapy in the prevention of variceal rebleeding. First stage of a randomized, controlled trial. In 1984 we started a prospective controlled trial comparing endoscopic sclerotherapy (ES) with the distal splenorenal shunt (DSRS) in the elective treatment of variceal hemorrhage in cirrhotic patients. The study population included 40 patients with cirrhosis and portal hypertension referred to our department from October 1984 to March 1988. These patients were drawn from a pool of 173 patients who underwent either elective surgery or endoscopic sclerotherapy during this time. Patients were assigned to one of the two groups according to a random-number table: 20 to DSRS and 20 to ES. During the postoperative period, no DSRS patient died, while one ES patient died of uncontrolled hemorrhage. One DSRS patient had mild recurrent variceal hemorrhage despite an angiographically patent DSRS. Four ES patients suffered at least one episode of gastrointestinal bleeding: two from varices and two from esophageal ulcerations. Five ES patients developed transitory dysphagia. Long-term follow-up was complete in all patients. Two-year survival rates for shunt (95%) and ES (90%) groups were similar. One DSRS patient rebled from duodenal ulcer, while three ES patients had recurrent bleeding from esophagogastric sources (two from varices and one from hypertensive gastropathy). One DSRS and two ES patients have evolved a mild chronic encephalopathy; four DSRS and two ES patients suffered at least one episode of acute encephalopathy. Two ES patients had esophageal stenoses, which were successfully dilated. Preliminary data from this trial seem to indicate that DSRS, in a subgroup of patients with good liver function and a correct portal-azygos disconnection, more effectively prevents variceal rebleeding than ES. However no significant difference in the survival of the two treatment groups was noted.\nStudy8: Endoscopic variceal ligation plus propranolol vs. transjugular intrahepatic portosystemic stent shunt: a long-term randomized trial. After a first variceal bleeding episode in patients with cirrhosis of the liver, treatment with transjugular intrahepatic portosystemic stent shunt (TIPS) and endoscopic variceal ligation (EVL) plus propranolol were compared, with regard to prevention of variceal rebleeding, complications, and mortality. 85 patients were randomly allocated to receive TIPS (n = 43) or EVL (n = 42). The groups were comparable regarding age, sex, etiology of liver cirrhosis, and liver function. The mean observation times were 4.1 years in the TIPS group and 3.6 years in the EVL group. Although the probability of rebleeding was higher in the EVL group (29.9%) than in the TIPS group (19.4%), the difference was not statistically significant. Three of five patients of the EVL group successfully underwent TIPS placement after treatment failure. The probability of TIPS dysfunction requiring shunt revision was 89 %. Hepatic encephalopathy was observed more often in the TIPS group (40.5%) than in the EVL group (20.5%; P < 0.05). The probability of survival was similar in both groups (TIPS group 75.9%, EVL group 82.2%; n.s.). In view of its good efficacy and the lower cost of treatment, endoscopic ligation plus propranolol may be recommended as initial procedure for prevention of recurrent variceal hemorrhage, whereas TIPS seems to be the preferable procedure in patients with recurrent bleeding after adequate endoscopic and pharmacological treatment.\nStudy9: Endoscopic sclerotherapy versus portacaval shunt in patient with severe cirrhosis and acute variceal hemorrhage. Long-term follow-up. In a continuation of a trial for which preliminary results were reported in the Journal two years ago, a total of 64 patients with Child Class C cirrhosis and variceal hemorrhage requiring six or more units of blood were randomly assigned to receive either a portacaval shunt (32 patients) or endoscopic sclerotherapy (32 patients). The duration of initial hospitalization and the total amount of blood transfused during hospitalization were significantly less in the patients receiving sclerotherapy (P less than 0.001). There was no difference in short-term survival (50 percent of the sclerotherapy group were discharged alive, as compared with 44 percent of the shunt-surgery group). Both groups were followed for a mean of 530 days after randomization. Rebleeding from varices, the duration of rehospitalization for hemorrhage, and transfusions received after discharge were all significantly greater in the sclerotherapy group (P less than 0.001). Forty percent of the sclerotherapy-treated patients discharged alive (7 of 16 patients) ultimately required surgical treatment for bleeding varices, despite a mean of 6.1 treatment sessions. Health care costs and long-term survival did not differ significantly between the groups (P greater than 0.05). We conclude that although endoscopic sclerotherapy is as good as surgical shunting for the acute management of variceal hemorrhage in poor-risk patients with massive bleeding, sclerotherapy-treated patients in whom varices are not obliterated and bleeding continues should be considered for elective shunt surgery.\nStudy10: Sclerotherapy vs. distal splenorenal shunt in the elective treatment of variceal hemorrhage: a randomized controlled trial. One hundred and twelve consecutive Child Class A and B cirrhotic patients were included in a prospective controlled trial aimed at investigating the efficacy and safety of endoscopic sclerotherapy vs. distal splenorenal shunt in the elective treatment of hemorrhage from esophagogastric varices. Fifty-seven patients were randomly allocated to splenorenal shunt and 55 to endoscopic sclerotherapy. Since only 4 of the 55 patients assigned to endoscopic sclerotherapy had to be excluded after randomization and before treatment as compared to 14 of the 57 patients assigned to splenorenal shunt, it is suggested that the applicability of endoscopic sclerotherapy is greater than that of splenorenal shunt. One patient in each group died within 30 days of the procedure and two in the endoscopic sclerotherapy group were lost to follow-up just after discharge. Variceal rebleeding during follow-up occurred in 37.5% (18/48) of patients in the endoscopic sclerotherapy group and in 14.3% of those in the splenorenal shunt group (6/42) (p less than 0.02), whereas hepatic encephalopathy was more frequent in patients submitted to splenorenal shunt (10/42, 24%) than in those treated by endoscopic sclerotherapy (4/48, 8%) (p less than 0.05). The therapeutic modality was the only variable with independent predictive value for rebleeding during follow-up, whereas for hepatic encephalopathy, the therapeutic modality, and the presence of encephalopathy related to the bleeding episode each showed independent predictive value. Early and long-term mortality, did not differ between the two therapeutic groups, being the 2-year survival was 71% for splenorenal shunt and 68% for endoscopic sclerotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)\n", + "output": "Conclusions: All shunts resulted in a significantly lower rebleeding rate at the expense of a higher incidence of encephalopathy. TIPS was complicated by a high incidence of shunt dysfunction. No survival advantage was demonstrated with any shunt." + }, + { + "input": "Study: An analysis of the utility of plasma immunoreactive estrogen measurements in determining delivery time of gravidas with a fetus considered at high risk. Although maternal estrogen excretion and plasma estrogen levels are widely used to assess fetal health, the utility of these tests in lowering perinatal mortality rates has not been established. In order to ascertain if, with the help of plasma immunoreactive estrogen measurements, a reduction in perinatal deaths could be achieved, a population of women with a fetus at high risk were randomly divided into two groups and studied prospectively: in 315 gravidas, the estrogen results were reported (Group A); in 307, they were not reported (Group B). Nine perinatal deaths occurred in Group A, 10 in Group B. Ten Group B women whose infant ultimately did well would have been delivered 28 days or more prematurely if management had been based solely on the basis of abnormal immunoreactive estrogen levels. Measurement of estrogen levels is of little value in management of women with a fetus at risk; it may even lead to erroneous premature delivery.\n", + "output": "Conclusions: The available trial data do not support the use of (o)estriol estimation in high-risk pregnancies. The single small trial available does not have the power to exclude a beneficial effect but this is probably of historical interest since biochemical testing has been superseded by biophysical testing in antepartum fetal assessment." + }, + { + "input": "Study1: Maternal cardiovascular consequences of positioning after spinal anaesthesia for Caesarean section: left 15 degree table tilt vs. left lateral. Sixty healthy women undergoing elective Caesarean section were randomly allocated to either a measured 15 degrees left table tilt position (n = 31) or full left lateral position (n = 29) for a 15-min period after spinal blockade. Arm and leg blood pressure, ephedrine requirements, symptoms, fetal heart rate, cord gases and Apgar scores were recorded. Mean ephedrine requirements and incidence of hypotension were similar in the two groups. Arm systolic arterial pressure over time was similar in both groups, but leg systolic arterial pressure over time was significantly lower in the tilt group (p < 0.001); the mean leg systolic arterial pressure was lower for all 15 sequential recordings in the tilt group, reaching statistical significance (p < 0.05) at 4, 5, 6 and 8 min. Differences in maternal nausea, vomiting and bradycardia and fetal outcome were not statistically significant. Following spinal anaesthesia, even a true 15 degrees left table tilt position is associated with aortic compression.\nStudy2: Manual displacement of the uterus during Caesarean section. Ninety ASA 1 and 2 pregnant women with term singleton pregnancies and no maternal and fetal complications, scheduled for elective or emergency Caesarean section, were randomly allocated to group LT (15 degrees left lateral table tilt, n = 45) and group MD (leftward manual displacement, n = 45). Subarachnoid block was established with a 25-gauge spinal needle at the L3-L4 interspace using 1.5 ml of 0.5% hyperbaric bupivacaine. A median sensory level of T6 was observed in both groups but the incidence of hypotension was markedly lower in group MD when compared to group LT (4.4% vs 40%; p < 0.001) with a significant reduction in mean (SD) ephedrine requirement (6 (0) vs 11.3 (4.9) mg; p < 0.001). The mean (SD) fall in systolic blood pressure was 28.8 (7.3) mmHg in group LT and 20 (12.7) mmHg in group MD. The time to maximum fall in systolic blood pressure was similar in both groups (4.5 min). We conclude that manual displacement of the uterus effectively reduces the incidence of hypotension and ephedrine requirements when compared to 15 degrees left lateral table tilt in parturients undergoing Caesarean section.\nStudy3: Hemodynamic effects of a right lumbar-pelvic wedge during spinal anesthesia for cesarean section. Aortocaval compression is a major cause of maternal hypotension. A randomized controlled trial was designed to determine the effectiveness of a mechanical intervention using a right lumbar-pelvic wedge in preventing hypotension after spinal anesthesia for cesarean delivery. Eighty healthy women undergoing elective cesarean section were randomly allocated immediately after spinal blockade to either a lumbar-pelvic wedge positioned under the right posterior-superior iliac crest (Wedge group, n=40) or the complete supine position (Supine group, n=40). Hemodynamic values, vasopressor consumption and adverse effects were collected during the surgical procedure. Hypotension was defined as a reduction in systolic blood pressure of 25% from baseline. Patient allocation, management and data collection were performed by a single unblinded anesthetist. There was no difference in the incidence of hypotension between the two groups (42.5% vs. 50%, P=0.51). During the first 5 min, blood pressure decreased less in the Wedge group. There were significant differences in median [interquartile range] vasopressor requirements between the Wedge group and the Supine group (1 [0-2] vs. 3 [1-4] mg, P<0.01) and in nausea during the procedure (6 vs. 22 patients, P<0.01). In our study population the use of right lumbar-pelvic wedge was not effective in reducing the incidence of hypotension during spinal anesthesia for cesarean section. Patients in whom the wedge was used had higher systolic blood pressure values during the first 5 min of anesthesia and fewer episodes of nausea. The risk of hypotension remains substantial. Copyright \u00a9 2011 Elsevier Ltd. All rights reserved.\nStudy4: Lack of benefits of left tilt in emergent cesarean sections: a randomized study of cardiotocography, cord acid-base status and other parameters of the mother and the fetus. To assess the benefits of performing the cesarean section in lateral tilt during active labor. University Hospital. 204 unselected women undergoing cesarean section (21.1% fetal distress, 45.6% cephalo-pelvic disproportion, 26.0% induction failure, 7.4% abnormal presentation) under general (86.8%) or spinal anesthesia (13.2%). Randomized study. During anesthesia induction and cesarean section 103 women were in partial left lateralization (20 degrees), whereas the remaining 101 remained in the supine position. Internal cardiotocography during cesarean section. Umbilical artery acid-base analysis. Newborn evaluation. Maternal hemodynamic parameters. Fetal heart rate during cesarean section was similar in both groups, except for a baseline heart rate which was slightly higher in the lateral tilt group (137.5 +/- 19.2 vs 131.1 +/- 20). The umbilical artery pH values, as well as pCO2, base deficit, CO3H and oxygen saturation were similar in both groups. The pO2 value was significantly lower in the lateral tilt group (14.03 +/- 6.04 Hg mm vs 16.02 +/- 7.65). Newborn evaluation was similar in both groups. The blood pressure and heart rate of the mother during the cesarean section were also similar in both groups. No benefits were found in performing cesarean section in left lateral tilt.\nStudy5: Lumbar wedge versus pelvic wedge in preventing hypotension following combined spinal epidural anaesthesia for caesarean delivery. Aortocaval compression is a major cause of maternal hypotension. A randomised controlled clinical trial was designed to compare two wedged supine positions for prevention of hypotension following combined spinal epidural anaesthesia for caesarean delivery. Sixty parturients undergoing elective caesarean delivery were randomly assigned to two different wedged supine positions. After the completion of subarachnoid injection, parturients were placed with either a wedge under the right pelvis (group P pelvic wedge) or under the right lumbar region (group L, lumbar wedge). Systolic blood pressure and heart rate were recorded every minute for 20 minutes from the subarachnoid injection. Hypotension, defined as systolic blood pressure <100 mmHg or 80% of the baseline, was treated with intravenous ephedrine 5 mg. The incidence of hypotension, ephedrine use and neonatal Apgar scores and umbilical arterial pH were recorded. The incidence of hypotension was significantly higher in group P than that in group L (23/30 [77%] vs. 14/30 [47%], P=0.016). Systolic blood pressure decreased significantly in both groups at seven, eight and nine minutes (P < 0.001); moreover it was lower at seven, eight and nine minutes in group P than in group L (P < 0.01). Heart rate did not change significantly in either group. There were no significant differences between the two groups for Apgar score and umbilical arterial pH. A lumbar wedge is more effective than a pelvic wedge in preventing hypotension following combined spinal epidural anaesthesia for caesarean delivery, although it does not eliminate hypotension.\nStudy6: The effect of head-down tilt position on arterial blood pressure after spinal anesthesia for cesarean delivery. The effect of the head-down tilt position after induction of spinal anesthesia for cesarean delivery on blood pressure and level of sensory block was examined. Patients were allocated randomly into two groups, the head-down tilt group (n = 17) and the horizontal group (n = 17). In the head-down tilt group, patients were positioned with a 10 degrees head-down tilt immediately after supine positioning, while those in the horizontal group were maintained in a horizontal position. All patients received 500 mL of lactated Ringer's solution intravenously over 10 minutes prior to spinal injection, a wedge was placed under the patient's right hip, and the operating table was rotated 5 degrees in a counterclockwise direction to provide left uterine displacement. Hypotension (defined as systolic blood pressure below 100 mm Hg) was treated with 5 mg ephedrine intravenously and an increase in the infusion rate of lactated Ringer's solution. The change in systolic blood pressure was expressed as percent change from the baseline value. Systolic blood pressure decreased 20% at 3 minutes after spinal block in both groups but recovered to half of this decrease. The incidence of postspinal hypotension was not different between the two groups. The total amount of ephedrine and lactated Ringer's solution administered during the first 20 minutes of spinal block did not differ between the two groups nor did the extent of the cephalad spread of analgesia 20 minutes after spinal block (T4 +/- 2 vs T4 +/- 1 for the head-down and horizontal groups, respectively). The head-down position is concluded to have no effect on the incidence of hypotension during spinal anesthesia for cesarean delivery.\nStudy7: Advantages of left over right lateral tilt for caesarean section. The relative merits of right and left lateral tilt were assessed in 75 parturients at elective caesarean section. Significant maternal hypotension (aortocaval occlusion) occurred more frequently with rightward tilt (left hip supported). The clinical and biochemical status of the fetus was generally more favourable with left lateral tilt, as were the maternal-to-fetal blood gas gradients and relationships. The routine use of left lateral tilt is advocated.\nStudy8: Incidence of venous air embolism during cesarean section is unchanged by the use of a 5 to 10 degree head-up tilt. One hundred healthy parturients were divided at random into two demographically similar groups and were positioned for cesarean section either horizontally or flexed 5 to 10 degrees head up, with a 15 degrees lateral tilt. A Doppler ultrasound transducer was positioned over the fourth intercostal space parasternally. Initially, two patients received spinal, three general, and 95 epidural anesthesia. Two patients subsequently needed general for failed epidural anesthesia. Changes in Doppler heart tones (greater than 15 sec duration) indicative of venous air embolism (VAE) were identified 15 times in 11 patients--seven in supine and four in head-up patients (no statistically significant difference). Six awake patients (three horizontal, three head-up) developed chest tightness or pain during surgery, but only one episode correlated with VAE. No patient developed breathlessness. Moderate hypotension (greater than 10% decrease in systolic arterial pressure [SAP]) occurred in seven of 11 (63.6%) patients with, and in 26 (29.2%) of 89 patients without, VAE (P less than 0.001). More severe hypotension (SAP less than 90 mm Hg) due to bleeding occurred once. We conclude that a modest (5-10 degrees) head-up position does not influence the occurrence of VAE in patients having cesarean section. An 11% incidence of clinically insignificant VAE, although low, is still worrisome, as even small air bubbles in the circulation are potentially harmful, especially if the foramen ovale is patent. VAE during cesarean section should be anticipated and the anesthetic management planned accordingly.\n", + "output": "Conclusions: There is limited evidence to support or clearly disprove the value of the use of tilting or flexing the table, the use of wedges and cushions or the use of mechanical displacers. A left lateral tilt may be better than a right lateral tilt and manual displacers may be better than a left lateral tilt but larger studies with more robust data are needed to confirm these findings." + }, + { + "input": "Study1: Effect of a low glycaemic index diet on blood glucose in women with gestational hyperglycaemia. The objectives of this pilot study were to determine the feasibility and effect on glycaemic control of a low-glycaemic-index (GI) diet in women with gestational diabetes or impaired glucose tolerance of pregnancy. participants, recruited from the Diabetes-in-Pregnancy Clinic of an inner-city teaching hospital serving a predominantly non-Caucasian population, were randomized to a low-GI (n=23) or control (n=24) diet and followed from 28 weeks gestation until delivery. Self-monitored-blood-glucose (SMBG), maternal and infant weight were collected from medical charts. Dietary intakes were assessed using diet records and questionnaires. diet GI on control (58, 95% CI: 56,60) was significantly higher than on low-GI (49, 95% CI: 47,51; p=0.001). Glycaemic control improved on both diets, but more postprandial glucose values were within target on low-GI (58.4% of n=1891) than control (48.7% of n=1834; p<0.001). SMBG post-breakfast was directly related to pre-pregnancy BMI in the control, but not the low-GI group (BMI*diet interaction; p=0.021). Participants accepted the study foods and were willing to consume them post-intervention. a low-GI diet was feasible and acceptable in this sample and facilitated control of postprandial glucose. A larger study is needed to determine the effect of a low-GI diet on maternal and infant outcomes. 2010. Published by Elsevier Ireland Ltd.\nStudy2: Management of women with one abnormal oral glucose tolerance test value reduces adverse outcome in pregnancy. In this study we sought to test the hypothesis that treatment of women with one abnormal oral glucose tolerance test value will result in reduction of adverse outcome. One hundred twenty-six women with one abnormal oral glucose tolerance test value and 146 women in the control group (normal oral glucose tolerance test values) participated in a prospective study during the third trimester of pregnancy. The subjects with one abnormal test result were randomized into treated (group 1) and untreated groups (group II). Group 1 subjects were treated with a strict diabetic protocol to maintain tight glycemic control by means of diet and insulin therapy. Group 2 subjects tested their capillary blood glucose for a baseline period. The study revealed that the level of glycemic control was similar before initiation of therapy (mean capillary blood glucose 118 +/- 14 vs. 119 +/- 15 mg/dl, p = NS) for groups 1 and 2, respectively. There was a significant difference in mean capillary blood glucose (95 +/- 10 vs. 119 +/- 15 mg/dl, p less than 0.0001), preprandial, and postprandial determinations between the treated and untreated groups. The overall incidence of neonatal metabolic complications (4% vs. 14%, p less than 0.05) and large infants (6% vs. 24%, p less than 0.03) was significantly lower in the treated group. Comparison between the control (normal oral glucose tolerance test) and the untreated groups showed a significantly higher incidence of large infants and metabolic complications. No difference was found between the normal and treated groups. Thus we conclude that treatment of individuals with one abnormal oral glucose tolerance test value will result in significant reduction in adverse outcome in pregnancy.\n", + "output": "Conclusions: This review found interventions including providing dietary advice and blood glucose level monitoring for women with pregnancy hyperglycaemia not meeting GDM and T2DM diagnostic criteria helped reduce the number of macrosomic and LGA babies without increasing caesarean section and operative vaginal birth rates. It is important to notice that the results of this review were based on four small randomised trials with moderate to high risk of bias without follow-up outcomes for both women and their babies." + }, + { + "input": "Study1: Achieving involvement: process outcomes from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice. A consulting method known as 'shared decision making' (SDM) has been described and operationalized in terms of several 'competences'. One of these competences concerns the discussion of the risks and benefits of treatment or care options-'risk communication'. Few data exist on clinicians' ability to acquire skills and implement the competences of SDM or risk communication in consultations with patients. The aims of this study were to evaluate the effects of skill development workshops for SDM and the use of risk communication aids on the process of consultations. A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. Half the consultations were randomly selected for audio-taping, of which 352 patients attended and were audio-taped successfully. After baseline, participating doctors were randomized to receive training in (i) SDM skills or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were allocated randomly to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations were audio-taped from each phase. Raters (independent, trained and blinded to study phase) assessed the audio-tapes using a validated scale to assess levels of patient involvement (OPTION: observing patient involvement), and to analyse the nature of risk information discussed. Clinicians completed questionnaires after each consultation, assessing perceived clinician-patient agreement and level of patient involvement in decisions. Multilevel modelling was carried out with the OPTION score as the dependent variable, and rater, consultation and clinician levels of data, standardized by rater within clinician. Following each of the interventions, the clinicians significantly increased their involvement of patients in decision making (OPTION score increased by 10.6 following risk communication training [95% confidence interval (CI) 7.9 -13.3; P < 0.001] and by 12.9 after SDM skill development (95% CI 10 -15.8, P < 0.001), a moderate effect size. The level of involvement achieved by the risk communication aids was significantly increased by the subsequent introduction of the skill development workshops (7.7 increase in OPTION score, 95% CI 3.4-12; P < 0.001). The alternative sequence (skills followed by risk communication aids) did not achieve this effect. The use of most risk information formats increased after the provision of specific risk communication aids (P < 0.001). Clinicians using the risk communication tools perceived significantly higher patient and clinician agreement on treatment (P < 0.001), patient satisfaction with information (P < 0.01), clinician satisfaction with decision (P < 0.01) and general overall satisfaction with the consultation (P < 0.001) than those who were exposed to SDM skill development workshops. These clinicians were able to acquire the skills to implement SDM competences and to use risk communication aids. Each intervention provided independent effects. Further progress towards greater patient involvement in health care decision making is possible, and skill development in this area should be incorporated into postgraduate professional development programmes.\nStudy2: Physician and patient communication training in primary care: effects on participation and satisfaction. To assess the effects of a communication skills training program for physicians and patients. A randomized experiment to improve physician communication skills was assessed 1 and 6 months after a training intervention; patient training to be active participants was assessed after 1 month. Across three primary medical care settings, 156 physicians treating 2,196 patients were randomly assigned to control group or one of three conditions (physician, patient, or both trained). Patient satisfaction and perceptions of choice, decision-making, information, and lifestyle counseling; physicians' satisfaction and stress; and global ratings of the communication process. The following significant (p < .05) effects emerged: physician training improved patients' satisfaction with information and overall care; increased willingness to recommend the physician; increased physicians' counseling (as reported by patients) about weight loss, exercise, and quitting smoking and alcohol; increased physician satisfaction with physical exam detail; increased independent ratings of physicians' sensitive, connected communication with their patients, and decreased physician satisfaction with interpersonal aspects of professional life. Patient training improved physicians' satisfaction with data collection; if only physician or patient was trained, physician stress increased and physician satisfaction decreased. Implications for improving physician-patient relationship outcomes through communication skills training are discussed. PsycINFO Database Record (c) 2008 APA, all rights reserved.\nStudy3: Cancer consultation preparation package: changing patients but not physicians is not enough. This study evaluated a cancer consultation preparation package (CCPP) designed to facilitate patient involvement in the oncology consultation. A total of 164 cancer patients (67% response rate) were randomly assigned to receive the CCPP or a control booklet at least 48 hours before their first oncology appointment. The CCPP included a question prompt sheet, booklets on clinical decision making and patient rights, and an introduction to the clinic. The control booklet contained only the introduction to the clinic. Physicians were blinded to which intervention patients received. Patients completed questionnaires immediately after the consultation and 1 month later. Consultations were audiotaped, transcribed verbatim, and coded. All but one patient read the information. Before the consultation, intervention patients were significantly more anxious than were controls (mean, 42 v 38; P = .04); however anxiety was equivalent at follow-up. The CCPP was reported as being significantly more useful to family members than the control booklet (P = .004). Patients receiving the intervention asked significantly more questions (11 v seven questions; P = .005), tended to interrupt the physician more (1.01 v 0.71 interruptions; P = .08), and challenged information significantly more often (twice v once; P = .05). Patients receiving the CCPP were less likely to achieve their preferred decision making style (22%) than were controls (35%; P = .06). This CCPP influences patients' consultation behavior and does not increase anxiety in the long-term. However, this intervention, without physician endorsement, reduced the percentage of patients whose preferred involvement in decision making was achieved.\nStudy4: Randomized controlled trial of the effectiveness of an intervention to implement evidence-based patient decision support in a nursing call centre. We evaluated the effect of an intervention on call centre nurses' knowledge of decision support and skills in coaching callers facing value-sensitive health decisions. Forty-one registered nurses at a health call centre were randomly assigned to an intervention or control group. The intervention was a coaching protocol, online tutorial, skills building workshop and performance feedback. The main outcome measures were: knowledge test; blinded quality assessment of coaching skills during simulated calls and call duration. Compared with controls, nurses in the intervention group had better knowledge (74 versus 60%, P = 0.007) and decision coaching skills (81 versus 44%, P < 0.001), particularly in assessing decisional needs (information, values clarity, support, stage and timing of decision) and addressing support issues. Call duration did not differ (18.5 versus 16.7 min, P = 0.73). The coaching protocol was rated as compatible with nurses' views on decision-making and more advantageous compared with their usual practices. The intervention improved the quality of nurses' decision coaching without affecting call duration.\nStudy5: A treatment decision aid may increase patient trust in the diabetes specialist. The Statin Choice randomized trial. Decision aids in practice may affect patient trust in the clinician, a requirement for optimal diabetes care. We sought to determine the impact of a decision aid to help patients with diabetes decide about statins (Statin Choice) on patients' trust in the clinician. We randomized 16 diabetologists and 98 patients with type 2 diabetes referred to a subspecialty diabetes clinic to use the Statin Choice decision aid or a patient pamphlet about dyslipidaemia, and then to receive these materials from either the clinician during the visit or a researcher prior to the visit. Providers and patients were blinded to the study hypothesis. Immediately after the clinical encounter, patients completed a survey including questions on trust (range 0 to total trust = 100), knowledge, and decisional conflict. Researchers reviewed videotaped encounters and assessed patient participation (using the OPTION scale) and visit length. Overall mean trust score was 91 (median 97.2, IQR 86, 100). After adjustment for patient characteristics, results suggested greater total trust (trust = 100) with the decision aid [odds ratio (OR) 1.77, 95% CI 0.94, 3.35]. Total trust was associated with knowledge (for each additional knowledge point, OR 1.3, 95% CI 1.1, 1.6), patient participation (for each additional point in the OPTION scale, OR 1.1, 95% CI 1.1, 1.2), and decisional conflict (for every 5-point decrease in conflict, OR 1.5, 95% CI 1.2, 1.9). Total trust was not associated with visit length, which the decision aid did not significantly affect. There was no significant effect interaction across the trial factors. Preliminary evidence suggests that decision aids do not have a large negative impact on trust in the physician and may increase trust through improvements in the decision-making process.\n", + "output": "Conclusions: The results of this Cochrane review do not allow us to draw firm conclusions about the most effective types of intervention for increasing healthcare professionals' adoption of SDM. Healthcare professional training may be important, as may the implementation of patient-mediated interventions such as decision aids. Given the paucity of evidence, however, those motivated by the ethical impetus to increase SDM in clinical practice will need to weigh the costs and potential benefits of interventions. Subsequent research should involve well-designed studies with adequate power and procedures to minimise bias so that they may improve estimates of the effects of interventions on healthcare professionals' adoption of SDM. From a measurement perspective, consensus on how to assess professionals' adoption of SDM is desirable to facilitate cross-study comparisons." + }, + { + "input": "Study1: Herbal medicines in migraine prevention Randomized double-blind placebo-controlled crossover trial of a feverfew preparation. The efficacy of feverfew capsules on migraine prophylaxis was investigated in a randomized double-blind, placebo-controlled crossover study in which 50 patients, who had not used feverfew before, participated. The capsules were filled with a dried alcoholic extract of feverfew on microcristalline cellulose and contained 0.5 mg parthenolide. The patients used one capsule (feverfew or placebo) a day. Fourty four patients completed the 9 month study. Both treatment groups suffered the same number of migraine attacks. A prophylactic effect could not be demonstrated for our feverfew preparation, but the patients seemed to have a tendency to use fever symptomatic drugs during the period they used feverfew. This result was not in accordance with the results from two other studies. The difference may be explained by the fact that both other studies included patients who previously reported positive experiences with feverfew preparations for migraine prophylaxis. Copyright \u00a9 1996 Gustav Fischer Verlag \u00b7 Stuttgart \u00b7 Jena \u00b7 New York. Published by Elsevier GmbH.. All rights reserved.\nStudy2: The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind, multicentre, randomized placebo-controlled dose-response study. Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic treatment of migraine. The primary objective was to show a dose-response of a new stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from feverfew (T. parthenium). Furthermore, the study should provide data on the safety and tolerability of MIG-99. In a randomized, double-blind, multicentre, controlled trial with an adaptive design, the clinical efficacy and safety of three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients (n = 147) suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients (n = 49) with at least four migraine attacks during the baseline period decreased in a dose-dependent manner (P = 0.001). The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.\n", + "output": "Conclusions: There is insufficient evidence from randomised, double-blind trials to suggest an effect of feverfew over and above placebo for preventing migraine. It appears from the data reviewed that feverfew presents no major safety problems." + }, + { + "input": "Study: Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial. To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. Prospective, double blind, placebo controlled trial randomised by household. 8 villages in rural southern Malawi. 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor.\n", + "output": "Conclusions: Based on the one available trial, we could draw no firm conclusion for the effectiveness of supplementary antioxidant micronutrients for the prevention of kwashiorkor in pre-school children." + }, + { + "input": "Study1: A pilot double-blind study of sodium-magnesium EDTA in peripheral vascular disease. Ten male patients with peripheral vascular disease, Type 2 (LaFontaine), were randomly assigned in a double-blind study to receive either Na2 ethylene diamine tetra acetic acid (EDTA) plus MgSO4, B complex, and vitamin C, or a placebo of MgSO4, B complex, and vitamin C in Ringer's lactate solution. A total of 20 intravenous infusions were planned for administration to each patient. Clinical and laboratory (noninvasive) tests showed dramatic improvements after 10 infusions in some patients, and thus was broken the code indicating who was receiving EDTA and who was receiving placebo. The group that improved had been receiving EDTA; there was no change in the placebo group. The trial was then completed in a single-blind fashion. Patients originally assigned to receive placebo then received 10 EDTA infusions, while the group originally assigned to EDTA received 20 EDTA infusions. The group that had formerly received placebo showed improvements comparable to those seen in the first EDTA group after 10 treatments.\nStudy2: Arteriographic findings in EDTA chelation therapy on peripheral arteriosclerosis. In a randomized, double-blind, controlled study, 153 patients with claudication were each given either 20 infusions of Na2EDTA or 20 infusions of saline. Walking distances and ankle/brachial indices were measured before, during, and after treatment. In 30 patients, angiograms and transcutaneous oxygen tensions were obtained before, during, and after treatment. The patients' subjective evaluations of the effect of treatment were also recorded. It is concluded that EDTA chelation therapy has no effect in patients with intermittent claudication in the legs caused by arteriosclerosis.\nStudy3: Disodium-ethylene diamine tetraacetic acid (EDTA) has no effect on blood lipids in atherosclerotic patients. A randomized, placebo-controlled study. To study whether intravenous disodium-ethylene diamine tetraacetic acid (EDTA) affects blood lipids in patients with intermittent claudication. Double-blind, randomized, placebo-controlled trial. Twenty-nine patients with intermittent claudication (systolic ankle-brachial blood pressure index < 0.8; pain free walking distance 50-200 m). 3 g EDTA or placebo (isotonic saline) per infusion over a period of 5-9 weeks to a total of 57 g EDTA. Patients received vitamins, minerals and trace-elements daily. 14 patients received EDTA and 15 placebo. There was no statistically significant difference in the plasma concentration of cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol or triglyceride between the 2 groups. Treatment with EDTA does not alter blood lipids in patients with intermittent claudication.\nStudy4: EDTA treatment of intermittent claudication--a double-blind, placebo-controlled study. A double-blind, randomized multicentre study was undertaken to evaluate the possible effect of chelation treatment with ethylenediamine-tetraacetic acid (EDTA) in patients with severe intermittent claudication. A total of 153 patients received 20 intravenous infusions of either 3 g Na2EDTA or placebo during a period of 5-9 weeks. Vitamin, mineral and trace element supplements were administered orally. The changes observed in the pain-free and maximal walking distances, measured on a treadmill, were similar in the two groups. During the 3-month (n = 149) and 6-month (n = 123) follow-up period, no long-term therapeutic effect of EDTA could be demonstrated. The ankle-brachial blood pressure index remained unchanged throughout the study period. This study failed to demonstrate any effect of EDTA chelation treatment in intermittent claudication.\nStudy5: Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial. The use of repeated intravenous infusions of EDTA, which has become known as \"chelation therapy,\" has been promoted for treating intermittent claudication as well as a wide range of other disorders. Multiple reports of excellent results in large numbers of patients have encouraged the use of this regimen. The lack of well-controlled studies substantiating the benefits of this treatment has limited its use mainly to private clinics. The aim of the study was to assess the benefits of chelation therapy in patients with intermittent claudication. A double-blind, randomized, controlled trial included 32 patients with intermittent claudication who were randomized to a treatment group (15) and a control group (17). Main outcome measures were subjective and measured walking distances and ankle/brachial pulse indices. Other outcome measures included lifestyle and subjective parameters of improvement, cardiac function, ECG, renal function, hematology, blood glucose, and lipid biochemistry. No clinically significant differences in main outcome measures between chelation therapy and placebo groups were detected up to 3 months after treatment. Measures of mood state, activities of daily living, and quality of life factors were not consistently affected by chelation therapy. An equal proportion (13%) of each group thought that they had received the active agent. The proportion of patients showing an improvement in walking distance was not significantly different between the chelation group (60%) and the control group (59%). Chelation therapy has no significant beneficial effects over placebo in patients with intermittent claudication.\n", + "output": "Conclusions: At present, there is insufficient evidence to decide on the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of people with atherosclerotic cardiovascular disease. This decision must be preceded by conducting randomized controlled trials that would include endpoints that show the effects of chelation therapy on longevity and quality of life among people with atherosclerotic cardiovascular disease." + }, + { + "input": "Study1: Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival (DFS) and secondarily on overall survival (OS) in patients with high-risk operable breast cancer. From June 1997 until November 2000, 604 patients with T1-3N1M0 or T3N0M0 tumors were randomized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) (group A), or to four cycles of epirubicin followed by four cycles of CMF, as in group A (group B). All cycles were given every 2 weeks with granulocyte colony-stimulating factor support. A total of 595 patients were eligible. Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80% in group A and 77% in group B. Survival rates were 93% and 90%, respectively. The effect of treatment on the hazard of death was different according to hormonal receptor status. More specifically, in patients with negative receptor status the hazard of death was significantly higher for group B (hazard ratio 2.42). Both regimens were well tolerated and severe acute side-effects were infrequent. No cases of severe cardiotoxicity or acute leukemia were recorded. The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups. However, our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy.\nStudy2: Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. The primary aim of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 was to determine whether four cycles of adjuvant paclitaxel (PTX) after four cycles of adjuvant doxorubicin/cyclophosphamide (AC) will prolong disease-free survival (DFS) and overall survival (OS) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes. Between August 1995 and May 1998, 3,060 patients were randomly assigned (AC, 1,529; AC followed by PTX [AC --> PTX], 1,531). Patients > or = 50 years and those younger than 50 years with estrogen receptor (ER) or progesterone receptor (PR) -positive tumors also received tamoxifen for 5 years, starting with the first dose of AC. Postlumpectomy radiotherapy was mandated. Postmastectomy or regional radiotherapy was prohibited. Median follow-up is 64.6 months. The addition of PTX to AC significantly reduced the hazard for DFS event by 17% (relative risk [RR], 0.83; 95% CI, 0.72 to 0.95; P = .006). Five-year DFS was 76% +/- 2% for patients randomly assigned to AC --> PTX compared with 72% +/- 2% for those randomly assigned to AC. Improvement in OS was small and not statistically significant (RR, 0.93; 95% CI, 0.78 to 1.12; P = .46). Five-year OS was 85% +/- 2% for both groups. Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction (for DFS, P = .30 and P = .44, respectively). Toxicity with the AC --> PTX regimen was acceptable for the adjuvant setting. The addition of PTX to AC resulted in significant improvement in DFS but no significant improvement in OS with acceptable toxicity. No significant interaction between treatment effect and receptor status or tamoxifen administration was observed.\nStudy3: Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive early breast cancer. Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS). Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P = .011; adjusted P = .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P = .014; adjusted P = .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P = .03), attributable mainly to the lower anthracycline cumulative dose. Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive breast cancer patients and has a favorable safety profile.\nStudy4: Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m(2), with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m(2), for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2). Tamoxifen was given to 94% of patients with hormone receptor-positive tumors. There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m(2), respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald chi(2) P =.0023; unadjusted Wilcoxon P =.0011) and 18% for death (adjusted P =.0064; unadjusted P =.0098). At 5 years, the disease-free survival (+/- SE) was 65% (+/- 1) and 70% (+/- 1), and overall survival was 77% (+/- 1) and 80% (+/- 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.\n", + "output": "Conclusions: This meta-analysis of studies supports the use of taxane containing adjuvant chemotherapy regimens with improvement of overall survival and disease-free survival for women with operable early breast cancer. The review did not identify a subgroup of patients where taxane containing treatment may have been more or less effective. Dosage and scheduling of the taxane drug is not clearly defined and we await results of the next generation of studies to determine the optimal use of taxanes in early breast cancer." + }, + { + "input": "Study1: [Treatment of sialorrhea in Parkinson's disease patients with clonidine. Double-blind, comparative study with placebo]. sialorrhea is one of the common nonmotor, non-neuropsychiatric symptoms in Parkinson's disease and its pre-sence can cause limitation in the patient's social life. The traditional treatment with anticholinergic medication is capable of triggering important neuropsychiatric complications. this is a prospective, double-blind, placebo compared study, which follow-up Parkinson's disease patients for 3 months. we measured the efficacy of clonidine in the management of sialorrhea. The study was performed in 32 patients (20 males and 12 females), with a mean age of 70.75 years and mean duration of the disease of 8.84 years. Randomly, 17 patients received clonidine 0.15 mg/day and the remaining 15 patients received placebo. Both groups were made up of subjects with similar characteristics, age, years of illness, sex, stage of disease (H and Y), disability (S and C) and motor score (UPDRS). Likewise, salivation affected both groups in the same intensity. We used the variable analysis and there was a p < 0.05 significance. the group which received clonidine showed a significant improvement of the salivation symptoms both at one month as well as at 3 months of treatment (p < 0.00001, respectively). There was no evidence of worsening of the stage of the disease, incapacity or motor score. The side effects were found only in the group that received clonidine (4 patients) without showing statistically significant. the use of clonidine can be useful in the management and treatment of sialorrhea in patients with Parkinso\u0144s disease.\nStudy2: Calcium channel blocker use and risk of Parkinson's disease. We investigated whether the use of calcium channel blockers (CCBs) was associated with a reduced risk of Parkinson's disease (PD) in two large prospective cohorts: the Nurses' Health Study (NHS) and Health Professionals' Follow-Up Study (HPFS). Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) to assess the association between use of CCBs and risk of PD adjusting for potential confounders. We identified 514 incident cases of PD during follow-up. No association between baseline use of CCBs (RR = 1.18, 95% CI: 0.73-1.92), frequency of use or duration of use of CCBs and PD risk was observed (P > 0.2 for all). These findings do not support a role for CCBs in providing neuroprotection against development of PD. \u00a9 2010 Movement Disorder Society.\nStudy3: Use of antihypertensives and the risk of Parkinson disease. Recent studies related angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers to possible neuroprotective effects. Little is known about neuroprotection of angiotensin II (AT II) antagonists or beta-blockers. To explore the association between antihypertensive drug use and the risk of developing a first-time diagnosis of Parkinson disease (PD). This was a case-control analysis within the UK-based General Practice Research Database. Cases were >or=40 years of age with an incident PD diagnosis between 1994 and 2005. We matched one control to each PD case on age, sex, general practice, index date, and duration of previous history in the database. We assessed antihypertensive drug use by timing and by exposure duration. We calculated ORs using conditional logistic regression, adjusted for body mass index, smoking, and various cardiovascular, metabolic, and psychiatric diseases and dementia. We identified 3,637 cases with a first-time diagnosis of idiopathic PD and an equal number of matched controls. As compared to nonuse of antihypertensive drugs, the adjusted OR for current use of >or=30 prescriptions was 1.08 (95% CI 0.85 to 1.37) for ACE inhibitors, 0.91 (95% CI 0.41 to 2.00) for AT II antagonists, 1.16 (95% CI 0.95 to 1.41) for beta-blockers, and 0.77 (95% CI 0.63 to 0.95) for calcium channel blockers. Current long-term use of calcium channel blockers was associated with a significantly reduced risk of a Parkinson disease diagnosis, while the risk was not materially altered for users of angiotensin converting enzyme inhibitors or beta-blockers and, with less statistical precision, for users of angiotensin II antagonists.\nStudy4: L-type calcium channel blockers and Parkinson disease in Denmark. This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood-brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk. We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis. Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54-0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications. Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers.\nStudy5: Antihypertensive agents and risk of Parkinson's disease, essential tremor and dementia: a population-based prospective study (NEDICES). Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson's disease (PD) or dementia. There are no data for essential tremor (ET). To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease). Prospective population-based study in Spain enrolling 5,278 participants at baseline. Use of antihypertensive medications (aside from beta-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not associated with prevalent or incident PD. Calcium channel blocker use was marginally reduced in prevalent dementia cases (OR(adjusted) = 0.63, p = 0.06) but was not associated with reduced risk of incident dementia (RR(adjusted) = 1.02, p = 0.95). We did not find evidence of a protective effect of antihypertensive medications in these three neurodegenerative disorders. Copyright 2009 S. Karger AG, Basel.\n", + "output": "Conclusions: There is currently a lack of evidence for the use of antihypertensive drugs for either the primary or secondary prevention of PD. More observational studies are required to identify potential drugs to go forward for safety and tolerability studies in people with early PD. The results of the ongoing trial will help inform further research." + }, + { + "input": "Study1: Evaluation of a stroke family support organiser: a randomized controlled trial. There is inconclusive evidence of the effectiveness of the Stroke Family Support Organiser (FSO) service. We report the results from a randomized controlled trial of the service. Stroke patients admitted to hospital and their informal caregivers were randomly allocated to receive the FSO service (n=126) or standard care (n=124). Outcome assessments were undertaken 4 and 9 months after recruitment with the General Health Questionnaire 12, Carer Strain Index, Barthel Index, Extended Activities of Daily Living scale, and a specially designed questionnaire to determine knowledge of stroke and satisfaction with services. There were no significant differences between groups in patients' mood and independence in personal or instrumental activities of daily living or caregivers' mood, strain, or independence. Patients in the intervention group were significantly more knowledgeable about whom to contact for stroke information, reducing the risk of stroke, practical help, community services, and emotional support. Patients in the intervention group were also significantly more satisfied with the stroke information received. Caregivers in the intervention group were significantly more knowledgeable about whom to contact for information on stroke, reducing the risk of stroke, community services, and emotional support. Caregivers in the intervention group were also significantly more satisfied with stroke information. The FSO service had no significant effect on mood, independence in activities of daily living, or reduction in caregiver strain, but it did increase knowledge of stroke and satisfaction with that knowledge. The results may not be representative of all FSO services, and the sample was small relative to the heterogeneity of the participants. However, results suggest that the policies and training procedures of FSOs need to be evaluated to ensure that a cost-effective service is being provided to stroke patients and their caregivers.\nStudy2: Evaluation of a stroke family care worker: results of a randomised controlled trial. To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers. Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation. A well organised stroke service in an Edinburgh teaching hospital. 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period. Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire. The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support. The introduction of a stroke family care worker improved patients' and their carers' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients' physical wellbeing.\nStudy3: A family support organiser for stroke patients and their carers: a randomised controlled trial. Previous trials of interventions to support stroke survivors and their families in the community have had contradictory and inconclusive results. Using the MRC Framework for Complex Interventions we developed a family support organiser (FSO) service and refined outcome measures for evaluation. We tested the effects of the intervention in a randomised controlled trial. From 1 March 1999 to 1 April 2001 all first-in-a-lifetime strokes (n = 513) were identified and 340 (96%) of eligible strokes randomised to receive FSO or usual care. Patients and their carers were followed up at 3 months and 1 year post-stroke. Outcomes included satisfaction (main outcome) with hospital staff and outpatient services, use of social services, reintegration to normal living (RNLI) and feelings about life after the stroke. The mean number of contacts with the FSO was 15 (SD = 9.8) per patient. More intervention than control patients received some social services and had increased patient and carer satisfaction in most aspects, particularly with information about recovery and feeling that someone had listened. There was little evidence at 3 or 12 months of differences in RNLI. A meta-analysis of trials in this area is now needed along with further trials of interventions in subgroups of the stroke population to fully identify any benefits of the FSO role. Copyright (c) 2005 S. Karger AG, Basel.\nStudy4: A randomized controlled trial of an education and counselling intervention for families after stroke. To determine whether education and counselling after stroke leads to improved family functioning and psychosocial outcomes for stroke patients and their spouses, and better functional and social outcomes for patients. Two-group randomized controlled trial. Data were collected on admission to and discharge from rehabilitation, and again six months later. Rehabilitation units at Repatriation General Hospital and Griffith Hospital, in Adelaide, South Australia. Sixty-two stroke patients and their spouses, 32 in the intervention group and 30 in the control group. Stroke information package and three visits from a social worker trained in family counselling. Family functioning: McMaster Family Assessment Device (FAD); functional status: Barthel Index (BI); social recovery: Adelaide Activities Profile (AAP); depression: Geriatric Depression Scale (GDS); anxiety: Hospital Anxiety and Depression Scale (HADS); mastery: Mastery Scale (MS); health status: SF-36. At six months the intervention group had better family functioning for both patients (mean FAD difference 0.19) and spouses (mean difference 0.09). A modest benefit in functional status for intervention patients (mean BI difference 1.3) was related to improved family functioning. Intervention patients reported better social recovery (mean AAP differences: domestic chores 5.7, household maintenance 4.6, social activities 11.5), but there were no significant effects on depression, anxiety, mastery or health status. An education and counselling intervention maintained family functioning, and in turn led to improved functional and social patient outcomes. This approach helps patients and their spouses to make the optimal adjustment to living with stroke.\nStudy5: Social work effectiveness in two-year stroke survivors: a randomised controlled trial. nan\nStudy6: Does behaviour modification affect post-stroke risk factor control? Three-year follow-up of a randomized controlled trial. Little is known about the long-term effectiveness after stroke of interventions for behaviour modification and ensuring concordance with therapies. We describe a follow-up study of a previous randomized controlled trial of a brief period of behaviour modification. The aim of this study was to determine outcomes three years after the initial intervention. Survivors of the original cohort were contacted and asked to attend for follow-up interview, within a geriatric day hospital. This study was carried out in the Geriatric Day Hospital at Stobhill Hospital, Balornock Road, Glasgow. Details of risk factor control, including blood pressure, cholesterol levels and diabetic control, were assessed. Questionnaires used in the initial study were repeated including the Geriatric Depression Scale score, Euroqol Perceived Health Status and Stroke Services Satisfaction Questionnaire. Primary outcome was collective risk factor control. Clinical outcomes including recurrent cerebrovascular events, medication persistence and perceived health status were also recorded. Mean length of follow-up was 3.6 years (SD 0.43). Of the 205 patients enrolled in the initial study, 102 patients attended for repeat interview(49 intervention/53 control). There were no significant differences in the percentage of controlled risk factors between groups (intervention 51.7% versus control 55.9%, P = 0.53). Similarities were observed in the number of recurrent clinical events and medication persistence between groups. No overall difference was observed in perceived health status, satisfaction with care or depression scores. Brief intervention with respect to behaviour modification and risk factor control does not appear to have any long-term benefit. These results must be cautiously interpreted in light of the small study number and further research is required.\nStudy7: Family support for stroke: a randomised controlled trial. Attention is currently focused on family care of stroke survivors, but the effectiveness of support services is unclear. We did a single-blind, randomised, controlled trial to assess the impact of family support on stroke patients and their carers. Patients with acute stroke admitted to hospitals in Oxford, UK, were assigned family support or normal care within 6 weeks of stroke. After 6 months, we assessed, for carers, knowledge about stroke, Frenchay activities index, general health questionnaire-28 scores, caregiver strain index, Dartmouth co-op charts, short form 36 (SF-36), and satisfaction scores, and, for patients, knowledge about stroke and use of services, Barthel index, Rivermead mobility index, Frenchay activities index, London handicap scale, hospital anxiety and depression scales, Dartmouth co-op charts, and satisfaction. 323 patients and 267 carers were followed up. Carers in the intervention group had significantly better Frenchay activities indices (p=0.03), SF-36 scores (energy p=0.02, mental health p=0.004, pain p=0.03, physical function p=0.025, and general health perception p=0.02), quality of life on the Dartmouth co-op chart (p=0.01), and satisfaction with understanding of stroke (82 vs 71%, p=0.04) than those in the control group. Patients' knowledge about stroke, disability, handicap, quality of life, and satisfaction with services and understanding of stroke did not differ between groups. Fewer patients in the intervention group than in the control group saw a physiotherapist after discharge (44 vs 56%, p=0.04), but use of other services was similar. Family support significantly increased social activities and improved quality of life for carers, with no significant effects on patients.\nStudy8: Multicenter randomized controlled trial of an outreach nursing support program for recently discharged stroke patients. Many stroke patients and informal carers experience a decreased quality of life after discharge home and are dissatisfied with the care received. We assessed the effectiveness of an outreach nursing care program. In a multicenter trial, 536 stroke patients were randomized at discharge to standard care (n=273) or standard care plus outreach care (n=263). The outreach care consisted of 3 telephone calls and 1 home visit within 5 months after discharge by 1 of 13 stroke nurses. Patients were masked for the trial objectives. Six months after discharge, they assessed the 2 primary outcomes: quality of life (Short Form 36 [SF-36]) and dissatisfaction with care. Secondary measures of outcome were disability, handicap, depression, anxiety, and use of health care services and secondary prevention drugs. Informal carers assessed strain, and social support. Analysis was by intention to treat. Twelve patients died before follow-up, 38 declined outcome assessment, and 486 completed the primary outcome assessments. Outreach care patients had better scores on the SF-36 domain \"Role Emotional\" than controls (mean difference 7.9 [95% confidence limit, 0.1 to 15.7]). No statistically significant differences were found on the other primary outcome measures. For secondary outcomes, no statistically significant differences were found, except that intervention patients used fewer rehabilitation services (relative risk, 0.66 [0.44 to 1.00]) and had lower anxiety scores (median difference 1 [0.19 to 2.79]). This outreach nursing stroke care was not effective in improving quality of life and dissatisfaction with care of recently discharged patients.\n", + "output": "Conclusions: There is no evidence for the effectiveness of this multifaceted intervention in improving outcomes for all groups of patients or carers. Patients with mild to moderate disability benefit from a reduction in death and disability. Patients and carers do report improved satisfaction with some aspects of service provision." + }, + { + "input": "Study1: Clinical trial of nimodipine in acute ischemic stroke. The American Nimodipine Study Group. A randomized, double-blind, multicenter clinical trial of placebo versus nimodipine was conducted to test the hypothesis that nimodipine would reduce the frequency of death and of worsening by 30% compared with placebo. Nimodipine was used in doses of 60 mg, 120 mg, and 240 mg daily in 1,064 patients treated for 21 days. Treatment was begun within 48 hours of stroke due to infarction as inferred by initial computed tomographic scan findings. The Toronto and motor scales were analyzed by analysis of covariance, using covariance-adjusted means, the last-value-carried-forward, to compare the baseline value with the 3 assessment days (days 4, 10, and 21). No difference in mortality or neurological outcome was found with any of the rating scales for the overall cohort. Planned but post hoc subgroup analysis showed a reduction in worsening frequency of 30% compared with placebo and significantly better outcome scores with 120 mg nimodipine daily started within 18 hours of stroke as measured by the Toronto scale (p less than 0.005) and when the pretreatment computed tomographic scan was negative (p less than 0.003). Nimodipine had no overall effect when treatment was begun within 48 hours. Confirmation of the benefits suggested by post hoc analyses for the subgroup treated with 120 mg nimodipine within 18 hours, and who had negative computed tomographic scans, would require a separate trial.\nStudy2: Nimodipine and perfusion changes after stroke. Meta-analysis of previous trials of oral nimodipine in acute stroke has suggested a benefit when commenced within 12 hours of onset. We sought to study the effect of oral nimodipine on reperfusion after acute stroke and the relation between reperfusion and outcome. Fifty patients with acute middle cerebral artery territory cortical infarction were blindly randomized within 12 hours of onset to either oral nimodipine (30 mg every 6 hours) or placebo. Treatment was continued for 2 weeks. Cerebral blood flow was assessed with the use of 99mTc-hexamethylpropyleneamine oxime single-photon emission CT before therapy, 24 hours later, and at 3 months. Hypoperfusion was measured by a validated volumetric technique. Neurological impairment and functional outcome were assessed with the Canadian Neurological Scale and Barthel Index, respectively. Tissue loss was measured with CT at 3 months. Four patients were excluded from analysis for technical reasons. Twenty-three patients received nimodipine, and 23 received placebo. In the nimodipine group, there was early reperfusion that was not maintained at outcome (P=0.01). In the placebo group, mean infarct hypoperfusion volumes showed no overall change. Nonnutritional reperfusion in nimodipine-treated patients was associated with adverse neurological (P=0.05) and functional outcome (P=0.06). There was, however, no difference in clinical outcome between the 2 groups. Oral nimodipine administered within 12 hours enhanced acute reperfusion, but this was largely nonnutritional. Larger studies using a shorter treatment delay are required to evaluate the clinical efficacy of nimodipine in acute ischemic stroke.\nStudy3: A randomized double-blind controlled study of nimodipine in acute cerebral ischemic stroke. A randomized placebo controlled double-blind clinical trial of nimodipine was conducted in 31 patients of acute cerebral infarction. Nimodipine was administered in dosage of 120 mg/day for 28 days. Treatment was begun within 48 hours of ischemic stroke. Diagnosis was confirmed by computed tomographic (CT) scan. Similar number of patients (control) received placebo. Neurological assessment was done at the time of entry into the trial, and after 4 weeks, by using Mathew's scale. After four weeks of treatment with nimodipine or placebo, Mathew's scale score improved significantly (< 0.001) in both groups, but difference in mean score between two groups was insignificant (> 0.05). However, significant difference (< 0.05) was noted in relative change in neurological deficit (mean X-value) of two groups. The nimodipine group had higher value in scores on Mathew's scale. No adverse reaction, was observed in either group. The study suggests a beneficial a effect of nimodipine in acute cerebral ischaemia.\nStudy4: Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial. The Very Early Nimodipine Use in Stroke (VENUS) trial was designed to test the hypothesis that early treatment with nimodipine has a positive effect on survival and functional outcome after stroke. This was suggested in a previous meta-analysis on the use of nimodipine in stroke. However, in a recent Cochrane review we were unable to reproduce these positive results. This led to the early termination of VENUS after an interim analysis. In this randomized, double-blind, placebo-controlled trial, treatment was started by general practitioners or neurologists within 6 hours after stroke onset (oral nimodipine 30 mg QID or identical placebo, for 10 days). Main analyses included comparisons of the primary end point (poor outcome, defined as death or dependency after 3 months) and secondary end points (neurological status and blood pressure 24 hours after inclusion, mortality after 10 days, and adverse events) between treatment groups. Subgroup analyses (on final diagnosis and based on the per-protocol data set) were performed. At trial termination, after inclusion of 454 patients (225 nimodipine, 229 placebo), no effect of nimodipine was found. After 3 months of follow-up, 32% (n=71) of patients in the nimodipine group had a poor outcome compared with 27% (n=62) in the placebo group (relative risk, 1.2; 95% CI, 0.9 to 1.6). A treatment effect was not found for secondary outcomes and in the subgroup analyses. The results of VENUS do not support the hypothesis of a beneficial effect of early nimodipine in stroke patients.\nStudy5: Double-blind study of nimodipine in non-severe stroke. We evaluated the effect of nimodipine (30 mg q.i.d. orally for 14 days) on acute ischemic stroke of mild or moderate severity in a unicenter, double-blind, randomized, placebo-controlled pilot study. Treatment had to be started after CT, within 48 h of infarct in patients with a Mathew scale sum score between 50 and 75. The duration of follow-up was 4 months. Eight of the 60 randomized patients were excluded because of incorrect diagnosis. For the remaining 52 patients, 24 were allocated to nimodipine and 28 to placebo. Analysis of variance and covariance and repeated measurements of the Mathew scale scores showed no difference between the two groups, who had continuous and parallel improvement. There was no recurrent stroke, but 1 control died 4 weeks after stroke. Treatment with nimodipine was well tolerated (hypotension: 1 treated patient, 3 controls; bradycardia: 1 treated patient, 2 controls; sGPT increase: 1 treated patient, 1 control). The lack of efficacy of nimodipine in this study may be due to: (1) the neurologic deficit not being severe enough, or (2) the delay before treatment was too long.\nStudy6: A randomized, double-blind, placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke. A randomized, double-blind, placebo-controlled multicenter trial was conducted to test the hypothesis that nimodipine would improve the functional outcome in acute ischemic hemispheric stroke. A total of 350 patients were randomized to nimodipine 120 mg/d PO or matching placebo for 21 days. Randomization was stratified by onset of therapy, age, and stroke severity. Treatment was begun within 48 hours of onset. The patients had neurological evaluation on admission, on days 1, 7, and 21, and at 3 and 12 months. The primary end points were Rankin grade, neurological score, and mobility at 12 months. We did not find any differences in the functional outcome between the treatment groups or between the stratified subgroups. We were also unable in post hoc analyses to find any groups of patients who benefited from nimodipine. During the first month and at 3 months the case-fatality rate was higher in the nimodipine-treated patients than in those on placebo (P = .004 and P = .030, respectively), but at the 1-year follow-up this difference had lost statistical significance. During the first week nimodipine had a statistically significant lowering effect on both systolic (P = .005) and diastolic (P = .013) blood pressure. Nimodipine did not improve the functional outcome of acute ischemic hemispheric stroke. The early case-fatality rate was higher in the nimodipine group, possibly due to the blood pressure-lowering effect of nimodipine.\nStudy7: Effect of nimodipine on regional cerebral glucose metabolism in patients with acute ischemic stroke as measured by positron emission tomography. In a randomized double-blind placebo-controlled study of 27 patients with acute ischemic stroke, the effect on regional CMRglc (rCMRglc) of the calcium channel blocking agent nimodipine administered in addition to routine treatment was investigated. Following computed tomography-supported diagnosis of focal ischemia in the middle cerebral artery territory, positron emission tomography (PET) of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was performed, and the patients were entered into the study within 48 h after onset of symptoms, randomly receiving either nimodipine (2 mg/h constant i.v. infusion for 5 days, 120 mg/day orally for another 16 days) or carrier/placebo. FDG PET was repeated after completion of therapy. The clinical course was followed during the treatment period and for 6 months after the stroke, using the Mathew Score for early and the Barthel Index for late assessment. During that observation period, five patients died in the nimodipine group and four in the control group. Subsequently, the code was broken, and the clinical and PET data were analyzed in relation to treatment assignment, with the nimodipine group comprising 11 and the control group 12 eligible cases. The two groups were similar with respect to age and sex distribution, initial clinical deficit, and infarct size and location. While the infarct rCMRglc showed comparable slight increases over time in both groups, the metabolic changes in the other evaluated regions (contralateral infarct mirror region, ipsi- and contralateral cerebral gray matter, contra- and ipsilateral cerebellar hemispheres) differed significantly between treatment groups (side x region x treatment interaction p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy8: The effects of nimodipine on the clinical course of patients with acute ischemic stroke. 60 patients with acute ischemic stroke were enrolled in a prospective single-blind, randomized trial to determine whether treatment with the calcium antagonist nimodipine would reduce their neurological deficit. All patients received a standard treatment. In addition, 29 received a daily dose of 120 mg nimodipine orally as 3 divided doses (treatment group). Evaluation of therapy was assessed with a neurological scoring system ( Mathew scale). Comparison of the Mathew sum scores in the standard group with those of the nimodipine group (analysis of variance) revealed a highly significant difference (P less than 0.0001) in favour of nimodipine during the 4 week period of treatment. Based on the individual items of the Mathew scale, the level of consciousness and disability were significantly improved under the nimodipine-therapy. Side effects were of minor importance and of no clinical relevance.\nStudy9: Effect of nimodipine on memory after cerebral infarction. Epidemiological studies indicate widespread memory impairment in patients with stroke in the early post-ictal stage. Nimodipine may have psychopharmacological properties and may improve memory. We conducted a single-blind randomized controlled trial to determine whether nimodipine given 7-14 days after cerebral infarction improved memory. One hundred patients with acute cerebral infarction were consecutively enrolled between D7 to D14. After stratification, patients were randomized to receive oral nimodipine 90 mg daily for 12 weeks, or no drug. Independent assessors administered Mini-Mental State Examination (MMSE) and Fuld Object-Memory Evaluation (FOME) at baseline, 6 weeks, and 12 weeks. Patients receiving nimodipine showed greater improvement in FOME mean scores at 12 weeks (P=0.0334), and also in FOME score change across time (P=0.0283). Patients with severe disability who received nimodipine also showed greater MMSE score change across time (P=0.0495). Nimodipine given 7-14 days after cerebral infarction for 3 months results in memory improvement.\nStudy10: Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands. An international, multicenter trial was conducted in 331 patients to determine the effect of a large dose of flunarizine (a calcium entry blocker) in the treatment of acute ischemic stroke in the territory of the Middle cerebral artery. The administration of the trial medication should start within 24 h after the initial symptoms of stroke. According to a random schedule, the patients were assigned to a 4-weeks double-blind treatment with either flunarizine (n = 166) or placebo (n = 165): one week intravenous administration (50 mg daily), followed by 3 weeks oral treatment (week 2, 21 mg daily; week 3-4, 7 mg daily). All patients had to be investigated by computerized tomography (CT) within 7 days after stroke onset; 36 patients were secundarily excluded because the CT showed another pathology. During the treatment period, other \"stroke therapies\" were not allowed. Patients were followed up for 24 weeks. After the 24 weeks trial period, the percentage of patients who were dead or pendent (modified Rankin score 3-5) was similar in both treatment groups (flunarizine 67%, placebo 65%). During the trial, the scores for handicap severity (modified Rankin scale), neurological status (Orgogozo) and activities of daily living (modified Barthel index) strongly improved in both treatment groups, but no differences were found between the treatment groups. In this trial, the administration of trial treatment started relatively late after stroke onset (flunarizine group: mean time interval 13.5 h; placebo 12.3 h). A subgroup of patients received trial medication within 6 h after stroke onset (flunarizine n = 31; placebo n = 29). Also in this subgroup, no differences were found between the flunarizine and placebo group. Flunarizine did not improve neurologic and functional outcome in patients with acute ischemic stroke.\n", + "output": "Conclusions: No evidence is available using calcium antagonists in patients with acute ischemic stroke is effective." + }, + { + "input": "Study1: Comparison of a hydrocolloid dressing and silver sulfadiazine cream in the outpatient management of second-degree burns. The purpose of this prospective randomized study was to evaluate the use of an occlusive hydrocolloid dressing (Duoderm hydroactive, Squibb) and silver sulfadiazine (Silvadene, Marion) cream in the outpatient management of second-degree burns. The inclusion criteria consisted of burns less than 15% total body surface area that were evaluated within 24 hours of injury and did not require hospital admission. Fifty patients were randomly assigned after having been screened through a list of seven exclusion criteria. On initial evaluation the burns were photographed and screened for causative agent, location, size, depth, tetanus status, and presence of associated burns and injuries. Patients were seen in followup at least biweekly and evaluated for wound bed healing, wound margin healing, pain, number of dressing changes between visits, and ease of dressing application and removal. On final evaluation the burns were photographed and inspected for appearance of the healed burn, repigmentation, wound contraction, approximate time for dressing change, patient compliance, limitation of activity, overall impression of the treatment, and number of days for complete healing. Results were compared using a two-tailed t-test with p less than 0.01. Both groups were statistically similar in age, sex, and size. Duoderm-treated burns had statistically significantly better wound healing, repigmentation, less pain, fewer dressing changes, less time for dressing changes, and less cost. Duoderm-treated patients had statistically significantly less limitation of activity, better patient compliance, greater patient comfort, better overall acceptance, and felt the treatment was more aesthetically pleasing. The results reveal that the Duoderm Hydroactive dressings are superior to Silvadene cream in the outpatient management of second-degree burns.\nStudy2: Comparison of efficacy of 1% silver sulfadiazine and Acticoat for treatment of partial-thickness burn wounds. Acticoat (Smith & Nephew, Hull, UK) is a silver-coated dressing reported to reduce infection and exhibit antimicrobial activity in wounds. The purpose of the present study was to compare the efficacy ofacticoat and 1% silver sulfadiazine (1% AgSD) for treatment of partial thickness burn wounds. The authors reviewed 50 patients who had partial thickness burn wounds less than 25% admitted to Siriraj Burn Unit from May 2002 to September 2005. All patients were divided into 2 groups: the acticoat treated group (25 patients) and the 1% silver sulfadiazine treated group (25 patients). The 2 groups were compared for the etiology of burn wound, demographic data including age, sex, % Total Body Surface Area burn (TBSA%), cultured organisms, wound infection and outcome of Length Of hospital Stay (LOS) and level of pain. The authors found no significant differences in age, TBSA (%) between both groups. 7 patients (28%) developed wound infection. There were no differences in wound infection and LOS between both groups (p > 0.05). All of the patients who developed wound infection responded well to targeted topical and systemic antibiotic treatment. The 1% AgSD treated group (6 of 25, 24%) obtained more split thickness skin graft to close the granulation defects compared to patients who were treated with acticoat (4 of 25, 16%) but no statistical significance, p = 0.32). Average pain scores in the acticoat treated groups were significantly lower than the 1% AgSD treated group (4 +/- 0.6 versus 5 +/- 0.7, respectively). The present study confirms the efficacy of acticoat treatment in partial thickness burn wound. The authors conclude that acticoat has an advantage of limiting the frequency of replacement of the dressing and provides a less painful alternative to wound care with 1% AgSD with comparable incidence of burn wound infection. This is due to its long wear time and the ease of application and removal.\nStudy3: A randomized prospective study of topical antimicrobial agents on skin grafts after thermal injury. We prospectively studied 52 consecutive patients who were treated by early tangential excision and grafting following thermal injury. The usefulness of two topical antimicrobial agents--0.5% silver nitrate (Ag) and neomycin (1 gm/liter) plus bacitracin (50,000 units/liter) (NB)--was compared with the effectiveness of Ringer's lactate (RL) for prevention of autogenous skin-graft loss due to infection. Graft loss of 10 percent or more occurred in 17 patients (33 percent)--due to infection in 16. Skin-graft loss was a minor problem in patients with less than 20 percent total body surface area (TBSA) burn (Ag: 0 of 6, NB: 1 of 6, RL: 1 of 5). The use of either antimicrobial (Ag or NB) resulted in less graft loss (1 of 14) than RL (4 of 6; p less than 0.05) in the 20 to 40 percent TBSA burn group. Large burns (greater than 40 percent) had a very high incidence of at least 10 percent graft loss (67 percent) regardless of treatment. Infection in the area of graft loss was caused by antibiotic-resistant organisms or yeast in 50 percent of the Ringer's lactate group and the entire neomycin plus bacitracin group. No graft infections were caused by resistant organisms or yeast in the silver nitrate group. This study demonstrates that topical antimicrobial agents reduce infection-related skin-graft loss in patients with medium-sized (20 to 40 percent TBSA) burns and that neomycin plus bacitracin is associated with rapid emergence of drug-resistant organisms whereas silver nitrate is not.\nStudy4: The use of silver coated dressings on donor site wounds: a prospective, controlled matched pair study. Acticoat, a new silver-coated dressing, produces a moist healing environment along with the sustained release of ionic silver for improved microbial control. These properties suggest that Acticoat might be a useful donor site dressing. However, there are no human studies which assess Acticoat for this use. The purpose of this study was to compare the healing of human skin graft donor sites dressed with Acticoat, to the healing of those dressed with Allevyn, an occlusive moist-healing environment material, which is our standard donor site dressing. In burn patients who had undergone burn excision and grafting, identical side-by-side split thickness donor site wound pairs were dressed with Allevyn and Acticoat. Re-epithelialization was directly assessed daily by a single observer from post-operative day 6 onward, and by four independent observers who rated the extent of re-epithelialization by viewing standardized digital images of the wounds that had been obtained on post-operative days 6, 8, 10,and 12. Donor sites were swabbed for bacterial culture on days 3, 6, and 9. Subsequently, each study donor site scar was rated by a blinded observer using the Vancouver Scar Scale at 1, 2, and 3 months. Sixteen paired sites in 15 patients (3 female, 12 male) were studied. Donor sites dressed with Allevyn were >90% re-epithelialized at a mean of 9.1+/-1.6 days while donor sites dressed with Acticoat required a mean of 14.5+/-6.7 days to achieve >90% re-epithelialization (P=0.004). The Allevyn sites had significantly greater estimated re-epithelialization at days 6, 8, 10 and 12 than the Acticoat sites based on the observations of the digital images. There were no significant differences in the incidence of positive bacterial cultures with either dressing at days 3, 6, and 9. Donor sites dressed with Acticoat had significantly worse scars at 1 and 2 months but this difference resolved by 3 months. Our findings do not support the use of Acticoat as a skin graft donor site dressing.\nStudy5: Randomised clinical trial of Hydrofiber dressing with silver versus povidone-iodine gauze in the management of open surgical and traumatic wounds. This prospective, randomised clinical trial compared pain, comfort, exudate management, wound healing and safety with Hydrofiber dressing with ionic silver (Hydrofiber Ag dressing) and with povidone-iodine gauze for the treatment of open surgical and traumatic wounds. Patients were treated with Hydrofiber Ag dressing or povidone-iodine gauze for up to 2 weeks. Pain severity was measured with a 10-cm visual analogue scale (VAS). Other parameters were assessed clinically with various scales. Pain VAS scores decreased during dressing removal in both groups, and decreased while the dressing was in place in the Hydrofiber Ag dressing group (n = 35) but not in the povidone-iodine gauze group (n = 32). Pain VAS scores were similar between treatment groups. At final evaluation, Hydrofiber Ag dressing was significantly better than povidone-iodine gauze for overall ability to manage pain (P < 0.001), overall comfort (P < or = 0.001), wound trauma on dressing removal (P = 0.001), exudate handling (P < 0.001) and ease of use (P < or = 0.001). Rates of complete healing at study completion were 23% for Hydrofiber Ag dressing and 9% for povidone-iodine gauze (P = ns). No adverse events were reported with Hydrofiber Ag dressing; one subject discontinued povidone-iodine gauze due to adverse skin reaction. Hydrofiber Ag dressing supported wound healing and reduced overall pain compared with povidone-iodine gauze in the treatment of open surgical wounds requiring an antimicrobial dressing.\nStudy6: Prospective comparison of silver sulfadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent (Silvazine) and silver sulfadiazine 1 per cent (Flamazine) as prophylaxis against burn wound infection. Patients with fresh full-thickness burn wounds were randomly assigned to receive wound treatment with daily applications of either 1 per cent silver sulfadiazine plus 0.2 per cent chlorhexidine digluconate cream (Silvazine) or 1 per cent silver sulfadiazine (Flamazine). Fifty-four patients treated with Silvazine were comparable to 67 treated with Flamazine with respect to extent and distribution of burn, age and all aspects of wound and associated treatment. Overall incidence of wound bacterial colonization was less in the Silvazine treated patients (65 per cent versus 88 per cent; P = 0.002). With Silvazine, wound colonization by Staphylococcus aureus was less (41 per cent versus 64 per cent; P = 0.01). Clinical wound infection with Staph, aureus developed in one Silvazine treated patient and five Flamazine treated patients (P = 0.16). Colonization by and infection due to all other organisms did not differ in the two groups. The incidence of graft failure was similar with both agents. In future increasing the concentration of chlorhexidine digluconate above 0.2 per cent might produce an improved prophylactic effect against Gram negative bacteria reported by other authors using the combined agent in in vitro and clinical trials. Silvazine was effective in reducing the incidence of Staph. aureus burn wound colonization without fostering supervening opportunistic infection.\nStudy7: Wound healing in partial-thickness burn wounds treated with collagenase ointment versus silver sulfadiazine cream. During burn care the wounds must be repeatedly debrided of adherent and loose debris until the decision is made to surgically excise and graft the wound or to await epithelialization. Though native proteolytic enzymes in the skin or those produced by colonizing bacteria can speed eschar separation, the use of exogenous enzymes for wound debridement may accelerate wound cleaning and healing. Collagenase digests native and denatured collagen in necrotic tissue. This multicenter trial of 79 patients with partial-thickness wounds compared the efficacy of collagenase ointment applied with polymyxin B sulfate/bacitracin powder with the efficacy of standard topical antimicrobial therapy (control) in which silver sulfadiazine cream (1%) was used to debride paired burn sites. Patients selected for the study had two noncontiguous, partial-thickness, comparably sized, and anatomically similar burn wounds. Ages of patients ranged from 5 to 60 years (mean 33 years). The total body surface area burned ranged from 2% to 30% (mean 13.6%). Mean burn sizes used for study treatment were 366 cm2 (26 to 2310 cm2) for collagenase sites and 355 cm2 (26 to 2394 cm2) for control sites. Sites on each patient were randomly assigned to treatment with either collagenase or control. Endpoints were time to clean wound bed (absence of retained debris) and time to healing (complete epithelialization). The sites treated with collagenase cleaned in less time (mean 9.3 days) than the control sites (mean 11.6 days). Similarly the collagenase sites healed faster than the control sites (mean 19 vs 22.1 days).(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy8: Collagenase ointment and polymyxin B sulfate/bacitracin spray versus silver sulfadiazine cream in partial-thickness burns: a pilot study. A multifaceted approach that involves early debridement and control of infection is critical to successful and rapid burn wound healing. This pilot study was conducted in 15 adult patients with burns to assess the usefulness of early enzymatic debridement with a combination of collagenase ointment and polymyxin B sulfate/bacitracin spray versus silver sulfadiazine cream in partial-thickness burns. Combination treatment with collagenase and polymyxin B sulfate/bacitracin resulted in significantly shorter time to achieve a clean wound bed than silver sulfadiazine (median 6 vs 12 days; p = 0.0012) and significantly more rapid wound healing than silver sulfadiazine (median 10 vs 15 days; p = 0.0007). These results are encouraging and justify implementation of a larger, multicenter, comparative study.\nStudy9: Prospective clinical study of Hydron, a synthetic dressing, in delivery of an antimicrobial drug to second-degree burns. This clinical trial prospectively evaluates the potential beneficial effects of antimicrobial drug delivery from a synthetic dressing (Hydron-AgSD) formed on second-degree burn wounds. A paste composed of polyethylene glycol-400, poly 2-OH ethylmethacrylate, and silver sulfadiazine (AgSD 1%-3%) matured within one hour to form a solid dressing. In 27 patients, comparable areas of second-degree wounds on the same patient were selected at random for test and control (silver sulfadiazine 1% only) sites. The mean total time of the synthetic dressing application per patient was about nine days, and each dressing remained in place for nearly four days. During this interval the control sites required four dressings changes. In 17 tests for infections, the control areas were contaminated but no bacteria were detected under the synthetic dressing; in three tests, the controls had no bacteria, whereas the synthetic dressing did. Healing of burns was similar under both types of dressing. Benefits of Hydron treatment included increased patient comfort because of the reduced number of dressing changes and, in some cases, greater freedom from contaminating bacteria.\nStudy10: Prospective evaluation of topical antibiotics for preventing infections in uncomplicated soft-tissue wounds repaired in the ED. To determine differences in infection rates among uncomplicated, repaired wounds managed with: topical bacitracin zinc (BAC); neomycin sulfate, bacitracin zinc, and polymyxin B sulfate combination (NEO); silver sulfadiazine (SIL); and petrolatum (PTR). This was a prospective, randomized, double-blind, placebo-controlled study conducted at a military community hospital with an emergency medicine residency program. Patients were enrolled if they: presented to the ED within 12 hours of injury and did not have puncture wounds, allergies to the agents used, or a history of immunocompromise; were not receiving antibiotics, chemotherapy, or steroids at the time of presentation; had not taken antibiotics within the preceding seven days; did not have an underlying fracture; and were not pregnant as determined by history. Local anesthetics without epinephrine and high-pressure irrigation with normal saline were used for all patients. Wound scrubbing, d\u00e9bridement, and polyglactin subcutaneous (SQ) suture placement were carried out when necessary. Interrupted simple sutures using a monofilament, nonabsorbable material were used for skin closure. Numbered, randomized vials were given to all patients, with standardized instructions to inspect, clean, and redress their wounds three times a day. The wounds were evaluated for clinical infection at the time of follow-up. Among the groups, there was no difference in patient ages; gender; wound location, type, length, or depth; time elapsed from injury to ED treatment; number of wounds scrubbed or necessitating d\u00e9bridement; number of SQ and cutaneous sutures used; and rate of compliance with returning the used vial of dispensed topical agent. The wound infection rates for the treatment groups were: BAC, six of 109 (5.5%); NEO, five of 110 (4.5%); SIL, 12 of 99 (12.1%); and PTR, 19 of 108 (17.6%) (p = 0.0034). The use of topical antibiotics resulted in significantly lower infection rates than did the use of a petrolatum control. BAC and NEO had the lowest wound infection rates.\n", + "output": "Conclusions: There is insufficient evidence to establish whether silver-containing dressings or topical agents promote wound healing or prevent wound infection; some poor quality evidence for SSD suggests the opposite." + }, + { + "input": "Study: Hyperglycemia in extremely- low-birth-weight infants. The cause of hyperglycemia in extremely-low-birth-weight (ELBW) infants is not well understood. We studied infants weighing <1,000 g to investigate the relationship of hyperglycemia to blood levels of insulin-like growth factor (IGF)-I and IGF-II. We also compared two methods of treatment for hyperglycemia: continuous insulin infusion and reduction of glucose intake. Fifty-six ELBW infants were enrolled on day 2 of life. Intravenous glucose intake was increased incrementally to a maximum of 12 mg/kg/min on day 6. Infants who developed hyperglycemia were randomly assigned to receive reduced glucose intake (n = 11) or insulin infusion (n = 12). Infants whose blood sugar remained normal served as controls (n = 33). Blood was drawn on days 3, 8 and 15 in all infants, and again when they developed hyperglycemia. Nutritional intake and laboratory results for the treatment groups were compared with controls. Hyperglycemic infants had lower birth weights than controls. Hyperglycemic infants treated with glucose reduction remained <60 kcal/kg/day longer than control or insulin infusion groups (8.6 +/- 1.3 days vs. 4.1 +/- 0.2 and 5.5 +/- 0.6 days). No infants became hypoglycemic during insulin infusion. There was no difference in baseline blood levels of IGF-I or IGF-II among the groups, and these growth factors did not change in response to hyperglycemia. Hyperglycemic infants had baseline levels of insulin which were similar to normal controls, and endogenous insulin increased in response to hyperglycemia in 15 of the 23 infants who developed hyperglycemia. IGF-I and IGF-II are not related to hyperglycemia. In our population, hyperglycemic infants did not have baseline insulin deficiency and most had a normal insulin response to hyperglycemia. Insulin infusion appears safe in these infants and helped to maintain normal caloric intake, whereas glucose reduction was associated with a prolonged caloric deprivation.\n", + "output": "Conclusions: Evidence from randomized trials in hyperglycemic VLBW neonates is insufficient to determine the effects of treatment on death or major morbidities. It remains uncertain whether the hyperglycemia per se is a cause of adverse clinical outcomes or how the hyperglycemia should be treated. Much larger randomized trials in hyperglycemic VLBW neonates that are powered on clinical outcomes are needed in order to determine whether, and how, the hyperglycemia should be treated." + }, + { + "input": "Study1: Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment. The aim of the present study was to compare the efficacy and safety of tiapride versus haloperidol and placebo in the treatment of agitation and aggressiveness in elderly patients with mild or moderate mental impairment. This international, multicentre, randomized, double blind, three parallel groups study compared efficacy and safety of a 21 -day regimen of tiapride 100-300 mg/day versus haloperidol 2-6 mg/day and placebo in 306 elderly patients with mild or moderate dementia according to DSM III R and behavioural troubles with the Multidimensional Observation Scale for the Elderly Subjects (MOSES) irritability/aggressiveness subscore ranging from 16 to 30. The percentage of responders (defined as patients with at least a 25% MOSES irritability/aggressiveness subscore decrease between the inclusion and the end of the treatment) was significantly greater in the tiapride (63%, P=0.04) and haloperidol (69%, P=0.004) groups than in the placebo group (49%), with no significant difference between the active drugs. Similar results were observed for the mean MOSES irritability/aggressiveness subscores on D7, D21 and at D(end) which were significantly smaller in the tiapride and haloperidol groups than in the placebo group. The decrease between D0 and D(end) was significantly greater in the tiapride (6.57, P=0.009) and haloperidol groups (6.75, P=0.005) than in the placebo group (4.71). The global improvement CGI was significantly better in the tiapride and haloperidol groups than in the placebo group (P=0.03 and P=0.02). No significant difference was observed between the two active drugs or among the three treatment groups for the Folstein's Mini Mental Status scale (MMS) total score, and there was no notable change during treatment. The number of patients with adverse events, assessed on the Udvalg Kliniske Undersogelser scale (UKU), and the number of UKU symptoms were smaller in the tiapride group (62 patients, 61%, 212 events) than in the haloperidol group (77 patients, 76%, 305 events) and identical to that observed in the placebo group (69 patients, 67%, 234 events). Of interest, the number of patients with at least one extrapyramidal symptom was significantly lower (P=0.003) in the tiapride group (16 patients, 16%) than in the haloperidol group (34 patients, 34%) and similar to that of the placebo group (18 patients, 17%); the difference observed between the haloperidol and placebo groups was significant (P=0.008). Tiapride is not different from haloperidol in the treatment of agitation and aggressiveness in elderly patients and better tolerated, in particular with significantly fewer extrapyramidal symptoms.\nStudy2: Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs. To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients. A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden. Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments. Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.\nStudy3: A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. To compare effects of risperidone with placebo (efficacy and tolerability) and haloperidol (tolerability) for treating demented patients with aggression and other behavioral symptoms. A 13-week double-blind study involving 344 patients with dementia randomly assigned to receive placebo or flexible doses (0.5 to 4 mg/d) of risperidone or haloperidol. Behavioral symptoms were assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression (CGI) scale. Tolerability assessments included the Extrapyramidal Symptom Rating Scale, sedation levels, Functional Assessment Staging, Mini-Mental State Examination, and incidence of adverse events. The mean dose at endpoint was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol. Although not significant, a higher percentage of patients receiving risperidone than those receiving placebo showed clinical improvement (> or =30% reduction from baseline to endpoint in BEHAVE-AD total score) at endpoint and week 12. Reductions in the BEHAVE-AD total score were significantly greater with risperidone than with placebo at week 12. In a further analysis of aggression, the most dominant symptom in these patients, BEHAVE-AD and CMAI aggression cluster scores were significantly reduced compared with placebo at endpoint and week 12. CGI scores were also significantly reduced at endpoint and week 12. Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol. A post hoc analysis showed significantly greater reductions in the BEHAVE-AD aggressiveness score with risperidone than haloperidol at week 12. Low-dose risperidone (mean 1.1 mg/d) was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms, particularly aggression, in elderly patients with dementia.\nStudy4: Pilot study of haloperidol, fluoxetine, and placebo for agitation in Alzheimer's disease. This pilot study compared haloperidol, fluoxetine, and placebo for reduction of agitation in 15 outpatients with AD. The two drugs were no more effective than placebo at reducing agitation in these subjects; however, both drugs produced more toxicity than did placebo.\n", + "output": "Conclusions: 1. Evidence suggests that haloperidol was useful in reducing aggression, but was associated with adverse effects; there was no evidence to support the routine use of this drug for other manifestations of agitation in dementia.2. Similar drop-out rates among haloperidol and placebo treated patients suggested that poorly controlled symptoms, or other factors, may be important in causing treatment discontinuation.3. Variations in degree of dementia, dosage and length of haloperidol treatment, and in ways of assessing response to treatment suggested caution in the interpretation of reported effects of haloperidol in the management of agitation in dementia.4. The present study confirmed that haloperidol should not be used routinely to treat patients with agitated dementia. Treatment of agitated dementia with haloperidol should be individualized and patients should be monitored for adverse effects of therapy." + }, + { + "input": "Study: Reactions to booster pneumococcal vaccination in patients with sickle cell disease. Repeat (booster) pneumococcal vaccination was administered to 32 patients with sickle cell disease in a double blind, placebo-controlled crossover study as early as 2.3 years after initial immunization. A significantly greater proportion of patients reported local pain, swelling or redness after booster, as compared to that after placebo (P less than 0.001), and pneumococcal antibody titer before vaccination was the predominant predictive variable for the development of fever, local pain and swelling after booster. A comparison of reaction rates following primary or booster immunization showed no significant differences in the frequency of reported symptoms except for muscle pain which occurred less frequently after booster (P less than 0.005). The concern for adverse reactions after repeat pneumococcal vaccination should not be an obstacle to the pursuit of further studies on the efficacy of pneumococcal vaccine and booster responses.\n", + "output": "Conclusions: Previous trials have shown that conjugate pneumococcal vaccines are safe and effective in normal healthy individuals, including those under the age of two years. The controlled trials included in this review have demonstrated immunogenicity (the ability to induce the body's immune response, without which there is no protection) of these vaccines, and observational studies in people with sickle cell disease support these findings. We therefore recommend that conjugate pneumococcal vaccines are used in people with sickle cell disease. Randomised trials in people with sickle cell disease will be needed to determine the optimal vaccination regimen when further, potentially more effective vaccines become available. Such trials should measure clinical outcomes of effectiveness. The trials included in this review were published between 1983 and 2003. We have not identified any further relevant trials up to December 2011. We therefore do not plan to update this review until new trials are published." + }, + { + "input": "Study: Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone. A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid (prednisolone) or an anabolic steroid (oxandrolone) in moderate or severe alcoholic hepatitis. One hundred thirty-two patients with moderate disease and 131 with severe disease were randomly assigned to one of three treatments: prednisolone, oxandrolone, or placebo. During the 30 days, mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group. Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died. Although neither steroid improved short-term survival, oxandrolone therapy was associated with a beneficial effect on long-term survival. This was especially true in patients with moderate disease: among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after oxandrolone and 19 to 20 per cent after placebo (P = 0.02). No consistent long-term effect was associated with prednisolone therapy.\n", + "output": "Conclusions: This systematic review could not demonstrate any significant beneficial effects of anabolic-androgenic steroids on any clinically important outcomes (mortality, liver-related mortality, liver complications, and histology) of patients with alcoholic liver disease." + }, + { + "input": "Study1: Routine oxytocin in the third stage of labour: a placebo controlled randomised trial. To compare intravenous oxytocin administration (Partocon 10 IU) with saline solution in the management of postpartum haemorrhage in the third stage of labour. A double-blind, randomised controlled trial involving 1000 parturients with singleton fetuses in cephalic presentation and undergoing vaginal delivery, randomly allocated to treatment with oxytocin (n = 513) or 0.9% saline solution (n = 487). Labour ward at a central county hospital. Mean blood loss (total, and before and after placenta delivery); frequencies of blood loss > 800 mL, need of additional oxytocic treatment, postpartum haemoglobin < 10 g/dL; and duration of postpartum hospitalisation. As compared with saline solution, oxytocin administration was associated with significant reduction in mean total blood loss (407 versus 527 mL), and in frequencies of postpartum haemorrhage > 800 mL (8.8% versus 5.2%), additional treatment with metylergometrine (7.8% versus 13.8%), and postpartum Hb < 10 g/dL (9.7% versus 15.2%), and a nonsignificant increase in the frequency of manual placenta removal (3.5% versus 2.3%). There was no group difference in the mean duration of postpartum hospitalisation (4.6 versus 4.5 days, respectively). Administration of intravenous oxytocin in the third stage of labour is associated with an approximately 22% reduction in mean blood loss, and approximately 40% reductions in frequencies of postpartum haemorrhage (> 500 mL or > 800 mL) and of postpartum haemoglobin < 10 g/dL. Identification of risk groups for oxytocin treatment does not seem worthwhile. Oxytocin is a cheap atoxic drug and should be given routinely after vaginal delivery.\nStudy2: INTRAMUSCULAR OXYTOCICS AND CORD TRACTION IN THIRD STATE OF LABOUR. nan\nStudy3: A comparison of oxytocic drugs in the management of the placental stage. nan\nStudy4: OXYTOCIC DRUGS IN FOURTH STAGE OF LABOR. nan\nStudy5: A randomized comparison of oxytocin, sulprostone and placebo in the management of the third stage of labour. To compare the effect on post partum bloodloss of the postpartum prophylactic administration of oxytocin or sulprostone in low risk women having an expectant management of the third stage. Randomized, placebo controlled, double-blind trial. Radboud University Hospital, Nijmegen (67 women) and Lievensberg Hospital, Bergen op Zoom (10 women). 77 women entered the trial (three were excluded). The intramuscular injection, immediately after the birth of the baby, of either oxytocin 5 IU, sulprostone 500 micrograms or 0.9% saline. Quantitative postpartum blood loss and length of third stage. Postpartum blood loss was reduced almost equally, by about 35%, by oxytocin (P = 0.02), or sulprostone (P = 0.05). The mean length of the third stage was shorter in both groups receiving the active treatment, this effect was significant in the sulprostone group (P = 0.01). Prophylactic administration of oxytocin or sulprostone directly after delivery followed by expectant management of the third stage reduces post partum blood loss and shortens the third stage.\nStudy6: CLINICAL EXPERIENCE WITH SIMULTANEOUS INTRAMUSCULAR INJECTION OF OXYTOCIN AND METHYLERMETRINE. nan\nStudy7: A placebo-controlled trial of oral ergometrine to reduce postpartum hemorrhage. Active management with oral ergometrine 0.4 mg was compared with expectant management for the control of blood loss in the third stage of labor in women at low risk of postpartum hemorrhage (PPH). A three-arms randomized trial in which 0.4 mg ergometrine (2 tablets of 0.2 mg) was set off against placebo, both groups allowing comparison with a standard oxytocin regimen of 5 IU. Women at low risk for PPH. Of 367 parturients, 146 were randomised to ergometrine 0.4 mg, 143 to placebo and 78 to intramuscular oxytocin in a 2:2:1 design. Compared with placebo, ergometrine reduced blood loss with 5% (-5%; Confidence interval: -20% to +13%). Oxytocin reduced blood loss with 9% (-9%; Confidence interval: -26% to +12%) versus placebo. Oral ergometrine has too little effect on blood loss after childbirth in order to be a good alternative to parenteral prophylactic management.\n", + "output": "Conclusions: Oxytocin appears to be beneficial for the prevention of postpartum haemorrhage. However, there is insufficient information about other outcomes and side-effects hence it is difficult to be confident about the trade-offs for these benefits. There seems little evidence in favour of ergot alkaloids alone compared to either oxytocin alone, or to ergometrine-oxytocin, but the data are sparse. More trials are needed in domiciliary deliveries in developing countries, which shoulder most of the burden of third stage complications.\n[Note: The ten citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]" + }, + { + "input": "Study: An exploratory trial of preventative rehabilitation on shoulder disability and quality of life in patients following neck dissection surgery. Patients commonly develop shoulder disability and reduction in quality of life (QOL) following neck dissection surgery. There is a lack of studies investigating the impact of preventative rehabilitation to prevent shoulder disability in this population. An exploratory trial was undertaken to investigate this gap in the head and neck cancer literature. Thirty-two subjects were randomly assigned to either one of two groups: early physiotherapy for a period of 3 months following surgery and current routine inpatient care and advice. Blinded measurement of shoulder function and QOL were recorded pre-operatively and at 1 year following surgery. No difference was found using between-group analysis (Mann-Whitney U-Test) for any outcome measures observed. Descriptive data analysis suggests that subjects receiving early physiotherapy had a perception of increased physical well-being when compared with subjects receiving routine care. There may be some clinical significance that subjects receiving a course of physiotherapy did appear to rate their physical well-being higher than those subjects not undergoing rehabilitation. Further research to investigate the preventative effects of physiotherapy on this population should consider the use of head and neck cancer-specific outcome measurement of both shoulder disability and QOL. \u00a9 2010 Blackwell Publishing Ltd.\n", + "output": "Conclusions: Limited evidence from two RCTs demonstrated that PRT is more effective than standard physiotherapy treatment for shoulder dysfunction in patients treated for head and neck cancer, improving pain, disability and range of motion of the shoulder joint, but it does not improve quality of life. However, although statistically significant the measured benefits of the intervention may be small. Other exercise regimes were not shown to be effective compared to routine postoperative physiotherapy. Further studies which apply other exercise interventions in head and neck cancer patients in the early postoperative and radiotherapy period are needed, with long-term follow-up." + }, + { + "input": "Study: Effect on birth weight of erythromycin treatment of pregnant women. To test the hypothesis that treatment with antibiotics prevents low birth weight, pregnant women whose vaginal cultures contained Ureaplasma urealyticum or Mycoplasma hominis (or both) and who gave written informed consent were treated with one of the following: identical looking capsules containing 250 mg of either erythromycin estolate or stearate (active against U urealyticum), or 150 mg of clindamycin hydrochloride (active against M hominis), or placebo, four times daily for six weeks in a randomized double-blind study. Treatment with clindamycin had no effect. Treatment with erythromycin initiated during the second trimester had no effect on mean birth weight or on the frequency of low-birth-weight infants. In contrast, women whose treatment with erythromycin was initiated in the third trimester gave birth to infants with a heavier mean birth weight (3331 g) than infants born to placebo-treated women (3187 g) (P = .042). Similarly, in women whose erythromycin was begun during the third trimester, the birth rate of infants weighing 2500 g or less was 3%, whereas in women treated with placebo, the birth rate for low-birth-weight infants was 12% (P = .047). These data suggest that treatment with erythromycin during the third trimester prevents low birth weight in mycoplasma-colonized pregnant women. Whether the effect is due solely to the action of erythromycin on U urealyticum is uncertain.\n", + "output": "Conclusions: There is insufficient evidence to assess whether pregnant women who have vaginal colonisation with ureaplasma should be treated with antibiotics to prevent preterm birth.\nPreterm birth is a significant perinatal problem. Upper genital tract infections, including ureaplasmas, are suspected of playing a role in preterm birth and preterm rupture of the membranes. Antibiotics are used to treat women with preterm prelabour rupture of the membranes; this may result in prolongation of pregnancy and lowers the risks of maternal and neonatal infection. However, antibiotics may be beneficial earlier in pregnancy to eradicate potentially causative agents." + }, + { + "input": "Study1: Effect of exercise on postural sway in the elderly. Fifty female subjects, aged 72-92 (mean 82) years, were enrolled in a 12-week (36 classes) exercise program aimed at increasing postural stability. Subjects were residents of sheltered apartments, rest homes or nursing homes, well enough and mobile enough to participate in the classes. The subjects were randomized into an exercise or a control group. Their postural sway, standing at rest on a force platform, was measured with eyes open and eyes closed. The groups were well matched in all respects. The results showed no improvement in the postural sway as a result of the exercise program. We hypothesize that increasing postural sway in the elderly represents a deterioration in, for the most part, the nervous system and may at this extreme of life indicate an irreversible loss of function. For this reason no improvement in postural sway may be possible.\nStudy2: A clinical trial of strengthening and aerobic exercise to improve gait and balance in elderly male nursing home residents. The purpose of this study was to determine whether a moderate to high intensity strengthening and aerobic exercise program can improve the strength, exercise capacity, gait and balance of deconditioned male nursing home residents. Ambulatory subjects who scored 30 or less on the modified Tinetti gait and balance assessment scale, who demonstrated less than 80% of age-matched lower extremity strength on isokinetic muscle testing and who gave informed consent were enrolled. Subjects were randomized to either an exercise (n = 8) or a control (n = 6) group. All participants underwent an exercise test to determine maximal oxygen uptake (VO2max) and received quantitative gait and balance measurements. The subjects assigned to the exercise group than completed a 12-wk program of weight training for the lower extremities and stationary cycling. Both the exercise and control groups were then retested. Ten outcome variables were assessed: Tinetti mobility scores, VO2max, isokinetic-tested lower extremity strength and endurance, stride length, gait velocity, stance time, gait duration, cadence and balance. The exercise group, after completion of the program, demonstrated significant improvements in Tinetti mobility scores (P < 0.05), combined right and left quadricep muscle strength (P < 0.01), right and left lower extremity muscular endurance (P < 0.01), left stride length and gait velocity (P < 0.05), although other outcome variables changed insignificantly. The control group revealed no changes of significance with the exception of improvement of the combined right and left hamstring muscle strength (P < 0.05). Nevertheless, for those outcome variables that had improved significantly in the exercise group, the changes amounted to only a 5 to 10% increase over the baseline measurements. These findings showed that an appropriately designed high intensity exercise program can result in significant although limited improvements for clinical mobility scores, strength, muscular endurance and certain gait parameters.\nStudy3: Exercise training in the debilitated aged: strength and functional outcomes. Resistance and endurance training result in gains in fitness in the aged. It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength, endurance, and function in this population. Randomized, controlled trial. Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home. They were older than 60 yrs with impairment in at least one physical activity of daily living. Seventy-eight subjects volunteered and 58 (mean age, 75 yrs; 9 women, 49 men) completed the intervention and initial posttest. Only one subject withdrew because of injury or disinterest. Thrice-weekly resistance training (using an isokinetic dynamometer) and twice-weekly endurance training for 4 to 8 weeks. Isometric strength in dominant arm and leg, heart rate response to timed endurance test, and activities of daily living score. The mean change in isometric strength across the muscle movements tested was 32.8% in the training group and 10.2% in the control group (difference, 22.6%; 95% confidence interval, 6.2% to 39.0%). No change in heart rate during exercise was seen in the training group. Trained subjects tended to have a greater improvement in functional activity than control subjects, which was statistically significant (p = .04) for those subjects who at enrollment were most dysfunctional (i.e., activities of daily living score less than 13 [maximum score 26]). This group of debilitated elderly patients effectively performed resistance training and increased their strength, with the most impaired gaining the most function. Few in the group could effectively perform endurance training.\nStudy4: Changes in postural balance in frail elderly women during a 4-week visual feedback training: a randomized controlled trial. Balance training programs have not shown consistent results among older adults, and it remains unclear how different training methods can be adapted to frail elderly people. The purpose of this study was to investigate the effects of a 4-week visual feedback-based balance training on the postural control of frail elderly women living in residential care homes. Elderly women of two residential care facilities were randomized to an exercise group (EG, n = 20) and to a control group (CG, n = 7). The EG participated in training sessions three times/week for 4 weeks. The exercises were carried out with a computerized force platform with visual feedback screen. The dimensions of balance function studied were standing body sway, dynamic weight shifting, and Berg Balance Scale performance. The EG showed significant improvement in balance functions. The performance time in dynamic balance tests improved on average by 35.9% compared with a 0.6% increase in the CG (p = 0.025-0.193). The performance distance in these tests decreased on average by 28.2% in the EG as compared with a 9.8% decrease seen in the CG. The Berg Balance Scale performance improved by 6.9% compared with a 0.7% increase in the CG (p = 0.003). The standing balance tests in the more demanding standing positions showed improvements in the EG, whereas similar changes in the CG were not found. Our findings suggest that balance training based on visual feedback improves the balance control in frail elderly women living in residential care, also enhancing the performance of functional balancing tasks relevant to daily living. The subjects were motivated to participate in the training, as indicated by the high compliance (97.5%) with the program. Copyright 2004 S. Karger AG, Basel\nStudy5: The effects of 16-week group exercise program on physical function and mental health of elderly Korean women in long-term assisted living facility. The purpose of this study was to compare the effects of 16-week group exercise program on the physical function (ie, strength, flexibility, and balance) and mental health (ie, self-esteem and depression) of older elderlyl women (>or=75 years old) compared with younger elderly women (<75 years old). Exercise is crucial in maintaining older women's health and well-being. However, because most elders have at least one chronic disease, their physical function declines, so their dependence on others for instrumental daily living activities often increases. Older women typically have multiple barriers to participation in physical activities including higher disability rates. Of the total of 40 older women (older than 65 years) enrolled, 21 were older elders and 16 were younger elders. Lower body strength (using 30-second chair test), flexibility (sit-and-reach test), and static balance (ability to balance on one leg with open and closed eyes) were assessed. Self-esteem (using Rosenberg's Self-esteem Questionnaire) and depressive symptoms (using Yesavage's Geriatric Depression Scale) were assessed. Two-way analysis of variance was used to examine the differences between the 2 age groups. The intervention program was effective in improving body strength, flexibility, static balance, and self-esteem, regardless of age. Furthermore, older elders receiving the intervention program demonstrated greater improvement in self-esteem than younger elders did, although there were intervention effects in both age groups. Elderly women can realize benefits from a group exercise program that can improve their functional ability and self-esteem, both important to cardiovascular health.\nStudy6: Nursing rehabilitation and exercise strategies in the nursing home. The purpose of this study was to evaluate how weight training or nursing-based rehabilitative care programs in nursing homes impact on resident performance of Activities of Daily Living (ADL) and objectives tests of physical performance. This study involved a quasi-experimental control, longitudinal comparison of functional status over a 10-month period, where baseline status was adjusted through a weighting procedure based on functional status, cognitive status, and age. All residents from six residential care nursing home facilities were eligible except those with a terminal prognosis, a projected stay of less than 90 days, or with health complications that prohibited contact. Homes were placed into matched triplets based on patient characteristics: two members of each triplet were randomly designated to be experimental sites, the third became the control site. Baseline data were available for 468 subjects, follow-up for 392. ADL self-performance measures derived from the Minimum Data Set, including indicators of early loss ADL, locomotion, and late loss ADL; a number of objective functional tests (including measures of balance, power, and endurance); and mood state as measured by the Geriatric Depression Scale. Mean ADL values in the two experimental groups declined at a significantly lower rate than did rates for the controls. Functional decline was also lower in more specific measures: locomotion, early loss ADL, and late loss ADL. With both interventions, facilities were able to implement a broad-based intervention that resulted in a significant reduction in ADL decline rates. A facility-wide nursing rehabilitation program can play a useful role in reversing functional decline, helping residents to maintain their involvement in a broad spectrum of ADL activities.\nStudy7: Tai Chi and health-related quality of life in nursing home residents. Health-related quality of life (HRQOL) that is good is regarded as the goal of elderly residential care. However, limited evidence exists indicating a promising intervention that can achieve this goal. The aim of this study is to examine the effect of Tai Chi on HRQOL in nursing home residents. A nonequivalent pretest-posttest control-group design. A convenience sample of 139 residents from six nursing homes in Hong Kong was used. The experimental group (n=66) joined a 26-week Tai Chi program, while the control group (n=73) continued with usual daily activities. The physical and mental components of HRQOL were designated as the dependent variables. Resident satisfaction was considered as a covariate. Doubly multivariate repeated measures analysis of covariance was done to examine the intervention effect. After adjusting for the confounding effect of resident satisfaction, a statistically significant difference (p<0.05) in the physical and mental components of HRQOL between the experimental and control groups was found. Findings showed significant improvement in HRQOL after residents practiced Tai Chi. These investigators contribute additional knowledge about the health benefits of Tai Chi among nursing home residents and indicates support for its use in this population to improve HRQOL. Tai Chi has unique characteristics as a health exercise that is particularly suitable for nursing home residents. The inclusion of Tai Chi exercise in elderly residential care practice is recommended.\nStudy8: Translating clinical research into practice: a randomized controlled trial of exercise and incontinence care with nursing home residents. To examine clinical outcomes and describe the staffing requirements of an incontinence and exercise intervention. Randomized controlled trial with blinded assessments of outcomes at three points over 8 months. Four nursing homes. Two hundred fifty-six incontinent residents. Research staff provided the intervention, which integrated incontinence care and exercise every 2 hours from 8:00 a.m. to 4:00 p.m. 5 days a week. Average and maximum distance walked or wheeled, level of assistance required to stand, maximum pounds lifted by arms, fecal and urinary incontinence frequency, and time required to implement intervention. Intervention residents maintained or improved performance whereas the control group's performance declined on 14 of 15 outcome measures. Repeated measures analysis of variance group-by-time significance levels ranged from P <.0001 to.05. The mean time required to implement the intervention each time care was provided was 20.7 +/- 7.2 minutes. We estimate that a work assignment of approximately five residents to one aide would be necessary to provide this intervention. The incontinence care and exercise intervention resulted in significant improvement for most residents, and most who could be reliably interviewed expressed a preference for such care. Fundamental changes in the staffing of most nursing homes will be necessary to translate efficacious clinical interventions into everyday practice.\nStudy9: Effects of a physiotherapy and occupational therapy intervention on mobility and activity in care home residents: a cluster randomised controlled trial. To compare the clinical effectiveness of a programme of physiotherapy and occupational therapy with standard care in care home residents who have mobility limitations and are dependent in performing activities of daily living. Cluster randomised controlled trial, with random allocation at the level of care home. Care homes within the NHS South Birmingham primary care trust and the NHS Birmingham East and North primary care trust that had more than five beds and provided for people in the care categories \"physical disability\" and \"older people.\" Care home residents with mobility limitations, limitations in activities of daily living (as screened by the Barthel index), and not receiving end of life care were eligible to take part in the study. A targeted three month occupational therapy and physiotherapy programme. Scores on the Barthel index and the Rivermead mobility index. 24 of 77 nursing and residential homes that catered for residents with mobility limitations and dependency for activities of daily living were selected for study: 12 were randomly allocated to the intervention arm (128 residents, mean age 86 years) and 12 to the control arm (121 residents, mean age 84 years). Participants were evaluated by independent assessors blind to study arm allocation before randomisation (0 months), three months after randomisation (at the end of the treatment period for patients who received the intervention), and again at six months after randomisation. After adjusting for home effect and baseline characteristics, no significant differences were found in mean Barthel index scores at six months post-randomisation between treatment arms (mean effect 0.08, 95% confidence interval -1.14 to 1.30; P=0.90), across assessments (-0.01, -0.63 to 0.60; P=0.96), or in the interaction between assessment and intervention (0.42, -0.48 to 1.32; P=0.36). Similarly, no significant differences were found in the mean Rivermead mobility index scores between treatment arms (0.62, -0.51 to 1.76; P=0.28), across assessments (-0.15, -0.65 to 0.35; P=0.55), or interaction (0.71, -0.02 to 1.44; P=0.06). The three month occupational therapy and physiotherapy programme had no significant effect on mobility and independence. On the other hand, the variation in residents' functional ability, the prevalence of cognitive impairment, and the prevalence of depression were considerably higher in this sample than expected on the basis of previous work. Further research to clarify the efficacy of occupational therapy and physiotherapy is required if access to therapy services is to be recommended in this population. ISRCTN79859980.\nStudy10: Exercise program for nursing home residents with Alzheimer's disease: a 1-year randomized, controlled trial. To investigate the effectiveness of an exercise program in improving ability to perform activities of daily living (ADLs), physical performance, and nutritional status and decreasing behavioral disturbance and depression in patients with Alzheimer's disease (AD). Randomized, controlled trial. Five nursing homes. One hundred thirty-four ambulatory patients with mild to severe AD. Collective exercise program (1 hour, twice weekly of walk, strength, balance, and flexibility training) or routine medical care for 12 months. ADLs were assessed using the Katz Index of ADLs. Physical performance was evaluated using 6-meter walking speed, the get-up-and-go test, and the one-leg-balance test. Behavioral disturbance, depression, and nutritional status were evaluated using the Neuropsychiatric Inventory, the Montgomery and Asberg Depression Rating Scale, and the Mini-Nutritional Assessment. For each outcome measure, the mean change from baseline to 12 months was calculated using intention-to-treat analysis. ADL mean change from baseline score for exercise program patients showed a slower decline than in patients receiving routine medical care (12-month mean treatment differences: ADL=0.39, P=.02). A significant difference between the groups in favor of the exercise program was observed for 6-meter walking speed at 12 months. No effect was observed for behavioral disturbance, depression, or nutritional assessment scores. In the intervention group, adherence to the program sessions in exploratory analysis predicted change in ability to perform ADLs. No adverse effects of exercise occurred. A simple exercise program, 1 hour twice a week, led to significantly slower decline in ADL score in patients with AD living in a nursing home than routine medical care.\n", + "output": "Conclusions: Physical rehabilitation for long-term care residents may be effective, reducing disability with few adverse events, but effects appear quite small and may not be applicable to all residents. There is insufficient evidence to reach conclusions about improvement sustainability, cost-effectiveness, or which interventions are most appropriate. Future large-scale trials are justified." + }, + { + "input": "Study: Orbital cobalt irradiation combined with systemic corticosteroids for Graves' ophthalmopathy: comparison with systemic corticosteroids alone. The effects of different methods of treatment of Graves' ophthalmopathy were evaluated in a series of 48 patients. Thirty-six patients were given combined treatment with orbital cobalt irradiation and systemic 6 alpha-methylprednisolone (methylprednisolone). Included in this group were 12 of 24 consecutive patients who were randomly assigned to either combined therapy or systemic methylprednisolone alone. The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index) and clinical assessment. Of the 36 patients treated by combined therapy, 12 (33%) showed excellent responses, 14 (39%) showed good responses, 9 (25%) showed slight responses, and 1 (3%) had no response. Treatment was more effective for soft tissue involvement, newly developed ophthalmoplegia, and optic neuropathy, while proptosis and longstanding ophthalmoplegia were less responsive. There was an inverse relationship between the duration of ophthalmopathy and the efficacy of treatment, more favorable results being observed when symptoms had been present for less than 2 yr. Treatment with systemic methylprednisolone alone was also effective, but, in general, responses were less satisfactory; 4 of the 12 patients of this group (33%) had good responses, 6 (50%) had slight responses, and 2 (17%) had no response. The results obtained in the 24 patients randomly assigned to combined therapy or steroid treatment alone were compared by evaluating changes in the ophthalmopathy index. Mean initial ophthalmopathy indices (6.4 vs. 6.2, respectively) showed no significant differences between the 2 groups, whereas the mean decrease in the group receiving combined therapy (4.8) was significantly greater (P less than 0.05) than that in the other group (3.2). In conclusion, the present study indicates that both orbital cobalt irradiation combined with systemic methylprednisolone treatment and systemic methylprednisolone therapy alone are valuable methods of treatment for Graves' ophthalmopathy, but the combined therapy proved to be more effective.\n", + "output": "Conclusions: This review found that orbital radiotherapy is more effective than sham radiotherapy for the treatment of mild-to-moderate thyroid eye disease. In a single trial no difference between radiotherapy and steroid monotherapy was found. A meta-analysis of our secondary outcome of disease severity was not possible but results from individual trials suggest a better outcome with combination treatment with steroids versus steroids alone. No significant changes in quality-of-life scores following treatment with radiotherapy versus alternative treatments were found. Short-term adverse events related to radiotherapy that were reported were local and mild but long-term data were lacking and development of retinal changes following radiotherapy was not reported on." + }, + { + "input": "Study: Domiciliary occupational therapy for patients with stroke discharged from hospital: randomised controlled trial. To establish if a brief programme of domiciliary occupational therapy could improve the recovery of patients with stroke discharged from hospital. Single blind randomised controlled trial. Two hospital sites within a UK teaching hospital. 138 patients with stroke with a definite plan for discharge home from hospital. Six week domiciliary occupational therapy or routine follow up. Nottingham extended activities of daily living score and \"global outcome\" (deterioration according to the Barthel activities of daily living index, or death). By eight weeks the mean Nottingham extended activities of daily living score in the intervention group was 4.8 points (95% confidence interval -0.5 to 10.0, P=0.08) greater than that of the control group. Overall, 16 (24%) intervention patients had a poor global outcome compared with 30 (42%) control patients (odds ratio 0.43, 0.21 to 0.89, P=0.02). These patterns persisted at six months but were not statistically significant. Patients in the intervention group were more likely to report satisfaction with a range of aspects of services. The functional outcome and satisfaction of patients with stroke can be improved by a brief occupational therapy programme carried out in the patient's home immediately after discharge. Major benefits may not, however, be sustained.\n", + "output": "Conclusions: Patients who receive occupational therapy interventions are less likely to deteriorate and are more likely to be independent in their ability to perform personal activities of daily living. However, the exact nature of the occupational therapy intervention to achieve maximum benefit needs to be defined." + }, + { + "input": "Study1: Once-daily ciclesonide improves lung function and is well tolerated by patients with mild-to-moderate persistent asthma. Inhaled corticosteroids are recommended as first-line therapy for persistent asthma. We sought to assess the efficacy and safety of ciclesonide once daily in patients with mild-to-moderate persistent asthma. An integrated analysis of 2 identical, multicenter, double-blind, randomized, parallel-group, placebo-controlled trials was conducted. Patients (n = 1015; aged > or =12 years) with mild-to-moderate asthma (FEV1 of 60% to 85% of predicted value) were randomized to ciclesonide 80 microg (CIC80), 160 microg (CIC160), or 320 microg (CIC320), once daily (exactuator doses) in the morning or placebo for 12 weeks. All ciclesonide groups showed significant improvements from baseline to week 12 in FEV1 compared with the placebo group (CIC80, 0.12 L [P = .0007]; CIC160, 0.13 L [P = .0004]; and CIC320, 0.14 L [P < .0001]). Likewise, FEV1 percent predicted, morning and evening peak expiratory flow, 24-hour asthma symptom score, daily albuterol use, and nighttime awakenings were significantly improved in all ciclesonide groups compared with the placebo group. Overall ciclesonide safety profile and rates of oropharyngeal adverse events for all groups were low and similar to those of the placebo group. Fewer ciclesonide-treated patients exhibited asthma-aggravated adverse events, and fewer ciclesonide-treated patients discontinued the study for any reason or because of a lack of efficacy compared with those in the placebo group. No suppression of hypothalamic-pituitary-adrenal-axis function (as assessed by means of 24-hour urinary cortisol levels corrected for creatinine and peak serum cortisol levels after stimulation with low-dose [1 microg] cosyntropin) was observed with any dose of ciclesonide. In this integrated analysis, ciclesonide once daily administered in the morning is effective and well tolerated.\nStudy2: Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma. Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events. To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma. This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator. For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate. These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.\n", + "output": "Conclusions: Ciclesonide was more effective than placebo, in the short term, in improving lung function in patients with mild to moderate asthma previously treated with inhaled corticosteroids. There remain questions as to dose response, and the lack of data on the longer term impact on exacerbations and safety profile should be addressed in future studies." + }, + { + "input": "Study1: Lack of effect of metoclopramide on colonic motility after cholecystectomy. The effect of metoclopramide on postoperative colonic ileus was evaluated in a randomised, double-blind study in 20 patients after cholecystectomy. The start of propulsive colonic motility and colonic transit time after operation were measured by radio-opaque markers and serial abdominal radiographs. Metoclopramide 20 mg given intravenously three times a day until the fourth postoperative day (n = 10) did not significantly reduce the duration of postoperative colonic paralysis compared with control patients (n = 10), nor were there any differences between the groups when the time of first postoperative passage of gas and faeces were compared. In conclusion, the use of metoclopramide in the postoperative period did not result in a quicker return of propulsive motility in the right or left colon as judged by the radio-opaque markers and serial abdominal radiographs.\nStudy2: The evolution of postoperative ileus after laparoscopic cholecystectomy. A comparative study with conventional cholecystectomy and sympathetic blockade treatment. Our study is prompted by the arrival of laparoscopic cholecystectomy in connection with the evolution of postoperative ileus (PI) and by its avoidance of the intraabdominal handling implied in conventional cholecystectomy. With this aim a prospective, controlled, randomized, and blind clinical trial was designed using 100 patients divided into five groups (n = 20): I, conventional cholecystectomy (CC): II, CC+injection of 20 ml bupivacaine 0.5% into the mesentery root; III, CC + 7.5 mg propranolol i.v. and 0.5 mg neostigmine s.c., postoperatively until the first defecation; IV, II+III; and V, laparoscopic cholecystectomy. The shortest period of PI was observed in group V. This period increases notably in group IV (53 h), group II (72 h), and group III (84 h) relative to the control group with (89 h). This reduction in PI time runs parallel with an improvement in the patient's general state of well-being. We concluded that after laparoscopic cholecystectomy PI is nonexistent. Furthermore, this study confirms the correlation between the avoidance of intraabdominal manipulation and the evolution of postoperative ileus.\nStudy3: Small bowel motility following major intra-abdominal surgery: the effects of opiates and rectal cisapride. Human small bowel motility is altered after laparotomy. Opiate analgesia is a possible cause of these alterations, and cisapride is a potential therapy. Continuous proximal small bowel manometry was performed for up to 92 hours in 23 patients after major intra-abdominal surgery. They were treated with rectal cisapride (30 mg three times daily) or placebo until the clinical resolution of ileus. Small bowel manometry was performed for 30 hours in 5 volunteers receiving 1 mg/kg meperidine over 3 hours. Phase III activity was present within 3 hours of the end of surgery in all patients. Initially, the migrating motor complex (MMC) period was markedly reduced (mean, 22 minutes) but gradually increased. Phase II activity was absent until a median of 40 hours had elapsed. Phase III contractile amplitude was markedly attenuated in the jejunum, in contrast to that in the duodenum, presumably as a result of dilatation and/or altered tone, increasing to normal by 72 hours. In the volunteer group, although the MMC period was reduced by meperidine, it remained significantly greater than that of the placebo patient group for approximately 48 hours and phase II was reduced but not eliminated. Cisapride induced some changes in motor activity but did not accelerate the recovery of normal motility. Clinical outcome, assessed by the return of bowel sounds and passage of flatus, was accelerated by cisapride, but the trend was not significant (P = 0.11). This is the first published study using prolonged manometry to show the gradual evolution of small bowel motor activity after major intra-abdominal surgery. The findings suggest that surgery decreases the MMC period to the equivalent of the absolute refractory period, thereby eliminating phase II, which returns as the MMC period lengthens. Cisapride, at the dosage given, confers only modest benefit.\nStudy4: Modulation of the adrenergic system in the treatment of postoperative bowel atonia. Sympathetic hyperactivity is considered to be the most important factor in the development of postoperative bowel atonia. In a double-blind study we evaluated the gut motor effects of dihydroergotamine, which predominantly acts as a sympatholytic agent in the gastrointestinal tract. Forty-six patients undergoing cholecystectomy received either 0.5 mg dihydroergotamine + 5000 U heparin or 5000 U heparin alone (controls) twice daily in a randomized order starting on the morning of the operation. The first postoperative bowel movement occurred 57 +/- 4 h (means +/- SEM) after operation in the patients receiving dihydroergotamine, compared with 102 +/- 4 h in the control patients (p less than 0.001). Electromyography performed in the stomach and upper small bowel on the 3rd postoperative day showed an increase in the number of activity fronts of the interdigestive migrating motor complex and in the duration of spike activity under the influence of dihydroergotamine compared with the controls (p less than 0.001). It is concluded that dihydroergotamine stimulates depressed gut motility after abdominal surgery and that sympatholysis is the likely mechanism of action.\nStudy5: Treatment of postoperative paralytic ileus by intravenous lidocaine infusion. The effects of continuous intravenous infusion of lidocaine on postoperative paralytic ileus in cholecystectomized patients was investigated in this double-blind study. An infusion of lidocaine (3 mg/min, n = 15) or an infusion of an equal volume of saline (n = 15) was started 30 min before induction of anesthesia and continued for 24 h after surgery. Postoperative colonic motility was evaluated by radiopaque markers and serial abdominal radiographs. A record was kept of the first passage of gas and feces. Results showed significantly earlier return of propulsive motility in the colon of lidocaine-treated patients. Radiopaque markers in the lidocaine group were propelled significantly earlier from the cecum/ascending colon to the transverse colon (P less than 0.05) and appeared significantly earlier in the descending colon (P less than 0.05) and the rectosigmoid colon (P less than 0.05) than in saline-treated patients. Despite the fact that the mean time for postoperative defecation occurred 17 h earlier in lidocaine-treated patients, differences between the groups were not statistically significant--a fact due, perhaps, to great individual variations in defecation habits. The time to first passage of gas, a variable representative of changes in anorectal or colonic tone rather than propagative motility, also did not differ significantly between the groups. No adverse reactions to lidocaine were reported. The results suggest that continuous intravenous infusion of lidocaine during the first postoperative day shortens the duration of paralytic ileus in the colon after abdominal surgery. Suppression of inhibitory gastrointestinal reflexes by reduction of postoperative peritoneal irritation is suggested as the mechanism of action.\nStudy6: Prokinetic effect of erythromycin after colorectal surgery: randomized, placebo-controlled, double-blind study. Nausea and vomiting three to seven days after an elective operation on the colon and rectum remain a persistent clinical problem. Erythromycin, a safe, inexpensive drug that stimulates intestinal motilin receptors, has previously been shown to accelerate gastric emptying significantly after upper gastrointestinal surgery. We aimed to evaluate the effect of postoperative intravenous erythromycin on postoperative ileus in patients undergoing elective surgery for primary colorectal cancer. Between May 1998 and April 1999, 150 patients undergoing primary resection of colon or rectal cancer were enrolled in this prospective, randomized, placebo-controlled trial. One hundred thirty-four patients completed the study. Patients were excluded if they had extensive metastatic disease, were taking medications known to interact with erythromycin, or if they required an ileostomy. Patients received either 200 mg of intravenous erythromycin or placebo every six hours. Clinical endpoints were recorded and continuous end-points are presented as mean +/- standard deviation. There were no significant complications related to erythromycin. The erythromycin (n = 65) and placebo (n = 69) groups were comparable regarding demographic and operative factors. The erythromycin group had a slightly shorter length of time to passage of flatus (4.1 +/- 1.3 vs. 4.4 +/- 1.1 days; P = 0.03). There was no significant difference between erythromycin and placebo in time to first solid food (5.6 +/- 1.9 vs. 5.4 +/- 1.8 days), time to first bowel movement (5.2 +/- 1.9 vs. 5.4 +/- 1.3 days), or time to discharge from hospital (7.5 +/- 2.0 vs. 7.6 +/- 2.8 days). There was no difference in the rate of clinically significant nausea (26 vs. 26 percent; P = 0.99), vomiting (17 vs. 16 percent; P = 0.88), or nasogastric tube placement (9 vs. 7 percent; P = 0.68). Erythromycin does not seem to alter clinically important outcomes related to postoperative ileus in patients undergoing resection for colorectal cancer.\nStudy7: Does pantothenic acid accelerate the return of bowel motility in post-operative patients? nan\nStudy8: Beta-adrenoceptor blockade in the treatment of postoperative adynamic ileus. Abdominal trauma, such as surgery and peritonitis, leads to inhibition of intestinal motility, partly mediated by alpha- and beta-adrenoceptors. To investigate the effect of nonselective beta-blockade on adynamic ileus, propranolol was compared with placebo in the postoperative course after elective colonic surgery in a double-blind randomized study. Ten patients received 4 mg propranolol intravenously twice daily, and ten received 10 mg intravenously twice daily. Nineteen patients received placebo. The time to first passage of stool was 110 +/- 9 h in the placebo group and 82 +/- 11 h in the 4-mg propranolol group. In the 10-mg propranolol group, the time was 79 +/- 8 h. The difference between the placebo-treated group and the propranolol-treated groups was significant (p less than 0.01). The effect of propranolol was most marked in older patients and after surgery on the distal colon. In patients older than 60 years the time to first stool in the placebo group was 127 +/- 13 h (n = 8), compared with 73 +/- 8 h (n = 11) in the propranolol group (p less than 0.01). In patients who had undergone surgery on the distal colon the time to first stool was 125 +/- 13 h (n = 8) in the placebo group and 76 +/- 8 h (n = 11) for propranolol (p less than 0.01). Adverse effects on the respiratory or cardiovascular system were not seen during medication. It is concluded that propranolol shortens the period of adynamic ileus after colonic surgery.\nStudy9: Treatment of postoperative paralytic ileus with cisapride. The effect of cisapride on postoperative colonic motility was studied in 40 patients undergoing cholecystectomy under randomized, double-blind conditions. The patients received 10 mg of cisapride or placebo by intravenous injection starting on the day of surgery and repeated every 12 h until the 3rd postoperative day. The return of propagative motility in the colon was visualized by means of radiopaque markers and serial abdominal radiographs. Cisapride induced a significantly earlier return of propulsive motility in the right colon, as indicated by the propagation of markers from the ascending colon to the transverse colon (p less than 0.05). Radiopaque markers reached the descending colon (p less than 0.05) and the rectosigmoid colon (p less than 0.05) significantly earlier in the cisapride group than in controls. The first passage of feces occurred significantly earlier in cisapride-treated patients than in controls (p less than 0.05). The first passage of gas after surgery did not differ significantly between the groups. Our results suggest that cisapride can be used to induce earlier return of propagative motility in the colon after major abdominal surgery.\nStudy10: Negative effect of Metoclopramide in postoperative adynamic ileus. A prospective, randomized, double blind study. In a double blind controlled study including 60 patients it was found that Metoclopramide has a negative effect upon the resolution of postoperative adynamic ileus. Metoclopramide causes a delay in the time from operation to the first passage of flatus.\n", + "output": "Conclusions: Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect." + }, + { + "input": "Study1: Furazolidone versus ampicillin in the treatment of traveler's diarrhea. Ninety-four U.S. students who acquired diarrhea in Mexico were treated with furazolidone (47 subjects) or ampicillin (47 subjects) on a double-blind random basis. Of 47 students, 26 (55%) who received furazolidone (100 mg four times daily for 5 days) recovered from illness within 48 h after initiation of therapy, in contrast to 15 of 47 (32%) who received ampicillin (500 mg four times daily for 5 days) (P less than 0.05). Altogether, 74% of students treated with furazolidone and 49% of those receiving ampicillin were well within 72 h (P less than 0.05). When furazolidone was compared with ampicillin, clinical illness was shortened on the average from 65 to 61 h for enterotoxigenic Escherichia coli diarrhea, from 83 to 58 h for shigellosis, from 82 to 51 h for diarrhea unassociated with a detectable agent, and from 72 to 57 h for all cases irrespective of etiology. Although not dramatically effective in the current trial, the broad spectrum of activity of furazolidone is of interest. Because of in vitro activity against Campylobacter strains and known effectiveness in treating giardiasis, furazolidone should be considered in therapy for diarrhea of unknown etiology in certain settings when laboratory processing of stools for etiological agent is not feasible.\nStudy2: Use of azithromycin for the treatment of Campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent. We evaluated the use of azithromycin (500 mg) or ciprofloxacin (500 mg) daily for 3 days for the treatment of acute diarrhea among United States military personnel in Thailand. Stool cultures were obtained and symptoms were recorded on study days 0, 1, 2, 3, and 10. Campylobacter species were the most common pathogen isolated (44 isolates from 42 patients). All Campylobacter isolates were susceptible to azithromycin; 22 were resistant to ciprofloxacin. Among the 42 patients with campylobacter infection, there were 2 clinical and 6 bacteriologic treatment failures in the ciprofloxacin group and no treatment failures in the azithromycin group (P = .021 for bacteriologic failures). Overall, azithromycin was as effective as ciprofloxacin in decreasing the duration of illness (36.9 hours vs. 38.2 hours, respectively) and the number of stools (6.4 vs. 7.8, respectively). Among those not infected with Campylobacter species (n = 30), the duration of illness was 32.9 hours vs. 20.7 hours (P = .03) for the azithromycin and ciprofloxacin groups, respectively. Azithromycin is superior to ciprofloxacin in decreasing the excretion of Campylobacter species and as effective as ciprofloxacin in shortening the duration of illness. Azithromycin therapy may be an effective alternative to ciprofloxacin therapy in areas where ciprofloxacin-resistant Campylobacter species are prevalent.\n", + "output": "Conclusions: Antibiotic treatment is associated with shorter duration of diarrhoea but higher incidence of side-effects. Trials generally do not report duration of post-treatment diarrhoea using time-to-event analyses, and should do." + }, + { + "input": "Study: Sacral nerve stimulation for treatment of refractory urinary urge incontinence. Sacral Nerve Stimulation Study Group. A prospective, randomized study was performed to evaluate sacral nerve stimulation for the treatment of refractory urinary urge incontinence. Primary outcome variables were obtained from voiding diaries. After baseline evaluation candidates who satisfied inclusion criteria were enrolled into the study. Test stimulation results determined eligibility for randomization into a stimulation (treatment) or delay (control) group. The stimulation group included 34 patients who underwent implantation and were followed for 6 months. The delay group comprised 42 patients who received standard medical therapy for 6 months and then were offered implantation. The stimulation group completed a therapy evaluation test (on versus off) after 6 months. At 6 months the number of daily incontinence episodes, severity of episodes and absorbent pads or diapers replaced daily due to incontinence were significantly reduced in the stimulation compared to the delay group (all p<0.0001). Of the 34 stimulation group patients 16 (47%) were completely dry and an additional 10 (29%) demonstrated a greater than 50% reduction in incontinence episodes 6 months after implantation. Efficacy appeared to be sustained for 18 months. During the therapy evaluation test the group returned to baseline levels of incontinence when stimulation was inactivated. Urodynamic testing confirmed that sacral nerve stimulation did not adversely affect voiding function. Complications included implantable pulse generator site pain in 15.9% of the patients, implant site pain in 19.1% and lead migration in 7.0%. Surgical revision was required in 32.5% of patients with implants to resolve a complication. There were no reports of permanent injury or nerve damage. Sacral nerve stimulation is safe and effective in treating refractory urinary urge incontinence.\n", + "output": "Conclusions: In spite of methodological problems, it would appear that some people benefit from implants which provide continuous nerve stimulation. More research is needed on the best way to improve patient selection, carry out the implant, and to find why so many fail. The effectiveness of implants should be tested against other interventions, particularly in people with an overactive bladder." + }, + { + "input": "Study1: A prospective, randomized, controlled trial comparing highly purified hMG with recombinant FSH in women undergoing ICSI: ovarian response and clinical outcomes. To assess the clinical profile and efficacy in assisted reproductive treatment of a new human-derived highly purified (HP) menotropin, we compared HP hMG and recombinant (r) FSHalpha use in ICSI within a prospective, randomized, controlled study. 100 infertile women were treated with HP hMG (50 patients) or rFSHalpha (50 patients). All patients received the same daily gonadotrophin dose (150 IU) following GnRH agonist suppression (long regimen) until more than three follicles >17 mm and estradiol (E(2)) levels >600 pg/ml were reached. Patients were monitored with daily LH, FSH, hCG, estradiol (E(2)), progesterone, and testosterone measurements; and alternate day pelvic ultrasound. Treatment duration (11.1 +/- 0.4 versus 12.9 +/- 0.5 days, P < 0.05) and gonadotrophin dose (22.4 +/- 1.0 versus 27.0 +/- 1.5 ampoules, P < 0.05) were lower in the HP hMG group. Conversely, peak pre-ovulatory E(2) (1342 +/- 127 versus 933 +/- 109 pg/ml, P < 0.005); and area under the curve of E(2) (3491 +/- 350 versus 2602 +/- 349 pg/ml.day, P < 0.05), immunoreactive serum FSH (65.9 +/- 2.1 versus 48.8 +/- 1.8 IU/l.day, P < 0.001). and hCG (1.7 +/- 0.3 versus 0.0 +/- 0.0 IU/l/day, P < 0.001) during treatment were higher in the HP hMG group. Cycle cancellation rates, transferred embryo number, pregnancy rates per started cycle (30 versus 28%) and per embryo transfer (35 versus 35%) and miscarriage rates (6 versus 6%) were not significantly different. HP hMG treatment was associated with: (i) a more efficient patient response, as reflected by reduced treatment duration and gonadotrophin requirements; (ii) increased serum levels of hCG, E(2), and immunoreactive FSH during treatment; (iii) an ICSI outcome indistinguishable from rFSHalpha.\nStudy2: Recombinant FSH vs. urinary FSH for ovarian stimulation in in vitro fertilization. To compare ovarian stimulation with recombinant FSH (rFSH) vs. urinary FSH (uFSH) in terms of hormonal events within ovarian follicles and the outcome of in vitro fertilization. A prospective randomized comparative study of rFSH (n = 70) vs. uFSH (n = 61) ovarian stimulation. Hormone determinations were serum estradiol (E2) on the day of human chorionic gonadotropin (hCG) administration, and E2, androstenedione (A) and testosterone (T) at the time of follicular aspiration in the follicular fluid and serum. The total dose of gonadotropins required and the length of ovarian stimulation were the same in the 2 groups. In follicular fluid the E2 and the A levels were significantly higher in the rFSH group (3,065 +/- 1,646 vs. 2,368 +/- 1,240 nmol/L, P = .004, and 103.7 +/- 51.6 vs. 89.0 +/- 42.3 nmol/L, P = .042, respectively), whereas A:E2 and T:E2 ratios were significantly lower (39.6 +/- 22.5 vs. 52.3 +/- 59.6, P = .042, and 9.1 +/- 4.7 vs. 17.6 +/- 26.9, P = .006, respectively). Serum hormonal levels, number of oocytes retrieved and pregnancy rates did not differ significantly between the groups. rFSH provides results similar to those of uFSH. rFSH enhances steroidogenesis and provokes different androgen/estrogen ratios than does uFSH without influencing the outcome of in vitro fertilization.\nStudy3: Clinical efficacy of highly purified urinary FSH versus recombinant FSH in volunteers undergoing controlled ovarian stimulation for in vitro fertilization: a randomized, multicenter, investigator-blind trial. To compare the efficacy of highly purified human urinary follicle stimulating hormone (HP-hFSH) versus human recombinant follitropin-alpha (rFSH) in volunteers undergoing controlled ovarian stimulation for IVF. A randomized, controlled, investigator-blind trial. Four assisted reproductive technology centers. One hundred fifty-two IVF patients. Volunteers, aged 18-39, were randomized to HP-hFSH (n = 76) versus rFSH (n = 76) at a starting dose of 300 IU in down-regulated cycles. Number of oocytes, clinical pregnancy rate, and live birth rate with HP-hFSH versus rFSH. The total IU of gonadotropin used did not differ between the two groups. There was no difference in number of oocytes retrieved with HP-hFSH (mean = 16.3) compared with rFSH (mean = 17.1), confidence interval (CI) of difference = -3.79 to +2.18. Clinical pregnancy rate, as defined by the presence of a gestational sac, was 48.7% (CI = 37.0%-60.4%) with HP-hFSH versus 44.7% (CI = 33.3%-56.6%) with rFSH (CI of difference = -11.9% to +19.8%). Live birth rate was 38.2% (29 of 76) in both groups (CI = 27.2%-50.0%), for a difference between groups of 0.0% (CI of the difference = -15.4% to +15.4%). There were no statistically significant differences in mean oocyte number, clinical pregnancy rate, or live birth rate between HP-hFSH versus rFSH.\nStudy4: Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques. A prospective, randomized, comparative, assessor-blind study was carried out in two centres to compare the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (u-hFSH HP; Metrodin HP), both administered s.c. in women undergoing ovarian stimulation for in-vitro fertilization including intracytoplasmic sperm injection (ICSI). A total of 235 patients started a long gonadotrophin-releasing hormone agonist protocol: 119 received r-hFSH and 114 received u-hFSH HP (150 IU/day) for the first 6 days. Two patients were excluded from the study because they mistakenly received the incorrect treatment combination. Human chorionic gonadotrophin (HCG; 10000 IU, s.c.) was administered once there was at least one follicle 18 mm in diameter and two others > or = 16 mm. In all, 119 (100%) and 102 (89%) of the patients respectively in the r-hFSH and u-hFSH HP groups achieved the criteria for HCG. The mean numbers (+/- SD) of oocytes recovered (the primary endpoint) were 12.2 +/- 5.5 and 7.6 +/- 4.4 in the r-hFSH and u-hFSH HP groups respectively (P < 0.0001). However, the number of FSH treatment days (11.0 +/- 1.6 versus 13.5 +/- 3.7) and the number of 75 IU ampoules (21.9 +/- 5.1 versus 31.9 +/- 13.4) used were significantly less (P < 0.0001) in the r-hFSH group than in the u-hFSH HP group. In patients treated using ICSI (63 patients in each group), no difference in oocyte maturation was observed. The mean numbers of embryos obtained were 8.1 +/- 4.2 and 4.7 +/- 3.5 (P < 0.0001), in favour of the r-hFSH group. In the majority of patients (96 and 99% respectively) only one or two embryos were replaced (mean 2.0 +/- 0.2 and 1.9 +/- 0.1 respectively) in the r-hFSH and u-hFSH HP groups. The clinical pregnancy rates per started cycle and per embryo transfer were 45 and 36%, and 48 and 47%, respectively in the r-hFSH and u-hFSH HP groups (not significant). There were six (5.1%) and two (1.7%) cases of ovarian hyperstimulation syndrome respectively. In conclusion, it was found that r-hFSH was more effective than u-hFSH at inducing multiple follicular development. However, the high rate of low ovarian response in the u-hFSH group compared with our general experience was unexpected. The availability of a gonadotrophin with less inter-batch variation would be beneficial for clinicians. r-hFSH seems to fulfil such a requirement.\nStudy5: Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. On behalf of The Feronia and Apis study group. This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F than with Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F had a higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F is clearly more effective than Metrodin HP in inducing multifollicular development.\nStudy6: Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome. To investigate possible differences between using recombinant FSH (rFSH) and hMG for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles. Parallel group design. Prospective, randomized clinical study. A tertiary care infertility clinic. A total of 578 patients of our IVF/ICSI routine were recruited. Treatment with hMG was used for 282 patients (282 cycles), whereas 296 patients (296 cycles) were treated with rFSH. The number of cycles leading to an embryo transfer were 248 and 259, respectively. Primary: clinical pregnancy rate. Secondary: treatment days, total dose of gonadotropin administered, number of oocytes retrieved, number of mature oocytes, and embryo quality. Of the cycles with embryo transfer, the pregnancy rates were 30.1% and 32.3% in the rFSH and the hMG groups, respectively. This difference is not statistically significant (P=0.798). Treatment with rFSH resulted in a significantly higher number of recovered oocytes compared with the hMG group but was also associated with a higher number of ampoules needed to reach the criterion for hCG administration. No significant differences were found with regard to the number of mature oocytes, the number of treatment days, and the embryo quality. In terms of the clinical pregnancy rate, no significant differences between the two stimulation regimens can be stated.\nStudy7: A prospective, randomized, assessor-blind, multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization. Urinary follicle stimulating hormone (FSH) is being used for the treatment of human infertility. Recently, FSH manufactured by means of recombinant DNA technology with a much higher purity (> 99%) has become available. A prospective, randomized, assessor-blind, multicentre (n = 18) study was conducted in infertile women undergoing in-vitro fertilization comparing recombinant FSH (Org 32489, Puregon) and urinary FSH (Metrodin). Eligible subjects were randomized (recombinant versus urinary FSH = 3:2) and pretreated with buserelin for pituitary suppression. FSH was given until three or more follicles with a diameter of at least 17 mm were seen. After oocyte retrieval, fertilization routines were applied according to local procedures. No more than three embryos were replaced. In all, 585 subjects received recombinant FSH and 396 urinary FSH. Significantly more oocytes were retrieved after recombinant FSH treatment (mean adjusted for centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancy rates per attempt and transfer in the recombinant FSH group were 22.17 and 25.97% respectively, and in the urinary FSH group, 18.22 and 22.02% respectively (not significant). Ongoing pregnancy rates including pregnancies resulting from frozen-thawed embryo cycles were 25.7% for recombinant and 20.4% for urinary FSH (P = 0.05). Compared to urinary FSH, the total dose of FSH was significantly lower with recombinant FSH (2138 versus 2385 IU, P < 0.0001) in a significantly shorter treatment period (10.7 versus 11.3 days, P < 0.0001). No clinically relevant differences between recombinant and urinary FSH were seen with respect to safety variables. It is concluded that recombinant FSH (Puregon) is more effective than urinary FSH in inducing multifollicular development and achieving an ongoing pregnancy.\nStudy8: Comparison of recombinant and urinary follicle-stimulating hormone preparations in short-term gonadotropin releasing hormone agonist protocol for in vitro fertilization-embryo transfer. To compare the efficiency and efficacy of two recombinant human FSH (r-FSH) and urinary (u-FSH) preparations in patients undergoing superovulation for IVF-ET using a short-term gonadotropin releasing hormone agonist (GnRH-a) (Triptorelin) protocol. A total of 88 women undergoing IVF-ET were included in this prospective study. They were randomized to receive u-FSH (150 IU/d), follitropin-alpha (100 IU/d), or follitropin-beta (100 IU/d) for 2 days, and dosages were subsequently adjusted according to the ovarian response. The FSH dose required for the overall stimulation was significantly lower in patients treated with r-FSH than in those treated with u-FSH while serum FSH values were higher in the latter group. There were no statistically significant differences in ovarian response and IVF outcome between r-FSH preparations. Recombinant FSH preparations have a higher efficiency than urinary ones in patients undergoing IVF-ET using a short-term GnRH-a protocol. In this situation, the two recombinant follitropins have comparable effectiveness.\n", + "output": "Conclusions: Clinical choice of gonadotrophin should depend on availability, convenience and costs. Differences between urinary gonadotrophins were considered unlikely to be clinically significant. Further research on these comparisons is unlikely to identify substantive differences in effectiveness or safety." + }, + { + "input": "Study1: A double-blind crossover trial of Oral Balance gel and Biotene toothpaste versus placebo in patients with xerostomia following radiation therapy. Following therapeutic irradiation of the head and neck, patients with profound xerostomia have complaints associated with oral dryness, effects upon use of oral prosthesis, speech, and taste. In addition, xerostomia may lead to risk of oral infections and rampant demineralization of teeth. The use of topical Oral Balance gel and Biotene toothpaste (Laclede Professional Products, Gardena, CA) versus carboxymethylcellulose gel and commercial toothpaste applications was assessed in a 2-week double-blind, crossover design. The palliative effects of Oral Balance gel and Biotene toothpaste were superior to the effects of a placebo. No effect on oral colonization by Candida species and cariogenic oral microflora was seen with use of the topical agents.\nStudy2: Randomized-controlled trial: effect of a reservoir biteguard on quality of life in xerostomia. To assess the effect of a reservoir biteguard for artificial saliva on the oral health-related quality of life of patients with xerostomia. Double-blind randomized placebo-controlled trial among 86 adults with xerostomia. Study group received the trial biteguard. Control group received a conventional biteguard. Outcomes were number of impacts and total scores as recorded by oral impacts on daily performances (OIDP). At 1-month follow up 84 people remained in the trial. The median number of impacts in the study and control groups was 3 and 4 respectively. The median total score was 6 and 12 respectively. In ANCOVA receipt of the reservoir biteguard reduced the number of impacts recorded by OIDP but there was no difference in the total score. Reservoir biteguards improved the quality of life of people with xerostomia by reducing the number of impacts on daily life.\nStudy3: Effects of a betaine-containing toothpaste on subjective symptoms of dry mouth: a randomized clinical trial. Our aim was to study the effects of mildly flavoured sodium lauryl sulphate (SLS)-containing and detergent-free toothpastes with and without betaine (BET) on subjective symptoms of dry mouth in a randomised clinical trial. BET is an osmoprotectant that reacts with molecules to supply the surface with a water coating that protects cells from surfactants. Twenty-seven xerostomic patients and 18 healthy controls took part in the randomised, double-blind clinical trial with a crossover design. Three mildly flavoured toothpastes: (1) 4% BET, (2) 1% SLS and 4% BET, and (3) 1% SLS were used for six weeks each. The reference or washout paste contained neither SLS nor BET. The subjects' dental appointments were at the beginning of the trial and before and after the use of each toothpaste. At each appointment, the subjects were interviewed about subjective sensations of dry mouth (Visual Assessment Scoring (VAS) Index). The subjects did not report any adverse effects in connection with the use of the toothpastes. The VAS scores for lip dryness and eating difficulties were significantly lower for the BET paste (lip dryness: BET6) in a greater proportion of subjects in the misoprostol (n = 18, 81.8%) and dinoprostone (n = 14, 66.7%) groups compared with the GTN group (n = 11, 55%). In subjects with a severely unfavorable cervix (Bishop score 0.05). The hematocrit, the reticulocyte and the ferritin values were similar in both the groups at the end of the therapy. Under the neonatal intensive care circumstances of developing countries where blood volumes needed for laboratory analysis are still very high, phlebotomy losses can not be avoided. Thus early erythropoietin and iron therapy at these doses are not effective in decreasing the need for transfusion and induction of endogenous erythropoiesis.\nStudy6: Oral iron is sufficient for erythropoietin treatment of very low birth-weight infants. The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3-week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8-7.2 mg/l to 10.5-11.3 mg/l. In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron.\nStudy7: Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity. The effectiveness of recombinant human erythropoietin (r-HuEpo) in raising haemoglobin concentrations in very low birthweight infants was examined in a randomised multicentre study. Twenty nine 'healthy' appropriate for gestational age infants with birth weights 900-1400 g entered the study at 3 weeks of age. All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age. Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l. Fourteen infants were randomised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7; 15 infants served as controls. After one week reticulocyte and haemoglobin concentrations were significantly higher in the r-HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants. No adverse effects were associated with the treatment. In stable very low birthweight infants with optimal iron and protein intakes, moderate dose r-HuEpo can produce significant gains in red cell production that may be clinically useful.\nStudy8: Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g. To investigate whether recombinant erythropoietin (rhEPO) reduces the need for transfusion in extremely low birth weight (ELBW) infants (birth weight 500-999 g) and to determine the optimal time for treatment. In a blinded multicenter trial, 219 ELBW infants were randomized on day 3 to one of 3 groups: early rhEPO group (rhEPO from the first week for 9 weeks, n = 74), late rhEPO group (rhEPO from the fourth week for 6 weeks, n = 74), or control group (no rhEPO, n = 71). All infants received enteral iron (3-9 mg/kg/day) from the first week. The rhEPO beta dose was 750 IU/kg/week. Success was defined as no transfusion and hematocrit levels never below 30%. Success rate was 13% in the early rhEPO group, 11% in the late rhEPO group, and 4% in the control group (P =.026 for early rhEPO versus control group). Median transfusion volume was 0.4 versus 0.5 versus 0.7 mL/kg/day (P =.02) and median donor exposure was 1.0 versus 1.0 versus 2.0 (P =.05) in the early rhEPO group, the late rhEPO group, and the control group, respectively. Infection risk was not increased and weight gain was not delayed with rhEPO beta. Early rhEPO beta treatment effectively reduces the need for transfusion in ELBW infants.\nStudy9: Effects of recombinant human erythropoietin in infants with very low birth weights. Anaemia of prematurity, a postnatal fall in haemoglobin concentration and haematocrit, is particularly common in those born at less than 32 weeks of gestation. Experimental and clinical data implicate inadequate erythropoietin production as an important reason. In this study recombinant human erythropoietin (r-HuEpo) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions. Premature infants (birth weight < or = 1250 g and gestational age < or = 32 weeks), who were likely to need transfusions, were randomly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo (200 U; n = 12) or placebo (n = 12), three times weekly. All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day. Treatment was started in the third week of life. Reticulocyte counts were significantly raised (P < 0.05) in the group treated with r-HuEpo at the end of treatment. The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment. There were no toxic effects attributable to r-HuEpo. The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte transfusions.\nStudy10: Double blind trial of recombinant human erythropoietin in preterm infants. Twenty four infants between 27 and 33 weeks' gestation were recruited into a double blind study to investigate the use of recombinant human erythropoietin (r-HuEpo) for the prevention of anaemia of prematurity. Between 50 and 150 U of r-HuEpo (n = 16) or placebo was administered subcutaneously twice a week from 7 days of age until discharge. There was a significant increase in the reticulocyte count in infants receiving r-HuEpo sustained from the second week of treatment until discharge compared with placebo. There was a reduction in the number of transfusions required in the r-HuEpo group with only 47% requiring a transfusion compared with 87% in the placebo group. During treatment with r-HuEpo there was a significant rise in the red cell folate concentration, a significant fall in the ferritin concentration, and a significantly higher percentage of haemoglobin F at discharge suggesting active erythropoiesis. The study provides strong evidence for the efficacy of r-HuEpo in stimulating erythropoiesis and reducing the requirement for transfusions for anaemia of prematurity.\n", + "output": "Conclusions: Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant but not the total volume of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes. Further research of the use of late EPO treatment to prevent donor exposure is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment." + }, + { + "input": "Study: The test of time: predictors and effects of duration in youth mentoring relationships. The effects and predictors of duration in youth mentor relationships were examined. The study included 1,138 young, urban adolescents (Mean age 12.25), all of whom applied to Big Brothers Big Sisters programs. The adolescents were randomly assigned to either the treatment or control group, and administered questions at baseline and 18 months later Adolescents in relationships that lasted a year or longer reported the largest number of improvements, with progressively fewer effects emerging among youth who were in relationships that terminated earlier. Adolescents who were in relationships that terminated within a very short period of time reported decrements in several indicators of functioning. Older adolescents, as well as those who had been referred for services or had sustained emotional, sexual or physical abuse, were most likely to be in early terminating relationships, as were married volunteers aged 26-30 and those with lower incomes. Several dyadic factors were also found to be related to earlier terminations, including race, gender, and relationship quality.\n", + "output": "Conclusions: All four RCTs were in the US, and included \u201cdeprived\u201d and mostly minority adolescents. Participants were young (in two studies age 12, and in two others 9-16). All students at baseline were non-users of alcohol and drugs. Two RCTs found mentoring reduced the rate of initiation of alcohol, and one of drug usage. The ability of the interventions to be effective was limited by the low rates of commencing alcohol and drug use during the intervention period in two studies (the use of marijuana in one study increased to 1% in the experimental and to 1.6% in the control group, and in another study drug usage rose to 6% in the experimental and 11% in the control group). However, in a third study there was scope for the intervention to have an effect as alcohol use rose to 19% in the experimental and 27% in the control group.\u00a0The studies assessed structured programmes and not informal mentors." + }, + { + "input": "Study1: Treatment of chronic rhinosinusitis with high-dose oral terbinafine: a double blind, placebo-controlled study. To evaluate antifungal terbinafine in patients with chronic rhinosinusitis. Randomized, double-blind, placebo-controlled multicenter pilot study. Fifty-three adults with chronic rhinosinusitis received terbinafine 625 mg/day (n = 25) or placebo (n = 28) once daily for 6 weeks. Sinus secretions were collected at screening for mycology. Computed tomography was graded for extent of opacification at baseline and at week 6 using a modification of the Lund-Mackay scoring system. Patients recorded rhinosinusitis symptoms on a visual analogue scale and completed the Rhinosinusitis Disability Index. Positive fungal cultures were found in 41 of 53 patients (17 terbinafine, 24 placebo). (Two subjects from the Terbinafine group and one subject from the control group had no week 6 data). The mean opacification scores pre- and posttreatment for the entire study group improved from 24.2 to 22.5 in placebo (n = 26) and from 26.3 to 24.2 in terbinafine group (n = 23). The least squares means for percent change from baseline (SE) were -6.0 (8.7) for placebo compared with -7.2 (8.1) for terbinafine; 95% confidence interval for treatment difference (-18.9, 21.1); P = .91. Results were similar when only patients with positive fungal cultures were evaluated in the efficacy analysis. Investigator therapeutic evaluations and sinus symptom scores were not significantly different between the two groups at baseline or at treatment completion. Treatment with terbinafine failed to improve the symptoms or radiographic appearance of chronic rhinosinusitis even when nasal irrigation samples were positive for fungus on culture. One consideration is that the fungi isolated were not a major pathologic factor in this cohort. It is also possible that, even at high dose, terbinafine may not have maintained therapeutic levels in the nasal secretions.\nStudy2: Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: a randomized, double-blind clinical trial. Recently, fungal elements were suspected to be the causative agent of chronic rhinosinusitis, and benefits of topical amphotericin B therapy have been reported. The effects of amphotericin B versus control nasal spray on chronic rhinosinusitis were compared in a double-blind, randomized clinical trial. Patients with chronic rhinosinusitis were administered 200 microL per nostril amphotericin B (3 mg/mL) or saline nasal spray 4 times daily over a period of 8 weeks. The response rate, defined as a 50% reduction of pretreatment computed tomography score, was the primary outcome variable. Additional outcome variables included a symptom score, a quality of life score, and an endoscopy score. Before and after treatment, nasal lavages were pretreated with dithiothreitol and examined for fungal elements by PCR and standard culture techniques. Seventy-eight patients were included, and 60 patients finished the study per protocol. In the control group, no positive response (0 of 32) was observed, and 2 of 28 patients responded in the amphotericin B group (P>.2). The symptom scores were distinctly worse after amphotericin B therapy (P <.005). The other parameters investigated did not differ remarkably between the treatment groups. Nasal amphotericin B spray in the described dosing and time schedule is ineffective and deteriorates patient symptoms.\nStudy3: Amphotericin B nasal lavages: not a solution for patients with chronic rhinosinusitis. Chronic rhinosinusitis (CRS) is one of the most common chronic diseases. Recently, it has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of the disease. On the basis of this hypothesis, intranasal treatment with amphotericin B should benefit patients with CRS. Data from 2 uncontrolled and 2 controlled trials are conflicting, however. To clarify the role of intranasal antifungal drugs in the treatment of CRS, we conducted a large, double-blind, placebo-controlled, multicenter study comparing the effectiveness of amphotericin B nasal lavages with placebo. A total of 116 randomly selected patients with CRS were instructed to instill 25 mL amphotericin B (100 microg/mL) or placebo to each nostril twice daily for 3 months. Primary outcomes included a reduction in total visual analog scale (VAS) score and nasal endoscopy score. Secondary outcome measures included peak nasal inspiratory flow, polyp score, quality of life (Short Form-36, Rhinosinusitis Outcome Measure-31), and individual VAS scores. Analysis was based on intention to treat and involved all patients randomly assigned. Mean VAS scores, Short Form-36 and Rhinosinusitis Outcome Measure-31 data, peak nasal inspiratory flow values, nasal endoscopy scores, and polyp scores were similar in both treatment groups at the time of randomization, and no significant differences were observed after 13 weeks of treatment. Amphotericin B nasal lavages in the described dosing and time schedule do not reduce clinical signs and symptoms in patients with CRS. Amphotericin B nasal lavages in the described dosing and time schedule are ineffective and therefore not advised in the treatment of patients with CRS.\nStudy4: Postoperative application of amphotericin B nasal spray in chronic rhinosinusitis with nasal polyposis, with a review of the antifungal therapy. Chronic rhinosinusitis (CRS) affects 1-4% of the adult population. The etiology of this multifactorial, chronic disease, which leads to a significant impairment of the quality of life, often accompanied by nasal polyposis, is not fully understood. In the past decade, it was presumed that the disease, which causes characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an enhanced (but not classical allergic IgE-type) immune response against fungal organisms in the nasal mucus. If this supposition is correct, then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients, and might even reduce the number of recurrent cases. To check on this assumption, we conducted a prospective randomized placebo-controlled trial involving 33 patients, 30 of whom remained in the study throughout. Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006; group A (14 randomly selected patients) were treated with a nasal spray containing 5 mg/ml amphotericin B, while the placebo group B (16 randomly selected patients) received a nasal spray lacking amphotericin B. We evaluated our results with the aid of a modified Lund-Mackay CT score, the SNAQ-11 test (which assesses changes in the symptoms), a quality of life test and endoscopy. The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and 1 year postoperatively. The CT scores of the group A patients 1 year after the operation exhibited wide scattering, without signs of recovery. The CT scores of the group B patients indicated a slight improvement, though this did not prove significant relative to group A. Both the SNAQ-11 test and the quality of life test revealed a significant improvement in each group, but the degrees of change in these tests did not differ significantly between the two groups of patients. The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation. These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in either CT score, clinical symptoms, or quality of life. The more favorable clinical aspects observed in the amphotericin B-treated group during the endoscopic follow-up did not correspond to an improvement in the symptoms. In connection with the conclusions drawn from this study, the authors discuss the controversial data available on the fungal etiology of CRS. They critically analyze the contradictory observations and conclusions of seven recent clinical studies.\n", + "output": "Conclusions: On the basis of this meta-analysis, there is no evidence to support the use of either topical or systemic antifungal treatment in the management of CRS." + }, + { + "input": "Study: Maximizing immunization coverage through home visits: a controlled trial in an urban area of Ghana. A strategy of home visits to maximize children's immunization coverage was implemented in three towns in Ghana. The strategy was tested in town 1 in a controlled trial where clusters of children were allocated to the intervention and control groups. A total of 200 mothers in the intervention group were visited at home by non-health workers and their children were referred to a routine under-fives' clinic. Subsequent home visits targeted at those who failed to complete immunization schedules were made by nurses. After 6 months, coverage had risen from 60% to 85%, which was 20% higher than in the town 1 control group of 219 age-matched children (P < 0.005). A similar home-visiting strategy in a neighbouring town resulted in a rise in coverage from 38% to 91% (n = 55), mainly through home immunizations. Children were more likely to complete the schedule if their fathers were interviewed and participated in the decision to send them to the clinic. Countries with national service programmes can use a home-visiting strategy to supplement and strengthen their routine immunization programmes. A wide range of other community-based primary health care interventions could also be tested and implemented using this methodology.\n", + "output": "Conclusions: Home visits and health education may improve immunization coverage but the quality of evidence is low." + }, + { + "input": "Study1: Effects of 3 analgesic regimens on the perception of pain after removal of femoral artery sheaths. Effective pain management after removal of femoral artery sheaths after percutaneous transluminal coronary angioplasty is highly individualized and requires frequent, accurate assessment and administration of analgesics as needed. To determine which of 3 analgesic regimens is most effective in decreasing patients' perception of pain with the fewest side effects after removal of a femoral artery sheath. 130 adult who had undergone percutaneous transluminal coronary angioplasty and were in an 8-bed cardiac short-stay unit in a 1400-bed acute care hospital. Patients were randomized to receive either intravenous morphine, intravenous fentanyl, subcutaneous lidocaine around the sheath site, or an intravenous placebo before sheath removal. Rescue analgesia (intravenous fentanyl) was made available to all groups. Patients used a visual analog scale to assess pain within 10 minutes before, 1 minute after, and 20 minutes after sheath removal. Pain levels, frequency of side effects, and use of rescue analgesia were compared among groups. Age, sex, number of stents, and frequency of hematomas did not differ significantly among groups. Pain ratings, use of rescue analgesia, and side effects (nausea, vomiting, or vasovagal symptoms) were not significantly different among treatment groups. Ratings of pain were slightly higher immediately after sheath removal in all groups. For most patients, removal of femoral artery sheaths and manual compression for hemostasis are relatively pain-free. Pain scores among patients given analgesia with subcutaneous lidocaine, intravenous morphine, or intravenous fentanyl were not significantly different from pain scores among control patients.\nStudy2: Randomized, controlled study of long-acting local anesthetic (levobupivacaine) in femoral artery sheath management during and after percutaneous coronary intervention. To assess the effect of long-acting local anesthetic (levobupivacaine) in addition to lidocaine for the management of femoral artery sheaths during and after percutaneous coronary intervention (PCI). Femoral artery sheaths are commonly used during PCI. Sheath removal is often delayed after the procedure by which time short-acting local anesthetic agents may no longer be effective. Sixty patients were randomized to either usual care or the administration of local levobupivacaine after PCI. Patients were asked to report their pain experienced on a visual analogue score. Thirty patients received additional levobupivacaine (0.5%) and 30 received standard care. There were no procedural differences between the groups, except that more patients in the control group received intravenous (IV) morphine at the time of sheath removal. There was no difference between the control group and levobupivacaine group in pain scores at the time of sheath insertion. (2.0 +/- 0.4 versus 1.8 +/- 0.3; p = 0.80). Both groups recorded low pain scores while waiting for sheath removal, and the score was slightly (but not significantly) lower in the levobupivacaine group (1.3 +/- 0.2 versus 0.8 +/- 0.2; p = 0.09). Pain scores were lower in the levobupivacaine group during sheath removal 2.2 +/- 0.4 versus 1.1 +/- 0.2; p = 0.02). There were no differences in terms of blood pressure between the groups at any time point. Levobupivacaine reduced the need for IV opiate and provided better analgesia than lidocaine alone in patients undergoing PCI.\nStudy3: Effect of local anesthesia and intravenous sedation on pain perception and vasovagal reactions during femoral arterial sheath removal after percutaneous coronary intervention. There is no consensus with respect to the use of analgesia during femoral arterial sheath removal after percutaneous coronary intervention (PCI). We performed a randomized controlled trial to assess the impact of intravenous sedation and local anesthesia during femoral sheath removal after PCI on patient comfort and the incidence of vasovagal reactions. All patients undergoing PCI whose femoral sheaths were to be removed with assisted manual compression were eligible. Patients were randomized to receive either intravenous sedation (Fentanyl and Midazolam) or local anesthesia (1% lignocaine) infiltrated around the sheath site or both or neither. The primary endpoint of the study was the patients reported worst pain according to a Visual Analogue scale (VAS) after sheath removal. The incidence and predictors of vasovagal reactions during sheath removal and occurrence of vascular complications was also determined. A total of 611 patients were randomized into this study. The mean pain score was highest in the local anesthesia only arm as compared to the sedation only arm, the combined local and sedation arm and the neither sedation or local arm (p=0.001). vasovagal reactions were experienced by 35 patients (5.1%) with the highest percentage in the local anesthesia only group (9.8%). Multivariate logistic regression analysis identified a higher pain score (OR 1.18, 95% CI 1.12-1.24, p=0.001), use of glyceryl trinitrate during sheath removal (OR 9.05, 95% CI 5.06-16.1, p<0.001), a lower body mass index (OR 1.12, 95% CI 1.08-1.18, p=0.009) and the left anterior descending artery as the treated vessel (OR 5.2, 95% CI 3.41-7.87, p<0.001) as independent predictors of the occurrence of a vasovagal reaction. There was no significant difference in vascular complications between the 4 study groups. The routine use of fentanyl and midazolam prior to sheath removal leads to a reduction in pain perception and vasovagal incidence, whilst the routine use of local infiltration during sheath removal should be discouraged as it leads to more pain and a trend to more vasovagal reactions.\n", + "output": "Conclusions: No new studies have been found since the last version of this review and the conclusions therefore remain the same. Intravenous pain regimens and levobupivacaine may have greater efficacy when compared to control for the management of pain related to femoral sheath removal. However, a definitive study is still required because the clinical difference is small. There is no evidence to support the use of subcutaneous lignocaine. There is insufficient evidence to determine if pain relief influences the rate of complications. One new study has been included as a 'study awaiting assessment' as we await further information from the study authors." + }, + { + "input": "Study: Intranasal capsaicin is lacking therapeutic effect in perennial allergic rhinitis to house dust mite. A placebo-controlled study. In a recent placebo-controlled study we demonstrated that capsaicin is an efficacious substance in the treatment of non-allergic non-infectious rhinitis. In this study the therapeutic effect lasted more than 9 months. This effect was not based on modulation of inflammation. To evaluate the effect of repeated application of capsaicin to patients with a nasal allergy to house dust mites (HDM), using the same treatment protocol as recently introduced in the treatment of non-allergic patients. Twenty-six patients with rhinitis, 15 females and 11 males (range: 20-46 years; mean 30.5), allergic to HDM were treated with either capsaicin or placebo in a double-blind, placebo-controlled, parallel group design. Nasal reactivity to HDM expressed as nasal symptoms, albumin and leukotriene levels in nasal lavage fluid and responsiveness to histamine, assessed as symptoms before and 6 weeks after treatment, were used to compare both treatment groups. In addition, visual analogue scales and rhinitis quality of life (RQL) assessment before, 6 weeks after and 3 months after treatment were used as outcome variables. No significant effect of capsaicin on nasal challenge tests with HDM (nasal symptoms, albumin and leukotriene levels), on VAS or RQL outcome 6 weeks or 3 month's after treatment, was demonstrated. Capsaicin did have a small effect on the area of the curve (AUC) of histamine dose response curves (P = 0.03). Desensitization with capsaicin in doses sufficient to control symptoms in patients with severe non-allergic rhinitis is lacking therapeutic effect in perennial allergic rhinitis.\n", + "output": "Conclusions: There is insufficient evidence to assess the use of capsaicin in clinical practice." + }, + { + "input": "Study1: Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group. A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis. From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (< or = 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurrence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features. The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0-21) in the mesalazine b.i.d. group, 32% (95% CI: 16-49) in the mesalazine u.i.d. group, and 47% (95% CI: 29-65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p = 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up. The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.\nStudy2: Use of mesalazine slow release suppositories 1 g three times per week to maintain remission of ulcerative proctitis: a randomised double blind placebo controlled multicentre study. Daily administration of rectal formulations of mesalazine is effective in preventing relapse of ulcerative proctitis. Maintenance of remission with lower doses would be an advantage. The efficacy of mesalazine suppositories (Pentasa) 1 g three times a week v placebo to maintain remission in patients with cryptogenetic proctitis was studied. Ninety five patients with cryptogenetic proctitis were randomised within two weeks of remission to receive for one year or until relapse three suppositories per week of either Pentasa (n = 48) or placebo (n = 47). In the case of a relapse, the patients received one suppository/day. It was found that 25 of 48 subjects v 18 of 47 remained in remission in the mesalazine and placebo groups respectively. The relapse rate was lower in the mesalazine group for the following time intervals: 0-90 days (19% v 38%, p = 0.035), 0-180 days (29% v 54%, p = 0.017), 0-270 days (38% v 60%, p = 0.031), and 0-365 days (48% v 62%, p = 0.18). Treatment of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26 patients in the mesalazine and placebo groups respectively (p = 0.001). Overall, 61% v 28% patients remained in the protocol and were in remission at one year (p = 0.001). Tolerance was good. Mesalazine suppositories 1 g three times a week are effective for preventing relapses of cryptogenetic proctitis. Increasing the dose to 1 g/day is effective in a high proportion of subjects who relapsed.\nStudy3: Intermittent therapy with high-dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis. Sixty patients who had presented recently with a relapse of mild to moderate ulcerative colitis with rectosigmoid involvement were randomly assigned to treatment with either 5-aminosalicylic acid enemas (N = 29) or oral sulfasalazine (N = 31). All patients were in remission, which was documented by clinical, histologic, and endoscopic criteria. Five-aminosalicylic acid treatment was administered on an intermittent schedule, consisting of 4 gm daily for the first seven days of each month; sulfasalazine was given as continuous therapy (2 gm daily as oral tablets). The study period was 2 years. Overall, 9 relapses occurred in the 5-aminosalicylic acid group and 12 occurred in the sulfasalazine group. The actuarial relapse rate at 12 months was 20 percent in the 5-aminosalicylic acid group and 24 percent in the sulfasalazine group; at 24 months, these rates were 37 and 43 percent, respectively. The actuarial relapse curves of the two groups were very similar. The relapse severity was also similar between the two groups. These results show that the authors proposed schedule of maintenance treatment with high-dose 5-aminosalicylic acid enemas is effective in subjects with rectosigmoiditis. This form of intermittent therapy may therefore be proposed for maintaining remission in patients who are refractory to oral and/or rectal treatment with sulfasalazine and steroids or who are intolerant or allergic to sulfasalazine. Treatment with 5-aminosalicylic acid enemas for seven days each month can also constitute an alternative for patients who favor the intermittent schedule over the classic continuous regimen of oral administrations.\nStudy4: Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis. The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission. In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy). Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events. The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.\nStudy5: 5-ASA enema versus oral sulphasalazine in maintaining remission in ulcerative colitis. This prospective trial in patients with left-sided ulcerative colitis evaluated the efficacy and acceptability of biweekly high-dose 5-aminosalicylic acid (5-ASA) enemas (4g/100ml) in maintaining a remission recently induced using daily 5-ASA enemas. Thirty-one patients were randomly assigned, 16 to 5-ASA and 15 to oral sulphasalazine (2g/day), and examined monthly. Sigmoidoscopy was performed \"blind\" at six months or at clinical relapse. Twelve patients on 5-ASA (75%) and nine on sulphasalazine (60%) remained in clinical and endoscopic remission throughout the study (NS), and the survival curve for 5-ASA was better at all points (NS). No patient stopped therapy due to side effects, and all those on 5-ASA chose to continue rectal maintenance therapy after the study. It was concluded that biweekly 5-ASA enemas is at least as effective as oral sulphasalazine in maintaining remission in unselected patients whose remission has been achieve using local therapy.\n", + "output": "Conclusions: The limited data available suggest that rectal 5-ASA is effective and safe for maintenance of remission of mild to moderately active distal UC. Well designed randomized trials are needed to establish the optimal dosing regimen for rectal 5-ASA, to compare rectal 5-ASA with rectal corticosteroids and to identify subgroups of patients who are more or less responsive to specific rectal 5-ASA regimens. The combination of oral and rectal 5-ASA appears to be more effective than either oral or rectal monotherapy for induction of remission. The efficacy of combination therapy for maintenance of remission has not been assessed and could be evaluated in future trials." + }, + { + "input": "Study: Effects of resident-oriented care on quality of care, wellbeing and satisfaction with care. In a resident-oriented care model applied in nursing homes, the residents are assigned to primary nurses. These primary nurses are responsible for the total care of the residents assigned to them. The purpose of the present study, using a pretest, post-test and control group quasi-experimental design, was to evaluate the effects of the implementation of resident-oriented care on the following aspects of quality of care: coordination of care, instrumental aspects, expressive aspects, resident wellbeing and satisfaction with care, and family satisfaction with care. The study was carried out on somatic and psycho-geriatric wards in three nursing homes in the Netherlands. Data were collected by questionnaires, interviews and observations. The results of the study showed that the intervention was partly successful in the experimental group. Some aspects of the resident-oriented care model were not clearly evident. Moreover, the effects on quality-of-care aspects were limited. The results revealed that the 'coordination of care' increased on half of the experimental wards. Furthermore, there was an indication that 'expressive aspects' changed in favour of the experimental wards. The implementation of resident-oriented care had no effect on resident wellbeing and satisfaction or on family satisfaction. Finally, the results are discussed in the light of some methodological limitations that often go together with intervention studies in the real world.\n", + "output": "Conclusions: Apart from two small studies evaluating primary care, no evidence in the form of concurrently controlled trials could be identified. While these two studies generally favour the use of primary care, the research designs of both ITS and CBA studies are considered prone to bias, specifically selection and blinding of participants and assessors. Therefore, these studies should be regarded with caution and there is little clear evidence for the effective use of any specific model of care in residential aged care to benefit either residents or care staff. Research in this area is clearly needed." + }, + { + "input": "Study1: Implementing an intervention to promote colon cancer screening through e-mail over the Internet: lessons learned from a pilot study. Colon cancer screening (CRCS) tests are underused. Multiple CRCS options may confuse patients and lead to inaction. E-mail between patients and physicians may raise awareness about CRCS and allow physicians to answer questions about test options. To develop and implement an electronic intervention, the InterNet LETter (NetLET), to increase interest in and use of CRCS among patients with and without e-mail access at home or work. During 2004-2005, 97 patients over 49 years old were recruited during a clinic visit. Patients with e-mail at home or work were assigned to the private access arm; patients without e-mail but willing to use the public library system were assigned to the public access arm. Within each arm, patients were randomized to the NetLET or control group. The NetLET consisted of a personalized e-mail from the physician reminding the patient to undergo CRCS and providing a link to a webpage with information about CRCS. Control groups were mailed a reminder letter from their physician. All were mailed a fecal occult blood test (FOBT) kit. In the public access intervention group, only 1 of 11 patients viewed the NetLET. In the private access intervention group, 10 of 42 viewed it. Eleven of 42 (26%) private access intervention group participants, and 8 of 35 (23%) private access control group participants returned an FOBT. No public access intervention group patients, but 3 of 9 control group patients, returned an FOBT. We concluded that it was not feasible to implement the NetLET, but reasons for lack of success differed for the private and public access arms.\nStudy2: Using the internet to provide information prescriptions. An information prescription is the provision of specific information to a patient on how to help manage a health problem. The Internet is being used increasingly as a source for information prescriptions, with clinicians directing patients to specific Web sites. As with any health care intervention, patients' lack of compliance is a barrier to the effectiveness of Web-based information prescriptions (WebIPs). WebIPs cannot be helpful if patients do not review the information prescribed for them. The main objective of this study was to quantify the percentage of families who visit a Web site that was specifically prescribed by their physician. In addition, the use of an e-mail reminder was used to determine if it increases the likelihood that families will visit the prescribed Web site. Finally, barriers to accessing the prescribed Web site were identified. Children were eligible if they presented to the pediatric gastroenterology clinic with chronic constipation and/or encopresis and their family had an active e-mail account and access to the Internet in their home. During their clinic visit, physicians instructed families to visit a Web site that provided educational information pertinent to their child's problem. Families were given a form with the Web-site address and a log-in identification number. Two days after their clinic visit, half of the families received an e-mail reminding them to visit the Web site. Families were contacted 1 week after their clinic visit to identify barriers to accessing the Web site. Eighty-three families participated in the study. Of the 83 families, 54 (65%) visited the prescribed Web site within 1 week of their clinic visit. Families who received e-mail reminders were significantly more likely to visit the Web site than families who did not receive an e-mail reminder (77% vs 53%). This difference could not be explained by the type or speed of Internet connection or how frequently they accessed the Internet or e-mail. The most common reasons that families cited for not accessing the Web site were \"I forgot\" and \"I didn't have time.\" Few families cited technical reasons for not accessing the Web site. Almost two thirds of the families given a WebIP logged on to the prescribed Web site. The probability that families would access the site was increased by 45% with an e-mail reminder. Clearly, e-mail prompts improve compliance to WebIPs. As content and treatment programs continue to proliferate on the Web, it is important to identify barriers and solutions to them to improve overall compliance.\n", + "output": "Conclusions: The evidence on the use of email for the provision of information on disease prevention and health promotion was weak, and therefore inadequate to inform clinical practice. The available trials mostly provide inconclusive, or no evidence for the outcomes of interest in this review. Future research needs to use high-quality study designs that take advantage of the most recent developments in information technology, with consideration of the complexity of email as an intervention." + }, + { + "input": "Study1: Early statin therapy restores endothelial function in children with familial hypercholesterolemia. This study was designed to determine whether simvastatin improves endothelial function in children with familial hypercholesterolemia (FH). Endothelial function measured by flow-mediated dilation of the brachial artery (FMD) is used as a surrogate marker of cardiovascular disease (CVD). Adult studies have shown that statins reverse endothelial dysfunction and therefore reduce the risk for future CVD. The study included 50 children with FH (9 to 18 years) and 19 healthy, non-FH controls. Children with FH were randomized to receive simvastatin or placebo for 28 weeks. The FMD was performed at baseline and at 28 weeks of treatment. At baseline, FMD was impaired in children with FH versus non-FH controls (p < 0.024). In the simvastatin FH group, FMD improved significantly, whereas the FMD remained unaltered in the placebo FH group throughout the study period (absolute increase 3.9% +/- 4.3% vs. 1.2% +/- 3.9%, p < 0.05). In the simvastatin FH group, FMD increased to a level similar to the non-FH controls (15.6% +/- 6.8% vs. 15.5% +/- 5.4%, p = 0.958). Upon treatment, the simvastatin FH group showed significant absolute reductions of total cholesterol (TC) (-2.16 +/- 1.04 mmol/l, 30.1%) and low-density lipoprotein cholesterol (LDL-C) (-2.13 +/- 0.99 mmol/l, 39.8%). The absolute change of FMD after 28 weeks of therapy was inversely correlated to changes of TC (r = -0.31, p < 0.05) and LDL-C (r = -0.31, p < 0.05). Our data show significant improvement of endothelial dysfunction towards normal levels after short-term simvastatin therapy in children with FH. These results emphasize the relevance of statin therapy in patients with FH at an early stage, when the atherosclerotic process is still reversible.\nStudy2: Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial. Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men. The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH. One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994. Fourteen pediatric outpatient clinics in the United States and Finland. Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second periods, respectively. Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo. The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development. Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety parameters. Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation. This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin. Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required.\nStudy3: Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. To determine the safety and efficacy of atorvastatin (10 to 20 mg) in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Subjects (n=187) were randomly assigned to 26 weeks of treatment with atorvastatin (10 mg) or placebo. Dosage was increased to 20 mg if LDL cholesterol (LDL-C) levels remained >3.4 mmol/L (130 mg/dL) at week 4. At week 26, subjects received 10 mg of atorvastatin for an additional 26 weeks. Efficacy variables included percent changes in LDL-C, total cholesterol, triglycerides, HDL cholesterol, and apolipoprotein B from baseline to week 26. Atorvastatin caused a highly significant reduction in LDL-C compared with placebo (-40% vs -0.4%, respectively; P<.001). Percent changes at week 26 also significantly favored atorvastatin for total cholesterol (-32% vs -1.5%; P<.001), triglycerides (-12% vs +1.0%; P=0.03), and apolipoprotein B (-34% vs +0.7%; P<.001), with a significantly greater increase in HDL cholesterol with atorvastatin compared with placebo (+2.8% vs -1.8%; P=.02). Atorvastatin was as well-tolerated as placebo. Treatment with atorvastatin for 12 months was effective and safe for pediatric subjects with known familial hypercholesterolemia or severe hypercholesterolemia.\nStudy4: Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia. The present study was designed to evaluate the lipid-altering efficacy, safety, and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia. A total of 54 postmenarchal girls, aged 10 to 17 years, were enrolled in a 24-week, double-blind, randomized, placebo-controlled study. After a 4-week diet/placebo run-in period, patients were randomized to 1 of 2 groups: (1) treatment with diet plus lovastatin 20 mg/day for 4 weeks, followed by diet plus lovastatin 40 mg/day for 20 weeks, or (2) diet plus placebo for 24 weeks. Baseline values of lipids, lipoproteins, and apolipoproteins (apo) were comparable between treatment groups. Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23% to 27%, total cholesterol by 17% to 22%, and apo B by 20% to 23% at weeks 4 and 24, respectively. Between-treatment group differences were not statistically significant for triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or apo A-I. Lovastatin was generally safe and well tolerated. There were no clinically significant alterations in vital signs (blood pressure and pulse rate), anthropomorphic measurements (height, weight, and BMI), hormone levels (luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, estradiol, and cortisol), menstrual cycle length, or tests of liver and muscle function. Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia.\nStudy5: Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia. Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years. Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands. After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108). The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels. Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], -0.010 [0.048] mm; P =.049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P =.28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P =.02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (-24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.\nStudy6: Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. The safety, tolerability, and efficacy of a 12-wk treatment with pravastatin, 5, 10, and 20 mg/d, was evaluated in 72 children with heterozygous familial hypercholesterolemia (FH) in a double-blind, randomized and placebo-controlled study. The results show that pravastatin was well tolerated and that adverse events were mild and equally distributed among the three treatment groups. Plasma total and LDL cholesterol levels were significantly reduced in all pravastatin treatment groups, in comparison with the control group; -24.6% (-28.1 to 21.0) and -32.9% (-37.0 to -28.6), for mean change and 95% confidence interval, respectively. In four children plasma LDL cholesterol levels were reduced within normal limits for sex and age. HDL cholesterol increased in the pravastatin 20-mg group, +10.8% (+3.4 to +18.8), whereas plasma apo B100 and very LDL (VLDL) cholesterol levels were reduced within all pravastatin-treated groups -26.8% (-31.2 [corrected] to -21.7) and -24.5% (-35.0 to -12.3). These data show that short-term pravastatin treatment of children with FH is safe and effective, although long-term dose titration studies with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors need to be performed, to reduce plasma LDL cholesterol levels below a predefined level. The results of these studies have to be awaited before new treatment strategies are to be considered in these children.\nStudy7: Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin. A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia (heFH). A total of 173 heFH children (98 boys and 75 girls) were included in this study. After a 4-week diet/placebo run-in period, children with heFH were randomized to either simvastatin or placebo in a ratio of 3:2. Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d. During a 24-week extension period, the patients continued to receive simvastatin (40 mg) or placebo according to their assignment. After 48 weeks of simvastatin therapy, there were significant reductions of LDL cholesterol (-41%), total cholesterol (-31%), apolipoprotein B (-34%), VLDL cholesterol (-21%), and triglyceride (-9%) levels. HDL cholesterol and apolipoprotein A-I levels were increased by 3.3% and 10.4%, respectively (not significant). No safety issues became evident. Except for small decreases in dehydroepiandrosterone sulfate compared with placebo, there were no significant changes from baseline in adrenal, gonadal, and pituitary hormones in either treatment group. Simvastatin significantly reduced LDL cholesterol, total cholesterol, triglyceride, VLDL cholesterol, and apolipoprotein B levels and was well tolerated in children with heFH. There was no evidence of any adverse effect of simvastatin on growth and pubertal development. Therefore, simvastatin at doses up to 40 mg is a well-tolerated and effective therapy for heFH children.\n", + "output": "Conclusions: Statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. It seems to be safe in the short term but long-term safety is unknown. Children treated with statins should be carefully followed up by their pediatricians. Large long-term randomized controlled trials are needed to establish the long-term safety of statins in children." + }, + { + "input": "Study1: Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B. To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia. A randomized, controlled, multicenter trial. 30 hematologic units in tertiary care or university hospitals. 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia. Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours. An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B. Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01). Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.\nStudy2: Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B. Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis. Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity. Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02). At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.\nStudy3: Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature. We conducted a prospective, randomized, multicenter study comparing fluconazole and amphotericin B in the treatment of candidal infections. One hundred and sixty-four patients (60 of whom were neutropenic) with documented or presumed invasive candidiasis were assigned to treatment with either fluconazole (400 mg daily) or amphotericin B (25-50 mg daily; 0.67 mg/kg daily for neutropenic patients). Clinical response and survival rates were assessed at 48 hours, after 5 days, and at the end of therapy. Overall response rates to fluconazole and amphotericin B were similar (66% and 64%, respectively). There were no differences in response as related to site of infection, pathogen, time to defervescence, relapse, or survival rates between the groups. Adverse effects were more frequent with amphotericin B (35%) than with fluconazole (5%; P < .0001). The results of this study confirm that fluconazole is as effective as but better tolerated than amphotericin B in the treatment of candidal infections.\nStudy4: Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group. Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p. o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively. Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.\nStudy5: Early empiric antifungal therapy of infections in neutropenic patients comparing fluconazole with amphotericin B/flucytosine. We compared the efficacy and tolerability of fluconazole (FCA) with amphotericin B/flucytosine (ABF) in neutropenic patients with haematological malignancies. Antifungal therapy started on day 4 when fever was unresponsive to antibiotics or on day 1 together with the antibiotics, if there was evidence of mycosis. If patients did not respond to FCA after 7 days they switched to ABF. 98 patients, 51 FCA and 47 ABF were included in the study. Response to fever was achieved in 28/51 FCA patients and in another 16 after switching to ABF. So in overall 44/51 (86.2%) of the FCA and 37/47 (78.8%) of the ABF group defervescence was observed. 46 patients (21 FCA, 25 ABF) developed radiological signs of pneumonia. Resolution of infiltrates was achieved in 5/21 FCA and 20/25 ABF patients, and another 10 of 15 initially not responding patients showed regression when switched to ABF, 5 of these had highly suspected aspergillosis. Adverse events occurred in 19.6% of FCA and 97.9% of ABF patients. In conclusion fluconazole and amphotericin B/flucytosine seem to be equally effective. In view of its lower toxicity fluconazole may be preferred as first line empiric antifungal agent, but in case of nonresponse, pneumonia or aspergillosis it may be replaced by amphotericin B combined with flucytosine.\nStudy6: Management of fungal infection in neutropenic patients with fluconazole. Fluconazole is a new orally absorbed antifungal azole which is effective in the treatment of mucosal and systemic infections caused by Candida, cryptococci and other fungi. In view of its favourable efficacy, safety and pharmacokinetic profile it was considered appropriate to evaluate its use prophylactically in patients undergoing a period of neutropenia. Two hundred and forty-eight patients receiving chemotherapy and/or bone marrow transplantation for the treatment of acute leukaemia, lymphoma or aplastic anaemia, and expected to be rendered temporarily neutropenic, have been entered into an ongoing multicentre comparative clinical study to compare the prophylactic efficacy of 50 mg daily oral fluconazole with that of widely used regimens of oral polyenes. The incidence of suspected fungal infection was less in the fluconazole group (27%) than in the polyene group (45%), the difference being statistically significant (P less than 0.05). Only one of the suspected infections in the fluconazole group was confirmed mycologically compared with 17 in the polyene group. Fluconazole prophylaxis was well tolerated and it therefore offers a promising new approach to the management of fungal infection in the neutropenic patient. Further studies are warranted to define the optimum dosage for use in this situation.\nStudy7: A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia. Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated. We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection. Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia. These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.\nStudy8: Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial. Amphotericin B, despite its intrinsic servere toxicity, is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy. The aim of this study was to show whether fluconazole was as effective as, and less toxic than, amphotericin, with no effort made to compare the antifungal activity of the two drugs. A group of 112 persistently febrile (> 38 degrees C) and granulocytopenic (< 1000 cells/mm3) cancer patients, not receiving any absorbable antifungal antibiotic for prophylaxis, with a mean age of 27 years (range 1-73 years), undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy, were randomised to receive either fluconazole (6 mg/kg/day up to 400 mg/day) or amphotericin B (0.8 mg/kg/day) as empirical antifungal treatment. Patients were required to have normal chest X-rays at randomisation, no previous history of aspergillosis and negative surveillance cultures for Aspergillus. The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients (75%) in the fluconazole group and in 37 of 56 (66%) in the amphotericin B group (P = 0.4). Duration of therapy was 6 days (95% CI = 4-8 days) in both groups. Death occurred in 3 patients (5%) in the fluconazole and in 2 (4%) in the amphotericin B group. No fungal death was documented in either group. Adverse events developed in 18 of 56 patients (32%) in the fluconazole group and in 46 of 56 (82%) in the amphotericin B group (P < 0.001). In the amphotericin B group, 5 patients had treatment discontinued because of toxicity, versus none in the fluconazole group, a difference which approached statistical significance (P = 0.06). This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B, in pragmatical terms and for this specific indication. However, numbers are too small to allow definitive conclusions about efficacy, and the use of fluconazole for this indication remains experimental. Future studies should try to identify patients more at risk of fungal infections, with the aim of individualising antifungal approaches.\nStudy9: Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation. Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation. Copyright 2002 Wiley-Liss, Inc.\n", + "output": "Conclusions: Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent." + }, + { + "input": "Study1: A randomized double-blind controlled trial of naftidrofuryl in acute stroke. There is evidence to support the use of naftidrofuryl in acute stroke with claims of increased recovery, reduced fatality and reduced bed occupancy in patients treated with either oral or intravenous preparations. One hundred patients presenting with acute hemisphere stroke (less than 72 hours) were randomized to receive either a new oral formulation of naftidrofuryl or placebo on a double-blind basis. Treatment was given for a total of 12 weeks and patients followed for 26 weeks with serial neurological and functional assessments by a single observer. Cumulative fatality and hospital-bed occupancy were determined at each assessment interval. No significant difference was demonstrated in cumulative fatality, hospital-bed occupancy or recovery of motor function in patients treated with either naftidrofuryl or placebo. There is no evidence from this study to support the use of oral naftidrofuryl in acute stroke.\nStudy2: Towards a model stroke trial. The single-centre naftidrofuryl study. It has been questionable whether the lack of proven pharmacological treatments in acute cerebral infarction (ACI) reflects ineffective drugs or only inadequacies in their assessment. The difficulties in developing a rationale for drug therapy in this condition favoured the former, although the latter possibility was supported by re-evaluation of most published trials. In this paper, a plausible rationale, in terms of our current understanding of both the drug and the condition, is expounded for treatment of ACI with naftidrofuryl. Guidelines for the design and conduct of clinical trials in acute stroke are discussed in relation to the particular problems posed: need for early initiation of treatment; need for, and difficulties of, diagnostic confirmation; matching of treatment groups by prognostic indicators of uncertain significance, and requirements for large numbers of patients and long-term follow-up. The practical application of these guidelines is tested in a clinical trial of naftidrofuryl conducted in a single centre on 100 patients with proven diagnoses. Rigorous attention to all aspects of selection, treatment and follow-up, with an explanatory approach to the trial design, was predicted to produce a positive result if the drug was effective. The findings were that naftidrofuryl treatment was associated with no change in death rate but with clinically and statistically significant improvements in neurological recovery and bed-occupancy. Better functional recovery was also noted, so that the trial result was coherent. It was concluded that a beneficial effect had been recorded, and consistency of this outcome with those of previous studies is demonstrated. A case is made for further studies to define exactly the role of this drug in the management of ACI.\nStudy3: New approach to treatment of recent stroke. Ninety-one patients with acute stroke participated in a double-blind, placebo-controlled trial of naftidrofuryl. Treatment was allocated at random and given over 12 weeks, neurological and neurophysical scores being obtained before treatment and at weeks 2, 4, 8, and 12. Both treatment groups greatly improved over the 12 weeks, but the naftidrofuryl-treated patients made greater neurological progress. Of the patients eventually discharged, those given naftidrofuryl spent only half as long in hospital as the controls. Deaths attributable to stroke were significantly fewer in the active-treatment group.\n", + "output": "Conclusions: There is not enough evidence to support the use of naftidrofuryl in the treatment of acute ischaemic or haemorrhagic stroke." + }, + { + "input": "Study: Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial). The study compared, by a prospective, randomized method, 6 treatment options: A: Sclerotherapy; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclerotherapy; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occurrence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. \"Standard,\" low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.\n", + "output": "Conclusions: There was insufficient evidence to preferentially recommend the use of sclerotherapy or surgery. There needs to be more research that specifically examines both costs and outcomes for surgery and sclerotherapy." + }, + { + "input": "Study1: The management of threatened abortion: A study of 100 cases. nan\nStudy2: Effect of stilbestrol on pregnancy compared to the effect of a placebo. nan\nStudy3: The use of diethylstilbestrol in threatened abortion. nan\nStudy4: Does the administration of diethylstilbestrol during pregnancy have therapeutic value? nan\n", + "output": "Conclusions: There was no benefit with the use of diethylstilbestrol in preventing miscarriages. Both short and long-term adverse outcomes in exposed offsprings were demonstration of the harm that this intervention caused women and their offspring during its usage." + }, + { + "input": "Study: Respiratory distress syndrome and inositol supplementation in preterm infants. We report a randomised double blind trial of myo-inositol (inositol) supplementation for 10 days in 74 preterm infants with a birth weight less than 2000 g (mean gestational age 29.5 weeks and mean birth weight 1266 g). All infants required artificial ventilation for treatment of respiratory distress syndrome. Inositol (120-160 mg/kg/day) was administered by the ingastric or intravenous route. The 37 infants who received inositol supplementation required less mechanical ventilation during days 4-10, had less failures of indomethacin to close ductus arteriosus, and had less deaths or bronchopulmonary dysplasia, or both, than the infants treated with placebo. There were no detectable adverse effects. These preliminary results suggest that inositol is an important nutrient in immature preterm infants.\n", + "output": "Conclusions: Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A multicenter randomized controlled trial of appropriate size is justified to confirm these findings." + }, + { + "input": "Study1: Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. The treatment of rest pain, ulceration, and gangrene of the leg (severe limb ischaemia) remains controversial. We instigated the BASIL trial to compare the outcome of bypass surgery and balloon angioplasty in such patients. We randomly assigned 452 patients, who presented to 27 UK hospitals with severe limb ischaemia due to infra-inguinal disease, to receive a surgery-first (n=228) or an angioplasty-first (n=224) strategy. The primary endpoint was amputation (of trial leg) free survival. Analysis was by intention to treat. The BASIL trial is registered with the National Research Register (NRR) and as an International Standard Randomised Controlled Trial, number ISRCTN45398889. The trial ran for 5.5 years, and follow-up finished when patients reached an endpoint (amputation of trial leg above the ankle or death). Seven individuals were lost to follow-up after randomisation (three assigned angioplasty, two surgery); of these, three were lost (one angioplasty, two surgery) during the first year of follow-up. 195 (86%) of 228 patients assigned to bypass surgery and 216 (96%) of 224 to balloon angioplasty underwent an attempt at their allocated intervention at a median (IQR) of 6 (3-16) and 6 (2-20) days after randomisation, respectively. At the end of follow-up, 248 (55%) patients were alive without amputation (of trial leg), 38 (8%) alive with amputation, 36 (8%) dead after amputation, and 130 (29%) dead without amputation. After 6 months, the two strategies did not differ significantly in amputation-free survival (48 vs 60 patients; unadjusted hazard ratio 1.07, 95% CI 0.72-1.6; adjusted hazard ratio 0.73, 0.49-1.07). We saw no difference in health-related quality of life between the two strategies, but for the first year the hospital costs associated with a surgery-first strategy were about one third higher than those with an angioplasty-first strategy. In patients presenting with severe limb ischaemia due to infra-inguinal disease and who are suitable for surgery and angioplasty, a bypass-surgery-first and a balloon-angioplasty-first strategy are associated with broadly similar outcomes in terms of amputation-free survival, and in the short-term, surgery is more expensive than angioplasty.\nStudy2: Surgery or balloon angioplasty for peripheral vascular disease: a randomized clinical trial. Principal investigators and their Associates of Veterans Administration Cooperative Study Number 199. Surgical revascularization and angioplasty (PTA) are effective therapies for patients with peripheral arterial disease, but there are no data on long-term survival, limb salvage, and hemodynamic status from a randomized study of such patients. A multicenter, prospective trial compared PTA with bypass surgery (BP) in 263 men who had iliac, femoral, or popliteal artery obstruction. Lesions in the iliac versus the femoropopliteal artery and rest pain versus claudication were separately randomized to the two treatment interventions. One hundred twenty-six patients underwent BP, 129 patients underwent PTA, and eight patients were not treated for lower extremity ischemia. Three operative deaths occurred in the BP group and none in the PTA group. For the entire study, average annual mortality was higher in the BP group, but survival was not significantly different on life-table analysis (P = .08). Primary success favored BP, while limb salvage favored PTA, but differences were not statistically significant (P = .08 and .35, respectively). Patients with iliac disease or claudication fared better, but there was no statistical difference in response to PTA or BP. Patients in both treatment groups had prompt and sustained increases in hemodynamics and quality of life. This study of patients randomly assigned to BP or PTA shows no significant difference in outcomes during a median follow-up of 4 years.\nStudy3: Angioplasty or bypass for superficial femoral artery disease? A randomised controlled trial. To evaluate whether angioplasty or above-knee bypass is the best treatment for symptomatic superficial femoral artery occlusive lesions, we performed a multicentre randomised trial. Between October 1995 and August 1998, 56 patients were enrolled, all with symptoms related to a 5-15 cm long occlusive lesion of the superficial femoral artery. Thirty-one patients were randomly assigned to percutaneous transluminal angioplasty (PTA); 25 patients to bypass surgery. All patients were followed at 1, 6 and 12 months after the procedure. The primary outcome of our study was re-occlusion of the femoral artery. Thirty patients underwent the allocated PTA and 24 patients underwent bypass surgery. Cumulative 1-year primary patency after PTA was 43 and 82% after bypass surgery. After PTA more than half of the patients had a re-occlusion with an absolute risk reduction of 31% (CI: 6-56%) in favour of bypass surgery. The hazard ratio for occlusion comparing PTA with bypass surgery is 2.24 (95% CI: 0.9-5.58). Despite 18 participating centres only 56 patients were randomised to PTA our bypass surgery. Based on our results, for every three patients treated with bypass surgery instead of PTA, one additional re-occlusion is prevented. Therefore, we conclude that with respect to patency, for long superficial femoral artery (SFA) stenoses or occlusions, surgery is better than PTA.\n", + "output": "Conclusions: There is limited evidence for the effectiveness of bypass surgery compared with other treatments; no studies compared bypass to no treatment. Further large trials are required." + }, + { + "input": "Study: Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group. Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy. The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat. Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up. Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made.\n", + "output": "Conclusions: The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervix carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity." + }, + { + "input": "Study: [Preliminary results of a multicenter randomized study on the treatment of acute promyelocytic leukemias]. To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial. The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5-day courses of cytostatic drugs which alternated or did not alternate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (65%)--bcr 3 variant. 65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also similar. Overall 2.5 year survival for all the patients was 77%, recurrence-free--80%. The survival analysis in patients with leukocytosis higher and lower 10 x 10(9)/l found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 x 10(9)/l (25% vs 5.3%, p = 0.03). The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%.\n", + "output": "Conclusions: Maintenance therapy compared to observation in APL patients improved DFS but not OS. Similarly, ATRA and chemotherapy compared to ATRA and probably ATRA based regimens compared to non-ATRA based regimens improved DFS but not OS. The significance of these findings is limited due to clinical heterogeneity between studies." + }, + { + "input": "Study1: Bowel obstruction in patients with ovarian carcinoma: analysis of prognostic factors. A retrospective study was performed in which patients with both bowel obstruction and ovarian carcinoma admitted to the gynecologic oncology service at the Milton S. Hershey Medical Center between July 1, 1980, and June 30, 1987, were examined. Thirty-three patients were identified who fulfilled the inclusion criteria for bowel obstruction that did not occur in the postoperative period. Historical, physical, nutritional, and laboratory variables thought to contribute to patient survival were evaluated by a retrospective chart review. Survival time was not significantly related to presence or absence of tumor at obstruction, type of intervention whether medical or surgical, patient age, or interval from initial diagnosis of ovarian cancer to obstruction. Survival time was found to be significantly related to the prognostic index initially proposed by H. B. Krebs and D. R. Goplerud [Obstet. Gynecol. 61, 327-330 (1983)], P = 0.002. This prognostic index incorporates a multifactorial assessment of patient status including age, nutritional status, tumor spread, ascites, and prior chemotherapy and radiotherapy and can be used to evaluate patients at the time of presentation with intestinal obstruction and to help select optimal treatment for palliation.\nStudy2: Management of intestinal obstruction after gastrectomy for carcinoma. nan\nStudy3: Palliative gastrojejunostomy for advanced carcinoma of the stomach. The outcome of 51 patients who underwent gastrojejunostomy for unresectable gastric cancer with outlet obstruction was studied to evaluate the palliative benefit. The operative mortality and postoperative complication rates were 22% and 55% respectively. The mean duration of postoperative hospital stay was 13 days and median survival period 14 weeks. Delayed gastric emptying occurred in 21%, mostly in patients with extensive tumour involvement of the stomach and was associated with a poor outcome. Among the survivors, 87.5% were able to take a soft diet by the eighth postoperative day and 60% could cope with the progression of the disease at home. We conclude that gastrojejunostomy offers satisfactory palliation in patients with advanced gastric cancer.\nStudy4: Intestinal obstruction in patients with advanced carcinoma of the ovaries treated with combination chemotherapy. An analysis of incidence, risk factors and treatment results of intestinal obstruction caused by carcinoma of the ovaries was performed in 310 consecutive patients with carcinoma of the ovaries, The International Federation of Gynecology and Obstetrics stage IIB to IV, treated with combination chemotherapy. With a median observation time of 46 months, the incidence was 14 per cent and the cumulated risk was estimated to be 26 per cent at five years after treatment was begun. Risk factors were stages IIIB and IV, residual primary tumor size greater than 2 centimeters and presence of intestinal carcinomatosis at primary laparotomy. There was no difference in the survival time between 16 conservatively treated patients and 25 surgically treated patients (a median of 30 and 68 days, respectively, p greater than 0.30). The complication risk of surgical treatment was high (64 per cent), and surgical benefit--defined as survival greater than 60 days with total palliation of intestinal symptoms--was achieved in only 32 per cent.\nStudy5: Survival following intestinal obstruction in ovarian cancer. A retrospective survey of 38 ovarian cancer patients who developed radiologically confirmed intestinal obstruction was performed. Twenty-six patients underwent surgery. In the surgical treatment group, obstruction was not due to recurrent disease in six cases. The median survival for the group as a whole was 56 days. Patients in the operative group survived significantly longer than those in the non-operative group. There was an operative mortality of 15% and major postoperative morbidity was seen in 42%. Neither the site of the obstruction nor the type of operation influenced survival. No postoperative chemotherapy responses were seen in previously treated patients.\nStudy6: Surgical management of bowel obstruction in advanced ovarian carcinoma. The surgical management of 118 instances of bowel obstruction associated with advanced ovarian cancer in 98 patients is reviewed. In 12% of the treatment episodes, patients were found to have inoperable disease at laparotomy. Surgical correction of the intestinal obstruction was associated with an operative mortality of 12%. In 35% of the cases, patients did not benefit from surgical treatment, as they died within 8 weeks of the operation. Patients' age, nutritional status, tumor spread, presence of ascites, and the type and amount of prior chemotherapy and/or radiation therapy correlate well with the patients' prognosis. A simple prognostic index based upon these 6 criteria is suggested as a means of predicting the possible benefit from surgical intervention.\nStudy7: Rectal cancer recurrence after prior resection and radiotherapy: palliation following additional surgery. Patients with rectal cancer may develop local recurrence despite cancer resection plus treatment with high dose radiation therapy. In this report, symptomatic patients received benefit from repeat resection. The morbidity and mortality can be maintained at an acceptable level with meticulous dissections and consistent use of reconstructive procedures. The primary treatment of rectal carcinoma is surgical excision to remove the primary tumor and its draining lymphatic systems. Postoperative radiotherapy may be recommended if tumor has penetrated through the full thickness of the bowel wall, and where there is lymph node involvement. Despite such treatments, tumor may recur locally, producing symptoms relieved by palliative surgery. Between 1989 and 1995, twenty patients underwent 21 reoperations for locally recurrent rectal cancer. All patients previously had not only surgical resection but also radiotherapy as treatment. The clinical data available on these patients was critically evaluated. Eighty-nine dissections (4.5 per patient) and 39 reconstructive procedures (2.0 per patient) were required on these 20 patients to re-resect rectal cancer in an irradiated site. Major complications occurred in 4 of 21 reoperative procedures (19%). There were no mortalities. Palliative benefits from pain control (8 of 9 patients), resolution of uncontrolled hemorrhage (2 of 2 patients), resolution of pelvic sepsis (2 of 2 patients), and reversal of intestinal obstruction (2 of 2 patients) were clearly demonstrated. The median survival following repeat resection was 24 months. Surgical cure following reoperation for recurrent rectal cancer treated initially with resection radiotherapy was uncommon. However, the morbidity and mortality of the procedures were acceptable, the survival was extensive and the palliative effects were substantial. The results of treatment suggest that repeat resection combined with aggressive reconstruction, is an important part of the treatment of symptomatic rectal cancer patients who recur locally, after resection combined with radiation therapy.\n", + "output": "Conclusions: The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures of symptom control and quality of life scores. Further information would include re-obstruction rates together with the morbidity associated with the various surgical procedures.\nCurrently, bowel obstruction is managed empirically, and there are marked variations in clinical practice by different units. There needs to be a greater standardisation of management so that comparisons between different series can be made." + }, + { + "input": "Study: A randomised controlled trial to compare the effectiveness of ice-packs and Epifoam with cooling maternity gel pads at alleviating postnatal perineal trauma. To evaluate the effectiveness of standard regimes (ice packs and Epifoam) at relieving perineal trauma and compare these with a new cooling device (maternity gel pad). A randomised controlled trial involving three treatment groups. The women were free to choose the time of initial application (within four hours after delivery) in all treatment groups and the number of subsequent treatments up to 48 hours after suturing. A midwifery unit in the north of England and then continued in the women's own homes. 120 women who had undergone an instrumental delivery and had a 48 hours post-delivery stay in a postnatal ward. The ordinal scale of none, mild, moderate and severe was used to determine the levels of perineal oedema and bruising at initial assessment (less than 4 hours), 24 hours and at 48 hours, by use of a newly developed visual evaluating tool. Self-assessed pain was recorded using a 10-point visual analogue scale within four hours, at 24 hours, 48 hours, and finally at five days after suturing. Women's opinions as to the effectiveness of their treatment was rated by use of a 5-point scale describing the categories; poor, fair, good, very good and excellent. A high proportion of women had some perineal oedema at initial assessment. A statistically significant difference in the proportion of women with oedema was found between treatment groups at 48 hours (p = 0.01), which was in favour of the maternity gel pad group. This was particularly noticeable for women with initial levels of mild oedema (p = 0.017). Localised treatment with the gel pad caused a significant decrease in reported pain at 48 hours in women who initially demonstrated moderate or severe pain (p = 0.048). A significant increase in the proportion of women with some bruising was seen across all treatment groups from initial assessment, through 24 hours to 48 hours (p < 0.0005). The bruising was significantly less in the gel-pad group in women who initially had no bruising (p = 0.021). There was no statistically significant effect of treatment at other initial levels of severity for oedema, bruising or pain at 24 hours, 48 hours and five days (for pain). Women in the gel-pad group rated the effectiveness of their localised treatment to be significantly higher than women in the other two treatment groups (p < 0.0005). This trial demonstrated that a high proportion of women experience perineal oedema, bruising and pain following an instrumental delivery, which continues for at least five days for perineal pain, despite oral analgesia. Maternity gel pads, which were specially designed to cool the perineal region, were more effective in alleviating perineal trauma when compared with hospital standard regimens and were more highly rated by women.\n", + "output": "Conclusions: There is only limited evidence to support the effectiveness of local cooling treatments (ice packs, cold gel pads, cold/iced baths) applied to the perineum following childbirth to relieve pain." + }, + { + "input": "Study1: Effects of orlistat on obesity-related diseases - a six-month randomized trial. To assess the effect of orlistat on body weight and concomitant diseases in patients with body mass index (BMI) of > 28 kg/m2 and poorly controlled type 2 diabetes, hypertension or hypercholesterolaemia. This trial was a six-month, randomized, double-blind, placebo-controlled study of orlistat 120 mg three times daily plus a mildly reduced-calorie diet. 1004 obese patients (BMI 28-40 kg/m2) were included by 253 private endocrinologists and received orlistat (n = 499) or placebo (n = 505). Patients were stratified by concomitant disorder (type 2 diabetes, n = 193; hypertension, n = 614; hypercholesterolaemia, n = 197). Body weight, anthropometry, lipid and glycaemic control parameters and blood pressure. After six months, orlistat produced a significantly greater weight loss than placebo in type 2 diabetes (-4.2% vs. -1.4%), hypertension (-6.2% vs. -1.9%) and hypercholesterolaemia (-5.5% vs. -2.3%) groups (p < 0.0001 for all). There was a greater decrease in HbA(1c) in the type 2 diabetes group (-0.54 vs. -0.18%; p = 0.002) and low-density lipoprotein (LDL)-cholesterol in the hypercholesterolaemia group (-11.7% vs. -4.5%; p = 0.004) with orlistat vs. placebo. Early weight loss (> or = 5% at 12 weeks) was associated with the highest weight loss in each group, and the highest decreases in HbA1c, LDL-cholesterol and diastolic blood pressure in patients with type 2 diabetes, hypercholesterolaemia and hypertension, respectively, at six months. The incidence of adverse events was similar for orlistat and placebo, except for certain generally well-tolerated gastrointestinal events that were more common with orlistat. Orlistat plus a mildly reduced-calorie diet produced clinically meaningful weight loss and improvements in risk factors in overweight and obese patients with poorly controlled type 2 diabetes, hypertension or hypercholesterolaemia. Copyright 2004 Blackwell Publishing Ltd\nStudy2: Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension. This 6-month randomized study evaluated the safety and efficacy of sibutramine in 57 overweight Hispanic patients with hypertension. Following a 2-week washout to confirm the diagnosis of hypertension, antihypertensive medication was adjusted to achieve a blood pressure less than 140/90 mm Hg before institution of either sibutramine 10 mg or placebo once a day. A body mass index in excess of 27 kg/m2 was required for entry. At study end, weight had changed from 75.4+/-9.6 to 70.0+/-9.5 kg in the sibutramine group and from 77.9+/-9.0 to 74.5+/-9.4 kg in the placebo group. In the sibutramine group, systolic blood pressure was 127.8+/-5.8 mm Hg after stabilization and 125.2+/-8.5 mm Hg after completion of the trial; respective values for diastolic blood pressure were 82.4+/-3.7 and 81.5+/-4.6 mm Hg. With placebo, blood pressure dropped from 129.0+/-7.1/80.9+/-4.9 mm Hg to 122.8+/-9.7/80.3+/-5.4 mm Hg at the same timepoints. In the sibutramine group, 14 patients reported 21 adverse events, most frequently headache (n=5), constipation (n=4), and dry mouth (n=4). In the placebo group, 13 patients had 20 adverse events. Sibutramine is safe and effective in overweight Hispanic patients with hypertension, but monitoring of blood pressure and titration of antihypertensive medication are necessary.\nStudy3: Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. To investigate the hypothesis that weight reduction with orlistat plus mild caloric restriction leads to better blood pressure control than diet alone in obese individuals with inadequately controlled hypertension. DESIGN This was a 1-year, prospective, randomized, double-blind, placebo-controlled, multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives. Participants were randomized to receive either orlistat or placebo; all received a 600 kcal deficient diet with no more than 30% of calories from fat. Weight and blood pressure, lipid levels and fasting glucose and insulin levels were followed. Patients on orlistat experienced greater weight loss (-5.4 +/- 6.4 versus -2.7 +/- 6.4 kg, P< 0.001) and greater reduction in body mass index (-1.9 +/- 2.3 versus -0.9 +/- 2.2 kg/m2, P<0.001). Target weight loss, defined as > or= 5% body weight (BW), was obtained in more orlistat-treated patients than in the placebo group (46 versus 23%, P<0.001). Diastolic BP decreased more in orlistat-treated patients than in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg, P = 0.002). A greater percentage of orlistat-treated patients reached goal diastolic blood pressure (BP), defined as final diastolic BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%, P< 0.001). The orlistat-treated group had significantly greater reductions in total cholesterol ( P<0.001), low-density lipoprotein cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol (P< 0.005) and target 30% cardiovascular risk reduction was obtained in more orlistat-treated patients (36.1 versus 24.0%, P< 0.04). A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction.\nStudy4: Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control.\nStudy5: Effects of sibutramine on the treatment of obesity in patients with arterial hypertension. To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months. The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo. The group using sibutramine had a greater weight loss than that using placebo (6.7% versus 2.5%; p<0.001), an increase in heart rate (78.3 +/- 7.3 to 82 +/- 7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105 +/- 29.3 versus 96.6 +/- 28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change. The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy.\nStudy6: Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial. Obesity is a highly prevalent medical condition and is commonly accompanied by hypertension. This study assessed the efficacy and safety of treatment with sibutramine hydrochloride for promoting and maintaining weight loss in obese patients with controlled hypertension, including a subset analysis of African American patients. Obese patients with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) between 27 and 40 and a history of hypertension controlled with a calcium channel blocker (with or without concomitant thiazide diuretic treatment) were randomized to receive sibutramine (n = 150) or placebo (n = 74) with minimal behavioral intervention for 52 weeks. African Americans constituted 36% of enrolled patients. Efficacy assessments were body weight and related parameters (BMI and waist and hip circumferences), metabolic parameters (serum levels of triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol, glucose, and uric acid), and quality-of-life measures. Safety assessments included recording of blood pressure, pulse rate, adverse events, and reasons for discontinuation. For patients receiving sibutramine, weight loss occurred during the first 6 months of the trial and was maintained to the end of the 12-month treatment period. Among patients receiving sibutramine, 40.1% lost 5% or more of body weight (5% responders) and 13.4% lost 10% or more of body weight (10% responders) compared with 8.7% and 4.3% of patients in the placebo group, respectively (P<.05). Changes in body weight were similar among African Americans and whites. Sibutramine-induced weight loss was associated with significant improvements in serum levels of triglycerides, HDL-C, glucose, and uric acid. Waist circumference and quality-of-life measures also improved significantly in patients receiving sibutramine. Sibutramine-treated patients had small but statistically significant mean increases in diastolic blood pressure (2.0 mm Hg) and pulse rate (4.9 beats/min) compared with placebo-treated patients (-1.3 mm Hg and 0.0 beats/min; P<.05); these changes were similar among African Americans and whites. Most adverse events were mild to moderate in severity and transient. The most common adverse event resulting in discontinuation among patients receiving sibutramine was hypertension (5.3% of patients receiving sibutramine vs 1.4% of patients receiving placebo). In obese patients with controlled hypertension, sibutramine was an effective and well-tolerated treatment for weight loss and maintenance. Sibutramine-induced weight loss resulted in improvements in serum levels of triglycerides, HDL-C, uric acid, and glucose, and in waist circumference and quality-of-life measures. Blood pressure and heart rate increased by a small amount. Efficacy and safety profiles for sibutramine among African American and white obese patients with controlled hypertension were similar.\n", + "output": "Conclusions: In patients with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree. In the same trials, orlistat reduced blood pressure and sibutramine increased blood pressure. No trials investigating rimonabant in people with elevated blood pressure could be included. Long-term trials assessing the effect of orlistat, sibutramine and rimonabant on mortality and morbidity are lacking. Rimonabant and sibutramine have been withdrawn from the market for the time being." + }, + { + "input": "Study1: Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth. This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance. AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01). Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. Trial registration: ClinicalTrials.gov Identifier: NCT00480870.\nStudy4: Two randomized placebo-controlled trials to evaluate the efficacy and tolerability of mirtazapine for the treatment of obstructive sleep apnea. Mirtazapine is an a2A antagonist and mixed 5-HT2/5-HT3 antagonist that has been proposed as a potential treatment for obstructive sleep apnea (OSA). A small, randomized, controlled trial has previously found an approximate halving in the severity of OSA with daily doses of 4.5 and 15 mg. We aimed to confirm and extend these findings in 2 randomized placebo-controlled, proof-of-concept trials. Two randomized, double-blind, placebo-controlled trials of mirtazapine for OSA (apnea-hypopnea index 10-40/h). Study 1: 3-way crossover, dose-finding study testing the self-administration of mirtazapine (7.5, 15, 30, and/or 45 mg) or placebo 30 minutes prior to bedtime for 2 weeks at each dose. Twenty patients were randomly assigned to 1 of 6 different dose-sequence groups, with each patient exposed to a maximum of 3 doses. Study 2: 3-arm, randomized, parallel-group trial of mirtazapine at 15 mg or mirtazapine 15 mg + Compound CD0012 or placebo for 4 weeks in 65 patients with OSA. Two patients withdrew from Study 1 after complaints of unacceptable lethargy. Fifteen patients were withdrawn from study 2, 7 after complaints of unacceptable lethargy or other side-effects. No measurement of sleep apnea improved due to mirtazapine in either study. Weight gain was significantly greater on mirtazapine than on placebo in both trials. Mirtazapine did not improve sleep apnea in either trial. Mirtazapine caused weight gain, which may further worsen OSA. Therefore, mirtazapine is not recommended for the treatment of OSA.\nStudy5: The effects of aminophylline on sleep and sleep-disordered breathing in patients with obstructive sleep apnea syndrome. The methylxanthine derivatives are known to have respiratory stimulant properties. To determine whether these drugs would improve obstructive sleep apnea, 10 male patients with obstructive sleep apnea (OSA) (Apnea Index greater than 15/h) were given infusions of aminophylline and a saline placebo on 2 separate nights a week apart, using a randomized crossover design. There was a significant decrease during aminophylline infusion in the frequency of those apneas, which contained periods of complete respiratory inactivity (central and mixed apneas; placebo, 4.3 +/- 1.8/h; aminophylline, 0.7 +/- 0.5/h; p less than 0.05). There was no change in either the frequency (placebo, 31.8 +/- 5.9/h; aminophylline, 28.7 +/- 8.7/h; NS) or duration of obstructive apneas. Mean and minimal arterial oxygen saturation values were also unchanged. Sleep architecture was markedly disturbed by aminophylline. There was a reduction in sleep efficiency (placebo, 84.8 +/- 2.0%; aminophylline, 60.2 +/- 5.0%; p less than 0.005), an increase in sleep fragmentation (sleep stage shifts/h: placebo, 11.6 +/- 1.3: aminophylline, 21.0 +/- 2.9; p less than 0.05) and less Stage 2 and more Stage 1 non-REM sleep. We conclude that aminophylline reduces central apnea and the central component of mixed apneas but has no effect on obstructive apnea. Theophylline is therefore unlikely to be therapeutically useful in patients with OSA, and because it leads to marked sleep disruption, its long-term use could conceivably increase the propensity to upper airway occlusion during sleep.\nStudy6: Cardiovascular effects of mibefradil in hypertensive patients with obstructive sleep apnea. Hypertension is often seen in obstructive sleep apnea (OSA) and is characterized by increased sympathetic activity, depressed baroreflex and accentuated vascular responsiveness. The objective of this study was to investigate the effects of the new T-selective calcium channel blocker mibefradil on invasively measured blood pressure (BP) and heart rate in hypertensive patients with OSA. The present study was a double-blind, randomized and placebo-controlled before and after trial in two parallel groups. Fifty-three men aged 23 69 years with systemic hypertension and OSA were recruited from the Outpatient Department of the Marburg University Sleep Laboratory and hospitalized for 10 days. Mibefradil (50 mg) or placebo were given orally in the morning for 8 days. The main outcome measure was the mean arterial (radial) BP monitored continuously during nocturnal sleep and during standardized daytime physical and psychological performance testing. Mibefradil lowered mean arterial BP and heart rate with (SD) during the entire measurement period compared with placebo: -7.25 (9.59) vs -2.11 (8.43) mmHg (P=0.039) and -4.83 (5.94) vs -1.34 (4.13) bpm (P=0.022), respectively. Both effects were observed during nocturnal sleep and performance testing, including graded exercise. Adverse events did not differ compared with placebo. Mibefradil is an effective but well-tolerated antihypertensive that also lowers heart rate over 24 h in OSA, in conditions known to increase BP.\nStudy7: Naltrexone improves blood gas patterns in obstructive sleep apnoea syndrome through its influence on sleep. Endogenous opiates have been shown to depress ventilation, and could therefore play a role in sleep apnoea syndrome (SAS). Hence, opiate antagonists have been used to treat SAS. The improvement they seem to give in blood-gas monitoring could derive either from a direct blocking of endorphins that inhibit respiration or else, indirectly, through an influence on sleep patterns. The present study used a double blind cross-over protocol to investigate the relationships between the effects on blood-gas and on sleep patterns of the oral opiate antagonist naltrexone in obstructive SAS. Sleep patterns and transcutaneous blood gas (tcPO2 and tcPCO2) were recorded in parallel. Control recordings, without treatment, were carried out over two nights, followed by two nights of recording after administration either of naltrexone followed by a placebo or of a placebo followed by naltrexone. The number of obstructive apnoea and hypopnoea events per hour of sleep (Apnoea-Hypopnoea Index: AHI), of hypoxic events (defined as a tcPO2 fall of at least 10, 15 or 20 mm Hg) and of hypercapnic events (defined as a tcPCO2 increase of at least 5 mm Hg) were counted. A Metabolic Suffering Index (MSI) was calculated, defined as the product of the number, duration and magnitude of hypoxic and hypercapnic events. Compared to placebo, naltrexone resulted in significant improvements in blood-gas patterns for the duration and MSI of hypoxic events and for the number, duration and MSI of hypercapnic events. Likewise, compared to placebo, naltrexone induced significant decreases in total sleep time, slow-wave sleep and rapid eye movement (REM) sleep, and, on the other hand, significant increases in total wake time and in the number of wakenings per hour of sleep (Nw h-1). Certain naltrexone-linked blood-gas improvements were closely correlated with certain of the sleep pattern changes: the decrease in number and duration of hypoxic events correlated with REM-time decrease and the decrease in number and duration of hypercapnic events correlated with the increase in Nwh-1. These findings suggest that the improvement in blood-gas patterns induced by naltrexone in SAS may be mediated by sleep pattern effects: i.e. a decrease in REM-time and an increase in intra-sleep wakening.\nStudy8: Prospective trial of efficacy and safety of ondansetron and fluoxetine in patients with obstructive sleep apnea syndrome. Incremental withdrawal of serotonin during wake to sleep transition is postulated as a key mechanism that renders the pharyngeal airway collapsible. While serotonin promotion with reuptake inhibitors have demonstrated modest beneficial effects during NREM sleep on obstructive sleep apnea (OSA), animal studies suggest a potential therapeutic role for selective serotonin receptor antagonists (5-HT3) in REM sleep. We aimed to test the hypothesis that a combination of ondansetron (Ond) and fluoxetine (Fl) may effectively reduce expression of disordered breathing during REM and NREM sleep in patients with OSA. A prospective, parallel-groups, single-center trial in patients with OSA. 35 adults with apnea hypopnea index (AHI) > 10; range 10-98. Subjects were randomized to placebo, n = 7; Ond (24 mg QD), n = 9; Fl (5 mg QD) + Ond (12 mg QD), n = 9; and Fl (10 mg QD) + Ond (24 mg QD), n = 10. AHI was measured by in-lab polysomnography after a 7-day no-treatment period (Baseline) and on days 14 and 28 of treatment. The primary endpoint was AHI reduction at days 14 and 28. OND+FL resulted in approximately 40% reduction of baseline AHI at days 14 and 28 (unadjusted P < 0.03 for each) and improved oximetry trends. This treatment-associated relative reduction in AHI was also observed in REM and supine sleep. Combined treatment with OND+FL is well-tolerated and reduces AHI, yielding a potentially therapeutic response in some subjects with OSA.\nStudy9: Proof of concept study: does fenofibrate have a role in sleep apnoea syndrome? To investigate the effect of fenofibrate on sleep apnoea indices. Proof-of-concept study comprising a placebo run-in period (1 week, 5 weeks if fibrate washout was required) and a 4-week randomized, double-blind treatment period. Thirty-four subjects (mean age 55 years, body mass index 34 kg/m 2 , fasting triglycerides 3.5 mmol/L) with diagnosed sleep apnoea syndrome not treated with continuous positive airways pressure were enrolled and randomized to once daily treatment with fenofibrate (145 mg NanoCrystal(R) tablet) or placebo. Overnight polysomnography, computerized attention/vigilance tests and blood sampling for measurement of lipids, insulin, fasting plasma glucose and fibrinogen were performed at the end of each study period. NCT00816829. As this was an exploratory study, a range of sleep variables were evaluated. The apnoea/hypopnoea index (AHI) and percentage of time spent with arterial oxygen saturation (SpO(2)) <90% were relevant as they have been evaluated in other clinical trials. Other variables included total apnoeas, hypopnoeas and oxygen desaturations, and non-cortical micro-awakenings related to respiratory events per hour. Fenofibrate treatment significantly reduced the percentage of time with SpO(2) <90% (from 9.0% to 3.5% vs. 10.0% to 11.5% with placebo, p = 0.007), although there was no significant change in the AHI (reduction vs. control 14% (95%CI -47 to 40%, p = 0.533). Treatment reduced obstructive apnoeas (by 44%, from 18.5 at baseline to 15.0 at end of treatment vs. 29.0 to 30.5 on placebo, p = 0.048), and non-cortical micro-awakenings per hour (from 23.5 to 18.0 vs. 24.0 to 25.0 with placebo, p = 0.004). Other sleep variables were not significantly influenced by fenofibrate. KEY LIMITATIONS: Exploratory study in patients with mild to moderate sleep apnoea, limited treatment duration; concomitant hypnotic treatment (35%); lack of correction for multiplicity of testing. The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome.\nStudy10: Efficacy of mirtazapine in obstructive sleep apnea syndrome. Decreased serotonergic facilitation of upper-airway motor neurons during sleep has been postulated as an important mechanism rendering the upper airway vulnerable to obstruction in patients with obstructive sleep apnea syndrome (OSA). Although serotonin reuptake inhibitors have been shown to produce modest reductions in the apnea-hypopnea index (AHI) during non-rapid eye movement (NREM) sleep, they have not been proven to be generally effective as treatments for OSA. Conversely, antagonists of type 3 (5-HT3) serotonin receptors effectively have been shown to reduce the frequency of central apneas during rapid eye movement (REM) sleep in a rodent model of sleep-related breathing disorder. We sought to determine whether mirtazapine, a mixed 5-HT2/5-HT3 antagonist that also promotes serotonin release in the brain would effectively reduce AHI during both NREM and REM sleep in patients with OSA. A randomized, double-blind, placebo-controlled, 3-way crossover study of mirtazapine in patients with OSA. Laboratory studies were conducted in the Center for Sleep and Ventilatory Disorders at the University of Illinois Medical Center. Seven adult men and 5 adult women with newly diagnosed (treatment-na\u00efve) and medically uncomplicated OSA were randomized into the study. Each subject self-administered oral medications 30 minutes before bedtime each night for 3 consecutive 7-day treatment periods. These treatments comprised (1) placebo, (2) 4.5 mg per day of mirtazapine, and (3) 15 mg per day of mirtazapine. The order of treatments was randomized for each subject, and orders were counterbalanced for the overall study. Each subject charted his or her sleep-wake schedule throughout the study and completed the Stanford Sleepiness Scale every 2 hours during the seventh day of each treatment period. Subjects were studied by laboratory polysomnography on the seventh night of each treatment period. With respect to placebo treatment, 4.5 mg of mirtazapine significantly reduced the AHI in all sleep stages to 52%, with 11 of 12 subjects showing improvement over placebo; 15 mg of mirtazapine reduced the AHI to 46%, with 12 of 12 subjects showing improvement over placebo. Sleep fragmentation was reduced only by the higher dose of mirtazapine. Gross changes in sleep architecture were unremarkable. Daily administration of 4.5 to 15 mg of mirtazapine for 1 week reduces AHI by half in adult patients with OSA. This represents the largest and most consistent drug-treatment effect demonstrated to date in a controlled trial. These findings suggest the therapeutic potential of mixed-profile serotonergic drugs in OSA and provide support for future studies with related formulations. Mirtazapine also is associated with sedation and weight gain-2 negative side effects in patients with OSA. In view of the above, we do not recommend use of mirtazapine as a treatment for OSA.\n", + "output": "Conclusions: There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short-term outcomes. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24% and 45%. For donepezil and fluticasone, studies of longer duration with a larger population and better matching of groups are required to establish whether the change in AHI and impact on daytime symptoms are reproducible. Individual patients had more complete responses to particular drugs. It is possible that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study." + }, + { + "input": "Study: A randomized clinical trial comparing primary overlap with approximation repair of third-degree obstetric tears. We compared, in a prospective, randomized clinical trial, the subjective and objective outcomes after primary anal sphincter overlap or approximation repair of third-degree obstetric tears. In a prospective, randomized clinical trial at our university teaching hospital, we studied 112 primiparous women who sustained a third-degree tear during a 1-year period (July 1998-June 1999); they were randomly selected, at diagnosis, to receive either an overlap or an approximation repair. Obstetric personnel, trained in both methods, carried out the repairs immediately after delivery. Fifty-five women underwent an overlap procedure, and 57 women underwent an approximation repair. Outcome measures assessed were symptoms of fecal incontinence, abnormal findings on anal manometry, and abnormal findings on endoanal ultrasonography at 3 months post partum. Obstetric factors, including mode of delivery, birth weight, duration of labor, and episiotomy incidence, did not differ significantly between the 2 groups. Experience of the operator, analgesia used, and place of repair were similar in both groups. The median incontinence scores were 0/20 after overlap repair and 2/20 after approximation repair (difference not significant). Eleven women (20%) complained of fecal urgency after overlap repair, in comparison with 17 (30%) after approximation repair (difference not significant). There were no significant differences in either anal manometry or endoanal ultrasonographic results between the 2 groups. Six women (11%) had a significant (>1 quadrant) anal sphincter defect after primary overlap repair, compared with 3 (5%) after approximation repair (difference not significant). Overall, 66% of women had ultrasonographic evidence of a residual full-thickness defect in the external anal sphincter after primary repair. The outcome after primary repair of third-degree obstetric tear was similar whether an approximation or an overlap technique was used. Overall symptomatic outcome was good, although two thirds of women had ultrasonographic evidence of residual anal sphincter damage irrespective of the method of repair.\n", + "output": "Conclusions: The limited data available show that compared to immediate primary end-to-end repair of OASIS, early primary overlap repair appears to be associated with lower risks for faecal urgency and anal incontinence symptoms. As the experience of the surgeon is not addressed in the three studies reviewed, it would be inappropriate to recommend one type of repair in favour of another.\n[Note: The six citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]" + }, + { + "input": "Study1: Effect of growth hormone on exercise tolerance in children with cystic fibrosis. The effect of growth hormone (GH) treatment on exercise tolerance in children with cystic fibrosis was investigated. 10 prepubertal children (mean +/- SD; age: 12.1 +/- 1.7 yr; height: 137.4 +/- 9.2 cm; body mass: 27.8 +/- 4.2 kg; forced expiratory volume in 1 s (FEV1): 68 +/- 22% predicted) were randomly assigned to either control period (CON, standard therapy) or recombinant human growth hormone (GH) period (additional GH treatment, 0.11-0.14 IU.kg-1, daily, s.c.) for the first 6 months, and then assigned to the other period for the next 6 months. At study entry and after each period, anthropometric data, pulmonary function, and exercise capacity (peak exercise capacity, .VO(2peak), and isokinetic muscle strength) were measured. Changes in height (+4.3 +/- 1.0 cm), total body mass (+2.2 +/- 0.8 kg), and lean body mass (LBM, +2.9 +/- 0.7 kg) were significantly higher (P < 0.01) after GH treatment compared with CON. Pulmonary function did not significantly change in either of the periods. In contrast to CON, GH treatment improved absolute .VO(2peak) (+19%, P < 0.01), peak ventilation (+14%, P < 0.01), and peak oxygen pulse (+18%, P < 0.01). Analysis of variance revealed that most of the changes (71%) in .VO(2peak) could be explained by those in LBM and FEV1 (P = 0.001). GH treatment clearly improved exercise tolerance, presumably resulting from the combined effects of GH on the muscular, cardiovascular, and pulmonary capacity.\nStudy2: A multi-center controlled trial of growth hormone treatment in children with cystic fibrosis. We evaluated safety and efficacy of recombinant human growth hormone (rhGH) for improving growth, lean body mass (LBM), pulmonary function, and exercise tolerance in children with cystic fibrosis (CF) and growth restriction. Multicenter, open-label, controlled clinical trial comparing outcomes in prepubertal children <14 years with CF, randomized in a 1:1 ratio to receive daily rhGH (Nutropin AQ) or no treatment (control) for 12 months, followed by a 6-month observation (month 18). Safety was monitored at each visit, including assessments of glucose tolerance. Sixty-eight subjects were randomized (control n\u2009=\u200932; rhGH n\u2009=\u200936). Mean height standard deviation score (SDS) in the rhGH group increased by 0.5\u2009\u00b1\u20090.4 at 12 months (mean\u2009\u00b1\u2009SD, P\u2009<\u20090.001); the control group height SDS remained unchanged. Weight increased by 3.8\u2009\u00b1\u20091.8 versus 2.8\u2009\u00b1\u20091.5\u2009kg, (mean\u2009\u00b1\u2009SD, P\u2009=\u20090.0356) and LBM increased by 3.8\u2009\u00b1\u20091.8 versus 2.1\u2009\u00b1\u20091.4\u2009kg (P\u2009=\u20090.0002) in the rhGH group versus controls, respectively. Forced vital capacity increased by 325\u2009\u00b1\u2009319 in the rhGH group compared with 178\u2009\u00b1\u2009152\u2009ml in controls (mean\u2009\u00b1\u2009SD, P\u2009=\u20090.032). Forced expiratory volume in 1\u2009sec improved in both groups with a significant difference between groups after adjustment for baseline severity (LS mean\u2009\u00b1\u2009SE: rhGH, 224\u2009\u00b1\u200937, vs. controls, 108\u2009\u00b1\u200940\u2009ml; P\u2009=\u20090.04). There was no difference between groups in exercise tolerance (6-min walk distance) at 1 year. Changes in glucose tolerance for the two groups were similar over the 12-month study period, with three subjects developing IGT and one CFRD in each group. One rhGH-treated patient developed increased intracranial pressure. Treatment with rhGH in prepubertal children with CF was effective in promoting growth, weight, LBM, lung volume, and lung flows, and had an acceptable safety profile. Copyright \u00a9 2011 Wiley Periodicals, Inc.\nStudy3: Prospective randomised treatment with recombinant human growth hormone in cystic fibrosis. To evaluate the efficacy and safety of treatment with recombinant growth hormone (rGH) in patients with cystic fibrosis (CF). Twenty patients with CF (aged 10-23 years) were randomised to age and sex matched treatment and control groups. The treatment group received daily subcutaneous injections of 1 IU/kg/wk rGH for 12 months. Pulmonary function (forced expiratory volume in one second (FEV1) and airway resistance), exercise capacity measured with a bicycle ergometer, body composition (dual energy x ray absorptiometry), and weight were assessed at the beginning of the study and after 6 and 12 months. rGH treatment did not improve weight and pulmonary function, but lean body mass increased significantly in the treatment group. Exercise capacity increased in the treatment group from 143 (16) W (mean (SD)) to 164 (19) W after 12 months of rGH treatment. Treatment of CF patients with rGH for one year improved the exercise capacity significantly but not pulmonary function. The improved exercise capacity needs confirmation in a larger population before such an expensive treatment is justified.\n", + "output": "Conclusions: Recombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in patients with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use in patients." + }, + { + "input": "Study1: A randomized, double-blind, celecoxib- and placebo-controlled study of the effectiveness of CS-706 in acute postoperative dental pain. CS-706 is a cyclooxygenase-2 (COX-2)-selective inhibitor with an in vitro selectivity ratio (COX-1:COX-2) similar to that of celecoxib. It has exhibited analgesic, anti-inflammatory, and antitumor properties in animal models. This study evaluated the tolerability of single doses of CS-706 and compared the analgesic efficacy of CS-706 with that of celecoxib and placebo in the dental pain model. This was a randomized, double-blind, double-dummy, active- and placebo-controlled study. Healthy male and female subjects with moderate to severe pain intensity (PI) after dental surgery were randomized ( approximately 50 per group) to receive a single oral dose of CS-706 10, 50, 100, or 200 mg; celecoxib 400 mg; or placebo. PI and pain relief (PR) were measured on categorical and visual analog scales through 24 hours after the dose. The primary efficacy variable was the time-weighted sum of PR scores at 4 hours after the dose (TOPAR4). The onset of analgesia was assessed by calculating the pain intensity difference (PID). Perceptible and meaningful pain relief were assessed using a 2-stopwatch method. The majority of subjects were female (62.0%) and white (59.5%). Subjects' mean (SD) age was 22.6 (3.9) years, and their mean body mass index was 25.3 (5.1) kg/m(2). All doses of CS-706 were associated with significant analgesic efficacy compared with placebo based on the primary end point, TOPAR4 (P<0.001), and on all secondary end points (P<0.05, comparisons of all CS-706 doses vs placebo) with the exception of time to 100% PR for CS-706 10 mg. Single 50-, 100-, and 200-mg doses of CS-706 also were significantly more effective than celecoxib for TOPAR4 (P=0.036, P=0.004, and P=0.006, respectively). The onset of analgesia (PID >or= 1) for all CS-706 doses occurred within 1 hour after dosing (P<0.001 vs placebo). The median duration of analgesia, measured as the time to administration of rescue medication, was significantly greater for all doses of CS-706 compared with placebo (5.7 hours for CS-706 10 mg, >24 hours for CS-706 50, 100, and 200 mg, and 1.7 hours for placebo; P<0.001 for CS-706 50, 100, and 200 mg). These data suggest that once-daily administration of CS-706 may be effective in providing relief of acute pain. The incidence of adverse events was similar among all treatment groups. Adverse events occurring in >or= 5 % of subjects in any treatment group were nausea, vomiting, dry socket, dizziness, headache, and paresthesia. Single doses of CS-706 had significant analgesic efficacy compared with celecoxib and placebo in the relief of postoperative dental pain in the healthy subjects enrolled in this study.\nStudy2: Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults. Current outpatient management of postoperative pain includes the use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; however, both types of medications are associated with side effects that can limit their usefulness in the outpatient setting. Two studies with identical protocols assessed the single- and multiple-dose analgesic efficacy and tolerability of celecoxib, a specific cyclooxygenase-2 inhibitor, in the treatment of acute pain after orthopedic surgery. These were multicenter, randomized, placebo- and active-controlled, double-blind, parallel-group trials conducted between January and June 1998. Both consisted of a single-dose assessment period (SDAP) and a multiple-dose assessment period (MDAP). In the SDAP, patients who had undergone orthopedic surgery received a single oral dose of celecoxib 200 mg, hydrocodone 10 mg/acetaminophen 1000 mg, or placebo within 24 hours after the end of anesthesia, with pain assessments conducted over the following 8-hour period. In the MDAP, extending from 8 hours after the first dose of study medication up to 5 days, patients who had received < or =1 dose of rescue medication during the SDAP continued on study medication (placebo recipients were rerandomized to active treatment), which could be taken up to 3 times a day as needed. A total of 418 patients were enrolled in the 2 trials. During the SDAP, 141 patients received celecoxib, 136 received hydrocodone/acetaminophen, and 141 received placebo. During the MDAP, 185 patients received celecoxib and 181 received hydrocodone/acetaminophen. When the combined data were analyzed, mean pain intensity difference (PID) scores generally favored the active treatments over placebo from 1 to 6 hours (with the exception of 1.5 hours) after dosing (P < or = 0.016) and favored celecoxib over the other treatments at 7 and 8 hours after dosing (P < 0.001). The active treatments demonstrated superior summed PID scores through 8 hours (P < 0.001), significantly shorter median times to onset of analgesia (P < 0.05), and significantly longer median times to first use of rescue medication (P < 0.05). During the MDAP, more hydrocodone/acetaminophen-treated patients (20%) than celecoxib-treated patients (12%) required rescue medication (P < 0.05), and the celecoxib group had significantly lower maximum pain intensity scores (P < 0.001, days 2-5), required fewer doses of study medication (P < or = 0.01, days 3-5), and had superior scores on a modified American Pain Society Patient Outcome Questionnaire (P < or = 0.013). In addition, a significantly lower proportion of celecoxib-treated patients experienced adverse events (43%) compared with hydrocodone/acetaminophen-treated patients (89%; P < 0.001). Over 8 hours, patients with moderate to severe pain after orthopedic surgery experienced comparable analgesia with single doses of celecoxib and hydrocodone/acetaminophen. Over a 5-day period, oral doses of celecoxib 200 mg taken 3 times a day demonstrated superior analgesia and tolerability compared with hydrocodone 10 mg/acetaminophen 1000 mg taken 3 times a day. Most patients required no more than 2 daily doses of celecoxib 200 mg for the control of their postorthopedic surgical pain.\n", + "output": "Conclusions: Single-dose oral celecoxib is an effective analgesic for postoperative pain relief. Indirect comparison suggests that the 400 mg dose has similar efficacy to ibuprofen 400 mg." + }, + { + "input": "Study1: Inefficacy of penicillin V in acute laryngitis in adults. Evaluation from results of double-blind study. Patients with acute laryngitis following an upper respiratory tract infection are often treated with antibiotics for their voice complaints, although, to our knowledge, the effect of such therapy has not been examined. In the present study, comprising 100 adults with laryngitis, the rate of resolution of vocal symptoms, as estimated from voice recordings or subjectively by the patients, was the same in patients who received penicillin V (pcV) as in those who received placebo. Similarly, the degree of rhinorrhea/nasal congestion and cough was not significantly influenced by pcV treatment. At the acute visit, nasopharyngeal cultures revealed Branhamella catarrhalis in 50%, Hemophilus influenzae in 15% and Streptococcus pneumoniae in 1% of the patients; the rate of elimination of these bacteria was the same in the pcV as in the placebo group. Thus, while suggesting that B catarrhalis and H influenzae are important for the pathogenesis of the disorder, our results do not provide support for the use of pcV in acute laryngitis.\nStudy2: Erythromycin in acute laryngitis in adults. Moraxella catarrhalis and Hemophilus influenzae are isolated from the nasopharynx in 50% to 55% and 8% to 15%, respectively, of cases of acute laryngitis in adults. This finding indicates that these organisms, M catarrhalis in particular, are in some way involved in the pathogenesis of the disorder. In the present double-blind, placebo-controlled trial, the effect of erythromycin ethylsuccinate (0.5 g twice a day for 5 days) on the elimination of nasopharyngeal pathogens and reduction of clinical signs of upper respiratory tract infection, as well as on subjective complaints, was evaluated in 106 adults with acute laryngitis. The bacterial isolation rates at presentation were M catarrhalis 50%, H influenzae 18%, and Streptococcus pneumoniae 4%. In the 99 patients who completed the study, the elimination of M catarrhalis after 1 week was better in the erythromycin group (25 of 30 cases) than in the placebo group (6 of 19 cases; p < or = .00038). The elimination of H influenzae was unaffected by erythromycin. Otolaryngologic examination did not reveal any significant group differences regarding laryngitis, pharyngitis, or rhinitis. Voice quality was improved after 1 week, irrespective of treatment. However, as compared to the placebo group, the erythromycin group reported fewer voice complaints after 1 week and fewer coughing complaints after 2 weeks. As acute laryngitis in adults is self-limiting, and subjective symptoms are spontaneously reduced after 1 week in most cases, antibiotic treatment does not seem warranted as a general policy. However, erythromycin may be justified in patients who are professionally dependent on voice function.\n", + "output": "Conclusions: Antibiotics appear to have no benefit in treating acute laryngitis. Erythromycin could reduce voice disturbance at one week and cough at two weeks when measured subjectively. We consider that these outcomes are not relevant in clinical practice. The implications for practice are that prescribing antibiotics should not be done in the first instance as they will not objectively improve symptoms." + }, + { + "input": "Study1: Nebulized hypertonic saline/salbutamol solution treatment in hospitalized children with mild to moderate bronchiolitis. The objective of this study was to determine the efficacy and safety of nebulized 3% hypertonic saline solution and salbutamol in the treatment of mild to moderate bronchiolitis. In a randomized controlled trial, 93 infants with mild to moderate bronchiolitis were divided into two groups. The infants received inhalation of 2.5 mg (0.5 mL) salbutamol dissolved in either 4.0 mL normal (0.9%) saline (control group, n= 43) or 4.0 mL hypertonic (3%) saline (treatment group, n= 50). The therapy was repeated three times daily until discharge. Cough, wheezing, pulmonary physical signs, and the length of hospital stay were recorded. Wheezing remission time was 3.8 + or - 1.1 days in the control group and 2.7 + or - 0.9 days in the treatment group (P < 0.01). Cough remission time was 6.3 + or - 0.9 days in the control group and 5.3 + or - 0.8 days in the treatment group (P < 0.01). The moist crackles disappeared at 5.4 + or - 0.8 days in the treatment group versus 6.2 + or - 0.9 days in the control group (P < 0.01). Furthermore, the average length of hospital stay decreased from 7.4 + or - 1.5 days in the control group to 6.0 + or - 1.2 days in the treatment group (P < 0.01). No obvious adverse effects were observed. Inhalation of nebulized 3% hypertonic saline solution and salbutamol is a safe and effective therapy for patients with mild to moderate bronchiolitis.\nStudy2: Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchiolitis reduces hospitalization stay: 2 years experience. We recently published preliminary evidence on the effectiveness of hypertonic saline in infants with viral bronchiolitis. To further establish the efficacy of nebulized hypertonic saline in these infants. In a continuing, second-year randomized, doubleblind controlled trial, an additional 41 infants (age 2.6 +/- 1 months) hospitalized with viral bronchiolitis were recruited during the winter of 2001-2002. The infants received inhalation of 1.5 mg epinephrine dissolved either in 4 ml normal (0.9%) saline (Group I, n=20) or 4 ml hypertonic (3%) saline (Group II, n=22). The therapy was repeated three times daily until discharge. Pooling our 2 years of experience (2000-2002), a total of 93 hospitalized infants with viral bronchiolitis were recruited; 45 were assigned to Group I and 48 to Group II. The clinical scores at baseline were 7.6 +/- 0.7 for Group I vs. 7.4 +/- 1.3 for Group II (P = NS). However, the clinical scores at days 1 and 2 after inhalation differed significantly between the two groups, invariably favoring Group II: 7 +/- 1 vs. 6.25 +/- 1.1 (P< 0.05), 6.45 +/- 1 vs. 5.35 +/- 1.35 (P< 0.05), respectively. Adding aerosolized 3% saline to 1.5 mg epinephrine reduced the hospitalization stay from 3.5 +/- 1.7 days in Group I to 2.6 +/- 1.4 in Group II (P< 0.05). The pooled data of both years revealed that adding 3% saline to the inhalation mixture decreased hospitalization stay from 3.6 +/- 1.6 to 2.8 +/- 1.3 days (P< 0.05). This second-year experience and our 2 year pooled data analysis strengthen the evidence that the combination of 3% saline/1.5 mg epinephrine benefits hospitalized infants with viral bronchiolitis.\nStudy3: A randomized trial of nebulized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department. To determine whether nebulized 3% hypertonic saline with epinephrine is more effective than nebulized 0.9% saline with epinephrine in the treatment of bronchiolitis in the emergency department. Randomized, double-blind, controlled trial. Single-center urban pediatric emergency department. Infants younger than 12 months with mild to moderate bronchiolitis. Patients were randomized to receive nebulized racemic epinephrine in either hypertonic or normal saline. The primary outcome measure was the change in respiratory distress, as measured by the Respiratory Assessment Change Score (RACS) from baseline to 120 minutes. The change in oxygen saturation was also determined. Secondary outcome measures included the rates of hospital admission and return to the emergency department. Forty-six patients were enrolled and evaluated. The 2 study groups had similar baseline characteristics. The RACS from baseline to 120 minutes demonstrated no improvement in respiratory distress in the hypertonic saline group compared with the normal saline control group. The change in oxygen saturation in the hypertonic saline group was not significant when compared with the control group. Rates of admission and return to the emergency department were not different between the 2 groups. In the treatment of acute bronchiolitis, hypertonic saline and epinephrine did not improve clinical outcome any more than normal saline and epinephrine in the emergency setting. This differs from previously published results of outpatient and inpatient populations and merits further evaluation. isrctn.org Identifier: ISRCTN66632312.\nStudy4: Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. To investigate the use of nebulized 3% hypertonic saline (HS) for treating viral bronchiolitis in moderately ill hospitalized infants by a prospective, randomized, double-blinded, controlled, multicenter trial. A total of 96 infants (mean age, 4.7 months; range, 0.3 to 18 months) admitted to the hospital for treatment of viral bronchiolitis were recruited from 3 regional pediatric centers over 3 bronchiolitis seasons (December 2003 to May 2006). Patients were randomized to receive, in a double-blind fashion, repeated doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group), in addition to routine therapy ordered by the attending physician. The principal outcome measure was hospital length of stay (LOS). On an intention-to-treat basis, the infants in the HS group had a clinically relevant 26% reduction in LOS to 2.6 +/- 1.9 days, compared with 3.5 +/- 2.9 days in the NS group (P = .05). The treatment was well tolerated, with no adverse effects attributable to the use of HS. The use of nebulized 3% HS is a safe, inexpensive, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis.\n", + "output": "Conclusions: Current evidence suggests nebulized 3% saline may significantly reduce the length of hospital stay among infants hospitalized with non-severe acute viral bronchiolitis and improve the clinical severity score in both outpatient and inpatient populations." + }, + { + "input": "Study1: A multicentre, double-blind, randomized study to compare the safety and efficacy of once-daily ORG 10172 and twice-daily low-dose heparin in preventing deep-vein thrombosis in patients with acute ischaemic stroke. A multicentre, double-blind, randomized study was performed in 179 patients with acute ischaemic stroke resulting in limb paresis. The purpose was to compare the safety and efficacy of Org 10172 (1250 anti-Xa Units s.c. once daily) and heparin sodium (5000 IU s.c. twice daily) in preventing deep-vein thrombosis (DVT). Prophylaxis started within 72 hours of the onset of stroke and continued for at least 9 days. To detect DVT, patients underwent a daily 125I-fibrinogen leg scanning which, if found positive, was followed by venography. A first computed tomography scan of the brain was performed at screening to rule out cerebral haemorrhage and a second at cessation of treatment to detect any haemorrhagic transformations. At the 2-3-months' follow-up period the patients were examined for signs and symptoms of DVT or pulmonary embolism. On an intention-to-treat analysis, DVT occurred in 14.6% of patients receiving Org 10172 and in 19.8% of those receiving heparin during the treatment period (p = 0.392, NS). Pulmonary embolism was diagnosed in one patient in each group. Major conversion to a symptomatic haemorrhagic brain infarct was found in one patient in each group. Death occurred in 13.5% of patients treated with Org 10172 and in 6.7% of patients treated with heparin (p = 0.135, NS). Deaths were mainly related to pulmonary infection and cerebral oedema, thus considered to be due directly to the clinical status of the patients. 1250 anti-Xa Units of Org 10172 once daily is both safe and as effective as 5000 IU of heparin sodium twice daily given for DVT prophylaxis in patients with acute ischaemic stroke of recent onset.\nStudy2: The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison. Venous thromboembolism prophylaxis with low molecular weight heparin or unfractionated heparin is recommended in acute ischaemic stroke, but which regimen provides optimum treatment is uncertain. We aimed to compare the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with stroke. 1762 patients with acute ischaemic stroke who were unable to walk unassisted were randomly assigned within 48 h of symptoms to receive either enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14, less severe stroke <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary safety endpoints were symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality. This study is registered with ClinicalTrials.gov, number NCT00077805. In the efficacy population (ie, one or more dose received, presence of deep vein thrombosis or pulmonary embolism, or assessment for venous thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%] vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The occurrence of any bleeding was similar with enoxaparin (69 [8%]) or unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%]; p=0.23). We noted no difference for symptomatic intracranial haemorrhage between groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs 0; p=0.015). Our results suggest that for patients with acute ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration.\n", + "output": "Conclusions: Since the last version of this review none of the three new relevant studies with 2397 participants have provided additional information to change the conclusions. Treatment with a low-molecular-weight heparin or heparinoid after acute ischaemic stroke appears to decrease the occurrence of deep vein thrombosis compared with standard unfractionated heparin, but there are too few data to provide reliable information on their effects on other important outcomes, including death and intracranial haemorrhage." + }, + { + "input": "Study1: Injections and physiotherapy for the painful stiff shoulder. Cost effective treatment is needed for common self limiting rheumatological conditions. Periarthritis of the shoulder is an example. There is no consensus for one type of treatment, though local steroids or physiotherapy are conventionally used. Their cost and efficacy were compared in a prospective randomised observer-blind trial--in essence a medical audit of the treatment of a common rheumatological problem. Sixty two consecutive patients presenting with a painful stiff shoulder were studied. Patients with coexistent diseases like cervical spondylosis or a stroke were excluded. They were randomly allocated to receive local steroids, six weeks' physiotherapy, or both. The three groups were of similar age, sex, and disease severity. Assessments of pain and shoulder movement were made initially, at six weeks, and at six months by a 'blinded' observer. Physiotherapy was given by one therapist and injections by one physician. All three groups showed significant improvements by six weeks, with further improvement at six months. Improvements were identical in all three groups. No treatment gave complications. The costs of treatment varied: an injection of triamcinolone cost 2.10 pounds; a six week course of physiotherapy cost 48.50 pounds; combination treatment cost 50.60 pounds. Patients expect treatment for a painful stiff shoulder. The results show that local steroid injections are as effective as physiotherapy alone or a combination. They provide rapid treatment and are less expensive. In the uncomplicated case a local steroid injection is the most cost effective treatment.\nStudy2: Efficacy of injections of corticosteroids for subacromial impingement syndrome. A prospective, randomized, controlled, double-blind clinical study was performed to determine the short-term efficacy of subacromial injection of corticosteroids for the treatment of subacromial impingement syndrome. Forty patients were randomized to receive either six milliliters of 1 per cent lidocaine without epinephrine (the control group) or two milliliters containing forty milligrams of triamcinolone acetonide per milliliter with four milliliters of 1 per cent lidocaine without epinephrine (the corticosteroid group). The patients were re-examined serially until completion of the study. Nineteen patients, whose mean age was fifty-six years (range, thirty-two to eighty years), were randomized to the corticosteroid group, and twenty-one patients, whose mean age was fifty-seven years (range, thirty-two to eighty-one years), were randomized to the control group. The mean duration of symptoms before the injection was eight months for both groups. Eighteen patients in the corticosteroid group and nineteen patients in the control group had moderate or severe pain before the injection. At the most recent follow-up evaluation, at a mean of thirty-three weeks for the corticosteroid group and twenty-eight weeks for the control group, three patients in the corticosteroid group had moderate or severe pain, compared with fifteen patients in the control group. The mean active range of forward elevation and external rotation improved by 24 and 11 degrees, respectively, for the corticosteroid group and by 10 and 5 degrees, respectively, for the control group. We concluded that subacromial injection of corticosteroids is an effective short-term therapy for the treatment of symptomatic subacromial impingement syndrome. The use of such injections can substantially decrease pain and increase the range of motion of the shoulder.\nStudy3: A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis. A prospective double blind placebo controlled study was carried out to compare the effects of subacromial injection of triamcinolone and oral diclofenac in patients with rotator cuff tendinitis over a 4-week period. Both forms of treatment were superior to placebo in reducing pain, improving active abduction and reducing functional limitation. Triamcinolone showed the greatest effect in these respects, and was significantly superior to diclofenac when patients showing improvements in all 3 variables together (responders) were considered.\nStudy4: Clinical evaluation of sodium hyaluronate for the treatment of patients with rotator cuff tear. A randomized study of two types of conservative treatment of 78 shoulders in 78 patients with rotator cuff tears was performed. Twenty-five milligrams of sodium hyaluronate (SH) was injected into shoulders in one group (SH group) and 2 mg of dexamethasone was injected in the other group (steroid group). Injection of each drug was planned for once per week for 5 consecutive weeks. In the SH group, University of California at Los Angeles score before treatment was 13.6 +/- 2.6 points in 16 patients who did not require surgery (satisfied patients) and 12.8 +/- 3.5 points in 22 patients who required surgery (unsatisfied patients) (not statistically significant). In the steroid group, University of California at Los Angeles score before treatment was 11.9 +/- 3.6 points for 15 satisfied patients and 12.6 +/- 3.9 points for 25 unsatisfied patients (again, not statistically significant). In the SH group, the score at 4 weeks after treatment for satisfied patients increased to 27.6 +/- 3.1 points, whereas that for unsatisfied patients was 14.9 +/- 1.2 points (P <.0001). Similarly, in the steroid group, the score at 4 weeks after the treatment for satisfied patients increased to 26.5 +/- 2.0 points, whereas that for unsatisfied patients was 15.0 +/- 4.0 points (P <.0001). At 24 weeks after treatment, the score for satisfied patients was 26.2 +/- 3.1 points in the SH group and 25.3 +/- 2.5 points in the steroid group. The effective rate of the SH group was 39.5% and that of the steroid group was 35%. Therapeutic efficacy in the SH group was equivalent to that in the steroid group. In both groups, the rate of patients who engaged in manual labor was significantly higher in the group of unsatisfied patients than in that of satisfied patients. No adverse reaction to either treatment was observed. These results suggest that SH is an effective conservative treatment for patients with rotator cuff tears.\nStudy5: Manipulation under anesthesia for frozen shoulder with and without steroid injection. To study the effect of manipulating a shoulder with adhesive capsulitis (frozen shoulder) under anesthesia with and without corticosteroid injection. Randomized trial. Hospital. Twenty-four patients referred for manipulation of a frozen shoulder. The patients were randomized into 2 groups. One group received an injection of corticosteroid and manipulation; the other was only administered manipulation during anesthesia. The degree of shoulder mobility and pain before and after the manipulation. Manipulation under anesthesia increased the mobility of the affected shoulder. Injection with lidocaine and betamethason did not enhance the effect of the manipulation. Manipulation under anesthesia without intraarticular corticosteroids is recommended as the therapy for frozen shoulder.\nStudy6: Local anaesthetic injection with and without corticosteroids for subacromial impingement syndrome. Fifty patients with impingement syndrome refractory to long-term conservative treatment were randomized to three treatment groups. All patients received an injection of 10 ml 0.5% bupivacaine, in group 1 without corticosteroid, in group 2 with crystalline corticosteroid and in group 3 with lipoid corticosteroid. Treatment in group 1 had to be stopped because of inefficacy. In groups 2 and 3 favorable results were achieved in 19 out of 40 patients.\nStudy7: Intra-articular triamcinolone acetonide injection in patients with capsulitis of the shoulder: a comparative study of two dose regimens. Although corticosteroid injections have been reported to be effective in capsulitis of the shoulder, the optimal dose has not been established. The purpose of this study was to compare relief of symptoms following a lower dose with that following a higher dose of triamcinolone acetonide given intra-articularly. Thirty-two patients were given low dose suspension; 25 patients were given high dose suspension. Randomized, double-blind clinical trial. Each patient was given a course of three injections. Pain, sleep disturbance, functional impairment and passive range of motion (ROM) were assessed at intake and at one, three and six weeks after the initial injection. Data were analysed by independent sample t-tests and nonparametric Mann-Whitney U-tests. The group which received the 40 mg dose showed significantly greater improvement than the group receiving the 10 mg dose. The study shows that in the treatment of frozen shoulder greater symptom relief is obtained with a dose of 40 mg triamcinolone acetonide intra-articularly than with a dose of 10 mg. The effect on pain and sleep disturbance was more marked than on ROM. Intra-articular injections with triamcinolone acetonide appear to be an effective method to obtain symptom relief for patients with painful capsulitis of the shoulder.\n", + "output": "Conclusions: Despite many RCTs of corticosteroid injections for shoulder pain, their small sample sizes, variable methodological quality and heterogeneity means that there is little overall evidence to guide treatment. Subacromial corticosteroid injection for rotator cuff disease and intra-articular injection for adhesive capsulitis may be beneficial although their effect may be small and not well-maintained. \nThere is a need for further trials investigating the efficacy of corticosteroid injections for shoulder pain. Other important issues that remain to be clarified include whether the accuracy of needle placement, anatomical site, frequency, dose and type of corticosteroid influences efficacy." + }, + { + "input": "Study: Persistent nocturnal cough: randomised controlled trial of high dose inhaled corticosteroid. To investigate the effect of a short course of inhaled corticosteroid in the treatment of isolated and persistent nocturnal cough in children. Randomised double blind placebo controlled study. Subjects' homes in east London, England. Consecutively referred children, 1-10 years old, with persistent nocturnal cough. Placebo or fluticasone propionate 1 mg twice daily for three nights and 500 microg twice daily for 11 nights. Videotaping of children at night: two nights' baseline, nights 3 and 4 after three days of inhaled corticosteroid, and nights 15 and 16. A fall in 75% of coughs from baseline. 50 subjects were recruited. The median number of coughs in the baseline period for the inhaled corticosteroid group and placebo group were 92 and 71, respectively (p = 0.43) and, on nights 15 and 16, 8 and 36, respectively (p < 0. 01). Compared to baseline, both groups of subjects improved significantly by nights 15 and 16 (p < 0.01; p < 0.01). Comparing the inhaled corticosteroid and placebo groups, coughs fell to a median of 22% and 57% of baseline totals on nights 3 and 4, respectively (p = 0.38), and 8% and 35% on nights 15 and 16, respectively (p = 0.02). 17 of 24 subjects on inhaled corticosteroid who completed the study and 8 of 23 on placebo improved by 75% after two weeks (p = 0.03). Children with persistent nocturnal cough improve in two weeks after referral on placebo. There is a modest benefit from a two week course of high dose inhaled corticosteroid.\n", + "output": "Conclusions: In one study beclomethasone dipropionate (400 micrograms per day) was no different from placebo in reducing the frequency of cough measured objectively or scored subjectively. There might be a small improvement with very high-dose inhaled corticosteroid but the clinical impact of this is unlikely to beneficial." + }, + { + "input": "Study1: Efficacy of cognitive-behavioural therapy by general practitioners for unexplained fatigue among employees: Randomised controlled trial. Fatigue is a common complaint that may lead to long-term sick leave and work disability. To assess the efficacy of cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue among employees. A randomised controlled trial, using a pre-randomisation design in primary care, investigated 151 employees on sick leave with fatigue. Participants in the experimental group were offered five to seven 30 min sessions of cognitive-behavioural therapy by a general practitioner; those in the control group were offered no treatment. Main outcome measures (fatigue severity, self-reported absenteeism, registered absenteeism and clinical recovery) were assessed at 4 months, 8 months and 12 months. At baseline, 44% of the patients already met research criteria for chronic fatigue syndrome. There was no significant difference between the experimental group and the control group on primary or secondary outcomes at any point. Cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue did not prove to be an effective intervention. Since these doctors were unable to deliver this therapy effectively under ideal circumstances, it is unlikely that doctors in routine practice would be more successful in doing so.\nStudy2: Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care. To determine whether, in the treatment of major depression in primary care, a brief psychological treatment (problem solving) was (a) as effective as antidepressant drugs and more effective than placebo; (b) feasible in practice; and (c) acceptable to patients. Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks. Primary care in Oxfordshire. 91 patients in primary care who had major depression. Observer and self reported measures of severity of depression, self reported measure of social outcome, and observer measure of psychological symptoms at six and 12 weeks; self reported measure of patient satisfaction at 12 weeks. Numbers of patients recovered at six and 12 weeks. At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant (5.3 (95% confidence interval 1.6 to 9.0) and 4.7 (0.4 to 9.0) respectively), but the difference between problem solving and amitriptyline was not significant (1.8 (-1.8 to 5.5) and 0.9 (-3.3 to 5.2) respectively). At 12 weeks 60% (18/30) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52% (16/31) given amitriptyline and 27% (8/30) given placebo. Patients were satisfied with problem solving treatment; all patients who completed treatment (28/30) rated the treatment as helpful or very helpful. The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours. As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients.\nStudy3: Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. To determine whether problem solving treatment combined with antidepressant medication is more effective than either treatment alone in the management of major depression in primary care. To assess the effectiveness of problem solving treatment when given by practice nurses compared with general practitioners when both have been trained in the technique. Randomised controlled trial with four treatment groups. Primary care in Oxfordshire. Patients aged 18-65 years with major depression on the research diagnostic criteria-a score of 13 or more on the 17 item Hamilton rating scale for depression and a minimum duration of illness of four weeks. Problem solving treatment by research general practitioner or research practice nurse or antidepressant medication or a combination of problem solving treatment and antidepressant medication. Hamilton rating scale for depression, Beck depression inventory, clinical interview schedule (revised), and the modified social adjustment schedule assessed at 6, 12, and 52 weeks. Patients in all groups showed a clear improvement over 12 weeks. The combination of problem solving treatment and antidepressant medication was no more effective than either treatment alone. There was no difference in outcome irrespective of who delivered the problem solving treatment. Problem solving treatment is an effective treatment for depressive disorders in primary care. The treatment can be delivered by suitably trained practice nurses or general practitioners. The combination of this treatment with antidepressant medication is no more effective than either treatment alone.\nStudy4: A randomized trial of smoking cessation interventions in general practice in Italy. The purpose of this study was to examine the effectiveness of different practice-based approaches to assist patients of primary care physicians to quit smoking and sustain cessation. Forty-four nonsmoking general practitioners volunteered for the study. After a period of training, they randomized 923 smoking clients, unselected for motivation toward quitting, to four different intervention groups: (i) minimal intervention, consisting of one single counselling session and a brief handout on quitting techniques; (ii) repeated counselling including reinforcing sessions at Months 1, 3, 6, and 9; (iii) repeated counselling and use of nicotine gum; and (iv) repeated counselling and spirometry. Biochemically validated smoking status was assessed at six and 12 months after recruitment. The proportion of verified quitters at 12 months was 4.8 percent among subjects randomized to the minimal intervention group, compared to 5.5 percent, 7.5 percent, and 6.5 percent among those randomized to the three repeated-counselling groups. In no treatment group was the outcome significantly different from that for one-time counselling at the (P less than 0.05) level. Lack of power, contamination, and low attendance at reinforcing sessions should be taken into account in interpreting the results.\nStudy5: Group therapy for somatization disorders in general practice: effectiveness of a short cognitive-behavioural treatment model. The objective of this study was to evaluate the effect of a short cognitive behavioural group therapy programme for somatization disorder in primary care. The treatment model was focused on patient education and stress relaxation. A controlled and prospective study design was used with repeated assessments of the patients' perception of their psychosocial problems, psychological distress and medication usage. The results were analysed up to 6 months after treatment and showed the treated patients to be moderately but significantly improved with respect to physical illness and somatic preoccupation, hypochondriasis, and medication usage. In a control group of untreated patients no such improvements were observed. In summary, the short group treatment programme used in this study may be beneficial for patients with somatization disorders. With some modifications it might be useful to practitioners in primary care for the management of psychosomatic disorders.\nStudy6: Psychosocial interventions for somatizing patients by the general practitioner: a randomized controlled trial. The objective of this study was to compare the effects of psychosocial interventions based on the modified reattribution model for somatizing patients in general practice (GP) with those of nonspecific psychosocial primary care (PPC) alone. Forty-two GPs were randomized, 23 into the intervention group (IG), who were trained in reattribution techniques, and 19 into the control group (CG). One hundred twenty-seven patients were included. Primary outcome measures were somatoform symptoms and quality of life. Multilevel modeling revealed a reduction of physical symptoms (P = .007), an improvement in physical functioning (P = .0172), and a reduction of depression (P = .0211) and anxiety (P = .0388) in the IG compared with the CG at the 3-month follow-up. However, results no longer remained significant after controlling for baseline and covariate variables besides a reduction of physical symptoms at 6-month follow-up (P = .029). Compared with nonspecific PPC, the effects of reattribution techniques were small and limited to physical symptoms.\nStudy7: Controlled evaluation of a general practice-based brief intervention for excessive drinking. In a controlled evaluation of general practitioner (GP)-based brief intervention, 378 excessive drinkers identified opportunistically by screening in 40 group practices in metropolitan Sydney were assigned to groups receiving: (i) a five-session intervention by the GP (the Alcoholscreen Program); (ii) a single session of 5 minutes' advice by the GP plus a self-help manual (minimal intervention); (iii) an alcohol-related assessment but no intervention; (iv) neither intervention nor assessment. Among all patients allocated to receive it, the Alcoholscreen Program did not result in a significantly greater reduction in consumption at follow-up than control conditions but patients offered Alcoholscreen reported a significantly greater reduction in alcohol-related problems in the period to 6 months follow-up. A greater proportion of patients who returned for the second Alcoholscreen visit were drinking below recommended levels at follow-up than in the remainder of the sample. There was no evidence that minimal intervention or alcohol-related assessment were effective in reducing alcohol consumption or problems. Implications for further research into GP-based brief interventions are discussed.\n", + "output": "Conclusions: In general, there is little available evidence on the use of psychosocial interventions by general practitioners. Of the psychosocial interventions reviewed, problem-solving treatment for depression may offer promise, although a stronger evidence-base is required and the effectiveness in routine practice remains to be demonstrated. More research is required to improve the evidence-base on this subject." + }, + { + "input": "Study1: Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome. Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished. Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth. The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.\nStudy2: Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial. We identified 19 women who had persistently positive test results for antiphospholipid antibodies who were considered to be at low risk because they had none of the associated signs or symptoms of the antiphospholipid antibody syndrome. They had had no (10/19, 53%) or just one prior spontaneous abortion and did not have a history of thrombosis or thrombocytopenia. Many (8/19, 42%) had had a prior uncomplicated pregnancy ending in a live birth. These women were randomly assigned to receive low-dose aspirin (81 mg daily) or usual care. There were few obstetric complications recorded in either treatment group. One woman in the aspirin group had a fetal death, and one in the usual care group had a low-birth-weight infant. The frequency of complications was so low that > 600 such women would need to be entered into a randomized trial to evaluate whether low-dose aspirin would be beneficial treatment during a pregnancy. We concluded that treatment of pregnant women with antiphospholipid antibodies who are otherwise at low risk cannot be justified on the basis of the available evidence.\nStudy3: A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group. Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen. This multicenter, randomized, double-blind pilot study compared treatment with heparin and low-dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at 12 weeks). The primary outcome measure was a successful pregnancy. Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.\n", + "output": "Conclusions: Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%. Large, randomised controlled trials with adequate allocation concealment are needed to explore potential differences between unfractionated heparin and LMWH.\n[Note: The 15 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]" + }, + { + "input": "Study: Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized, placebo-controlled, double-blind trial. In a randomized, placebo-controlled, double-blind study, we investigated whether statins alter cholesterol metabolites and reduce Abeta levels in the cerebrospinal fluid of 44 patients with Alzheimer's disease. Individuals were given up to 80mg simvastatin daily or placebo for 26 weeks. Overall, simvastatin did not significantly alter cerebrospinal fluid levels of Abeta40 and Abeta42. In post hoc analysis, simvastatin significantly decreased Abeta40 levels in the cerebrospinal fluid of patients with mild Alzheimer's disease. The reduction of Abeta40 correlated with the reduction of 24S-hydroxycholesterol. These changes were not observed in more severely affected patients.\n", + "output": "Conclusions: There is insufficient evidence to recommend statins for the treatment of dementia. Analysis from the studies available, including one large RCT, indicate statins have no benefit on the outcome measures ADAS-Cog or MMSE. We need to await full results from CLASP 2008 before we can be certain. This Cochrane review will be updated as these results become available." + }, + { + "input": "Study1: Effects of breathable disposable diapers: reduced prevalence of Candida and common diaper dermatitis. Infants wearing breathable disposable diapers experienced significantly less diaper dermatitis (DD) compared to infants wearing standard, nonbreathable disposable diapers in a series of double-blind clinical trials. Severe DD, including confirmed infection with Candida albicans, was reduced by 38-50% among infants wearing highly breathable (HB) diapers. The prevalence of DD was inversely related to the breathability of the garments. The inhibitory effect of breathable diapers on the survival of Candida was further confirmed in controlled experiments with adult volunteers. A suspension of C. albicans cells was applied to delineated sites on the volar forearm. Each site was then covered by a full-thickness patch from either an HB or a standard diaper. Survival of Candida colonies was reduced by almost two-thirds in the breathable diaper-covered sites compared to the control sites.\nStudy2: Comparison of disposable diapers with fluff absorbent and fluff plus absorbent polymers: effects on skin hydration, skin pH, and diaper dermatitis. Diaper dermatitis results from the action of a number of physical and chemical factors on the skin. While its etiology is complex, there is agreement that prolonged contact between wet diapers and the skin leading to excessive hydration of the stratum corneum and reduced barrier function is a primary factor. Recent research also indicates that pH elevation resulting from ammonia production increases the probability of skin damage due to fecal enzyme activity. New diapers containing absorbent polymers blended with cellulose fluff in the absorbent core have been developed. The absorbent polymer binds fluids and controls pH in the diaper environment. To assess the effectiveness of these diapers, a clinical study was conducted with approximately 150 infants over 15 weeks, using fluff diapers and absorbent polymer diapers. The results clearly showed that the diapers with absorbent polymer provide a better skin environment than those with fluff only with respect to lower skin wetness and pH control (instrumental measurements). In addition, the clinicians' grades indicated a directional reduction in diaper rash severity.\nStudy3: Clinical studies with disposable diapers containing absorbent gelling materials: evaluation of effects on infant skin condition. Disposable infant diapers with absorbent gelling material (cross-linked sodium polyacrylates) incorporated into the core were clinically evaluated for their effect on infant skin condition. Absorbent gelling materials tightly hold water and provide pH control by a buffering capacity as well as by helping to segregate urine apart from feces. Four clinical studies were conducted with each following a rigid protocol that controlled for variables of diet and age in addition to the diaper material that may influence the development of diaper dermatitis and helped to control for any inherent bias in the study. This allowed for the controlled assessment of skin condition with respect to diaper type. Absorbent gelling material-containing disposable, conventional (100% cellulose core) disposable, and home-laundered cloth diapers were test products. In these studies 1614 infants were initially enrolled with 522 of them assigned to absorbent gelling material disposable, 738 to conventional disposable, and 354 to home-laundered cloth diapers. Objective measurements of skin wetness (transepidermal water loss) and skin pH, as well as double-blind grading of diaper dermatitis, were the measures of skin condition. Absorbent gelling material disposable diapers were associated with significantly reduced skin wetness, closer to normal skin pH, and lower degrees of diaper dermatitis when compared to conventional disposable or home-laundered cloth diapers. The results are consistent with the hypothesis that better control in the diaper area of skin wetness, skin pH, and the prevention of the mixing of urine and feces produces a better diaper environment.\nStudy4: Incidence of diaper rash when using cloth and disposable diapers. nan\nStudy5: Skin benefits from continuous topical administration of a zinc oxide/petrolatum formulation by a novel disposable diaper. Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have advanced in our development of a novel diaper that delivers dermatological formulations to help protect the skin from over-hydration and irritation. To determine the clinical benefits of a novel disposable diaper designed to deliver a zinc oxide and petrolatum-based formulation continuously to the skin during use. All studies were independent, blinded, randomized clinical trials. Study A was conducted to confirm transfer of the zinc oxide/petrolatum (ZnO/Pet) formulation from the diaper to the child's skin during use. Children wore a single diaper for 3 h or multiple diapers for 24 h. After the use period, stratum corneum samples were taken from each child and analysed for ZnO/Pet. Study B evaluated the prevention of skin irritation and barrier damage from a standard skin irritant (SLS) in an adult arm model. Study C evaluated skin erythema and diaper rash in 268 infants over a 4-week usage period. One half of the infants used the ZnO/Pet diaper, while the other half used a control diaper that was identical except for the absence of the ZnO/Pet formulation. The ointment formulation and ZnO transferred effectively from the diaper to the child's skin during product use. Transfer of ZnO increased from 4.2 microg/cm2 at 3 h to > 8 microg/cm2 at 24 h. Exposure to the formulations directly on adult skin prior to an irritant challenge was associated with up to a 3.5 reduction in skin barrier damage and skin erythema. Greatest reductions were seen for the ZnO containing formulations. Wearing of the formulation treated diaper was also associated with a significant reduction in skin erythema and diaper rash compared to the control product. The results demonstrated the clinical benefits associated with continuous topical administration of a zinc oxide/petrolatum-based formulation by this novel diaper.\nStudy6: Clinical effects of diaper types on the skin of normal infants and infants with atopic dermatitis. Cloth diapers, cellulose core diapers (conventional disposable diapers), and cellulose core diapers containing absorbent gelling material were examined for their effects on diaper rash and skin microbiology of normal infants and infants with atopic dermatitis in a 26-week double-blind clinical trial. Infants with atopic dermatitis wearing the diapers containing absorbent gelling material had significantly lower diaper rash grades than infants with atopic dermatitis wearing cloth diapers at five of eight grading visits. Infants with atopic dermatitis wearing conventional cellulose core diapers had statistically less rash at one of eight visits. There was no statistically significant difference between diaper types at three of the eight visits. At no time did the cloth group have less diaper rash than the conventional cellulose or absorbent gelling material disposable diaper group. A statistical correlation between the severity of general atopic dermatitis outside the diaper area and the diaper rash condition under the diaper occurred only in the atopic dermatitis group wearing cloth diapers. Isolation of microorganisms from the intact, uninvolved skin surface both inside and outside the diaper showed no biologically significant changes in the presence or numbers of selected skin organisms. Repeated isolation, at multiple grading visits of Staphylococcus aureus from uncompromised skin inside the diaper area was infrequent but correlated with the diagnosis of atopic dermatitis when observed.\nStudy7: Evaluations of diapers containing absorbent gelling material with conventional disposable diapers in newborn infants. We evaluated 149 infants diapered in either conventional cellulose core disposable diapers or diapers containing cellulose core with absorbent gelling material. The infants were evaluated from 1 day of age to 14 weeks of age for the prevalence and severity of diaper dermatitis. We identified a low prevalence of diaper dermatitis throughout the study period. At 14 weeks of age, we noted that infants in diapers containing absorbent gelling material had significantly less diaper dermatitis than those in conventional disposable diapers. Despite the overall low prevalence of diaper dermatitis in the newborn period, 7 of 204 infants evaluated had small skin erosions in the diaper area noted within the first 4 days of age. Both diaper types were associated with infants with erosions. This surprisingly high incidence of erosions in newborn infants suggests previously undocumented increased skin fragility of full-term infants.\nStudy8: Continuous topical administration of a petrolatum formulation by a novel disposable diaper. 2. Effect on skin condition. Diaper dermatitis is a common childhood affliction. Aiming to help reduce the prevalence of this problem, we have developed a novel diaper to deliver to the skin dermatological formulations intended to help protect the skin from overhydration and irritation. To determine the clinical benefits of a novel disposable diaper designed to deliver a petrolatum-based formulation continuously to the skin during use. Two independent, blinded, randomized clinical trials were conducted, involving an aggregate total of 391 children, 8-24 months of age. All comparisons were done versus a control diaper, identical to the test product except for the absence of the petrolatum formulation. The studies determined the effects of the novel diaper on skin erythema and diaper rash. Use of the formulation-treated diaper was associated with significant reductions in severity of erythema and diaper rash compared to the control product. The results demonstrated the clinical benefits associated with continuous topical administration of a petrolatum-based formulation by this novel diaper. We anticipate that this advance in diaper design will contribute significantly to further reduce the prevalence and severity of irritant contact dermatitis in the diaper area. Copyright 2000 S. Karger AG, Basel.\n", + "output": "Conclusions: There is not enough evidence from good quality randomised controlled trials to support or refute the use and type of disposable napkins for the prevention of napkin dermatitis in infants." + }, + { + "input": "Study: Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty. Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Although results indicate that prolonged CPM use might have a small short-term effect on RoM, routine use of prolonged CPM in patients with limited RoM at hospital discharge should be reconsidered, since neither long-term effects nor transfer to better functional performance was detected. ISRCTN85759656.\n", + "output": "Conclusions: There is not enough evidence from the available RCTs to conclude that CPM reduces VTE after TKA. We cannot assess the effect of CPM on death because no such events occurred amongst the participants of these trials." + }, + { + "input": "Study1: Contraceptive efficacy of the Copper T380A and the Multiload Cu250 IUD in three developing countries. The clinical performance of the Copper T380A (TCu380A) and the Multiload 250 (MLCu250) intrauterine devices (IUDs) were evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a randomized clinical trial conducted at four collaborating research sites located in three developing countries. The gross cumulative life-table pregnancy rate of the TCu380A IUD was significantly lower than the rate with the MLCu250 IUD at 12 months (0.5 and 1.2, respectively, p < 0.01). No statistically significant differences between the two study IUDs were found with regard to IUD expulsion or IUD removal due to bleeding/pain, personal reasons, medical reasons, or planned pregnancy. TCu380A IUD users were more likely to report experiencing increased dysmenorrhea (p < 0.01) or intermenstrual pelvic pain (p < 0.01) than were MLCu250 IUD users. However, few of these users discontinued use of their assigned IUD because of having experienced menstrual bleeding disturbances or intermenstrual pelvic pain. These data indicate that the TCu380A IUD may be a better option than the MLCu250 IUD for women wishing to practice highly effective long-term birth control without having to resort to hormonal methods.\nStudy2: Contraceptive efficacy of the Copper T 380A and Copper T 200 intrauterine devices: results from a comparative clinical trial in six developing countries. The clinical performance of the Copper T 380A (TCu 380A) and the Copper T 200 (TCu 200) intrauterine devices (IUDs) was evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a multicenter randomized clinical trial at one site in each of six developing countries. The pregnancy rate with the TCu 380A IUD was significantly lower than the pregnancy rate with the TCu 200 IUD at 12 months (0.5 and 2.6 per 100 women, respectively, p < 0.01). No statistically significant differences between the two study IUDs were found with regards to expulsion or removals due to bleeding/pain, personal, medical, or planned pregnancy. The TCu 380A IUD did not have a disproportionately higher incidence of side effects such as intermenstrual bleeding or pain, inflammations or infections, or insertion-related events compared to the TCu 200 IUD. TCu 380A IUD users, however, were significantly more likely to report increased dysmenorrhea than were TCu 200 IUD users. The performance of the TCu 380A IUD in preventing pregnancy during this trial indicates that this IUD may be a better option than the TCu 200 IUD for women wishing to practice effective, long-term, reversible birth control without having to resort to hormonal methods.\nStudy3: An evaluation of the TCu 380Ag and the Multiload Cu375. The TCu 380Ag (Outokumpu Oy, Pori, Finland) and the Multiload Cu375 (Multilan, Organon, Oss, The Netherlands) were evaluated in 1477 women in a multicenter clinical trial. The intrauterine devices showed similar, low-event rates. Cumulative life-table pregnancy rates were less than 1.0, and continuation rates were approximately 90 per 100 women at 1 year after insertion. The risk of subsequent hospitalization or pelvic infection was low.\nStudy4: Performances of copper T 380A and multiload copper 375/250 intrauterine contraceptive devices in a comparative clinical trial. An evaluation of the performances of copper T 380A (TCU 380A) and multiload copper 375/250 (MLCU 375/250) intrauterine contraceptive devices (IUCDS) was carried out at University College Hospital, Ibadan, Nigeria (UCH) in a clinical comparative trial. The IUCDS showed similar low vent rates at one year of continuous use. The difference in cumulative net probabilities for termination due to pelvic inflammatory disease was weakly significant at the sixth month of follow up with MLCU 250 having the highest rate. (TCU 380A-0%; MLCU 375-0%; MLCU 250-3.1%; X2 = 6.0; P < 0.05). This significant difference disappeared by the twelfth month of continuous use. Likewise, the difference in cumulative net probabilities for overall termination was significant at six months and insignificant at twelve months of follow up. The continuation rate after one year were 86%, 92% and 87% respectively for TCU 380A, MLCU 375 and MLCU 250. These rates were higher than 80% and 51% quoted for the previously available Lippes loop in the same environment [1,2]. It was therefore concluded that the three IUCDS are comparable in performances in the first year of use and could be used at our family planning clinic or any other clinic in a similar setting.\n", + "output": "Conclusions: TCu380A or TCu380S appear to be more effective than other IUDs. No IUD showed consistently lower removal rates for bleeding and pain in comparison to other IUDs. There is no evidence that any particular framed copper device is better suited to women who have not had children." + }, + { + "input": "Study1: Benefit of \"one-stage full-mouth disinfection\" is explained by disinfection and root planing within 24 hours: a randomized controlled trial. The beneficial effects of the one-stage, full-mouth disinfection remain controversial in the scientific literature. This might be due to the fact that an entire mouth disinfection with the use of antiseptics has been confused with a full-mouth scaling and root planing. This parallel, single blind RCT study aimed to compare several full-mouth treatment strategies with each other. Seventy-one patients with moderate periodontitis were randomly allocated to one of the following treatment strategies: scaling and root planing, quadrant by quadrant, at two-week intervals (negative control, NC), full-mouth scaling and root planing within 2 consecutive days (FRP), or three one-stage, full-mouth disinfection (FM) protocols within 2 consecutive days applying antiseptics to all intra-oral niches for periopathogens using as antiseptics: chlorhexidine (FMCHX) for 2 months, amine fluoride/stannous fluoride for 2 months (FMF), or chlorhexidine for 2 months followed by amine fluoride/stannous fluoride for another 6 months (FMCHX+F). At baseline and after 2, 4, and 8 a series of periodontal parameters were recorded. All treatment strategies resulted in significant (p<0.05) improvements of all clinical parameters over the entire duration of the study. Inter-treatment differences were often encountered. The NC group nearly always showed significant smaller improvements than the two CHX groups. The differences between the FRP or FM groups, and the two CHX groups only sporadically reached a statistical significance. These observations indicate that the benefits of the \"OSFMD\" protocol are partially due to the use of the antiseptics and partially to the completion of the therapy in a short time.\nStudy2: Clinical outcomes of quadrant root planing versus full-mouth root planing. To determine the clinical effects of full mouth compared with quadrant wise scaling and root planing. Twenty patients with chronic periodontitis (> or = 2 teeth per quadrant with probing pocket depths (PPD) > or = 5 mm and bleeding on probing (BOP) were randomized into a test group treated in two sessions with subgingival scaling and root planing within 24 h (full-mouth root planing (FMRP)) and a control group treated quadrant by quadrant in four sessions in intervals of 1 week (quadrant root planing (QRP)). PPD, relative attachment level (RAL) and BOP were recorded at baseline, 3 and 6 months. Analysing first quadrant data, in moderately deep pockets (5 mm < or = PPD < 7 mm) there was no evidence for a difference (FMRP-QRP) between both groups for PPD reduction (mean: -0.128 mm; CI: [-0.949, 0.693]; p=0.747), RAL gain (mean: 0.118 mm; CI: [-0.763, 1.000]; p=0.781), and BOP reduction (mean: -20.1%; CI: [-44.3, 4.2]; p=0.099). Likewise, no significant differences between treatments were found for initially deep pockets (PPD > or = 7 mm), neither for first quadrant nor for whole mouth data. The results of the present study demonstrated equally favourable clinical results following both treatment modalities.\n", + "output": "Conclusions: In patients with chronic periodontitis in moderately deep pockets slightly more favourable outcomes for pocket reduction and gain in probing attachment were found following FMD compared to control. However, these additional improvements were only modest and there was only a very limited number of studies available for comparison, thus limiting general conclusions about the clinical benefit of full-mouth disinfection." + }, + { + "input": "Study: Rapid tranquilization of acutely psychotic patients with intramuscular haloperidol and chlorpromazine. nan\n", + "output": "Conclusions: Overall the quality of evidence is limited, poor and dated. Where drugs that have been better evaluated are available, it may be best to avoid use of chlorpromazine. Where chlorpromazine is used for acute aggression or where choices are limited, relevant trials are possible and urgently needed." + }, + { + "input": "Study1: Transitory hyperphenylalaninaemia in children with continuously treated phenylketonuria. Cognitive and behavioral effects of temporarily challenging the CNS with elevated levels of phenylalanine in treated phenylketonuria (PKU) were investigated in a triple-blind, cross-over study. A high phenylalanine supplement was given over 3 months to sixteen 10- to 16-year-old early and continuously treated children with classical PKU. We used the WISC and Rivermead tests to measure cognitive function and the Rutter Scales to assess disordered behavior. Parents and children guessed at the condition imposed. The Group x Phase interaction for phenylalanine level was statistically significant, but this pattern was not mirrored in the psychological test data, and guessing was random. Results suggest that intellectual ability, memory, and conduct are not affected by medium-term hyperphenylalaninaemia in PKU after 10 or more years of treatment.\nStudy2: Termination of restricted diet in children with phenylketonuria: a randomized controlled study. This study demonstrates the feasibility of a randomized controlled investigation of terminating the phenylalanine-restricted diet in four-year-old children with phenylketonuria. The parents of 14 of 16 children gave informed consent, knowing their children would be randomly assigned to either a diet-continuation or a diet-termination group. Compared with the continuation group, the mean serum phenylalanine of the termination group was 15.1 mg per dl higher (P less than 0.005) one year, and 9.2 mg per dl higher (P less than 0.025) two years after diet termination. Mean weight gain between four and six years of age was 3.4 kg greater in the terminated than in the continued group (P less than 0.01). There were no significant differences in mean head circumferences, height or performances on psychologic tests. At age six, mean I.Q. in the terminated group was 99.8, in those continuing the diet 103.6. Children in both groups showed some subtest scatter in memory and concentration. Thus, no harmful effects of diet termination were noted, but a longer period of observation in a larger number of subjects is needed.\nStudy3: Phenylalanine intakes of 1- to 6-year-old children with phenylketonuria undergoing therapy. Mean of median phenylalanine intakes of 1- to 6-yr-old treated phenylketonuria patients who were growing normally were evaluated by age, sex, and treatment group assignment. Total daily means of median phenylalanine intakes of subjects in treatment group 1 were significantly different from those of subjects in treatment group 2 except at the median age of 69 months. Total daily phenylalanine intakes varied from 285 +/- 10 to 453 +/- 30 mg (mean +/- SEM) by subjects in treatment group 1. Total daily phenylalanine intakes of subjects in treatment group 2 varied from 349 +/- 12 to 530 +/- 42 mg (mean +/- SEM). Mean, median phenylalanine intakes by males ranged from 30 mg/kg of body weight by the younger to 23 mg/kg of body weight by the older subjects. Means of median phenylalanine intakes of females varied from 32 mg/kg of body weight by the younger to 21 mg/kg of body weight by the older subjects. No child had a median phenylalanine intake below 10 mg/kg of body weight.\n", + "output": "Conclusions: The results of non-randomised studies have concluded that a low-phenylalanine diet is effective in reducing blood phenylalanine levels and improving intelligence quotient and neuropsychological outcomes. We were unable to find any randomised controlled studies that have assessed the effect of a low-phenylalanine diet versus no diet from diagnosis. In view of evidence from non-randomised studies, such a study would be unethical and it is recommended that low-phenylalanine diet should be commenced at the time of diagnosis. There is uncertainty about the precise level of phenylalanine restriction and when, if ever, the diet should be relaxed. This should be addressed by randomised controlled studies." + }, + { + "input": "Study: Donepezil in the prevention and treatment of post-surgical delirium. Delirium is a frequent complication of major surgery in older persons. The authors evaluated the possible benefit of donepezil versus placebo in the prevention and treatment of postoperative delirium in an older population without dementia undergoing elective total joint-replacement surgery. A sample of 80 patients participated in this randomized, double-blind, placebo-controlled trial of donepezil. Each participant was evaluated before surgery and then received donepezil or placebo for 14 days before surgery and 14 days afterward. Postoperative delirium was assessed with the Delirium Symptom Interview, Confusion Assessment Method, daily medical record, nurse-observation reviews, and DSM-IV diagnostic criteria for delirium. Subsyndromal delirium was also assessed for each participant. Delirium, diagnosed by DSM-IV criteria, was found on at least 1 postoperative day in 18.8% of subjects, but there were no significant differences between the donepezil and placebo groups. When delirium was present, it lasted only 1 day, and there was no difference between the groups. Subsyndromal delirium was found on at least 1 postoperative day for 68.8% of subjects, and, when this occurred, lasted 2 days or less, on average. There was no difference between the groups in the occurrence or duration of subsyndromal delirium. There was no difference between the groups in disposition to home or to another facility. This pilot study was unable to demonstrate a benefit for donepezil in preventing or treating delirium in a relatively young and cognitively-intact group of elderly patients undergoing elective orthopedic surgery. Furthermore, postoperative delirium was not a major problem in this population.\n", + "output": "Conclusions: There is currently no evidence from controlled trials that donepezil is effective in the treatment of delirium. Further trials using cholinesterase inhibitors for the treatment of delirium are needed." + }, + { + "input": "Study1: Diclofenac sodium and occlusal splint therapy in TMJ osteoarthritis: a randomized controlled trial. The aim of the study was to compare treatment with diclofenac sodium (Voltaren 3 x 50 mg) to occlusal splint therapy in a randomized, single-blind controlled trial of patients with a diagnosis of temporomandibular joint (TMJ) osteoarthritis (OA) in accordance with Research Diagnostic Criteria for temporomandibular disorders. Patients with general joint disorders or restrictions against medication with non-steroidal anti-inflammatory drug were not included. Twenty-seven females and two males (aged 36-76 years) included, answered a standardized questionnaire and were clinically examined and they underwent TMJ tomography. The treatment was randomized to either splint (n = 15) or diclofenac (n = 14). The temperatures over the TMJs were determined. The patients were re-examined 1 week, 1 month and 3 months after the start of treatment. A 1-year follow-up was carried out using questionnaires. After 1 week of treatment with diclofenac, significant reductions of pain and discomfort, TMJ tenderness and joint pain on jaw movements were noted. The splint therapy gave a significant reduction of reported symptoms after 1 month of treatment. Both treatments gave few adverse effects and were on an equal level. Estimation of the degree of inflammation by measuring the surface temperature over the TMJ was not reliable. Structural changes of the symptomatic TMJs were radiographically found in 82%, the contralateral, symptom-free TMJ had changes in 36%. There was a discrepancy between the clinical and the radiographical findings. Diclofenac gave a more rapid improvement, but both treatments gave a significant reduction of symptoms of TMJ OA within 3 months which remained at the one-year follow-up.\nStudy2: Osteoarthritis of the temporomandibular joint: an evaluation of the effects and complications of corticosteroid injection compared with injection with sodium hyaluronate. The purpose of this study was to compare the efficacy and the complications of intra-articular temporomandibular joint (TMJ) injections in 40 patients with osteoarthritis of the TMJ. The subjects were randomly divided into two groups, and the patients received either two intra-articular injections with sodium hyaluronate or two intra-articular injections with corticosteroids, 14 days apart. The effect of the treatment was evaluated 14 days, 1 and 6 months after the initial injection and was based on the following measurements: pain intensity, pain localization, joint sounds, mandibular function and complications. Both groups of patients had less pain intensity at the 6-month follow-up, and there was significantly less pain intensity in the group of patients receiving sodium hyaluronate compared with corticosteroids (P = 0.001). A decrease in crepitation was seen in both groups. In the 20 subjects receiving sodium hyaluronate both the mandibular vertical opening and protrusion increased significantly (P < 0.000). Lateral movement from the affected side increased both in subjects injected with sodium hyaluronate (P = 0.024), and those injected with corticosteroids (P = 0.042). In conclusion, this study confirms that injections in the TMJ with sodium hyaluronate or corticosteroids may reduce pain and improve function in patients with osteoarthritis. The injections were more effective in patients with only TMJ pain compared with patients suffering from both TMJ and myofascial pain. Injection with sodium hyaluronate was significantly more effective in decreasing pain intensity than corticosteroids. Temporary pain after injections may be observed.\nStudy3: Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial. To compare the treatment potential of glucosamine sulfate (GS) and ibuprofen in patients diagnosed with temporomandibular joint (TMJ) osteoarthritis (OA). Forty women and 5 men received either GS (500 mg tid) or ibuprofen (400 mg tid) for 90 days in a randomized double blind study. Assessment: TMJ pain with function, pain-free, and voluntary maximum mouth opening, Brief Pain Inventory (BPI) questionnaire and masticatory muscle tenderness were performed after a one week washout and at Day 90. Acetaminophen (500 mg) dispensed for breakthrough pain was counted every 30 days to Day 120. In total, 176 adults were interviewed, 45 (26%) qualified, 39 (87%) completed the study (21 GS, 18 ibuprofen). Four discontinued due to stomach upset (3 ibuprofen, one GS), one due to dizziness (GS), one due to inadequate pain control (ibuprofen). Within-group analysis revealed significant improvement compared to baseline of all variables in both treatment groups but no change in acetaminophen used. Fifteen GS (71%) and 11 ibuprofen (61%) improved, with positive clinical response taken as a 20% decrease in primary outcome (TMJ pain with function). The number of patients with positive clinical response was not statistically different between groups (p = 0.73). Between-group comparison revealed that patients taking GS had a significantly greater decrease in TMJ pain with function, effect of pain, and acetaminophen used between Day 90 and 120 compared with patients taking ibuprofen. GS and ibuprofen reduce pain levels in patients with TMJ degenerative joint disease. In the subgroup that met the initial efficacy criteria, GS had a significantly greater influence in reducing pain produced during function and effect of pain with daily activities. GS has a carryover effect.\n", + "output": "Conclusions: In view of the paucity of high level evidence for the effectiveness of interventions for the management of TMJ OA, small parallel group RCTs which include participants with a clear diagnosis of TMJ OA should be encouraged and especially studies evaluating some of the possible surgical interventions." + }, + { + "input": "Study1: Botulinum toxin type A for control of drooling in Asian patients with cerebral palsy. nan\nStudy2: Randomized trial of botulinum toxin injections into the salivary glands to reduce drooling in children with neurological disorders. The primary aim of this randomized, controlled trial was to assess the effectiveness of botulinum toxin A (BoNT-A) injections into the submandibular and parotid glands on drooling in children with cerebral palsy (CP) and other neurological disorders. Secondary aims were to ascertain the duration of any such effect and the timing of maximal response. Of the 48 participants (27 males, 21 females; mean age 11y 4mo [SD 3y 3mo], range 6-18y), 31 had a diagnosis of CP and 15 had a primary intellectual disability; 27 children were non-ambulant. Twenty-four children randomized to the treatment group received 25 units of BoNT-A into each parotid and submandibular gland. Those randomized to the control group received no treatment. The degree and impact of drooling was assessed by carers using the Drooling Impact Scale questionnaire at baseline and at monthly intervals up to 6 months postinjection/baseline, and again at 1 year. Maximal response was at 1 month at which time there was a highly significant difference in the mean scores between the groups. This difference remained statistically significant at 6 months. Four children failed to respond to the injections, four had mediocre results, and 16 had good results. While the use of BoNT-A can help to manage drooling in many children with neurological disorders, further research is needed to fully understand the range of responses.\nStudy3: Treatment of sialorrhea with glycopyrrolate: A double-blind, dose-ranging study. To determine the safety and efficacy of glycopyrrolate in the treatment of developmentally disabled children with sialorrhea. Placebo-controlled, double-blind, crossover dose-ranging study. Outpatient facilities in 2 pediatric hospitals. Thirty-nine children with both developmental disabilities and excessive and bothersome sialorrhea. Parent and investigator evaluation of change in sialorrhea and adverse effects. Glycopyrrolate in doses of 0.10 mg/kg per dose is effective at controlling sialorrhea. Even at low doses, 20% of children may exhibit adverse effects severe enough to require discontinuation. Glycopyrrolate is effective in the control of excessive sialorrhea in children with developmental disabilities. Approximately 20% of children given glycopyrrolate may experience substantial adverse effects, enough to require discontinuation of medication. Arch Pediatr Adolesc Med. 2000;154:1214-1218.\nStudy4: Effect of botulinum toxin in the treatment of drooling: a controlled clinical trial. To investigate the clinical effectiveness of botulinum neurotoxin type A (BoNT) to reduce drooling in children with cerebral palsy (CP). A controlled clinical trial was performed in which the results of single-dose BoNT injections in the submandibular glands were compared with treatment with scopolamine. Forty-five children who had CP and experienced severe drooling were enrolled. Drooling severity was measured at baseline, during application of scopolamine, and at different intervals after BoNT injections up to 24 weeks, using the Drooling Quotient (DQ), the Teacher Drooling Scale (TDS), and Visual Analog Scales (VAS). Drooling was reduced during scopolamine application as well as after BoNT injections. Compared with baseline, the mean DQ showed a significant decrease throughout the study. Greatest reductions were achieved 2 to 8 weeks after BoNT injection. No significant differences were found between scopolamine measurements and those up to 24 months after BoNT injection. Using VAS, parents recorded the effect on drooling in which significant differences were found between baseline VAS score and all follow-up assessments. According to our definition of \"success to therapy,\" demanding a 2-point decrease on the TDS, 61.5% of patients responded to BoNT injections. Analysis of the DQ demonstrated a response rate of 53% of the patients to scopolamine and 48.7% to BoNT until 24 weeks after BoNT injections, the actual duration of this study. As a reaction to scopolamine, 71.1% of the patients had moderate to severe side effects. Only nonsevere, incidental side effects were reported after BoNT injections. During scopolamine application as well as after intraglandular BoNT injections, a clinically relevant reduction in drooling was achieved in children with CP, demonstrating maximum effect 2 to 8 weeks after injections. This is the first controlled clinical trial that confirmed a significant effect of BoNT injections in the treatment of drooling. General anesthesia was needed for all children. BoNT injections show fewer and less serious side effects than transdermal scopolamine treatment.\n", + "output": "Conclusions: It was not possible to reach a conclusion on the effectiveness and safety of either BoNT-A or the pharmaceutical interventions, benztropine and glycopyrrolate. There is insufficient evidence to inform clinical practice on interventions for drooling in children with CP. Directions for future research are provided." + }, + { + "input": "Study1: A double-blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow-release oral morphine versus methadone in opioid-dependent in-patients willing to undergo detoxification. Evaluation of the efficacy and safety of slow-release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment. Randomized, double-blind, double-dummy, comparative multi-centre study with parallel groups. Three psychiatric hospitals in Austria specializing in in-patient detoxification. Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence. Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days. Efficacy analyses were based on the number of patients per treatment group completing the study, as well as on the control of signs and symptoms of withdrawal [measured using Short Opioid Withdrawal Scale (SOWS)] and suppression of opiate craving. In addition, self-reported somatic and psychic symptoms (measured using Symptom Checklist SCL-90-R) were monitored. Of the 208 patients enrolled into the study, 202 were eligible for analysis (SROM: n = 102, methadone: n = 100). Completion rates were 51% in the SROM group and 49% in the methadone group [difference between groups: 2%; 95% confidence interval (CI): -12% to 16%]. The rate of discontinuation in the study was high mainly because of patients voluntarily withdrawing from treatment. No statistically significant differences between treatment groups were found in terms of signs and symptoms of opiate withdrawal, craving for opiates or self-reported symptoms. SROM and methadone were both well tolerated. Detoxification from maintenance treatment with tapered dose reduction of SROM is non-inferior to methadone.\nStudy2: Withdrawal from heroin in three or six weeks. Comparison of methadyl acetate and methadone. A randomized clinical trial compared four methods of outpatient withdrawal from heroin. Sixty-one subjects were assigned in a double-blind manner to treatment with either methadone or methadyl acetate. Within each drug group, subjects were assigned to detoxification programs either within the standard three-week period or in an extended six weeks of treatment. Outcome measures included retention to the end of the dosing schedule, use of illicit drugs during treatment, subjective discomfort, satisfaction, staff ratings of global progress, and durability of change at a three-month follow-up. Methadyl acetate performed similarly to methadone in most respects. Six-week withdrawal showed some temporary benefits over standard treatment, but these advantages should be weighed against the greater cost of the longer treatment and similarity of follow-up outcome.\n", + "output": "Conclusions: Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long-\nacting opioids, can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use." + }, + { + "input": "Study1: The effect of drinking and driving interventions on alcohol-involved traffic crashes within a comprehensive community trial. The Drinking and Driving Component, one of five elements of the Community Trials Project, involved the implementation of a special drink driving countermeasure in the three experimental communities, one in Northern California, one in Southern California and another in South Carolina. This intensified enforcement of driving under the influence (DUI) was designed to deter potential drinking drivers by increasing their perception of the risk of being arrested leading to a reduction in the consumption of alcohol before driving. See component detailed description in Voas (1997, this issue). The evaluation found that media advocacy training and technical assistance resulted in increased DUI news coverage and that additional police officer hours for DUI enforcement, greater use of breathalyzer equipment, increased officer training and more checkpoints produced increased DUI enforcement. The combined effects of increased DUI news coverage and DUI enforcement yielded increased public perceived risk of arrest and subsequently less drinking and driving. Overall the evaluation found that alcohol-involved traffic crashes were reduced as a result of this component in the experimental communities as contrasted with the matched comparison communities.\nStudy2: Operation safe crossing: using science within a community intervention. To evaluate a large drunk-driving enforcement program at the US/Mexican border to reduce the number of youths crossing the border to drink in Tijuana. This paper also describes the research data used to develop and manage the program. Data from a border breath-test survey were used to dramatize the problem and gain public support for action. The data were also used to help design the enforcement effort and measure progress in reducing the cross-border drinking problem. The number of news events generated around the occurrence of special enforcement efforts were used to measure project activity and to predict changes in the numbers of youths crossing into Mexico, their returning BACs and reductions in alcohol-related crashes during a 3-year period. An urban county on the Mexican border. Underage youths aged 18-20 years and young adults aged 21-30 years residing in San Diego County. Immigration and Naturalization Services provided population counts of the number of individuals crossing each weekend night from Tijuana into the United States through the San Ysidro border facility. Breath-test surveys of a random sample of these returning crossers provided data on the number of US residents visiting bars and nightclubs in Tijuana and on alcohol consumption at Tijuana bars and nightclubs. Night-time had-been-drinking crash data involving young drivers in several California counties served as an outcome measure of public health and safety. Analysis of data involving more than 2 million pedestrians returning from Tijuana indicated that the Operation Safe Crossing program reduced the number of late-night crossers by 31.6%. Effective use of data through media advocacy programs to support an enforcement effort can reduce alcohol-related crashes.\nStudy3: Deterring the drinking driver: the Stockton experience. The effectiveness of drunk driving enforcement patrols is generally assumed. However, few adequate evaluations are available in the traffic safety literature. The U.S. Department of Transportation funded a special program in Stockton, a city with a population of 120,000 in the central valley of California, to test the effectiveness of special drunk driving patrols on weekend evenings, applied within a setting in which no other major alcohol safety programs were present. The objective of this effort was to determine the effectiveness of a \"traditional\" approach to enforcing driving while impaired (DWI) laws; one in which innovative procedures such as sobriety checkpoints were not used. The results indicated that nighttime collisions in Stockton were reduced during the three and a half year period of the special enforcement program.\nStudy4: Reducing alcohol-impaired driving in Massachusetts: the Saving Lives Program. The purpose of this study ws to assess whether a community program begun in March 1988 that organized multiple city departments and private citizens could reduce alcohol-impaired driving, related driving risks, and traffic deaths and injuries. Trends in fatal crashes and injuries per 100 crashes were compared in Saving Lives Program cities and the rest of Massachusetts from March 1984 through February 1993. In annual roadside surveys conducted at randomly selected locations, safety belt use among occupants of 54577 vehicles and travel speeds of 118442 vehicles were observed. Four statewide telephone surveys (n = 15188) monitored self-reported driving after drinking. In program cities relative to the rest of Massachusetts during the 5 program years in comparison with the previous 5 years, fatal crashes declined 25%, from 178 to 120, and fatal crashes involving alcohol decreased 42%, from 69 to 36. Visible injuries per 100 crashes declined 5%, from 21.1 to 16.6. The proportions of vehicles observed speeding and teenagers who drove after drinking were cut in half. Interventions organized by multiple city departments and private citizens can reduce driving after drinking, related driving risks, and traffic deaths and injuries.\n", + "output": "Conclusions: Studies examining increased police patrol programs were generally consistent in reporting beneficial effects on traffic crashes and fatalities, but study quality and reporting were often poor. Methodological limitations included inadequate sample size, dissimilar baseline measures, contamination, and inadequate data analysis. Thus existing evidence, although supportive, does not firmly establish whether increased police patrols, implemented with or without other intervention elements, reduce the adverse consequences of alcohol-impaired driving." + }, + { + "input": "Study: Mental health of children in foster and kinship care in New South Wales, Australia. To report baseline mental health measures from the Children in Care study, a prospective epidemiological study of children in court-ordered foster and kinship care in New South Wales, Australia. Mental health, socialization and self-esteem were assessed in 347 children in a statewide mail survey, using two carer-report checklists, the Child Behavior Checklist (CBCL) and the Assessment Checklist for Children (ACC). Children in the study had exceptionally poor mental health and socialization, both in absolute terms, and relative to normative and in-care samples. Levels and rates of disturbance for children in foster care exceeded all prior estimates. Rates of disturbance for children in kinship care were high, but within the range of prior estimates. Boys presented with higher scope and severity of mental health problems than girls on the CBCL, while gender-specific patterns of disturbance were shown on the ACC. A moderate age effect was accounted for by children's age at entry into care. Children in care are at high risk of mental health problems. Psychological support for the children and their carers is an essential secondary prevention strategy. Implications for service delivery are discussed.\n", + "output": "Conclusions: This review supports the practice of treating kinship care as a viable out-of-home placement option for children removed from the home for maltreatment. However, this conclusion is tempered by the pronounced methodological and design weaknesses of the included studies." + }, + { + "input": "Study: A comparative study of the safety and efficacy of FemCap, a new vaginal barrier contraceptive, and the Ortho All-Flex diaphragm. The FemCap Investigators' Group. The FemCap is a new silicone rubber barrier contraceptive shaped like a sailor's hat, with a dome that covers the cervix, a rim that fits into the fornices, and a brim that conforms to the vaginal walls around the cervix. It was designed to result in fewer dislodgments and less pressure on the urethra than the cervical cap and diaphragm, respectively, and to require less clinician time for fitting. This was a phase II/III, multicenter, randomized, open-label, parallel group study of 841 women at risk for pregnancy. A subset of 42 women at one site underwent colposcopy. Women were randomized to use the FemCap or Ortho All-Flex contraceptive diaphragm, both with 2% nonoxynol-9 spermicide, for 28 weeks. The objectives were to compare the two devices with regard to their safety and acceptability and to determine whether the probability of pregnancy among FemCap users was no worse than that of the diaphragm (meaning not more than 6 percentage points higher). The 6-month Kaplan-Meier cumulative unadjusted typical use pregnancy probabilities were 13.5% among FemCap users and 7.9% among diaphragm users. The adjusted risk of pregnancy among FemCap users was 1.96 times that among diaphragm users, with an upper 95% confidence limit of 3.01. Clinical equivalence (noninferiority) of the FemCap compared with the diaphragm, as defined in this study, would mean that the true risk of pregnancy among FemCap users was no more than 1.73 times the pregnancy risk of diaphragm users. Because the observed upper 95% confidence limit (and even the point estimate) exceeded 1.73, the probability of pregnancy among FemCap users, compared with that among diaphragm users, did not meet the definition of clinical equivalence used in this study. The FemCap was believed to be safe and was associated with significantly fewer urinary tract infections. More women reported problems with the FemCap with regard to insertion, dislodgement, and especially removal, although their general assessments were positive. The two devices were comparable with regard to safety and acceptability, but a 6-point difference in the true 6-month pregnancy probabilities of the two devices could not be ruled out. Further studies are needed to determine whether design modifications can simplify insertion and removal.\n", + "output": "Conclusions: The Prentif cap was as effective as its comparison diaphragm in preventing pregnancy, but the FemCap was not. Both cervical caps appear to be medically safe." + }, + { + "input": "Study: A prospective, randomized multicenter study comparing APD and CAPD treatment. The goals for maintenance dialysis treatment are to improve patient survival, reduce patient morbidity, and improve patient quality of life. This is the first randomized prospective study comparing automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) treatment with respect to quality of life and clinical outcomes in relation to therapy costs. A prospective, randomized multicenter study. Three Danish CAPD units. Thirty-four adequately dialyzed patients with high or high-average peritoneal transport characteristics were included in the study.Twenty-five patients completed the study. After randomization, 17 patients were allocated to APD treatment and 17 patients to CAPD treatment for a period of 6 months. Medical and biochemical parameters were evaluated at monthly controls in the CAPD units. Quality-of-life parameters were assessed at baseline and after 6 months by the self-administered short-form SF-36 generic health survey questionnaire supplemented with disease- and treatment-specific questions. Therapy costs were compared by evaluating dialysis-related expenses. Quality-of-life parameters, dialysis-related complications, dialysis-related expenses. The quality-of-life studies showed that significantly more time for work, family, and social activities was available to patients on APD compared to those on CAPD (p < 0.001). Although the difference was not significant, there was a tendency for less physical and emotional discomfort caused by dialysis fluid in the APD group. Sleep problems, on the other hand, tended to be more marked in the APD group. Any positive effect of APD compared to CAPD on dialysis-related hospital days or complication rates could not be confirmed. With larger patient samples, it is possible, however, that a significant difference might have been achieved. The running costs for APD treatment were US $75 per day and for CAPD treatment US $61 per day. If APD treatment can help to keep selected patients vocationally or socially active, paying the extra cost seems reasonable.\n", + "output": "Conclusions: APD has not been shown to have significant advantages over CAPD in terms of important clinical outcomes. APD may however be considered advantageous in select group of patients such as in the younger PD population and those in employment or education due to its psychosocial advantages. There is a need for a RCT comparing CAPD with APD with sufficiently large patient numbers looking at important clinical outcomes including residual renal function, accompanied by an economic evaluation to clarify the relative clinical and cost-effectiveness of both modalities." + }, + { + "input": "Study1: Adenoidectomy: selection criteria for surgical cases of otitis media. Nasopharyngeal adenoids may serve as a mechanical obstruction to the eustachian tube and contribute to the pathophysiology of otitis media (OM). The purpose of this study was to determine whether abutment of adenoids laterally against the torus tubaris affects the outcome of patients requiring pressure equalization tubes (PET) for OM. Randomized, controlled, prospective clinical trial. Patients requiring PET for recurrent acute OM or OM with persistent effusion were randomized into two groups: 1) PET placement and 2) PET placement and adenoidectomy, regardless of whether the adenoids were abutting or not abutting the torus tubaris. Patients were followed for a minimum of 1 year to determine rate of treatment failure, defined as recurrence of acute OM (>3 times/year), OM with effusion, or reinsertion of PET. Of the 34 patients in the abutting group, 16 patients underwent only PET insertion, of whom 8 (50%) failed, whereas 18 patients had combined PET placement and adenoidectomy, of whom 3 (17%) failed. There was a statistical difference between these two groups (P < 05). Of the 29 patients in the nonabutting group, 24 patients underwent only PET insertion, of whom 9 (37.5%) failed, whereas 5 patients underwent combined PET placement and adenoidectomy, of whom 2 (40%) failed. There was no statistical difference between these two groups (P =.92). This study demonstrates that the position of hypertrophied adenoids may alter the final otologic outcome of patients requiring PET insertion for OM. Patients with adenoids abutting the torus tubaris may benefit most from an adjuvant adenoidectomy.\nStudy2: Efficacy of adenoidectomy for recurrent otitis media in children previously treated with tympanostomy-tube placement. Results of parallel randomized and nonrandomized trials. We studied the efficacy of adenoidectomy in 213 children who had received tympanostomy-tube placement because of persistent and/or recurrent otitis media and had again developed otitis media after tubal extrusion. Ninety-nine of the children were assigned randomly to either an adenoidectomy group or a control group; in a separate trial, 114 children whose parents withheld consent for randomization were assigned according to parental preference. In both trials, control group outcomes appeared to have been biased favorably by the withdrawal of certain severely affected subjects from control status to receive adenoidectomy. Nonetheless, in both trials, adenoidectomy group outcomes were more favorable than control group outcomes during the first 2 follow-up years. Statistically significant differences were found mainly in the randomized trial, where during the first and second years, respectively, adenoidectomy subjects had 47% and 37% less time with otitis media than control subjects and 28% and 35% fewer suppurative (acute) episodes than control subjects. We conclude that adenoidectomy is warranted on an individualized basis for children who develop recurrent otitis media after extrusion of tympanostomy tubes.\nStudy3: Adenoidectomy for middle ear disorders: a randomized controlled trial. Repeated tympanometric screening of a regionally defined population of 3-year-old children defined a group of 42 children with middle ear disease which had persisted for at least 6 months. These children were treated by either myringotomy with adenoidectomy or myringotomy without adenoidectomy decided by random allocation. Postoperative observation during 6 months failed to disclose any difference in middle ear status between the two groups.\nStudy4: Adenoidectomy for otitis media with mucoid effusion. This random controlled study was undertaken to determine the extent to which nonsurgical treatment can control otitis media with effusion (OME); and if surgical treatment is indicated, and myringotomy, removal of middle ear liquid with insertion of aeration tubes is carried out, and whether removal of the adenoids produces any beneficial effect. A preparatory two-month nonsurgical treatment consisting of measures to improve the functional state of the nose was undertaken to eliminate from the study those children (42%) who would respond to medical treatment alone. The cure rate was similar in each of the operation groups with a greater relapse rate in the nonadenoidectomy groups who required 9% more aeration tube insertions. An estimation from x-rays of the size of the adenoids, shows that the group cured without surgery has a tendency towards the smaller adneoids. The relapse rate in the nonadenoidectomy group was independent of the size of the adenoids, and the study failed to show that any benefit accrued though adenoidectomy. Accordingly, the removal of adenoids should cease to be indicated in cases of OME as a primary form of treatment.\nStudy5: Effectiveness of adenoidectomy and tympanostomy tubes in the treatment of chronic otitis media with effusion. To study the effectiveness of adenoidectomy and of the placement of tympanostomy tubes in the treatment of chronic otitis media with effusion, we randomly assigned 578 children, aged four through eight years, to receive bilateral myringotomy and no additional treatment (Group 1), placement of tympanostomy tubes (Group 2), adenoidectomy (Group 3), or adenoidectomy and placement of tympanostomy tubes (Group 4). The 491 children who underwent one of these treatments were examined at six-week intervals for up to two years. The mean time spent with effusion of any type in either ear over the two-year follow-up in the four groups was 51, 36, 31, and 27 weeks, respectively (P less than 0.0001), comparing Group 1 with each of the other groups. Hearing was equivalent in Groups 2, 3, and 4, and was significantly better than in Group 1. The most frequent sequela, purulent otorrhea, occurred one or more times in 22, 29, 11, and 24 percent of the subjects in Groups 1, 2, 3, and 4, respectively (P less than 0.001). Adenoidectomy plus bilateral myringotomy lowered the overall post-treatment morbidity (as measured by hearing acuity in the most severely affected ear [P = 0.0174] and the number of surgical retreatments required [P = 0.009]) more than did tympanostomy tubes alone and to the same degree as did adenoidectomy and tympanostomy tubes. We conclude that adenoidectomy should be considered when surgical therapy is indicated in children four to eight years old who are severely affected by chronic otitis media with effusion.\nStudy6: Adenoidectomy versus chemoprophylaxis and placebo for recurrent acute otitis media in children aged under 2 years: randomised controlled trial. To evaluate the efficacy of adenoidectomy compared with long term chemoprophylaxis and placebo in the prevention of recurrent acute otitis media in children aged between 10 months and 2 years. Randomised, double blind, controlled trial. Oulu University Hospital, a tertiary centre in Finland. 180 children aged 10 months to 2 years with recurrent acute otitis media. Adenoidectomy, sulfafurazole (sulphisoxazole) 50 mg/kg body weight, given once a day for six months or placebo. Follow up lasted for two years, during which time all symptoms and episodes of acute otitis media were recorded. Intervention failure (two episodes in two months or three in six months or persistent effusion) during follow up, number of episodes of acute otitis media, number of visits to a doctor because of any infection, and antibiotic prescriptions Number of prescriptions, and days with symptoms of respiratory infection. Compared with placebo, interventions failed during both the first six months and the rest of the follow up period of 24 months similarly in the adenoidectomy and chemoprophylaxis groups (at six months the differences in risk were 10% (95% confidence interval -9% to 29%) and 18% (-2% to 38%), respectively). No significant differences were observed between the groups in the numbers of episodes of acute otitis media, visits to a doctor, antibiotic prescriptions, and days with symptoms of respiratory infection. Adenoidectomy, as the first surgical treatment of children aged 10 to 24 months with recurrent acute otitis media, is not effective in preventing further episodes. It cannot be recommended as the primary method of prophylaxis.\nStudy7: A randomized study of the surgical management of children with persistent otitis media with effusion associated with a hearing impairment. The object of this study was to compare the effect on the hearing of the insertion of a grommet, with or without adenoidectomy, against a non-surgically managed control ear in children with persistent hearing impairment due to otitis media with effusion. Seventy-eight children (44 boys, 34 girls, mean age 5.8 years) with documented bilateral otitis media with effusion associated with a bilateral hearing impairment (pure tone average air conduction thresholds over 0.5, 1 and 2 kHz of > or = 25 dB HL) over a three month period were admitted to a randomized, controlled trial. Each child was randomized to have or not to have an adenoidectomy. The ears in each child were then randomly allocated to have a grommet (tympanostomy tube) inserted. The children's hearing status was reviewed six and 12 months post-operatively. During follow-up, should a child redevelop a persistent bilateral hearing impairment (as defined above) for three months they were managed with a hearing aid. Thus no child had repeat insertion of a grommet. Surgery of each type had an effect on the hearing and the presence of otitis media with effusion at six months post-operatively but not at 12 months when it was no different from natural resolution. If resolution of the otitis media with effusion is the outcome measure, then adenoidectomy alone is significantly better than no surgery but only in boys rather than in girls. Even in boys it only resolves about 60 per cent of effusions. However, when combined with a grommet (one insertion) adenoidectomy gives no greater resolution (89 per cent compared with 86 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy8: Otoscopic, impedance, and audiometric findings in glue ear treated by adenoidectomy and tonsillectomy. A prospective randomised study. 150 children aged between 2 and 9 years (mean 5.25 years) with chronic bilateral otitis media with effusion were randomly allocated to three groups who, in addition to unilateral myringotomy and grommet insertion, would have an adenotonsillectomy, an adenoidectomy, or neither. The contralateral ear was assessed. Otoscopic, impedance, and audiometric findings were recorded preoperatively and at six and twelve months postoperatively. Subtraction of the no-surgery results indicates that at twelve months adenoidectomy produces otoscopic resolution of OME in 41.7% and no-peak/peak conversion of impedance in 29.8%. The hearing gain from adenoidectomy alone was similar to that resulting from insertion of a grommet alone, but the children having adenoidectomy required fewer reinsertions to maintain adequate subjective hearing thresholds in the treated ear (26% versus 54%). Tonsillectomy conferred no additional benefit. Without treatment there was a small but significant improvement in all indices at twelve months but not at six months postoperatively.\nStudy9: Adenoidectomy and adenotonsillectomy for recurrent acute otitis media: parallel randomized clinical trials in children not previously treated with tympanostomy tubes. Adenoidectomy and adenotonsillectomy are commonly performed in US children to reduce the occurrence of persistent or recurrent otitis media, but evidence supporting the efficacy of the operations is limited. To test the efficacy of adenoidectomy and adenotonsillectomy in children with persistent or recurrent otitis media who had not previously undergone tube placement and to compare the relative efficacy of adenoidectomy alone vs adenotonsillectomy in such children. Two parallel randomized clinical trials. A total of 461 children aged 3 to 15 years were enrolled at Children's Hospital of Pittsburgh, Pa, between April 1980 and April 1994. Four hundred ten children were observed for up to 3 years. Children without recurrent throat infection or tonsillar hypertrophy (304 enrolled; 266 followed up) were randomized to either an adenoidectomy, adenotonsillectomy, or control group; children who had such conditions (157 enrolled; 144 followed up) were randomized to an adenotonsillectomy or control group. Occurrence rate of episodes of acute otitis media by treatment group and estimated proportion of time with otitis media. In both trials, most subjects were eligible because of recurrent acute otitis media, with or without persistent otitis media with effusion. A total of 47 children assigned to surgical treatment groups had no surgery. The efficacy of surgery in both trials was modest and limited mainly to the first follow-up year. The largest differences in that year were found in the 3-way trial between the adenotonsillectomy group and the control group: mean annual rate of episodes of acute otitis media, 1.4 vs 2.1 (P<.001); and mean estimated percentage of time with otitis media, 18.6% vs 29.9% (difference, 11.3%; 95% confidence interval, 4.4%-18.2%; P=.002). Perioperative and postoperative complications or other adverse events occurred not infrequently, especially among subjects undergoing adenotonsillectomy (14.6%). Our study showed limited and short-term efficacy of both adenoidectomy and adenotonsillectomy; given the risks, morbidity, and costs of these procedures, these data suggest that neither operation should ordinarily be considered as a first surgical intervention in children whose only indication is recurrent acute otitis media.\nStudy10: Effects of adenoidectomy: a controlled two-year follow-up. A prospective controlled study was made on the effect of adenoidectomy performed on 105 children. For various reasons, mainly severe long-standing nasal obstruction, 29 children were omitted from the study. The remaining 76 children were randomly divided into two groups, one adenoidectomy, and one control. Both groups were slightly reduced in number due to drop out. Thus 36 adenoidectomized children were followed during one year and 35 children during two years. The corresponding numbers for the children in the control group were 37 and 33. The incidence of common cold, purulent and serous otitis media and moderate nasal obstruction was compared in the two groups. A considerable reduction in the incidence of these variables was observed in both groups. The occurrence of moderate nasal obstruction was reduced more among the operated than among the unoperated children. The difference was only slightly significant during the first and not at all during the second year. Regarding the other variables, the differences were not significant, implying that adenoidectomy seems to have no effect on the incidence of common cold, serous and purulent otitis media.\n", + "output": "Conclusions: Our review shows a significant benefit of adenoidectomy as far as the resolution of middle ear effusion in children with OME is concerned. However, the benefit to hearing is small and the effects on changes in the tympanic membrane are unknown. The risks of operating should be weighed against these potential benefits.\nThe absence of a significant benefit of adenoidectomy on AOM suggests that routine surgery for this indication is not warranted." + }, + { + "input": "Study1: Effects of volume-targeted synchronized intermittent mandatory ventilation on spontaneous episodes of hypoxemia in preterm infants. BACKGROUND: Hypoxemic episodes in ventilated preterm infants are frequently caused by reduced ventilation due to a decrease in lung volume and acute worsening of respiratory mechanics. OBJECTIVE: To compare the efficacy of conventional time-cycled, pressure-limited flow synchronized intermittent mandatory ventilation (SIMV) and volume-targeted SIMV (VT-SIMV) in reducing the frequency and severity of these episodes. METHODS: SIMV and VT-SIMV were compared in preterm infants with frequent spontaneous episodes of hypoxemia. VT-SIMV was provided with the Draeger Babylog 8000plus ventilator in volume-guarantee mode. Results: In all, 32 infants (birth weight 668 +/- 126 g, gestational age 24.8 +/- 1.1 weeks, age 37.5 +/- 17.3 days) were studied during 2-hour periods of SIMV and VT-SIMV in random sequence. In an initial phase, a group of 12 infants was supported during VT-SIMV with a target tidal volume of 4.5 ml/kg (VT-SIMV 4.5). A planned interim analysis did not show differences in frequency and duration of hypoxemia between VT-SIMV 4.5 and SIMV, and the initial phase was stopped. In a second phase of the study, 20 infants were studied while supported with a target tidal volume of 6.0 ml/kg during VT-SIMV (VT-SIMV 6.0). In the second phase of the study, the frequency of the hypoxemic episodes did not change but the mean episode duration was shorter during VT-SIMV compared to SIMV. The proportion of mechanical breaths with small tidal volumes (< or =3 ml/kg) was reduced during VT-SIMV 6.0 versus SIMV, while the peak inspiratory pressure and mean airway pressure were increased. Conclusion: VT-SIMV did not reduce the frequency of hypoxemic episodes, but VT-SIMV 6.0 was effective in reducing the duration of the hypoxemic episodes.\nStudy2: Is there an advantage of using pressure support ventilation with volume guarantee in the initial management of premature infants with respiratory distress syndrome? A pilot study. To evaluate the feasibility of using the pressure support ventilation with volume guarantee (PSV-VG) as an initial ventilatory mode in preterm infants with respiratory distress syndrome (RDS) after surfactant treatment to achieve accelerated weaning of peak inspiratory pressure (PIP) and mean airway pressure (MAP). Initial 24-hour ventilatory parameters were compared in two groups of preterm infants managed by PSV-VG and the synchronized intermittent mandatory ventilation (SIMV) mode in a randomized controlled pilot study after surfactant treatment for RDS. A total of 16 babies were randomized to PSV-VG (1198+/-108 g [mean+/-SEM]; 27.9+/-0.6 weeks) and 18 babies to SIMV (birth weight 1055+/-77 g; gestational age 27.4+/-0.5 weeks). Repeated measures analysis of variance was used to compare serial values of PIP and MAP in the two groups. The PIP and MAP decreased over time (p<0.001) during the first 24 hours after surfactant administration in both groups but the decrease in MAP was faster in the SIMV group compared to PSV-VG group (p=0.035). The median numbers of blood gases during the first 24 hours were four and two in the SIMV and PSV-VG groups, respectively (p<0.001). The overall outcomes were not significantly different between the two groups. PSV-VG did not offer any ventilatory advantage over SIMV in the initial management of surfactant-treated premature newborns with RDS except for minimizing the number of blood gases.\nStudy3: Volume-controlled intermittent mandatory ventilation in preterm infants with hypoxemic episodes. To test the hypothesis in ventilated very low birth weight infants with frequent hypoxemic episodes that volume-controlled synchronized intermittent mandatory ventilation (SIMV) vs. pressure-controlled SIMV reduces by at least 20% the time with hypoxemia (defined as SpO(2)<80%). Randomized cross-over design. University-based tertiary neonatal intensive care unit. 15 mechanically ventilated very low birth weight infants with frequent hypoxemic episodes. The infants were exposed in random order to volume-controlled and pressure-controlled SIMV for 4 h each. The target tidal volume during volume-controlled SIMV was matched to the tidal volume measured during pressure-controlled SIMV. FIO(2) was adjusted using uniform criteria to maintain SpO(2) within the target range (SpO(2) 80-92%). Primary outcome measure was the time with an SpO(2)<80%. Although tidal volume was maintained better during desaturations with volume-controlled SIMV, there was neither a significant difference in time with an SpO(2)<80% (expressed as proportion of total experimental time; median, interquartile range)-volume-control 10.6% (9.2-13.7%) vs. pressure-control 10.8% (8.3-13.3%)-nor in FIO(2) exposure. During volume-controlled SIMV the infants spent less time with an SpO(2) above the target range and had fewer associated bradycardias. Volume-controlled SIMV did not decrease the time with an SpO(2)<80%, although tidal volume was better maintained during these episodes and bradycardias were less frequent than with pressure-controlled SIMV in this population of very low birth weight infants with frequent hypoxemic episodes.\nStudy4: Patient-initiated, pressure-regulated, volume-controlled ventilation compared with intermittent mandatory ventilation in neonates: a prospective, randomised study. To compare the effects of patient-initiated, pressure-regulated, volume-controlled ventilation (PRVC) with pressure-preset intermittent mandatory ventilation (IMV) in neonates with respiratory failure. Randomised, prospective study. Intensive care unit (14 beds) in a 300-bed paediatric teaching hospital. 60 neonates with respiratory distress syndrome (RDS) or congenital pneumonia, weighing < 2500 g and requiring mechanical ventilation. Ventilatory support until extubation via either IMV (n = 30) or PRVC (n = 27). In PRVC, the tidal volume (VT) was preset and pressure-controlled breaths delivered with peak inspiratory pressure values adapted to achieve the preset VT. Main outcome measures were duration of ventilation and incidence of bronchopulmonary dysplasia (BPD). Pulmonary air leaks and intraventricular haemorrhage (IVH) were considered major adverse effects. Demographic data, ventilation parameters and arterial/alveolar oxygen tension ratio were similar at randomisation. Duration of ventilation and incidence of BPD were not decreased by the use of PRVC. Air leaks occurred in 3 neonates in the PRVC group and in 7 babies treated with IMV (NS). The incidence of IVH grade > II was lower in babies treated with PRVC (p < 0.05). In a subgroup of neonates weighing < 1000 g, the duration of ventilation and incidence of hypotension were reduced in the PRVC group (p < 0.05). Patient-initiated, pressure-regulated, volume-controlled ventilation can be safely used in neonates and may contribute to a lower incidence of complications.\nStudy5: Impact of targeted-volume ventilation on lung inflammatory response in preterm infants with respiratory distress syndrome (RDS). Volutrauma and pulmonary inflammation are thought to be the most important predisposing factors of chronic lung disease (CLD), a major complication of prematurity. A new option in patient-triggered ventilation (PTV), the volume guarantee (VG), a volume-targeted ventilation, seems to be a promising approach in reducing the risk of CLD, by limiting lung inflammatory injury and volutrauma. Our aim was to evaluate lung inflammatory response in preterm infants with respiratory distress syndrome (RDS), mechanically ventilated with and without VG, as measured by proinflammatory cytokines (IL-6, IL-8, and TNF-alpha) in tracheobronchial aspirate (TA) fluid. Fifty-three preterm infants (GA = 25-32 weeks) with RDS were randomized at birth to be ventilated using pressure support ventilation (PSV) with VG (Vt = 5 ml/kg) (n = 30) and without VG (n = 23) (Draeger Babylog 8000 Plus, 5.n). IL-6, IL-8, and TNF-alpha were determined by ELISA in TA samples on days 1, 3, and 7 of life. We observed a significant difference (ANOVA) in IL-8 and IL-6 levels on day 3 between the two groups (P < 0.05), and an increasing significative trend in IL-8 values in PSV group (P < 0.05). Mechanical ventilation lasted longer in the PSV group (12.3 +/- 3 vs. 8.8 +/- 3 days) (P = no significance). In conclusion, these preliminary data suggest a role for volume-targeted ventilatory strategy in reducing acute inflammatory response in preterm infants with RDS. Further studies are required in order to define whether this ventilatory strategy prevents lung injury. Copyright 2004 Wiley-Liss, Inc.\nStudy6: Effects of volume-guaranteed synchronized intermittent mandatory ventilation in preterm infants recovering from respiratory failure. Volume guarantee (synchronized intermittent mandatory ventilation [SIMV]+VG) is a novel mode of SIMV for automatic adjustment of the peak inspiratory pressure to ensure a minimum set mechanical tidal volume (V(T mech)). The objective of this study was to compare the effects of SIMV+VG with conventional SIMV on ventilation and gas exchange in a group of very low birth weight infants recovering from acute respiratory failure. Nine infants were initially studied during 2 consecutive 60-minute ventilatory modalities of conventional SIMV (ventilator settings by clinical team) and SIMV+VG 4.5 (V(T mech) set at 4.5 mL/kg) in random order. Eight additional infants were studied during the same ventilatory modalities plus 1 additional epoch consisting of SIMV+VG 3.0 (V(T mech) set at 3.0 mL/kg). Peak inspiratory pressure was significantly lower during SIMV+VG 3.0. Mean airway pressure, V(T mech), number of large V(T mech) (>7 mL/kg), and mechanical minute ventilation (V'(E)) were reduced during SIMV+VG 4.5 compared with SIMV and were further reduced during SIMV+VG 3.0. Spontaneous V'(E) increased during SIMV+VG 4.5 and was even higher during SIMV+VG 3.0. The resulting total V'(E) was higher during both SIMV+VG modes compared with SIMV. Arterial oxygen saturation by pulse oximetry, transcutaneous carbon dioxide tension, and fraction of inspired oxygen did not differ significantly, although transcutaneous carbon dioxide tension increased slightly during SIMV+VG 3.0. The short-term use of SIMV+VG resulted in automatic weaning of the mechanical support and enhancement of the spontaneous respiratory effort while maintaining gas exchange relatively unchanged in comparison to conventional SIMV.\nStudy7: Randomised trial of volume controlled versus time cycled, pressure limited ventilation in preterm infants with respiratory distress syndrome. Fifty preterm infants weighing 1200 g or more with clinical and radiographic evidence of respiratory distress syndrome, requiring both mechanical ventilation and exogenous surfactant replacement, were randomly allocated to receive either volume controlled ventilation or time cycled, pressure limited ventilation. Tidal volume delivery in each group was deliberately controlled at 5-8 ml/kg so that the only difference between the two groups was the ventilatory modality, the manner in which tidal volume was delivered. The rest of the ventilatory management and clinical care was done according to protocol. The two modes of ventilation were compared by determining the time required to achieve pre-determined success criteria, based on either the alveolar-arterial oxygen gradient or the mean airway pressure as a standard against which the speed of weaning could be objectively assessed. Infants randomised to volume controlled ventilation met success criteria sooner and had a shorter duration of mechanical ventilation. These babies also had a significantly lower incidence of intraventricular haemorrhages and abnormal periventricular echodensities on ultrasound scans. Volume controlled ventilation seems to be both safe and effective in this group of patients.\n", + "output": "Conclusions: Infants ventilated using VTV modes had reduced death and chronic lung disease compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies." + }, + { + "input": "Study1: Heart volume and physical fitness of parturients. One hundred and three primigravidae were studied to establish the correlation between physical fitness and heart volume. Twenty-three of the mothers were allocated at random to the exercise group and 21 to control group 1, between the 10th and 14th weeks of pregnancy. In addition, 59 mothers were allocated to control group 2, which was formed two weeks before term. The exercise group underwent a rather strenuous training programme during pregnancy. Physical fitness was measured by work tests on a bicycle ergometer two weeks before term. The heart volume was determined radiologically on the 6th day post partum. There was a positive correlation between physical fitness and the relative heart volume, which was greatest when physical fitness was measured by a method which takes the level of training into consideration. The relative heart volume of the exercise group was almost significantly greater than that of control group 1. The physical performance of the exercise group was very significantly greater than in the control groups. There was no significant correlation between either physical fitness or relative heart volume and the duration of pregnancy or the weight of newborn.\nStudy2: Continuing regular exercise during pregnancy: effect of exercise volume on fetoplacental growth. The purpose of this study was to test the null hypothesis that the volume of exercise at different times during pregnancy has no effect on fetoplacental growth. Seventy-five women who exercised regularly were evaluated before pregnancy and randomly assigned at 8 weeks' gestation to one of 3 exercise regimens for the remainder of pregnancy. Primary outcome variables included placental growth rate, birth weight, and placental volume at term. The offspring of the women who were randomly assigned to a high volume of exercise in mid and late pregnancy were significantly lighter (3.39 kg vs 3.81 kg) and thinner (8.3% fat vs 12.1% fat) than those offspring born of women who were randomly assigned to reduce their exercise volume after the 20th week. Maternal weight gain, fresh placental volumes, and histomorphometric indices of placental function were greater in the high-low group. These data indicate that a high volume of moderate-intensity, weight-bearing exercise in mid and late pregnancy symmetrically reduces fetoplacental growth, whereas a reduction in exercise volume enhances fetoplacental growth with a proportionally greater increase in fat mass than in lean body mass.\nStudy3: Beginning regular exercise in early pregnancy: effect on fetoplacental growth. Our purpose was to test the null hypothesis that beginning regular, moderate-intensity exercise in early pregnancy has no effect on fetoplacental growth. Study Design: Forty-six women who did not exercise regularly were randomly assigned at 8 weeks either to no exercise (n = 24) or to weight-bearing exercise (n = 22) 3 to 5 times a week for the remainder of pregnancy. Outcome variables included antenatal placental growth rate and neonatal and placental morphometric measurements. The offspring of the exercising women were significantly heavier (corrected birth weight: 3.75 +/- 0.08 kg vs 3.49 +/- 0.07 kg) and longer (51.8 +/- 0.3 cm vs 50.6 +/- 0.3 cm) than those born to control women. The difference in birth weight was the result of an increase in both lean body mass and fat mass. In addition, midtrimester placental growth rate was faster (26 +/- 2 cm(3)/wk vs 21 +/- 1 cm(3)/wk) and morphometric indexes of placental function were greater in the exercise group. There were no significant differences in neonatal percentage body fat, head circumference, ponderal index, or maternal weight gain. These data indicate that beginning a moderate regimen of weight-bearing exercise in early pregnancy enhances fetoplacental growth.\nStudy4: Swimming and physical fitness during pregnancy. nan\nStudy5: Antenatal exercise and birthweight. Does strenuous antenatal exercise reduce birthweight? Does reducing maternal exercise increase birthweight? What to advise about exercise during pregnancy? We recruited 117 women who intended to exercise 5 or more times weekly during pregnancy to a study of whether reducing the amount of maternal exercise during pregnancy is associated with an increase in birthweight. Only 61/117 (52%) of women agreed to be randomised to either continue or to reduce (to 3 or fewer sessions of exercise weekly) their intended pregnancy exercise program. Most women who refused randomisation did not want to risk being asked to reduce their exercise during pregnancy. Within the randomised trial, there was no statistically significant difference between the mean birthweight of babies born to women who continued and those who reduced their intended exercise program. The high rate of refusal of randomisation limits the power of the study to find a difference in birthweight, limits the generalisability of the results and shows that many women intending to exercise at this level during pregnancy have an uncompromising attitude to exercise.\nStudy6: Aerobic exercise and submaximal functional capacity in overweight pregnant women: a randomized trial. To evaluate the effects of aerobic training on submaximal cardiorespiratory capacity in overweight pregnant women. We conducted a randomized clinical trial in a referral center prenatal clinic during the period 2000-2002. Of 132 overweight (body mass index 26-31 kg/m2) but otherwise healthy volunteers, at 20 years of age or older, with gestational age of 20 weeks or less, and without diabetes or hypertension, 92 consented to participate and were randomized. Intervention consisted of 3 one-hour aerobic exercise sessions per week; the control group received weekly relaxation and focus group discussions. The main outcome measure was submaximal exercise capacity evaluated by oxygen uptake at the anaerobic (first ventilatory) threshold during cardiopulmonary treadmill testing 12 weeks after randomization. Oxygen uptake at the anaerobic threshold increased 18% (15.9 +/- 2.6 to 18.1 +/- 3.1 mL . min(-1) . kg(-1)) in the exercise group but decreased 16% (16.9 +/- 3.0 to 15.8 +/- 2.6 mL . min(-1) . kg(-1)) among the control group. Oxygen consumption at the anaerobic threshold, adjusted through analysis of covariance for baseline oxygen uptake, was 2.68 (95% confidence interval 1.23 to 4.12) mL . min(-1) . kg(-1) greater in the exercise group. Women in the exercise group were approximately 5 times more likely than those in the control group to have regular or good cardiorespiratory capacity (12/38 versus 2/38; relative risk 5.2, 95% confidence interval 1.2 to 22.0, number needed to treat 5). Aerobic training in overweight pregnant women substantially increases submaximal exercise capacity, overcoming the otherwise negative effects of pregnancy in this regard. Additional studies are required to evaluate its effect on major clinical outcomes.\nStudy7: The effect of participation in a regular exercise program upon aerobic capacity during pregnancy. This study examined the questions of whether pregnancy decreases physical fitness, as measured by maximal oxygen consumption, between the second and third trimesters, and whether maintaining a regular exercise program during the second half of pregnancy affects fitness. At the beginning of their second trimester, pregnant women were randomly assigned to either a nonexercising control group or an exercising group. They completed a maximal progressive exercise test on a cycle ergometer at 20 and 30 weeks, during which pulmonary parameters of aerobic capacity were measured. The exercising group demonstrated greater improvement in aerobic capacity than did the control group, manifested by increases in tidal volume and oxygen consumption and a stable ventilatory equivalent for oxygen. Pregnancy did not reduce maximal oxygen consumption between the second and third trimesters of pregnancy.\nStudy8: Maternal and fetal responses to a maternal aerobic exercise program. To investigate the effects of exercise on the pregnant woman and her fetus, 20 pregnant women were studied during the second and third trimesters. Twelve of the women participated in an aerobic exercise program while eight women did not perform any regular exercise and served as a control group. On the basis of submaximal exercise test results, an 18% improvement and a 4% decline in absolute aerobic capacity (liters of oxygen per minute) were observed in the exercise and control groups, respectively. Functional aerobic capacity (milliliters of oxygen per kilogram per minute) rose 8% in the exercise group and declined 10% in the control group. A small but significant rise in fetal heart rate was measured during the exercise sessions. A comparison of pregnancy outcome of the two groups showed no differences in labor duration, Apgar scores, or fetal growth.\nStudy9: Physical and psychological changes with vigorous exercise in sedentary primigravidae. The present study examined the effects of exercise on physical and psychological variables in sedentary primigravidae (PRA). A total of nine women randomly assigned to an exercise (E) (mean age = 31.3 +/- 3.1 yr) and six subjects randomly assigned to a control (C) group (mean age = 27.8 +/- 3.1 yr) fulfilled all requirements for the study. Exercise included a variety of exercise activities performed to a target heart rate of 150-156 beats x min(-1), three times per week for 15 wk. Results showed no significant differences between E and C groups in physical characteristics initially. A repeated measures ANOVA showed a significant group effect (P < 0.05) and a significant group by time interaction (P = 0.001) with the E group showing a significantly longer amount of time on the PWC150 test than the C group. There was no significant group, time, or group by time interaction for lactate accumulation. This occurred, despite the fact that the E group spent 56% longer on the PWC150 test and the C group spent 30% less time on the same test at the conclusion of the study. Finally, the E group in comparison to the C group showed more favorable improvements in several items related to health and well-being on the Body Cathexis Scale. There were no significant differences between E and C groups in any pregnancy outcome measures. All babies were delivered healthy at term. These data suggest that a vigorous exercise program can lead to significant improvements in aerobic fitness at similar lactate concentrations compared to a control group and can be well tolerated by low risk sedentary PRA without any deleterious effects occurring to herself or unborn child.\n", + "output": "Conclusions: Regular aerobic exercise during pregnancy appears to improve (or maintain) physical fitness. Available data are insufficient to infer important risks or benefits for the mother or infant. Larger and better trials are needed before confident recommendations can be made about the benefits and risk of aerobic exercise in pregnancy." + }, + { + "input": "Study1: The effects of acute relaxation on indices of anxiety during pregnancy. Antenatal maternal anxiety has adverse effects on the fetus and the child. In this study we determined whether a short period of directed or of passive relaxation reduced maternal self-rated anxiety, heart rate, plasma catecholamines, cortisol and uterine artery resistance index, in pregnant women. Fifty-eight women (28-32 wks gestation) were assigned randomly to a session of directed active or passive (sitting quietly) relaxation. Spielberger self-rating anxiety questionnaires were completed, and a venous blood sample taken, before and after a Doppler scan. Both active and passive relaxation significantly reduced State Anxiety and maternal heart rate, but the effect was significantly greater with the active relaxation. In contrast, the passive relaxation significantly reduced noradrenaline levels whereas active did not. Adrenaline levels were not changed significantly with either type of relaxation. Both methods significantly reduced cortisol, with a trend for the passive to have a greater effect. The active relaxation had no effect on uterine artery blood flow, whereas there was a statistically significant, but clinically negligible, increase in mean resistance index after passive relaxation. Both methods reduced maternal State Anxiety and heart rate, the active method more so. However there was a striking lack of correlation with the other biological indices studied. In order to reduce specific biological effects of anxiety during pregnancy, different methods may be needed from those which are most effective at reducing subjective anxiety.\nStudy2: An educational intervention to improve women's ability to cope with childbirth. To test the effectiveness of an efficacy-enhancing educational intervention to promote women's self-efficacy for childbirth and coping ability in reducing anxiety and pain during labour. The evidence of the effective application of the self-efficacy theory in health-promoting interventions has been well established. Little effort has been made by health professionals to integrate self-efficacy theory into childbirth care. Randomised controlled trial. An efficacy-enhancing educational intervention based on Bandura's self-efficacy theory was evaluated. The eligible Chinese first-time pregnant women were randomly assigned to either an experimental group (n = 60) or a control group (n = 73). The experimental group received two 90-minute sessions of the educational programme in between the 33rd-35th weeks of pregnancy. Follow-up assessments on outcome measures were conducted within 48 hours after delivery. The short form of the Chinese Childbirth Self-Efficacy Inventory was used to measure maternal self-efficacy prior to labour. Evaluation of pain and anxiety during the three stages of labour and performance of coping behaviour during labour were measured by the Visual Analogue Scale and Childbirth Coping Behaviour Scale respectively. The experimental group was significantly more likely than the control group to demonstrate higher levels of self-efficacy for childbirth (p < 0.0001), lower perceived anxiety (p < 0.001, early stage and p = 0.02, middle stage) and pain (p < 0.01, early stage and p = 0.01, middle stage) and greater performance of coping behaviour during labour (p < 0.01). The educational intervention based on Bandura's self-efficacy theory is effective in promoting pregnant women's self-efficacy for childbirth and reducing their perceived pain and anxiety in the first two stages of labour. Relief of pain and anxiety is an important issue for both women and childbirth health professionals. The efficacy-enhancing educational intervention should be further developed and integrated into childbirth educational interventions for promoting women's coping ability during childbirth.\nStudy3: Preparation courses for childbirth in primipara. A comparison. nan\nStudy4: An exploratory study of the effectiveness of a relaxation with guided imagery protocol. An exploratory study was done to examine the effectiveness of a relaxation with guided imagery protocol in reducing anxiety and depression and increasing self-esteem in new mothers during the first 4 weeks postpartum. The results indicate that anxiety and depression declined and self-esteem increased in subjects in both the experimental and control groups over the 4-week period. However, the decline in anxiety and the increase in self-esteem was greater in the experimental group than in the control group. The decline in depression was about the same in both groups. Further study, using more precise methodology and instrumentation, needs to be done to verify the results.\nStudy5: Effects of relaxation on psychobiological wellbeing during pregnancy: a randomized controlled trial. Prenatal maternal stress is associated with adverse birth outcomes and may be reduced by relaxation exercises. The aim of the present study was to compare the immediate effects of two active and one passive 10-min relaxation technique on perceived and physiological indicators of relaxation. 39 healthy pregnant women recruited at the outpatient department of the University Women's Hospital Basel participated in a randomized controlled trial with an experimental repeated measure design. Participants were assigned to one of two active relaxation techniques, progressive muscle relaxation (PMR) or guided imagery (GI), or a passive relaxation control condition. Self-reported relaxation on a visual analogue scale (VAS) and state anxiety (STAI-S), endocrine parameters indicating hypothalamic-pituitary-adrenal (HPA) axis (cortisol and ACTH) and sympathetic-adrenal-medullary (SAM) system activity (norepinephrine and epinephrine), as well as cardiovascular responses (heart rate, systolic and diastolic blood pressure) were measured at four time points before and after the relaxation exercise. Between group differences showed, that compared to the PMR and control conditions, GI was significantly more effective in enhancing levels of relaxation and together with PMR, GI was associated with a significant decrease in heart rate. Within the groups, passive as well as active relaxation procedures were associated with a decline in endocrine measures except epinephrine. Taken together, these data indicate that different types of relaxation had differential effects on various psychological and biological stress systems. GI was especially effective in inducing self-reported relaxation in pregnant women while at the same time reducing cardiovascular activity. Copyright \u00a9 2010 Elsevier Ltd. All rights reserved.\nStudy6: Effect of relaxation with guided imagery on anxiety, depression, and self-esteem in primiparas. A pretest-posttest experimental design with a convenience sample of 60 subjects was used to examine the effects of a relaxation with guided imagery protocol on anxiety, depression, and self-esteem in primiparas during the first 4 weeks of the postpartum period. The results showed that the experimental group had less anxiety and depression and greater self-esteem than did the control group at the end of the period. Positive correlations were obtained between anxiety and depression; negative correlations between self-esteem and anxiety and depression. All findings were significant at the .05 level.\nStudy7: Effects of a mindfulness-based intervention during pregnancy on prenatal stress and mood: results of a pilot study. Stress and negative mood during pregnancy increase risk for poor childbirth outcomes and postnatal mood problems and may interfere with mother-infant attachment and child development. However, relatively little research has focused on the efficacy of psychosocial interventions to reduce stress and negative mood during pregnancy. In this study, we developed and pilot tested an eight-week mindfulness-based intervention directed toward reducing stress and improving mood in pregnancy and early postpartum. We then conducted a small randomized trial (n=31) comparing women who received the intervention during the last half of their pregnancy to a wait-list control group. Measures of perceived stress, positive and negative affect, depressed and anxious mood, and affect regulation were collected prior to, immediately following, and three months after the intervention (postpartum). Mothers who received the intervention showed significantly reduced anxiety (effect size, 0.89; p<0.05) and negative affect (effect size, 0.83; p<0.05) during the third trimester in comparison to those who did not receive the intervention. The brief and nonpharmaceutical nature of this intervention makes it a promising candidate for use during pregnancy.\n", + "output": "Conclusions: Mind-body interventions might benefit women\u2019s anxiety during pregnancy. Based on individual studies, there is some but no strong evidence for the effectiveness of mind-body interventions for the management of anxiety during pregnancy. The main limitations of the studies were the lack of blinding and insufficient details on the methods used for randomization." + }, + { + "input": "Study1: Willingness of men who have sex with men (MSM) in the United States to be circumcised as adults to reduce the risk of HIV infection. Circumcision reduces HIV acquisition among heterosexual men in Africa, but it is unclear if circumcision may reduce HIV acquisition among men who have sex with men (MSM) in the United States, or whether MSM would be willing to be circumcised if recommended. We interviewed presumed-HIV negative MSM at gay pride events in 2006. We asked uncircumcised respondents about willingness to be circumcised if it were proven to reduce risk of HIV among MSM and perceived barriers to circumcision. Multivariate logistic regression was used to identify covariates associated with willingness to be circumcised. Of 780 MSM, 133 (17%) were uncircumcised. Of these, 71 (53%) were willing to be circumcised. Willingness was associated with black race (exact odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.3-9.8), non-injection drug use (OR: 6.1, 95% CI: 1.8-23.7) and perceived reduced risk of penile cancer (OR: 4.7, 95% CI: 2.0-11.9). The most commonly endorsed concerns about circumcision were post-surgical pain and wound infection. Over half of uncircumcised MSM, especially black MSM, expressed willingness to be circumcised. Perceived risks and benefits of circumcision should be a part of educational materials if circumcision is recommended for MSM in the United States.\nStudy2: Circumcision status and HIV infection among Black and Latino men who have sex with men in 3 US cities. To examine characteristics of circumcised and uncircumcised Latino and black men who have sex with men (MSM) in the United States and assess the association between circumcision and HIV infection. Using respondent-driven sampling, 1154 black MSM and 1091 Latino MSM were recruited from New York City, Philadelphia, and Los Angeles. A 45-minute computer-assisted interview and a rapid oral fluid HIV antibody test (OraSure Technologies, Bethlehem, PA) were administered to participants. Circumcision prevalence was higher among black MSM than among Latino MSM (74% vs. 33%; P < 0.0001). Circumcised MSM in both racial/ethnic groups were more likely than uncircumcised MSM to be born in the United States or to have a US-born parent. Circumcision status was not associated with prevalent HIV infection among Latino MSM, black MSM, black bisexual men, or black or Latino men who reported being HIV-negative based on their last HIV test. Further, circumcision was not associated with a reduced likelihood of HIV infection among men who had engaged in unprotected insertive and not unprotected receptive anal sex. In these cross-sectional data, there was no evidence that being circumcised was protective against HIV infection among black MSM or Latino MSM.\nStudy3: Prevalence of circumcision and herpes simplex virus type 2 infection in men in the United States: the National Health and Nutrition Examination Survey (NHANES), 1999-2004. To study the prevalence of circumcision in the United States and to examine the association between circumcision and herpes simplex virus Type 2 (HSV-2) infection. As part of National Health and Nutrition Examination Surveys from 1999 to 2004, 6174 men were interviewed about circumcision status and sexual behaviors, and were tested for HSV-2 antibodies. Medical artwork was used to aid the reporting of circumcision status. The overall prevalence of circumcision was 79% and varied by race/ethnicity (88% in non-Hispanic whites, 73% in non-Hispanic blacks, 42% in Mexican Americans, and 50% in others). For men born in the United States from 1940 through 1979, the prevalence of circumcision increased, with larger increases in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites; the prevalence of circumcision decreased significantly in those born in the 1980s (84%) compared to those born in 1970s (91%) (P <0.001). Circumcision status was not associated with sexual behaviors we assessed. In multivariate analyses, circumcision was not associated with HSV-2 infection (P = 0.47). The prevalence of circumcision apparently peaked in those born in the 1970s and declined in those born in the 1980s. Circumcision was not associated with HSV-2 infection.\nStudy4: Circumcision among men who have sex with men in Scotland: limited potential for HIV prevention. Male circumcision has been shown to reduce the risk of HIV acquisition among heterosexual men but the impact among men who have sex with men (MSM) is not known. In this paper, we explore the feasibility of research into circumcision for HIV prevention among MSM in Scotland. Anonymous, self-complete questionnaires and Orasure oral fluid collection kits were distributed to men visiting the commercial gay scenes in Glasgow and Edinburgh. 1508 men completed questionnaires (70.5% response rate) and 1277 provided oral fluid samples (59.7% response rate). Overall, 1405 men were eligible for inclusion in the analyses. 16.6% reported having been circumcised. HIV prevalence was similar among circumcised and uncircumcised men (4.2% and 4.6%, respectively). Although biologically, circumcision is most likely to protect against HIV for men practising unprotected insertive anal intercourse (UIAI), only 7.8% (91/1172) of uncircumcised men reported exclusive UIAI in the past 12 months. Relatively few men reported being willing to participate in a research study on circumcision and HIV prevention (13.9%), and only 11.3% of uncircumcised men did so. The lack of association between circumcision and HIV status, low levels of exclusive UIAI, and low levels of willingness to take part in circumcision research studies suggest circumcision is unlikely to be a feasible HIV prevention strategy for MSM in the UK. Behaviour change should continue to be the focus of HIV prevention in this population.\nStudy5: The association between lack of circumcision and HIV, HSV-2, and other sexually transmitted infections among men who have sex with men. Observational studies evaluating the association of circumcision and HIV infection among men who have sex with men (MSM) have yielded mixed results. We examined the relationship between circumcision and HIV, herpes simplex virus type-2 (HSV-2), syphilis, urethral gonorrhea, and urethral chlamydia among MSM stratified by anal sexual role. Between October 2001 and May 2006, 4749 MSM who reported anal intercourse in the previous 12 months attended the Public Health-Seattle and King County STD clinic for 8337 evaluations. Clinicians determined circumcision status by examination and anal sexual role in the previous year by interview. Blood samples were used to test HIV, syphilis, and HSV-2 serostatus. Urethral gonorrhea and chlamydia were tested by culture or nucleic acid amplification. We used generalized estimating equations to evaluate the association between circumcision and specific diagnoses, adjusted for race/ethnicity and age. Among the 3828 men whose circumcision status was assessed, 3241 (85%) were circumcised and 587 (15%) were not. The proportion of men newly testing HIV-positive or with previously diagnosed HIV did not differ by circumcision status when stratified by men's anal sexual role in the preceding year, even when limited to men who reported only insertive anal intercourse in the preceding 12 months (OR = 1.45; 95% CI: 0.30, 7.12). Similarly, we did not observe a significant association between circumcision status and the other sexually transmitted infections (STI). Our findings suggest that male circumcision would not be likely to have a significant impact on HIV or sexually transmitted infections acquisition among MSM in Seattle.\nStudy6: Circumcision and risk of sexually transmissible infections in a community-based cohort of HIV-negative homosexual men in Sydney, Australia. Circumcision status was examined as an independent risk factor for sexually transmissible infections (STIs) in the Health in Men cohort of homosexual men in Sydney. From 2001 through 2004, 1427 initially human immunodeficiency virus (HIV)-negative men were enrolled and followed up until mid-2007. All participants were offered annual STI testing. The history of STIs was collected at baseline, and information on sexual risk behaviors was collected every 6 months. At annual face-to-face visits, participants reported STI diagnoses received during the previous year. Circumcision was not associated with prevalent or incident herpes simplex virus 1, herpes simplex virus 2, or self-reported genital warts. There was also no independent association of circumcision with incident urethral gonorrhea or chlamydia. Being circumcised was associated with a significantly reduced risk of incident (hazard ratio, 0.35 [95% confidence interval, 0.15-0.84]) but not prevalent (odds ratio, 0.71 [95% confidence interval, 0.35-1.44]) syphilis. The association was somewhat stronger among men who reported predominantly insertive unprotected anal intercourse (hazard ratio, 0.10 [95% confidence interval, 0.01-0.82]). These are the first prospective data obtained from homosexual men to assess circumcision status as a risk factor for STIs. Circumcised men were at reduced risk of incident syphilis but no other prevalent or incident STIs. Circumcision is unlikely to have a substantial public health impact in reducing acquisition of most STIs in homosexual men.\nStudy7: Circumcision and risk of HIV infection in Australian homosexual men. To assess circumcision status as a risk factor for HIV seroconversion in homosexual men. The Health in Men (HIM) study was a prospective cohort of homosexual men in Sydney, Australia. HIV-negative men (n = 1426) were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007. Participants underwent annual HIV testing, and detailed information on sexual risk behaviour was collected every 6 months. HIV incidence in circumcised compared with uncircumcised participants, stratified by whether or not men predominantly practised the insertive role in anal intercourse. There were 53 HIV seroconversions during follow-up; an incidence of 0.78 per 100 person-years. On multivariate analysis controlling for behavioural risk factors, being circumcised was associated with a nonsignificant reduction in risk of HIV seroconversion [hazard ratio 0.78, 95% confidence interval (CI) 0.42-1.45, P = 0.424]. Among one-third of study participants who reported a preference for the insertive role in anal intercourse, being circumcised was associated with a significant reduction in HIV incidence after controlling for age and unprotected anal intercourse (UAI) (hazard ratio 0.11, 95% CI 0.03-0.80, P = 0.041). Those who reported a preference for the insertive role overwhelmingly practised insertive rather than receptive UAI. Overall, circumcision did not significantly reduce the risk of HIV infection in the HIM cohort. However, it was associated with a significant reduction in HIV incidence among those participants who reported a preference for the insertive role in anal intercourse. Circumcision may have a role as an HIV prevention intervention in this subset of homosexual men.\nStudy8: The association between circumcision status and human immunodeficiency virus infection among homosexual men. To evaluate whether uncircumcised status is correlated with acquisition of human immunodeficiency virus (HIV), 502 homosexual men were surveyed; 85% were circumcised. HIV infection was significantly associated with uncircumcised status (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2, 3.8), nonwhite race, intravenous drug use, sexual contact with an intravenous drug user, number of male partners, frequency of unprotected receptive anal intercourse, and with history of genital herpes, anal herpes, or syphilis. Uncircumcised status was significantly associated with older age, nonwhite race, and history of syphilis; it was inversely associated with intravenous drug use. Using logistic regression analysis, the adjusted OR for the association between HIV infection and uncircumcised status was 2.0 (95% CI, 1.0, 4.0). Uncircumcised homosexual men had 2-fold increased risk of HIV infection. The role of circumcision as an intervention strategy to reduce sexual transmission of HIV warrants consideration.\nStudy9: High HIV prevalence among men who have sex with men in Soweto, South Africa: results from the Soweto Men's Study. The Soweto Men's Study assessed HIV prevalence and associated risk factors among MSM in Soweto, South Africa. Using respondent driven sampling (RDS) recruitment methods, we recruited 378 MSM (including 15 seeds) over 30 weeks in 2008. All results were adjusted for RDS sampling design. Overall HIV prevalence was estimated at 13.2% (95% confidence interval 12.4-13.9%), with 33.9% among gay-identified men, 6.4% among bisexual-identified men, and 10.1% among straight-identified MSM. In multivariable analysis, HIV infection was associated with being older than 25 (adjusted odds ratio (AOR) 3.8, 95% CI 3.2-4.6), gay self-identification (AOR 2.3, 95% CI 1.8-3.0), monthly income less than ZAR500 (AOR 1.4, 95% CI 1.2-1.7), purchasing alcohol or drugs in exchange for sex with another man (AOR 3.9, 95% CI 3.2-4.7), reporting any URAI (AOR 4.4, 95% CI 3.5-5.7), reporting between six and nine partners in the prior 6 months (AOR 5.7, 95% CI 4.0-8.2), circumcision, (AOR 0.2, 95% CI 0.1-0.2), a regular female partner (AOR 0.2, 95% CI 0.2-0.3), smoking marijuana in the last 6 months (AOR 0.6, 95% CI 0.5-0.8), unprotected vaginal intercourse in the last 6 months (AOR 0.5, 95% CI 0.4-0.6), and STI symptoms in the last year (AOR 0.7, 95% CI 0.5-0.8). The results of the Soweto Men's Study confirm that MSM are at high risk for HIV infection, with gay men at highest risk. HIV prevention and treatment for MSM are urgently needed.\nStudy10: Circumcision status and HIV infection among MSM: reanalysis of a Phase III HIV vaccine clinical trial. Determine whether male circumcision would be effective in reducing HIV transmission among men who have sex with men (MSM). Retrospective analysis of the VAXGen VAX004 HIV vaccine clinical trial data. Survival analysis was used to associate time to HIV infection with multiple predictors. Unprotected insertive and receptive anal sex predictors were highly correlated, thus separate models were run. Four thousand eight hundred and eighty-nine participants were included in this reanalysis; 86.1% were circumcised. Three hundred and forty-two (7.0%) men became infected during the study; 87.4% were circumcised. Controlling for demographic characteristics and risk behaviors, in the model that included unprotected insertive anal sex, being uncircumcised was not associated with incident HIV infection [adjusted hazards ratio (AHR) = 0.97, confidence interval (CI) = 0.56-1.68]. Furthermore, while having unprotected insertive (AHR = 2.25, CI = 1.72-2.93) or receptive (AHR = 3.45, CI = 2.58-4.61) anal sex with an HIV-positive partner were associated with HIV infection, the associations between HIV incidence and the interaction between being uncircumcised and reporting unprotected insertive (AHR = 1.78, CI = 0.90-3.53) or receptive (AHR = 1.26, CI = 0.62-2.57) anal sex with an HIV-positive partner were not statistically significant. Of the study visits when a participant reported unprotected insertive anal sex with an HIV-positive partner, HIV infection among circumcised men was reported in 3.16% of the visits (80/2532) and among uncircumcised men in 3.93% of the visits (14/356) [relative risk (RR) = 0.80, CI = 0.46-1.39]. Among men who reported unprotected insertive anal sex with HIV-positive partners, being uncircumcised did not confer a statistically significant increase in HIV infection risk. Additional studies with more incident HIV infections or that include a larger proportion of uncircumcised men may provide a more definitive result.\n", + "output": "Conclusions: Current evidence suggests that male circumcision may be protective among MSM who practice primarily insertive anal sex, but the role of male circumcision overall in the prevention of HIV and other sexually transmitted infections among MSM remains to be determined. Therefore, there is not enough evidence to recommend male circumcision for HIV prevention among MSM at present. Further research should be of high quality and further explore interaction with the predominant sexual role." + }, + { + "input": "Study1: Prevention of central venous catheter-related infections and thrombotic events in immunocompromised children by the use of vancomycin/ciprofloxacin/heparin flush solution: A randomized, multicenter, double-blind trial. To determine whether an antibiotic flush solution containing vancomycin, heparin, and ciprofloxacin (VHC) can prevent the majority of line infections. A prospective double-blind study was performed comparing VHC to vancomycin and heparin (VH) to heparin alone in 126 pediatric oncology patients. The 153 assessable lines resulted in 36,944 line days studied. There were 58 blood stream infections (43 gram-positive, 14 gram-negative, and one fungal). Forty were defined as line infections (31 heparin, three VH, six VHC). The time to develop a line infection was significantly increased using either antibiotic flush (VH, P =.011; VHC, P =.036). The rate of total line infections (VH, P =.004; VHC, P =.005), gram-positive line infections (VH, P =. 028; VHC, P =.022), and gram-negative line infections (VH, P =.006; VHC, P =.003) was significantly reduced by either VH or VHC. Sixty-two (41%) of the lines developed 119 occlusion episodes (heparin, 3.99 per 1,000 line days; VHC, 1.75 per 1,000 line days; P =.0005). Neither antibiotic could be detected after flushing, and no adverse events were detected, including increased incidence of vancomycin-resistant Enterococcus colonization or disease. The use of either VH or VHC flush solution significantly decreased the complications associated with the use of tunneled central venous lines in immunocompromised children and would save significant health care resources.\nStudy2: Central venous catheter-related infections after bone marrow transplantation in patients with malignancies: a prospective study with short-course vancomycin prophylaxis. Infections associated with double-lumen central venous catheters (CVCs) in patients undergoing BMT are presented. We prospectively studied infections occurring with 46 CVCs in 40 patients with malignancies during and up to 30 days after BMT. We randomised patients with insertions of CVCs to receive either a short course of vancomycin 500 mg x 3 peri-operatively (16 CVCs) or no VCM (11 CVCs). Six per cent of CVCs in the group with vancomycin prophylaxis became infected with Gram positive microorganisms compared with 55% in the control group (P < 0.05). Next, 19 patients with CVCs were all given prophylaxis, so finally 35 patients were given vancomycin compared with 11 patients with no vancomycin. In a total of 11 CVC-related infections, 79% of the microbiological isolates were staphylococci, all of which were sensitive to vancomycin. Vancomycin prophylaxis reduced the number of infected CVCs to 11% compared with 45% (P < 0.05) and bacteraemias to 6% compared with 45% (P < 0.01). All infections responded to antibiotic treatment. Prophylactic short-duration vancomycin during insertion of CVCs may reduce the incidence of line-associated infections and Gram positive bacteraemias in patients undergoing BMT.\nStudy3: Peroperative teicoplanin for prevention of gram-positive infections in neutropenic patients with indwelling central venous catheters: a randomized, controlled study. A prospective, randomized, open study comparing two doses of teicoplanin with no therapy administered at the time of insertion of a central venous catheter was performed in patients with hematological malignancies and in patients scheduled to undergo allogeneic or autologous stem cell transplantation. The study was designed as a group sequential study. At predetermined intervals statistical analysis was performed for the main efficacy variable, which was the number of days to treatment failure. Sixty-five patients were randomized. Three patients were judged to be not evaluable. Baseline characteristics were identical in the two groups. No differences were found in overall infections, bacteremias, gram-positive infections, or local infections between the teicoplanin and control groups. Teicoplanin given at the time of insertion of central venous catheters did not reduce the risk of bacteremias or other line-associated infections.\nStudy4: Prevention of indwelling central venous catheter sepsis. In an attempt to decrease the incidence of central venous catheter sepsis in children with cancer, we conducted a study to evaluate the benefit of adding broad-spectrum antibiotics to the catheter \"flush solution.\" In a prospective, placebo-controlled, double-blinded, randomized trial, 69 children with different types of malignancies were studied. The central venous catheters in these children were flushed with either the standard solution (normal saline + 100 U/ml of heparin) or the study solution (25 microgram/ml of both amikacin and vancomycin added to the standard solution). At the conclusion of the study, 64 children with a total of 67 indwelling central venous lines were assessable. The total catheter days on study were 20,700 days, with a median of 323 catheter days per patient. We documented 10 events of catheter-related infections (0.49 events/1,000 catheter days at risk). Five of these events were catheter-related sepsis (0.24 sepses/1,000 catheter days): two were fungal and three were bacterial. Due to the low incidence of catheter-related sepsis in this study, no statement regarding the prophylactic use of antibiotics could be made. The extremely low rate of catheter-related sepsis reported herein may be retrospectively attributed to continuous staff education regarding aseptic techniques in handling these catheters. Staff education is essential, and probably the most effective factor in preventing catheter-related sepsis.\nStudy5: A prospective randomized study of prophylactic teicoplanin to prevent early Hickman catheter-related sepsis in patients receiving intensive chemotherapy for haematological malignancies. In all, 88 patients with haematological malignancies requiring Hickman catheters for intensive chemotherapy were randomized to receive either one single bolus intravenous injection of teicoplanin, 400 mg, or no teicoplanin immediately before insertion of a double-lumen Hickman catheter. Lower incidences of catheter-related Gram-positive sepsis were recorded in patients receiving prophylactic teicoplanin; exit site infection, tunnel infection and catheter-related Gram-positive septicaemia were all reduced. The benefit of prophylactic teicoplanin was observed particularly among patients who were already neutropenic at the time of catheterization. All Gram-positive organisms isolated from infected skin sites or from blood cultures taken from Hickman catheters were susceptible to teicoplanin. No adverse reaction was reported in any of the patients receiving prophylaxis. Prophylactic teicoplanin, therefore, may be used routinely for patients requiring insertion of Hickman catheters for intensive chemotherapy, to reduce the early incidence of catheter-related sepsis, particularly during the period of neutropenia following chemotherapy.\nStudy6: Prevention of bacteremia attributed to luminal colonization of tunneled central venous catheters with vancomycin-susceptible organisms. Forty-five children with oncologic or hematologic disorders requiring tunneled central venous catheters (TCVC) for the administration of immunosuppressive therapy were randomized to receive either 10 U/mL heparin (H) (24 patients) or a solution of 10 U/mL H and 25 micrograms/mL vancomycin (H-V) (21 patients) for all catheter flushes. Episodes of fever or suspected sepsis were evaluated to determine whether the addition of vancomycin to the flush solution would alter the incidence of symptomatic bacteremia attributed to luminal colonization of TCVC with vancomycin-susceptible bacteria. Patients were enrolled for 247 +/- 150 days, accounting for a total of 11,095 days of catheter use. Bacteremia attributed to luminal colonization with vancomycin-susceptible organisms occurred in five patients (six infections) receiving H alone compared with zero patients receiving H-V (P = .035). The time to the first episode of bacteremia with vancomycin-susceptible organisms, analyzed by Kaplan-Meier survival curves, was significantly longer in patients receiving H-V (P = .04). There were no differences in the incidence of other infections including bacteremia attributed to luminal colonization with vancomycin-resistant organisms, other bacteremias (including those arising from the catheter exit site), exit-site cellulitis, or fungal infections. No organisms resistant to vancomycin were identified. Vancomycin could not be detected in the peripheral blood of patients receiving vancomycin in the flush solution. No vancomycin-related toxicities were noted. We conclude that the use of an H-V flush solution in immunocompromised patients with TCVC can decrease the frequency of bacteremia attributed to luminal colonization with vancomycin-susceptible bacteria.\n", + "output": "Conclusions: Flushing of the catheter with a vanco/heparin lock solution leads to a positive overall effect. Depending on the baseline TCVC infection rate it is justified to flush the catheter with a combination of an antibiotic and heparin, if the catheter related infection-rate is high." + }, + { + "input": "Study1: Effects of triptorelin versus placebo on the symptoms of endometriosis. To compare the effect of a GnRH-agonist, triptorelin, versus placebo on the symptoms of endometriosis. A prospective, randomized, double-blind study of 6 months of treatment followed by 12 months of follow-up. Departments of Obstetrics and Gynecology at two universities and one general hospital. Forty-nine women with symptoms of laparoscopically verified endometriosis. Triptorelin depot or placebo was given every 4 weeks. Clinical evaluation, including the Duration Intensity Behavior Scale and Visual Analogue Scale for pain, was performed before the injections and up to 12 months after treatment. A control laparoscopy was performed 4-6 weeks after the last injection. Quantitation of pain. Twenty-four patients had active treatment and 25 received placebo. Pain symptoms according to both scales were significantly more reduced after 2 months of triptorelin treatment compared to placebo. The extent of endometriotic lesions was reduced 50% during triptorelin treatment and increased 17% during placebo. The average area of endometriotic lesions was reduced 45% during triptorelin treatment but was unchanged during placebo. Side effects, mainly hot flushes, were experienced by 80% of the actively treated group but also by 33% of patients in the placebo group. Because of recurrent symptoms, only five patients could be observed for 12 months after completion of treatment. Triptorelin reduces endometriotic lesions and pain to a significantly higher degree than placebo.\nStudy2: An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team. To compare the efficacy and safety of goserelin depot and danazol for endometriosis. Open, randomized comparative trial. Multicenter European academic clinical institutions. A total of 307 patients with laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204) or danazol (n = 103); 249 patients underwent second look laparoscopy (175 received goserelin and 74 danazol) and were analyzed for efficacy. A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks. Efficacy assessments were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks. Safety was assessed by adverse event reporting and clinical laboratory measures. There were similar proportions of symptomatic (73%) and asymptomatic (but infertile) (27%) and comparable distribution of different severity of endometriosis randomized to each treatment. Significantly fewer patients randomized to goserelin (6.4%) withdrew during treatment compared with 20.4% randomized to danazol (P less than 0.05). There were significantly reduced visible deposits of endometriosis found post-treatment (P less than 0.0001) within each group but no differences between the treatments. The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment (P less than 0.05). Hypoestrogenic side effects were more common in those receiving goserelin, particularly hot flushes, but anabolic/androgenic side effects of weight gain and muscle cramps were more common in those receiving danazol. The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients. However, results were not significantly different from those achieved with danazol 600 mg/d.\nStudy3: Nafarelin for endometriosis: a large-scale, danazol-controlled trial of efficacy and safety, with 1-year follow-up. The Nafarelin European Endometriosis Trial Group (NEET). To compare the efficacy and safety of nafarelin and danazol for endometriosis. Randomized, double-blind, double-dummy. Multiple European institutions. In total, 307 patients with laparoscopically diagnosed endometriosis received nafarelin (n = 206) or danazol (n = 101); 263 (171 nafarelin, 92 danazol) were analyzed for efficacy. Intranasal nafarelin 200 micrograms two times a day or oral danazol 200 mg three times a day were administered for 6 months. Efficacy assessments were based on preadmission and end-of-treatment laparoscopic scores and subjective symptom scores at admission, end of treatment, 1, 3, 6, and 12 months after treatment. Safety was evaluated by adverse events and clinical laboratory tests. In each group, endometriosis growth and symptoms significantly improved during treatment (P less than 0.001). After treatment, symptoms returned in each group, but severity was less than at admission at all time points (P less than or equal to 0.016). Mean body weight increased in the danazol-treated group (P less than 0.001), serum glutamic oxaloacetic transaminase increased in both groups (P less than 0.001 for both) but significantly more in danazol users (P less than 0.002), and more nafarelin recipients had hot flushes (P less than 0.001). Nafarelin and danazol were equally effective in reducing endometriosis growth and symptoms during treatment and in preventing the return of symptoms during 12-month follow-up.\nStudy4: A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis. To investigate the role of adjuvant treatment with gonadotropin-releasing-hormone agonist (GnRHa) following conservative surgical treatment of endometriosis. Sixty patients in the reproductive age (mean age 28.6 years), with symptomatic stages III and IV endometriosis following laparoscopic surgery and without previous hormonal treatment were enrolled in a prospective, randomized, controlled trial to compare the effects of 3-month treatment with triptorelin depot-3.75 i.m. (30 patients) versus expectant management using placebo injection (30 patients). Six patients (one in triptorelin group and five in placebo group) were lost at follow-up, the remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence, endometrioma relapses and pregnancy rate were evaluated during a 5-year follow-up. The results of 29 cases treated with triptorelin and 25 that received placebo did not show significant differences in pain recurrence (P=1, RR=0.94, 95% CI=0.57-1.55), endometrioma relapse (P=0.67, RR=1.29, 95% CI=0.66-2.50), and pregnancy rate in infertile women (P=0.80, RR=0.81, 95% CI=0.37-1.80). Curves of time of pain recurrence and pregnancy during 5-year follow-up did not show significant differences between the two groups (P=0.79 and P=0.51, respectively, using Mantel-Haenzsel logrank test). Triptorelin treatment after operative laparoscopy for stage III/IV endometriosis does not appear to be superior to expectant management in terms of prevention of symptoms recurrence and endometrioma relapse, and has no influence on pregnancy rate in endometriosis-associated infertility.\n", + "output": "Conclusions: There is no evidence of benefit in the use of ovulation suppression in subfertile women with endometriosis who wish to conceive." + }, + { + "input": "Study: Some epidemiologic features of motorcycle collision injuries. I. Introduction, methods and factors associated with incidence. Using official police reports and hospital admission and emergency room medical records, 1273 persons with confirmed medically treated motorcycle injury were identified in Sacramento County, California, during 1970. Less than 39% of all injured motorcyclists were identified in this study using only official police reports. The annual incidence rate was highest for 18-year-old male drivers. In addition to age of driver, risk of injury was associated with drivers of short stature (less than 173 cm) operating an intermediate or larger size motorcycle. Risk of injury was higher for drivers with training than for those without training or those who operated their motorcycles frequently regardless of type of use. Risk of injury was not related to make of motorcycle but was related to engine size. Two-thirds of the injury-producing collisions involved a motorcycle and a second motor vehicle. Motorcycle collisions occurred most fre quently during the afternoon and early evening hours and during the summer months, but peaks in incidence of collisions occurred during weeks which included a holiday.\n", + "output": "Conclusions: Due to the poor quality of studies identified, we were unable to draw any conclusions about the effectiveness of rider training on crash, injury, or offence rates. The findings suggest that mandatory pre-licence training may be an impediment to completing a motorcycle licensing process, possibly indirectly reducing crashes through a reduction in exposure.\u00a0It is not clear if training (or what type) reduces the risk of crashes, injuries or offences in motorcyclists, and a best rider training practice can therefore not be recommended. As some type of rider training is likely to be necessary to teach motorcyclists to ride a motorcycle safely, rigorous research is needed." + }, + { + "input": "Study: Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel. This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol. This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years. Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG. A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.\n", + "output": "Conclusions: The available evidence is insufficient to determine whether quadriphasic differ from monophasic oral contraceptives in contraceptive effectiveness, bleeding pattern, minor side effects and acceptability. Studies that compare quadriphasic and monophasic oral contraceptives with an identical progestogen and estrogen type are needed to determine whether the quadriphasic approach differs from the monophasic approach. Studies that compare quadriphasic pills with monophasic pills containing 30 \u03bcg ethinylestradiol are indicated to determine whether quadriphasic oral contraceptives have an advantage over the current, first choice oral contraceptive. Until then, we recommend monophasic pills containing 30 \u03bcg estrogen as the first choice for women starting oral contraceptive use." + }, + { + "input": "Study: A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program. The potentially damaging effect of free O(2) radicals to cultured embryos may be reduced by adding scavengers to the culture media or by reducing the incubator O(2) levels. However, lowering the O(2) in the culture environment can be expensive, troublesome and may not be justifiable. The objective of this study was to evaluate the effect of lowered incubator O(2) tension on live birth rates in a predominately Day 5 embryo transfer program. Two hundred and thirty first-cycle women undergoing routine IVF or ICSI with ejaculated sperm were randomized in a prospective clinical trial and stratified for patient age and physician. Embryos of patients were randomly assigned for culture in either a 21% O(2) (atmospheric) or 5% O(2) (reduced) environment. Clinical endpoints monitored were rates of implantation, clinical pregnancy, live birth and blastocyst cryopreservation. Embryos cultured in a 5% O(2) environment consistently resulted in higher rates of live birth implantation (106/247, 42.9% versus 82/267, 30.7%; difference of 12.2% with 95% confidence interval (CI) of 3.9-20.3, P = 0.005) and live births (66/115, 57.4% versus 49/115, 42.6%; difference of 14.8% with 95% CI of 1.9-27.0, P = 0.043) when compared with rates among women whose embryos were cultured in an atmospheric O(2) environment. The overall increase in live births demonstrated by this study indicates that the effort and expense to culture embryos in a low-O(2) environment is justified. The study was registered at clinicaltrials.gov. NCT00708487.\n", + "output": "Conclusions: The results of this systematic review and meta-analysis suggest that culturing embryos under conditions with low oxygen concentrations improves the success rates of IVF and ICSI, resulting in the birth of more healthy newborns." + }, + { + "input": "Study1: A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a long-term comparison of a newer, atypical antipsychotic drug, risperidone, and an older, conventional neuroleptic drug, haloperidol, in terms of the rate of relapse in patients with schizophrenia and schizoaffective disorder. In a double-blind, prospective study at 40 sites, we randomly assigned adult outpatients in stable condition with chronic schizophrenia or schizoaffective disorder to receive treatment with flexible doses of either risperidone or haloperidol for a minimum of one year. Of the 397 patients who underwent randomization, data from 2 were excluded because they did not receive study medication; data from all 30 patients from one site were excluded by the sponsor, the Janssen Research Foundation, because of concern about the integrity of the data. The median duration of treatment was 364 days in the risperidone group and 238 days in the haloperidol group (P=0.02). Of the 177 patients assigned to risperidone and the 188 assigned to haloperidol who remained in the analysis, 44.1 percent and 52.7 percent, respectively, discontinued treatment for reasons other than relapse. The Kaplan-Meier estimate of the risk of relapse at the end of the study was 34 percent for the risperidone group and 60 percent for the haloperidol group (P<0.001); the risk ratio for relapse with haloperidol, from the Cox model, was 1.93 (95 percent confidence interval, 1.33 to 2.80; P<0.001). Early discontinuation of treatment for any reason was more frequent among haloperidol-treated patients (risk ratio, 1.52; 95 percent confidence interval, 1.18 to 1.96). Patients in the risperidone group had greater reductions in the mean severity of both psychotic symptoms and extrapyramidal side effects than those in the haloperidol group. Adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they are treated with haloperidol.\nStudy2: Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial. A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication. Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men). An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone (P=0.025), while the parkinsonism total score tended to be better with risperidone (P<0. 10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication. In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol.\nStudy3: Risperidone in treatment-refractory schizophrenia. The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia. Sixty-seven medication-unresponsive subjects were randomly assigned to treatment with risperidone (N = 34) or haloperidol (N = 33). After a 3-7 day-placebo washout period, there was a 4-week, double-blind, fixed-dose comparison trial that was followed by a 4-week, flexible-dose phase. Measures of clinical change were quantified by standard psychopathologic and neuromotor instruments. Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale (BPRS) after the first 4 weeks of treatment. Risperidone did not show any advantage over haloperidol after an additional 4 weeks. Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group (24%) than for the haloperidol group (11%). Risperidone-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks (20% versus 63%); they also had significantly les observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia. Baseline characteristics that correlated significantly with risperidone response were positive symptoms, conceptual disorganization, akathisia, and tardive dyskinesia. Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone.\nStudy4: Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations. Risperidone (RIS), a new neuroleptic with 5-HT2- and dopamine D2 receptor-blocking properties, was compared with perphenazine (PER) in a double-blind, multicentre, parallel-group study in 107 chronic schizophrenics with acute exacerbation. RIS 5-15 mg or PER 16-48 mg daily was given for 8 weeks. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression. Seventy-eight patients completed the trial; there was an equal number of dropouts on both drugs. The mean daily dose at endpoint was 8.5 mg RIS and 28 mg PER. The reduction in total PANSS score to endpoint did not differ significantly, although there was a tendency in favour of RIS. The number of patients with predominantly negative symptoms who showed at least 20% reduction in total PANSS score was significantly larger in the RIS group. Furthermore, the number of patients showing at least 20% reduction in Brief Psychiatric Rating Scale (BPRS) score (BPRS being a subscale of PANSS) was significantly larger in the RIS group. The hostility cluster of BPRS improved more on RIS than on PER in the endpoint analysis. The overall prevalence of side effects was fairly similar in the two groups.\n", + "output": "Conclusions: Risperidone may be more acceptable to those with schizophrenia than older antipsychotics and have marginal benefits in terms of limited clinical improvement. Its adverse effect profile may be better than haloperidol. With the addition of more studies to this review, the publication bias evident in previous versions is no longer a significant issue. Any marginal benefits this drug may have have to be balanced against its greater cost and increased tendency to cause side effects such as weight gain.\nRecent important longer term data favouring risperidone's effect on relapse needs to be replicated by researchers independently of the manufacturers of the drug." + }, + { + "input": "Study1: Circuit class therapy versus individual physiotherapy sessions during inpatient stroke rehabilitation: a controlled trial. To compare the effectiveness of circuit class therapy and individual physiotherapy (PT) sessions in improving walking ability and functional balance for people recovering from stroke. Nonrandomized, single-blind controlled trial. Medical rehabilitation ward of a rehabilitation hospital. Sixty-eight persons receiving inpatient rehabilitation after a stroke. Subjects received group circuit class therapy or individual treatment sessions as the sole method of PT service delivery for the duration of their inpatient stay. Five-meter walk test (5MWT), two-minute walk test (2MWT), and the Berg Balance Scale (BBS) measured 4 weeks after admission. Secondary outcome measures included the Iowa Level of Assistance Scale, Motor Assessment Scale upper-limb items, and patient satisfaction. Measures were taken on admission and 4 weeks later. Subjects in both groups showed significant improvements between admission and week 4 in all primary outcome measures. There were no significant between group differences in the primary outcome measures at week 4 (5MWT mean difference, .07m/s; 2MWT mean difference, 1.8m; BBS mean difference, 3.9 points). A significantly higher proportion of subjects in the circuit class therapy group were able to walk independently at discharge (P=.01) and were satisfied with the amount of therapy received (P=.007). Circuit class therapy appeared as effective as individual PT sessions for this sample of subjects receiving inpatient rehabilitation poststroke. Favorable results for circuit classes in terms of increased walking independence and patient satisfaction suggest this model of service delivery warrants further investigation.\nStudy2: Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke: a randomized controlled trial. Mudge S, Barber PA, Stott NS. Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke: a randomized controlled trial. To determine whether circuit-based rehabilitation would increase the amount and rate that individuals with stroke walk in their usual environments. Single-blind randomized controlled trial. Rehabilitation clinic. Sixty participants with a residual gait deficit at least 6 months after stroke originally enrolled in the study. Two withdrew in the initial phase, leaving 58 participants (median age, 71.5y; range, 39.0-89.0y) who were randomized to the 2 intervention groups. The exercise group had 12 sessions of clinic-based rehabilitation delivered in a circuit class designed to improve walking. The control group received a comparable duration of group social and educational classes. Usual walking performance was assessed using the StepWatch Activity Monitor. Clinical tests were gait speed (timed 10-meter walk) and endurance (six-minute walk test [6MWT]), confidence (Activities-Based Confidence Scale), self-reported mobility (Rivermead Mobility Index [RMI]), and self-reported physical activity (Physical Activity and Disability Scale). Intention-to-treat analysis revealed that the exercise group showed a significantly greater distance for the 6MWT than the control group immediately after the intervention (P=.030) but that this effect was not retained 3 months later. There were no changes in the StepWatch measures of usual walking performance for either group. The exercise and control groups had significantly different gait speed (P=.038) and scores on the RMI (P=.025) at the 3-month follow-up. These differences represented a greater decline in the control group compared with the exercise group for both outcome measures. Circuit-based rehabilitation leads to improvements in gait endurance but does not change the amount or rate of walking performance in usual environments. Clinical gains made by the exercise group were lost 3 months later. Future studies should consider whether rehabilitation needs to occur in usual environments to improve walking performance.\n", + "output": "Conclusions: CCT is safe and effective in improving mobility for people after moderate stroke and may reduce inpatient length of stay. Further research is required, investigating quality of life, participation and cost-benefits, that compares CCT to standard care and that also investigates the differential effects of stroke severity, latency and age." + }, + { + "input": "Study: Comparing couples' and individual voluntary counseling and testing for HIV at antenatal clinics in Tanzania: a randomized trial. Voluntary counseling and testing (VCT) for couples (CVCT) is an important HIV-prevention effort in sub-Saharan Africa where a substantial proportion of HIV transmission occurs within stable partnerships. This study aimed to determine the acceptance and effectiveness of CVCT as compared to individual VCT (IVCT). 1,521 women attending three antenatal clinics in Dar es Salaam were randomized to receive IVCT during that visit or CVCT with their husbands at a subsequent visit. The proportion of women receiving test results in the CVCT arm was significantly lower than in the IVCT arm (39 vs. 71%). HIV prevalence overall was 10%. In a subgroup analysis of HIV-positive women, those who received CVCT were more likely to use preventive measures against transmission (90 vs. 60%) and to receive nevirapine for themselves (55 vs. 24%) and their infants (55 vs. 22%) as compared to women randomized to IVCT. Uptake of CVCT is low in the antenatal clinic setting. Community mobilization and couple-friendly clinics are needed to promote CVCT.\n", + "output": "Conclusions: We found only one eligible study that assessed the effectiveness of male involvement in improving women\u2019s uptake of PMTCT services, which only focused on one part of the perinatal PMTCT cascade. We urgently need more rigorously designed studies assessing the impact of male engagement interventions on women\u2019s uptake of PMTCT services to know if this intervention can contribute to improve uptake of PMTCT services and reduce vertical transmission of HIV in children." + }, + { + "input": "Study: Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. To compare the effects of a single nocturnal dose of buckwheat honey or honey-flavored dextromethorphan (DM) with no treatment on nocturnal cough and sleep difficulty associated with childhood upper respiratory tract infections. A survey was administered to parents on 2 consecutive days, first on the day of presentation when no medication had been given the prior evening and then the next day when honey, honey-flavored DM, or no treatment had been given prior to bedtime according to a partially double-blinded randomization scheme. A single, outpatient, general pediatric practice. One hundred five children aged 2 to 18 years with upper respiratory tract infections, nocturnal symptoms, and illness duration of 7 days or less. A single dose of buckwheat honey, honey-flavored DM, or no treatment administered 30 minutes prior to bedtime. Cough frequency, cough severity, bothersome nature of cough, and child and parent sleep quality. Significant differences in symptom improvement were detected between treatment groups, with honey consistently scoring the best and no treatment scoring the worst. In paired comparisons, honey was significantly superior to no treatment for cough frequency and the combined score, but DM was not better than no treatment for any outcome. Comparison of honey with DM revealed no significant differences. In a comparison of honey, DM, and no treatment, parents rated honey most favorably for symptomatic relief of their child's nocturnal cough and sleep difficulty due to upper respiratory tract infection. Honey may be a preferable treatment for the cough and sleep difficulty associated with childhood upper respiratory tract infection. clinicaltrials.gov Identifier: NCT00127686.\n", + "output": "Conclusions: Honey may be better than 'no treatment' and diphenhydramine in the symptomatic relief of cough but not better than dextromethorphan. There is no strong evidence for or against the use of honey." + }, + { + "input": "Study1: The first international urokinase/warfarin trial in colorectal cancer. Three hundred and forty-four patients with operable colorectal adenocarcinoma, Dukes' stage B or C, were entered into a randomized controlled trial of intraoperative and postoperative intravenous urokinase and/or long-term sodium warfarin therapy. The factorial design of the trial allowed evaluation of each therapy separately. Age, sex, Dukes' stage and cancer site were similar in the treatment groups. Using life-table methods, survival and recurrence/metastases free survival were estimated up to 6 years postoperatively. No significant effects of either therapy on these endpoints were found.\nStudy2: Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Patients receiving chemotherapy for metastatic breast cancer are at high risk of thromboembolic disease. Long-term oral anticoagulant therapy is needed but increases the risk of haemorrhagic complications. We have assessed the safety and efficacy of warfarin in very low doses as prophylaxis. Women receiving chemotherapy for metastatic breast cancer were randomly assigned either very-low-dose warfarin (152 patients) or placebo (159). The warfarin dose was 1 mg daily for 6 weeks and was then adjusted to maintain the prothrombin time at an international normalised ratio (INR) of 1.3 to 1.9. Study treatment continued until 1 week after the end of chemotherapy. The average daily dose from initiation of titration was 2.6 (SD 1.2) mg for the warfarin group and the mean INR was 1.52. The mean time at risk of thrombosis was 199 (126) days for warfarin-treated patients and 188 (137) days for placebo recipients (p = 0.45). There were 7 thromboembolic events (6 deep-vein thrombosis, 1 pulmonary embolism) in the placebo group and 1 (pulmonary embolism) in the warfarin group, a relative risk reduction of about 85% (p = 0.031). Major bleeding occurred in 2 placebo recipients and 1 warfarin-treated patient. There was no detectable difference in survival between the treatment groups. Very-low-dose warfarin is a safe and effective method for prevention of thromboembolism in patients with metastatic breast cancer who are receiving chemotherapy.\nStudy3: Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study. Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of warfarin to chemotherapy might enhance response and/or survival in small-cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. Patients were randomized to receive warfarin or no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with < or = 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103). Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.\nStudy4: A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease.\n", + "output": "Conclusions: Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer while increasing the risk for bleeding." + }, + { + "input": "Study1: Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Within the intensive-care unit, non-invasive ventilation (NIV) can prevent the need for intubation and the mortality associated with severe episodes of chronic obstructive pulmonary disease (COPD). The aim of this study was to find whether the introduction of NIV, early after the admission on a general respiratory ward, was effective at reducing the need for intubation and the mortality associated with acute exacerbations of COPD. We did a prospective multicentre randomised controlled study comparing NIV with standard therapy in patients with mild to moderate acidosis. NIV was administered on the ward with a simple non-invasive ventilator and a standardised predefined protocol. Patients were recruited from 14 UK hospitals over 22 months. 236 patients were recruited, 118 received standard therapy alone and 118 additional NIV. The two groups had similar characteristics at enrolment. The use of NIV significantly reduced the need for intubation as defined by the failure criteria. 32/118 (27%) of the standard group failed compared with 18/118 (15%) of the NIV group (p=0.02). In-hospital mortality was also reduced by NIV, 24/118 (20%) died in the standard group compared with 12/118 (10%) in the NIV group (p=0.05). In both groups pH, PaCO2, and respiratory rate improved at 4 h (p<0.01). However, NIV led to a more rapid improvement in pH in the first hour (p=0.02) and a greater fall in respiratory rate at 4 h (p=0.035). The duration of breathlessness was also reduced by NIV (p=0.025). The early use of NIV for mildly and moderately acidotic patients with COPD in the general ward setting leads to more rapid improvement of physiological variables, a reduction in the need for invasive mechanical ventilation (with objective criteria), and a reduction in in-hospital mortality.\nStudy2: Noninvasive ventilation for acute respiratory failure: a prospective randomised placebo-controlled trial. The aim of the present study was to clarify whether the known effects of noninvasive positive-pressure ventilation (NPPV) in patients with respiratory failure are real or due to placebo effects and whether early application of NPPV in the emergency department leads to rapid improvement of the patients condition and outcome. A prospective randomised placebo-controlled study was conducted in 20 patients with severe acute respiratory failure (ARF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute pulmonary oedema, not improving under conventional medical therapy and on the edge of intubation. Patients received either conventional medical therapy plus two-level NPPV (hi-level NPPV) or conventional medical therapy plus \"placebo\" NPPV. The main outcome measures involved the need for endotracheal intubation in the bi-level NPPV arm and in the placebo arm after crossing over to active NPPV. Morbidity, length of stay, mortality and the effect of the ventilatory mode on clinical, arterial-blood gas parameters, and the sternocleidomastoid muscles electromyogram (EMG) activity were also measured. The 10 patients in the active NPPV group rapidly improved and none needed intubation. Placebo NPPV resulted in no change in the clinical condition of patients that continued to worsen and the 10 patients were crossed over to active NPPV. Three patients were intubated. No differences in terms of morbidity, length of stay or mortality between the two groups were observed. Active NPPV (but not placebo NPPV) led to a rapid and significant improvement in the clinical parameters, pH and the carbon dioxide tension in arterial blood and to a decrease in respiratory frequency and sternocleidomastoid EMG activity. Early application of bi-level noninvasive positive-pressure ventilation in patients with severe acute respiratory failure, due to chronic obstructive pulmonary disease and acute pulmonary oedema, leads to a rapid improvement in clinical status and blood gases. Noninvasive positive-pressure ventilation had no placebo effect.\n", + "output": "Conclusions: Data from good quality randomised controlled trials show benefit of NPPV as first line intervention as an adjunct therapy to usual medical care in all suitable patients for the management of respiratory failure secondary to an acute exacerbation of COPD. NPPV should be considered early in the course of respiratory failure and before severe acidosis ensues, as a means of reducing the likelihood of endotracheal intubation, treatment failure and mortality." + }, + { + "input": "Study1: Efficacy and safety of rofecoxib 12.5 mg versus nabumetone 1,000 mg in patients with osteoarthritis of the knee: a randomized controlled trial. To evaluate the use of starting doses of rofecoxib and nabumetone in patients with osteoarthritis (OA) of the knee. A 6-week, randomized, parallel-group, double-blind, placebo-controlled study. One hundred thirteen outpatient sites in the United States. A total of 1,042 male and female patients aged 40 and older with OA of the knee (>6 months). Rofecoxib 12.5 mg once a day (n=424), nabumetone 1,000 mg once a day (n=410), or placebo (n=208) for 6 weeks. The primary efficacy endpoint was patient global assessment of response to therapy (PGART) over 6 weeks, which was also specifically evaluated over the first 6 days. The main safety measure was adverse events during the 6 weeks of treatment. The percentage of patients with a good or excellent response to therapy as assessed using PGART at Week 6 was significantly higher with rofecoxib (55.4%) than nabumetone (47.5%; P=.018) or placebo (26.7%; P<.001 vs rofecoxib or nabumetone). Median time to first report of a good or excellent PGART response was significantly shorter in patients treated with rofecoxib (2 days) than with nabumetone (4 days, P=.002) and placebo (>5 days, P<.001) (nabumetone vs placebo; P=.007). The safety profiles of rofecoxib and nabumetone were generally similar, including gastrointestinal, hypertensive, and renal adverse events. Rofecoxib 12.5 mg daily demonstrated better efficacy over 6 weeks of treatment and quicker onset of OA efficacy over the first 6 days than nabumetone 1,000 mg daily. Both therapies were generally well tolerated.\nStudy2: Comparing the efficacy of cyclooxygenase 2-specific inhibitors in treating osteoarthritis: appropriate trial design considerations and results of a randomized, placebo-controlled trial. To compare the efficacy of the cyclooxygenase 2 (COX-2)-specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA). In this randomized, placebo-controlled, double-blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination). In primary measures of efficacy (OA pain score on a 100-mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34-mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was -2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events. Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA.\nStudy3: Comparative evaluation of the effectiveness and tolerability of nimesulide versus rofecoxib taken once a day in the treatment of patients with knee osteoarthritis. The treatment of osteoarthritis, a common degenerative joint disease, is focused on the relief of symptoms, mainly pain, and sometimes joint stiffness. Nonsteroidal antiinflammatory drugs are considered the treatment of choice in cases where the pain cannot be reduced with acetaminophen. This trial was conducted to compare the effectiveness of 2 nonsteroidal antiinflammatory drugs taken once daily to relieve the symptoms of osteoarthritis. To compare the safety and efficacy of 2 nonsteroidal antiinflammatory drugs, nimesulide versus rofecoxib, given once a day in patients with knee osteoarthritis. 114 patients with the diagnosis of knee osteoarthritis were recruited in a randomized, double-blinded fashion, and they received a daily dose of either 300 mg of nimesulide retard or 25 mg of rofecoxib. The effectiveness was evaluated by means of: visual analog scale 0 to 10 cm measured at 0, 15, 30, and 45 minutes after the first dose and then after 2, 3, 15, and 30 days of continuous drug dosing. The quality of life was assessed by the scale of the Western Ontario and McMaster Universities on days 0, 15, and 30. The patients' opinions and that of the physicians were recorded at the end of the study. The 2 groups of patients were matched for race, sex, menopause status (for females), pathologic antecedents, the duration of osteoarthritis, and the history of nonsteroidal antiinflammatory drug therapy; however, patients' affected knees could differ in the 2 treatments. The 2 drugs were equally effective in terms of overall improvement of pain and the quality of life; they were equally well tolerated. However, significant differences were found between the 2 drugs in favor of nimesulide in the relief of the pain on days 2, 3, and 30, and in the scale of Western Ontario and McMaster Universities Osteoarthritis index on day 15 and 30. In this trial, both medications were effective in improving the pain and the quality of life in patients with knee osteoarthritis; however, nimesulide, compared with rofecoxib, was quicker in reducing the pain and was more effective on days 2, 3, and 30. Nimesulide was also superior in improving the quality of life after 30 days of treatment.\nStudy4: Effect of rofecoxib therapy on measures of health-related quality of life in patients with osteoarthritis. Bodily pain and physical disability can negatively impact health-related quality of life (HRQL) in patients with osteoarthritis (OA). To assess the effects of treatment with a new agent, rofecoxib, on HRQL in patients with OA. Randomized, double-blind, 6-week clinical trial comparing treatment with rofecoxib, 5 to 50 mg, with placebo in 672 patients with OA of the hip or knee. Patient HRQL was assessed at baseline and at the end of treatment using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). At 6 weeks, mean change from baseline in all SF-36 mental and physical health domain scores demonstrated significant improvement with rofecoxib use (P < .05 for all doses for all SF-36 domains), with evidence of a dose-response relation. Improvements in mental and physical HRQL domains with rofecoxib treatment were significantly greater than those with placebo treatment (P < .05 for each dose of rofecoxib vs placebo for all domains except general health) and highly correlated with improvements observed using disease-specific OA outcome measures such as the Western Ontario and McMaster Universities Osteoarthritis Index-visual Analog 3.0 OA index pain and physical function subscales. The effect of rofecoxib vs placebo treatment on mental health largely disappeared after adjustment for improvement in OA disease-specific measures. Rofecoxib treatment increased physical and mental HRQL domain scores on the SF-36. Improvements in mental health with rofecoxib use primarily resulted from effective treatment of OA (i.e., reduction in pain and improvement in physical function).\nStudy5: Renal tolerability of three commonly employed non-steroidal anti-inflammatory drugs in elderly patients with osteoarthritis. The primary endpoint of this study was to compare the renal tolerability of amtolmetin guacyl (AMG), diclofenac and rofecoxib in elderly patients with symptomatic osteoarthritis (OA). The assessment of efficacy was the secondary endpoint. 90 patients who satisfied the American College of Rheumatology classification criteria for hand, hip or knee OA were randomly assigned to 3 treatment groups receiving either: AMG 1,200 mg over thefirst 3 days and and 600 mg/day thereafter; diclofenac 150 mg/day; or rofecoxib 25 mg/day for 2 weeks. At baseline and after therapy patients were clinically assessed by the same examiner who was unaware of the treatment arm assignement. Serum and urinary parameters of renal function and the outcome measures of efficacy were evaluated before (t(0)) and after therapy (t(1)). Diclofenac produced a significant reduction in creatinine clearance (t(0) = 88.93 +/- 11.59; t(1) = 75.90 +/- 16.32; p: < 0.001) and in the daily urine volume (t(0) = 1,337.93 +/- 202.07; t(1) = 1,027.59 +/- 249.14; p: < 0.001). In the same treatment group a significant increase in serum creatinine, blood urea nitrogen, uric acid and potassium were observed. Rofecoxib treated patients showed a significant increase in body weight (t(0) = 75.31 +/- 4.26; t(1) = 76.54 +/- 4.84; p: < 0.001), systolic blood pressure (t(0) = 144 +/- 10.86; t(1) = 154 +/- 11.8; p < 0.001), diastolic blood pressure (t(0) = 80 +/- 6.05; t(1) = 89 +/- 7.66; p < 0.001) and serum sodium (t(0) = 138.73 +/- 1.28; t(1) = 140.12 +/- 1.80; p < 0.005) associated with a significant decrease in the daily urine volume (t(0) = 1294.64 +/- 205.21; t, = 1,115.48 +/- 238.47; p < 0.001) and creatinine clearance (t(0)= 86.73 +/- 8.14; t(1) = 83.15 +/- 7.96; p < 0.01). No significant changes in the clinical and humoral parameters were recorded in AMG treated patients. Diclofenac was more efficacious than the other 2 drugs (p < 0.001). No differences were observed between AMG and rofecoxib. Side effects related to altered kidney function were significantly higher in the rofecoxib group (p < 0.005). Diclofenac mainly impaired blood renal flow and the glomerularfiltration rate, while rofecoxib negatively influenced the renal sodium-water exchange. AMG demonstrated a renal sparing effect, although the eract mechanism is unclear\nStudy6: Rofecoxib, a new cyclooxygenase 2 inhibitor, shows sustained efficacy, comparable with other nonsteroidal anti-inflammatory drugs: a 6-week and a 1-year trial in patients with osteoarthritis. Osteoarthritis Studies Group. Rofecoxib, a cyclooxygenase 2 inhibitor (sometimes known as a specific cyclooxygenase 2 inhibitor or Coxib), is used in osteoarthritis (OA). Published information indicates rofecoxib's improved gastrointestinal safety profile over nonselective nonsteroidal anti-inflammatory agents (NSAIDs). To evaluate the efficacy and safety of rofecoxib in treating OA in 2 studies. Two randomized, double-blind, parallel-group studies in patients with OA of the knee or hip were conducted using identical entry criteria and end points. A 6-week placebo-controlled trial in 736 patients compared 12.5 and 25 mg of rofecoxib once daily with 800 mg of ibuprofen 3 times daily, and a 1-year study compared 12.5 and 25 mg of rofecoxib once daily with 50 mg of diclofenac 3 times daily in 693 patients. Rofecoxib, at 12.5 and 25 mg, demonstrated efficacy clinically comparable with ibuprofen, assessed by 3 primary end points according to predefined comparability criteria. Both rofecoxib doses and ibuprofen provided significantly greater efficacy than placebo on all primary end points at 6 weeks. Both rofecoxib doses and diclofenac showed similar efficacy over 1 year. All treatments were well tolerated. Rofecoxib is effective in treating OA with once-daily dosing for 6 weeks and 1 year. Rofecoxib was generally safe and well-tolerated in OA patients for 6 weeks and 1 year. Arch Fam Med. 2000;9:1124-1134\n", + "output": "Conclusions: Rofecoxib was voluntarily withdrawn from global markets in October 2004 therefore there are no implications for practice concerning its use. There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing." + }, + { + "input": "Study1: Traditional Chinese acupuncture in tension-type headache: a controlled study. Thirty patients with tension-type headache were randomly chosen to undergo a trial of traditional Chinese acupuncture and sham acupuncture. Five measures were used to assess symptom severity and treatment response: intensity, duration and frequency of headache pain episodes, headache index and analgesic intake. The five measures were assessed during a 4 week baseline period, after 4 and 8 weeks of treatment, and 1, 6 and 12 months thereafter. Before the start of the study, each patient was administered the MMPI. Split-plot ANOVAs showed that, compared to baseline, at 1 month after the end of treatment and for the 12 month follow-up, the frequency of headache episodes, analgesic consumption and the headache index (but not the duration or intensity of headache episodes) significantly decreased over time; however, no difference between acupuncture and placebo treatment was found. No single MMPI scale predicted the response to treatment, but the mean MMPI profile of acupuncture non-responders showed the presence of 'Conversion V'.\nStudy2: Does psychological testing help to predict the response to acupuncture or massage/relaxation therapy in patients presenting to a general neurology clinic with headache? Patients with chronic headache were offered treatment by acupuncture or massage with relaxation instead of a change in their prescribed medication. They were randomly allocated to either treatment. There was a significant improvement in pain ratings with both treatment types. Specifically a greater effect was seen in migraine patients treated by massage with relaxation when compared to acupuncture. No psychological factors were found to predict response to either treatment. At the end of the study, 13% of patients were significantly more worried that there may be a more serious cause underlying their headache despite reassurance and an improvement in their headache scores.\nStudy3: Acupuncture for episodic tension-type headache: a multicentre randomized controlled trial. A multicentre, randomized clinical trial was undertaken to test the hypothesis that acupuncture is more efficacious than sham control procedure in the prevention of episodic tension-type headache. Fifty subjects were randomized to receive a course of treatment with either brief acupuncture or a sham procedure. Subjects were followed up for 3 months. Changes in headache were assessed by daily diary, the primary outcome measure being the number of days with headache. No significant differences were found between the changes in the two groups for any measure at any time point. Results also show that patient blinding was successful. In conclusion, this study does not provide evidence that this form of acupuncture is effective in the prevention of episodic tension-type headache.\nStudy4: Health status in patients with tension headache treated with acupuncture or physiotherapy. Sixty-two female patients with chronic tension headache were randomly divided into two treatment groups--acupuncture and physiotherapy. Their overall function (Sickness Impact Profile), and mental well-being (Mood Adjective Check List) and the intensity and frequency of headache were assessed before and after treatment. Before treatment the patients showed significantly more dysfunction and less positive mental well-being than a general population sample. Both treatment groups improved in overall function, the physiotherapy group somewhat more. The mental well-being increased only in the physiotherapy group. The intensity and frequency of headache was significantly reduced in both the physiotherapy group and the acupuncture group. The intensity of headache was significantly more improved in the physiotherapy group. The improvement of headache intensity persisted unchanged 7-12 months after treatment.\nStudy5: Acupuncture in patients with headache. We aimed to investigate the effectiveness of acupuncture in addition to routine care in patients with primary headache (> 12 months, two or more headaches/month) compared with treatment with routine care alone and whether the effects of acupuncture differ in randomized and non-randomized patients. In a randomized controlled trial plus non-randomized cohort, patients with headache were allocated to receive up to 15 acupuncture sessions over 3 months or to a control group receiving no acupuncture during the first 3 months. Patients who did not consent to randomization received acupuncture treatment immediately. All subjects were allowed usual medical care in addition to study treatment. Number of days with headache, intensity of pain and health-related quality of life (SF-36) were assessed at baseline, and after 3 and 6 months using standardized questionnaires. Of 15,056 headache patients (mean age 44.1 +/- 12.8 years, 77% female), 1613 were randomized to acupuncture and 1569 to control, and 11,874 included in the non-randomized acupuncture group. At 3 months, the number of days with headache decreased from 8.4 +/- 7.2 (estimated mean +/-s.e.) to 4.7 +/- 5.6 in the acupuncture group and from 8.1 +/- 6.8 to 7.5 +/- 6.3 in the control group (P < 0.001). Similarly, intensity of pain and quality of life improvements were more pronounced in the acupuncture vs. control group (P < 0.001). Treatment success was maintained through 6 months. The outcome changes in non-randomized patients were similar to those in randomized patients. Acupuncture plus routine care in patients with headache was associated with marked clinical improvements compared with routine care alone.\nStudy6: Acupuncture in patients with tension-type headache: randomised controlled trial. To investigate the effectiveness of acupuncture compared with minimal acupuncture and with no acupuncture in patients with tension-type headache. Three armed randomised controlled multicentre trial. 28 outpatient centres in Germany. 270 patients (74% women, mean age 43 (SD 13) years) with episodic or chronic tension-type headache. Acupuncture, minimal acupuncture (superficial needling at non-acupuncture points), or waiting list control. Acupuncture and minimal acupuncture were administered by specialised physicians and consisted of 12 sessions per patient over eight weeks. Difference in numbers of days with headache between the four weeks before randomisation and weeks 9-12 after randomisation, as recorded by participants in headache diaries. The number of days with headache decreased by 7.2 (SD 6.5) days in the acupuncture group compared with 6.6 (SD 6.0) days in the minimal acupuncture group and 1.5 (SD 3.7) days in the waiting list group (difference: acupuncture v minimal acupuncture, 0.6 days, 95% confidence interval -1.5 to 2.6 days, P = 0.58; acupuncture v waiting list, 5.7 days, 3.9 to 7.5 days, P < 0.001). The proportion of responders (at least 50% reduction in days with headache) was 46% in the acupuncture group, 35% in the minimal acupuncture group, and 4% in the waiting list group. The acupuncture intervention investigated in this trial was more effective than no treatment but not significantly more effective than minimal acupuncture for the treatment of tension-type headache. ISRCTN9737659.\nStudy7: Needle acupuncture in tension-type headache: a randomized, placebo-controlled study. A study with needle acupuncture was performed in tension-type headache employing a new placebo acupuncture Sixty-nine patients (mean age 48.1 years, SD = 14.1) fulfilling the International Headache Society criteria for tension-type headache were randomly assigned to verum or placebo condition. No significant differences between placebo and verum with respect to visual analogue scale and frequency of headache attacks could be observed immediately, 6 weeks and 5 months after the end of treatment. There was a significant but weak improvement in quality of life parameters (clinical global impressions, Nottingham Health Profile) after verum treatment. In decision tree analyses, the changes in clinical global impressions and headache frequency depended significantly on primary headache frequency with a limit value of 24.5 days headache per month. High values in the von Zerssen Depression Score resulted in high mean visual analogue scale values.\n", + "output": "Conclusions: In the previous version of this review, evidence in support of acupuncture for tension-type headache was considered insufficient. Now, with six additional trials, the authors conclude that acupuncture could be a valuable non-pharmacological tool in patients with frequent episodic or chronic tension-type headaches." + }, + { + "input": "Study1: Supervised exercise training improves cardiopulmonary fitness in HIV-infected persons. We attempted to measure cardiopulmonary effects, CD4 counts, and perceived sense of well-being in 25 individuals moderately to severely immunocompromised from HIV infection (mean entry CD4 count = 144.microliters-1) before and after a 24-wk program of exercise training. Only six subjects completed the 24-wk program. All six showed evidence of a training effect. Statistically significant improvements were seen in maximal oxygen consumption (VO2max), oxygen pulse, and minute ventilation. Submaximal exercise performance improved significantly by 12 wk in the 10 individuals available for testing: decreases were seen in heart rate, rate pressure product, and rate of perceived exertion. White blood cell counts and T-lymphocyte subsets were stable at 12 and 24 wk in the subjects available for testing. High depression/anxiety scores on a mental health inventory (General Health Questionnaire) correlated with low CD4 counts. Scores did not correlate with compliance with the exercise program. There was a trend (P < 0.10) for scores to improve over time among those individuals who attended > or = 80% of scheduled exercise sessions. We conclude that exercise training is feasible and beneficial for some HIV-infected individuals.\nStudy2: Effects of a supervised home-based aerobic and progressive resistance training regimen in women infected with human immunodeficiency virus: a randomized trial. Women infected with human immunodeficiency virus (HIV) increasingly demonstrate abnormalities in fat distribution and metabolism; however, the effects of a home-based exercise regimen in this group have not been investigated. We conducted a 16-week randomized intervention study of a supervised home-based progressive resistance training and aerobic exercise program in 40 HIV-infected women with increased waist-hip ratio and self-reported fat redistribution. Cross-sectional muscle area and muscle attenuation were measured by computed tomography. Cardiorespiratory fitness was determined by calculated maximum oxygen consumption (VO2max) and strength by 1-repetition maximum. Cardiorespiratory fitness (VO2max) was markedly lower at baseline (median [95% confidence interval], 15.4 [8.3-25.2] mL x kg(-1) x min(-1)) than reported values for healthy female subjects (26-35 mL x kg(-1) x min(-1)). Subjects randomized to exercise had significant improvement in mean +/- SEM VO2max (1.5 +/- 0.8 vs -2.5 +/- 1.6 mL x kg(-1) x min(-1); P<.001) and endurance (1.0 +/- 0.3 vs -0.6 +/- 0.3 minute; P<.001). Strength increased at the knee extensors, pectoralis, knee flexors, shoulder abductors, ankle plantar flexors, and elbow flexors (all P<.001). Total muscle area (6 +/- 1 vs 2 +/- 1 cm2; P = .02) and attenuation (2 +/- 1 vs -1 +/- 1 Hounsfield unit; P = .03) increased in the exercise group. No significant difference was seen in lipid levels, blood pressure, or abdominal visceral fat between the groups, but subjects randomized to exercise reported improved energy and appearance. A 16-week, supervised, home-based exercise regimen improved measures of physical fitness in HIV-infected women. The effects on strength were most significant, but improvements in cardiorespiratory fitness, endurance, and body composition were also seen.\nStudy3: The effect of exercise training on aerobic fitness, immune indices, and quality of life in HIV+ patients. Thirty four HIV+ patients participated in a 6-wk aerobic exercise training program to determine whether exercise improved aerobic fitness, immune indices, and quality of life. Subjects were assigned to three groups: control (no regular aerobic exercise), moderate exercise, and heavy exercise training. At study entry and exit (in each subject) we evaluated aerobic function with a symptom limited cardiopulmonary exercise test, immune indices with CD4 counts and Candida skin tests, viral replication with plasma HIV RNA measurements, and quality of life with a HIV+ population validated questionnaire. Aerobic fitness increased significantly in both exercise groups relative to the control group; immune indices changed very little among all three groups; however, the Candida skin tests (mm2) increased significantly in the moderate group; viral replication was essentially unchanged in all three groups; quality of life (QOL) markers improved in both exercising groups but not the control group. There were no opportunistic infections during the study. Exercise training resulted in a substantial improvement in aerobic function while immune indices were essentially unchanged. Quality of life markers improved significantly with exercise. Exercise training is safe and effective in this patient group and should be promoted for HIV+ patients.\nStudy4: Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection. The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse. Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded. Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05). We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.\nStudy5: Exercise training in HIV-1-infected individuals with dyslipidemia and lipodystrophy. Highly active antiretroviral therapy has improved the prognosis of human immuno deficiency virus type 1 (HIV-1)-infected individuals, but it has been associated with the development of metabolic and fat distribution abnormalities known as the lipodystrophy syndrome. This study tested the hypothesis that aerobic exercise training added to a low-lipid diet may have favorable effects in HIV-1-infected individuals with dyslipidemia and lipodystrophy. Thirty healthy subjects, carriers of HIV-1, with dyslipidemia and lipodystrophy, all of whom were using protease inhibitors and/or non-nucleoside reverse transcriptase inhibitors, were randomly assigned to participate in either a 12-wk program of aerobic exercise or a 12-wk stretching and relaxation program. All subjects received recommendations for a low-lipid diet. Before and after intervention, peak oxygen uptake, body composition, CD4, viral load, lipid profile, and plasma endothelin-1 levels were measured. Peak oxygen uptake increased significantly in the diet and exercise group (mean +/- SD: 32 +/- 5 mL x kg(-1) x min(-1) before; 40 +/- 8 mL x kg(-1) x min(-1) after) but not in the diet only group (34 +/- 7 mL x kg(-1) x min(-1) before; 35 +/- 8 mL x kg(-1) x min(-1) after). Body weight, body fat, and waist-to-hip ratio decreased significantly and similarly in the two groups. There were no significant changes in immunologic variables in either group. Likewise, plasma triglycerides, total cholesterol, and HDL cholesterol levels did not change significantly in either group. Plasma endothelin-1 levels were elevated in both groups and presented no significant changes during the study. HIV-seropositive individuals with lipodystrophy and dyslipidemia submitted to a short-term intervention of low-lipid diet and aerobic exercise training are able to increase their functional capacity without any consistent changes in plasma lipid levels.\nStudy6: Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial. Substantial loss of muscle mass occurs among men with AIDS wasting. To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting. Randomized, controlled trial. University hospital. 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%). In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks. Cross-sectional muscle area and other indices of muscle mass. Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm2 vs. 206 +/- 264 mm2 [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm2 vs. 523 +/- 872 mm2 [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm2 vs. 194 +/- 215 mm2 [P< 0.001]; change in leg muscle mass, 1,236 +/- 881 mm2 vs. 399 +/- 729 mm2 [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P= 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052). In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting.\nStudy7: Effectiveness of a home-based exercise intervention for HIV-infected adults: a randomized trial. The authors conducted a randomized controlled trial to assess the impact of a 15-week (20 minutes three times per week) home-based aerobic exercise intervention versus usual care on the physical endurance, immune status, and self-reported health status of 99 HIV-infected adults. In the exercise group, there was no improvement in physical endurance or health-related quality of life (HRQOL), except in the Medical Outcomes Study-HIV Health Survey Overall Health subscale (difference = 12.1, 95% confidence interval = 2.0-22.2, p = .02). Although physical endurance levels were maintained at baseline levels in the intervention group and declined in the control group, differences between the groups were small and not significant. There were also no significant changes in CD4+ T-lymphocyte counts. Exercise appears to be safe in HIV-infected patients. Improvements in physical endurance and HRQOL might result if the exercise protocol is longer or progressive. Further research is needed to establish guidelines for exercise in patients on highly active antiretroviral therapy.\nStudy8: Aerobic exercise: effects on parameters related to fatigue, dyspnea, weight and body composition in HIV-infected adults. The purpose of the study was to examine the effects of aerobic exercise on physiological fatigue (time on treadmill), dyspnea [rate of perceived exertion (RPE) and forced expiratory volume at 1 s (FEV1)], weight, and body composition in HIV-1-infected adults (200-499 x 106 CD4+ cells/l). The study was a randomized, wait-listed, controlled clinical trial of aerobic exercise in HIV-1-infected adults on signs and symptoms associated with HIV-1 infection or its treatment. Sixty subjects were recruited and randomized to two groups. Experimental subjects completed a 12-week supervised exercise program. Control subjects continued usual activity from baseline to week 12 and were then were enrolled in the exercise program. At baseline, the groups were similar in age, weight, body mass index [mean body mass index (BMI) > 27], time since diagnosis, number of symptoms, CD4+ cell count, and number on protease inhibitor therapy (n = 7). Despite disproportionate attrition from the exercise group (38%), exercise subjects were able to remain on the treadmill longer, lost weight, decreased BMI, subcutaneous fat, and abdominal girth when compared to controls. The improvement in weight and body composition occurred without a decrease in kilocalories consumed. Exercise did not seem to have an effect on RPE, a surrogate for dyspnea, and FEV1. There was no significant difference in either the change in CD4+ cell count, percentage or copies of plasma HIV-1 RNA between groups. We conclude that supervised aerobic exercise training safely decreases fatigue, weight, BMI, subcutaneous fat and abdominal girth (central fat) in HIV-1-infected individuals. It did not appear to have an effect on dyspnea.\nStudy9: The effects of exercise training on quality of life in HAART-treated HIV-positive Rwandan subjects with body fat redistribution. Our objective was to examine the effects of exercise training (EXS) on quality of life (QoL) in highly active antiretroviral therapy (HAART)-treated HIV-positive (HIV+) subjects with body fat redistribution (BFR) in Rwanda. The effects of a randomised controlled trial of EXS on QoL were measured using World Health Organisation Quality of Life (WHOQOL)-BREF in HIV+ subjects with BFR randomised to EXS (n = 50; BFR + EXS) or no exercise training (n = 50; BFR + noEXS). At 6 months, scores on the psychological [1.3 (0.3) vs. 0.5 (0.1); P < 0.0001], independence [0.6 (0.1) vs. 0.0 (0.0); P < 0.0001], social relationships [0.6 (0.2) vs. 0.0 (0.0); P < 0.0001] and HIV HAART-specific QoL domains [1.4 (0.2) vs. -0.1 (0.2); P < 0.0001] improved more in BFR + EXS than BFR + noEXS group, respectively. Self-esteem [1.3 (0.8) vs. 0.1 (0.6); P < 0.001], body image [1.5 (0.6) vs. 0.0 (0.5); P < 0.001] and emotional stress [1.6 (0.7) vs. 0.2 (0.5); P < 0.001] improved more in the BFR + EXS group than BFR + noEXS group, respectively. Psychological [1.5 (0.2) vs. 1.1 (0.3); P < 0.0001], social relationship [0.8 (0.2) vs. 0.4 (0.2); P < 0.0001], and HIV HAART-specific well-being [1.8 (0.2) vs. 1.0 (0.0); P < 0.0001] improved more in BFR + EXS female than male subjects. Exercise training improved several components of QoL in HAART-treated HIV+ African subjects with BFR. Exercise training is an inexpensive and efficacious strategy for improving QoL in HIV+ African subjects, which may improve HAART adherence and treatment initiatives in resource-limited areas of sub-Saharan Africa.\nStudy10: Moderate and high intensity exercise training in HIV-1 seropositive individuals: a randomized trial. HIV-infected individuals are frequently active, but guidelines for exercise in this population lack scientific support, since studies on the effects of exercise training on immunologic variables of HIV-1 positive individuals have shown conflicting results. Exercise capacity, immunologic markers (CD4, CD8 and CD4:CD8 ratio), anthropometric measurements, and depression scores were evaluated to compare the effects of two intensities of aerobic exercise on HIV-1 seropositive individuals. Twenty-one healthy subjects (14 men, 7 women), carriers of the HIV-1 virus (CD4>200 cells x mm(-3)), and inactive for at least 6 months, completed a 12 week exercise training program (36 sessions of 1 h, 3 times per week), in a moderate intensity group (60+/-4% of maximal heart rate) or a high intensity group (84+/-4% of maximal heart rate). Exercise capacity estimated by treadmill time was increased significantly in both moderate intensity (680+/-81 s before; 750+/-151 s after) and high intensity (651+/-122 s before; 841+/-158 s after) groups, but the high intensity group presented a significantly larger increment (p<0.01). There were no significant changes in the immunologic variables, anthropometric measurements or depression scores. Thus, HIV-seropositive individuals that participate in moderate and high intensity exercise programs are able to increase their functional capacity without any detectable changes in immunologic variables, anthropometric measurements or depression scores.\n", + "output": "Conclusions: Aerobic exercise appears to be safe and may be beneficial for adults living with HIV. These findings are limited by the small sample sizes and large withdrawal rates described in the studies. Future research would benefit from participant follow-up and intention-to-treat analysis. Further research is required to determine the optimal parameters in which aerobic exercise may be most beneficial for adults living with HIV." + }, + { + "input": "Study1: Linoleic acid in multiple sclerosis: failure to show any therapeutic benefit. We have studied the effect of a dietary supplement with linoleic acid (LA) in 76 patients with MS. We could detect no effect of this supplement on the progression of neurological findings, the relapse rate, or the severity of relapses. We were also able to show that oral supplementation with a linoleic acid preparation would raise the blood level of LA in these patients. We were unable to show that there was any reduction in the linoleic acid blood levels associated with acute relapses of MS during this study.\nStudy2: A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. A trial of n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis has been conducted over a 5 year period. Ambulant patients (312) with acute remitting disease were randomly allocated to treatment or placebo. Both groups were given dietary advice to increase the intake of n-6 polyunsaturated fatty acids and the treatment group in addition received capsules containing n-3 polyunsaturated fatty acids. Analysis of clinical outcome at the end of 2 years of treatment was made in terms of the duration, frequency and severity of relapses and the number of patients who had improved or remained unchanged. The results showed no significant difference at the usual 95% confidence limits but there was a trend in favour of the group treated with n-3 polyunsaturated fatty acids in all parameters examined.\nStudy3: Double-blind trial of linoleate supplementation of the diet in multiple sclerosis. Seventy-five patients in London and Belfast with multiple sclerosis were given daily supplements of a vegetable oil mixture containing either linoleate or oleate for two years in a double-blind control trial. Relapses tended to be less frequent and were significantly less severe and of shorter duration in the linoleate-supplemented group than in those receiving the oleate mixture, but clear evidence that treatment affected the overall rate of clinical deterioration was not obtained.\nStudy4: Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. To determine whether a low fat diet supplemented with omega-3 positively affects quality of life (QOL) in relapsing-remitting MS (RRMS) patients. In this 1-year long double-blind, randomized trial, patients were randomized to two dietary interventions: the \"Fish Oil\" (FO) group received a low fat diet (15% fat) with omega-3 FOs and the \"Olive Oil\" (OO) group received the AHA Step I diet (fat 30%) with OO supplements. The primary outcome measure was the Physical Components Summary Scale (PCS) of the Short Health Status Questionnaire (SF-36). Additional measures using MS specific QOL questionnaires, neurological status and relapse rate were obtained. 31 RRMS patients were enrolled, with mean follow up over 11 +/- SD 2.9 months. Clinical benefits favoring the FO group were observed on PCS/SF-36 (P = 0.050) and MHI (P = 0.050) at 6 months. Reduced fatigue was seen on the OO diet at 6 months (P = 0.035). The relapse rate decreased in both groups relative to the rates during the 1 year preceding the study: mean change in relapse rate in the FO group: -0.79 +/- SD 1.12 relapses/year (P = 0.021) vs. -0.69 +/- SD 1.11 (P = 0.044) in the OO group. This study suggests that a low fat diet supplemented with omega-3 PUFA can have moderate benefits in RRMS patients on concurrent disease modifying therapies.\n", + "output": "Conclusions: PUFAs seem to have no major effect on the main clinical outcome in MS (disease progression), but they may tend to reduce the frequency of relapses over two years. However, the data that are available are insufficient to assess a real benefit or harm from PUFA supplementation because of their uncertain quality.\nEvidence on the possible benefits and risks of vitamin supplementation and antioxidant supplements in MS is lacking. More research is required to assess the effectiveness of dietary interventions in MS." + }, + { + "input": "Study1: Comparison of three- and ten-day regimens with a sulfadiazine-trimethoprim combination and pivmecillinam in acute lower urinary tract infections. 132 female hospital employees (mean age 32 years) with uncomplicated, bacteriologically verified acute lower urinary tract infection were included in a randomized study. The patients were treated for 3 or 10 days with a sulfadiazine-trimethoprim combination (500 mg + 150 mg) b.i.d. or for 3 or 10 days with pivmecillinam (500 mg) t.i.d. The first follow-up evaluation was performed 3-5 days after the treatment. In both sulfadiazine-trimethoprim groups the cure rate was 97% and in both pivmecillinam groups 80%. This difference was mainly due to the occurrence of pivmecillinam-resistant Staphylococcus saprophyticus strains. 109 patients attended the second follow-up visit about 4 weeks after treatment. The prevalences of reinfections and relapses were 18% in both 3-day regimens and 4-7% in both 10-day regimens. No side-effects were reported in the 3-day sulfadiazine-trimethoprim group, while about 20% in the corresponding 10-day group had side-effects. Side-effects were not common in patients treated with pivmecillinam.\nStudy2: [Treatment of uncomplicated recurrent cystitis in women: lomefloxacin versus norfloxacin]. compare the acceptability of 3-day regimen with that of 10-day regimen of fluoroquinolones for the treatment of recurrent uncomplicated lower urinary tract infection in women. a multicentric, randomized open trial was conduced in 421 patients by gynecologic and general practitioners to determine acceptability, efficacy and safety of lomefloxacin 400 mg in a once a day dose given for three days compared with norfloxacin 800 mg in twice a day dose given for ten days for the treatment of recurrent uncomplicated lower urinary tract infection in women. acceptability, assessed at day 14, was significantly better for lomefloxacin group than norfloxacin group, respectively 57,1 p.100 and 38,0 p.100. Clinical success rate at day 14 was 97,2 p.100 for lomefloxacin and 97,5 p.100 for norfloxacin; at day 30 clinical success rate was respectively 97,6 p.100 and 98,1 p.100 relapse at one year was comparable between two groups. Adverse events were reported respectively in 15,6 p.100 and 16,6 p.100 of the patients, vaginal infections, dermatologic disorders and digestive disorders (abdominal pain, nausea) predominated. There were no serious adverse event. the acceptability is better for a 3-day regimen of lomefloxacin than a 10-day regimen of norfloxacin for treatment of recurrent uncomplicated lower urinary tract infection in women for comparable efficacy and safety.\nStudy3: Pivmecillinam treatment in acute cystitis. Three versus seven days study. In an open randomized study pivmecillinam (Selexid; CAS 32886-97-8) was studied by general practitioners in 345 female patients with uncomplicated acute cystitis. Out of the bacteriologically evaluated 299 patients 151 patients were treated for three days with two tablets of pivmecillinam 200 mg t.i.d. and 148 patients for seven days with one tablet t.i.d. There were no significant differences in the bacteriological effect between the two regimens. In the 3-day group 91% and 88% were cured at the first and the second control; in the 7-day group 94% and 95%, respectively. There was no significant difference in the total clinical effect, either. Adverse reactions, usually gastrointestinal disturbances, occurred in 10% of the 3-day group and in 11% of the 7-day group (N.S.). Pivmecillinam treatment in acute cystitis in women was equally effective whether given for three or seven days, with the same total frequency of adverse reactions for the two regimens.\nStudy4: [Pivmecillinam (Selexid) in acute cystitis. A comparative study of 3- and 7-day treatments]. nan\nStudy5: Nalidixic acid and pivmecillinam for treatment of acute lower urinary tract infections. Women, 15-45 years of age, with symptoms of lower urinary tract infection (UTI) were randomly treated with nalidixic acid (1 g X 3) or pivmecillinam (200-400 mg X 3) for three or seven days, respectively. Therapeutic failure, relapse, or reinfection occurred among 18% of 82 women, even though the isolated strains of gram-negative rods in these patients were susceptible in vitro to the antibiotics used. Therapeutic failure, i.e. no effect or at best only a minor effect on the symptoms, was registered in 10 of 13 cases of UTI caused by Staphylococcus saprophyticus and treated with nalidixic acid, which was consistent with the high minimum inhibitory concentrations (MIC) (128-512 micrograms/ml) of this antibiotic. S. saprophyticus was isolated in 9 of 12 patients during treatment with nalidixic acid. On the other hand, pivmecillinam therapy was clinically effective in 16 of 18 patients with UTI caused by S. saprophyticus, even though the MIC of mecillinam to these strains was considerably higher (8-64 micrograms/ml) than that vis-\u00e0-vis gram-negative rods. Thus the clinical effect of pivmecillinam was significantly better than that of nalidixic acid in cases of UTI caused by S. saprophyticus. The organism was not isolated from 14 patients receiving pivmecillinam therapy.\nStudy6: A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection. The study was undertaken to compare the safety and efficacy of twice-daily ciprofloxacin for 3 days with standard 7 day therapy with either co-trimoxazole or nitrofurantoin in the treatment of women with acute, uncomplicated urinary tract infections (UTI). This multicentre, prospective, randomized, double-blind trial compared oral ciprofloxacin (100 mg bd) for 3 days with co-trimoxazole (160/800 mg bd) or nitrofurantoin (100 mg bd) for 7 days. Bacteriological and clinical evaluations were performed at study entry, during therapy and 4-10 days and 4-6 weeks after the completion of therapy. The primary efficacy parameter was eradication of the causative organism 4-10 days following treatment. Of 713 women enrolled and evaluable for safety, 521 were evaluable for efficacy (168 ciprofloxacin, 174 co-trimoxazole, 179 nitrofurantoin). Escherichia coli (83%) was the most frequently isolated pathogen in all treatment groups. Bacteriological eradication was reported in 88% of ciprofloxacin patients, 93% of co-trimoxazole patients and 86% of nitrofurantoin patients. At the 4-6 week follow-up, ciprofloxacin had statistically significantly higher eradication rates (91%) than co-trimoxazole (79%; 95% confidence limit (CL) = -20.6%, -3.9%) and nitrofurantoin (82%; 95% CL = -17.1%, -0.9%). Clinical resolution 4-10 days after therapy and at the 4-6 week follow-up was similar among the three treatment groups. The overall incidence of treatment-emergent adverse events was not significantly different (P = 0.093) among the three drug regimens, although co-trimoxazole was associated with a greater number of adverse events than ciprofloxacin (P < or = 0.05). Ciprofloxacin also caused fewer episodes of nausea than either of the other agents (P < or = 0.01).\nStudy7: Comparison of three-day temafloxacin with seven-day ciprofloxacin treatment of urinary tract infections in women. Temafloxacin is a new broad-spectrum arylfluoroquinolone antimicrobial with an extended serum half-life. In this large, multicenter, double-blind clinical trial, 404 women with acute, uncomplicated urinary tract infections (UTI) were randomized to receive temafloxacin 400 mg once daily for 3 days, or ciprofloxacin 250 mg twice daily for 7 days. Clinical and microbiologic evaluations were repeated at 4 to 5 days after initiation of treatment, at the end of therapy, and at 5 to 9 days posttreatment. One hundred fifteen patients who received temafloxacin and 105 patients who received ciprofloxacin met the eligibility criteria for efficacy evaluation. The predominant urinary pathogens were Escherichia coli, Proteus mirabilis, and coagulase-negative staphylococci. No pretherapy isolate was resistant to either study drug. Bacteriologic eradication was observed in 112 (97%) of 115 women treated with temafloxacin and 101 (96%) of 105 women treated with ciprofloxacin. Clinical cure rates at 5 to 9 days posttreatment were 90% (the remaining 10% improved) with temafloxacin and 95% (the remaining 5% improved) with ciprofloxacin. Adverse effects associated with treatment occurred in 24 (12%) women who received temafloxacin and 31 (15%) women who received ciprofloxacin. Headache (2% with temafloxacin and 2% with ciprofloxacin), nausea (3% with temafloxacin and 6% with ciprofloxacin), and somnolence (4% with temafloxacin and 3% with ciprofloxacin) were reported most often. Only three and five patients who were treated with temafloxacin and ciprofloxacin, respectively, discontinued treatment because of adverse effects. In this study, a 3-day treatment regimen using a single daily 400-mg dose of temafloxacin was found to be as effective as a 7-day course of ciprofloxacin in women with acute uncomplicated UTI.\nStudy8: Different lengths of treatment with co-trimoxazole for acute uncomplicated urinary tract infections in women. To compare three days' and seven days' treatment with co-trimoxazole in women with acute dysuria, strangury, and urinary frequency or urgency. Randomised double blind placebo controlled trial. General practices in the south east of The Netherlands. 327 Non-pregnant female patients aged 12 to 65. 161 Women were allocated to three days' treatment (co-trimoxazole 960 mg twice a day), and 166 women were allocated to seven days' treatment (co-trimoxazole 960 mg twice a day). Resolution of symptoms at one, two, and six weeks. The rates for resolution of symptoms were not significantly different between the two groups. Cumulative rates of recurrence after three days' and seven days' treatment were 31/139 (22%) and 23/151 (15%) respectively six weeks after entry (p = 0.16). Adverse effects occurred in a quarter of women given three days' treatment compared with a third of women receiving seven days' treatment (p = 0.29). In only two patients did adverse effects necessitate stopping treatment. Three days of co-trimoxazole seems to be as effective as a seven days' course for treating acute urinary tract infection in non-pregnant women.\nStudy9: A comparison of a 3-day course of Mictral with a 7-day course of ampicillin in the treatment of urinary tract infection. This general practice study compared a 3-day course of a new preparation, Mictral, with a standard 7-day course of ampicillin in the treatment of uncomplicated urinary tract infection. Mictral achieved bacteriological cure in all infected patients by Day 4 while only 69% of infected patients in the ampicillin group were abacteriuric by Day 8. Symptomatic relief and the incidence of side-effects were similar for both groups. It is concluded that Mictral appears to be a useful addition to currently available therapy for urinary tract infection and merits further investigation.\nStudy10: Treatment of acute urinary tract infection with three doses of co-trimoxazole. nan\n", + "output": "Conclusions: Three days of antibiotic therapy is similar to 5-10 days in achieving symptomatic cure during uncomplicated UTI treatment, while the longer treatment is more effective in obtaining bacteriological cure. In spite of the higher rate of adverse effects, treatment for 5-10 days could be considered for treatment of women in whom eradication of bacteriuria is important." + }, + { + "input": "Study: Long-term effects of specific stabilizing exercises for first-episode low back pain. A randomized clinical trial with 1-year and 3-year telephone questionnaire follow-ups. To report a specific exercise intervention's long-term effects on recurrence rates in acute, first-episode low back pain patients. The pain and disability associated with an initial episode of acute low back pain (LBP) is known to resolve spontaneously in the short-term in the majority of cases. However, the recurrence rate is high, and recurrent disabling episodes remain one of the most costly problems in LBP. A deficit in the multifidus muscle has been identified in acute LBP patients, and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity. Any relation between this deficit and recurrence rate was investigated in the long-term. Thirty-nine patients with acute, first-episode LBP were medically managed and randomly allocated to either a control group or specific exercise group. Medical management included advice and use of medications. Intervention consisted of exercises aimed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle. One year and three years after treatment, telephone questionnaires were conducted with patients. Questionnaire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group. One year after treatment, specific exercise group recurrence was 30%, and control group recurrence was 84% (P < 0.001). Two to three years after treatment, specific exercise group recurrence was 35%, and control group recurrence was 75% (P < 0.01). Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone.\n", + "output": "Conclusions: There is moderate quality evidence that post-treatment exercise programmes can prevent recurrences of back pain but conflicting evidence was found for treatment exercise. Studies into the validity of measurement of recurrences and the effectiveness of post-treatment exercise are needed." + }, + { + "input": "Study1: Low-dose D-penicillamine therapy in rheumatoid arthritis. A controlled, double-blind clinical trial. Two hundred twenty-five patients with active severe rheumatoid arthritis were admitted to a multiclinic, controlled, double-blind trial comparing the use of 500 mg D-penicillamine per day, 125 mg D-penicillamine per day, and placebo. One hundred seventy-one patients completed at least 30 weeks of therapy. The 500 mg D-penicillamine group demonstrated statistically significant improvement over the placebo group in grip strength, average circumference of swollen proximal interphalangeal joints, and patient assessment. While the trend was for greater improvement with the larger dose of D-penicillamine, there was no statistically significant difference among the 3 groups in duration of morning stiffness, walking time, physician's assessment, number of swollen joints, or scores for tender and swollen joints. The slight increase in efficacy of higher dose D-penicillamine was associated with increased toxicity.\nStudy2: Clinical evaluation of D-penicillamine by multicentric double-blind comparative study in chronic rheumatoid arthritis. In order to evaluate clinical efficacy of D-penicillamine (DP) a double-blind study was conducted by the Metalcaptase Research Group consisting of forty-one rheumatological centers in Japan. A total of 179 patients with rheumatoid arthritis (RA) was divided into two groups; one treated with 5 mg (control group) and the other with 100 mg (drug group) of DP in capsule form. The trial lasted 24 weeks. Global judgment by physicians revealed that improvement was found in 27% in the controls and 65% in the drug group. Adverse reactions occurred in 34% of the controls and 49% of the drug group. Skin rashes, taste disturbances, gastrointestinal upset and proteinuria were frequent in the drug group, but severe or fatal reactions could not be seen in this trial.\n", + "output": "Conclusions: D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review." + }, + { + "input": "Study1: The Misgav Ladach method for cesarean section compared to the Pfannenstiel method. The aim of the study was to evaluate the outcome of two different methods of cesarean section (CS). The study was designed as a prospective, randomized, controlled trial. All CS were performed at the University Hospital in Uppsala, Sweden. Fifty women admitted to hospital for a first elective CS were consecutively included in the study. They were randomly allocated to two groups. One group was operated on by the Misgav Ladach method for CS and the other group by the Pfannenstiel method. All operations were performed by the same surgeon. Duration of operation, amount of bleeding, analgesics required, scar appearance and length of hospitalization. Operating time was significantly different between the two methods, with an average of 12.5 minutes with the Misgav Ladach method and 26 minutes with the Pfannenstiel method (p<0.001). The amount of blood loss differed significantly, with 448 ml and 608 ml respectively (p=0.017). Significantly less analgesic injections and tablets (p=0.004) were needed after the Misgav Ladach method. The Misgav Ladach method of CS has advantages over the Pfannenstiel method by being significantly quicker to perform, with a reduced amount of bleeding and diminished postoperative pain. The women were satisfied with the appearance of their scars. In this study no negative effects of the new operation technique were discovered.\nStudy2: A randomized clinical trial of two surgical techniques for cesarean section. The Joel-Cohen incision followed by nonclosure of pelvic and parietal peritoneum has been advocated as an alternative method to the Pfannenstiel incision with peritonealization at cesarean section. A randomized trial was designed to compare intra- and postoperative morbidity between the two techniques. Women to undergo a cesarean section were randomly allocated to have either the Joel-Cohen incision with the parietal and pelvic peritoneum left open (group 1) or to have the Pfannenstiel incision with both peritoneal layers sutured (group 2). The myometrium was closed with 1-0 polyglactin 910 suture using a continuous single-layer nonlocking technique. Patients in group 2 had the peritoneum approximated with 2-0 polyglactin 910 suture. The fascia was sutured with continuous 1-0 polyglactin 910 suture in all cases. Opening time was defined as the interval from skin incision to the opening of the uterine cavity. Febrile morbidity was defined as a temperature > or =38 degrees C on two occasions 4 hours (hr) apart excluding the first postoperative day. Endometritis was defined as postpartum temperature > or =38 degrees C on two occasions 4 hr apart, with uterine tenderness and/or foul-smelling lochia. One hundred forty-nine and 150 patients were allocated to group 1 and to group 2, respectively. A shorter median (range) opening time [4 min (2-21) vs. 6 min (2-19), respectively, p < 0.01] and a shorter median (range) operative time [30 min (10-65) vs. 40 min (20-110), respectively, p < 0.01] were observed in group 1. No difference was found in terms of intraoperative complications, proportion of patients who required transfusion, endometritis, sepsis, febrile morbidity, and urinary tract infections. A higher rate of wound infections was found in group 2 than in group 1 [14 of 150 (9.3%) vs. 2 of 149 (1.3%), respectively, p < 0.01]. The Joel-Cohen incision without peritonealization resulted in a shorter opening and total operative time than the Pfannenstiel laparotomy with peritonealization. This was accomplished with a reduction of wound infections.\nStudy3: The modified Misgav-Ladach versus the Pfannenstiel-Kerr technique for cesarean section: a randomized trial. Modifications to the classic cesarean section technique described by Pfannenstiel and Kerr have been proposed in the last few years. The objective of this trial was to compare intraoperative and short-term postoperative outcomes between the Pfannenstiel-Kerr and the modified Misgav-Ladach (MML) techniques for cesarean section. This prospective randomized trial involved 162 patients undergoing transverse lower uterine segment cesarean section. Patients were allocated to one of the two arms: 88 to the MML technique and 74 to the Pfannenstiel-Kerr technique. Main outcome measures were defined as the duration of surgery, analgesic requirements, and bowel restitution by the second postoperative day. Additional outcomes evaluated were febrile morbidity, postoperative antibiotic use, postpartum endometritis, and wound complications. Student's t, Mann-Whitney, and Chi-square tests were used for statistical analysis of the results, and a p < 0.05 was considered as the probability level reflecting significant differences. No differences between groups were noted in the incidence of analgesic requirements, bowel restitution by the second postoperative day, febrile morbidity, antibiotic requirements, endometritis, or wound complications. The MML technique took on average 12 min less to complete (p = 0.001). The MML technique is faster to perform and similar in terms of febrile morbidity, time to bowel restitution, or need for postoperative medications. It is likely to be more cost-effective.\nStudy4: [In Process Citation] This paper was intended to settle the question whether the so-called gentle sectio caesarea with a high skin incision as described by Cohen in 1972 [2] could be applied in combination with a sectio on the level of the classic Pfannenstiel's incision which would be more satisfying cosmetically. Furthermore a comparison was to be drawn between the postoperative condition of those patients on whom this surgical method had been performed and the condition following a classic Pfannenstiel's incision. Between January 1997 and July 1997 we compared the classic method of Pfannenstiel's incision with the variant of Cohen's method as described above in a prospective randomised study. On applying this surgical technique, the abdomen was opened according to Cohen's method using a surgical knife but for the skin, and the tissue layers underneath were opened blunt with two fingers. Following the extraction of the child only three sutures were made: Uterus, fascia and skin. Redon drainages were not inserted. We were able to show that this method of applying mainly blunt \"incision\" to sectio caesarea the tissue is at least equal to the sharp opening of the abdominal cavity. In some respects, such as the early postoperative mobilisation, it is, in fact, superior, because the blunt opening causes less bleeding and the reduction to three sutures only, deliberately leaving the two peritoneal membranes open, as well as leaving away the redon drainages, considerably increases the patients' postoperative well-being. It is for these reasons that we call for this method to become part of the routine procedures in caesarean sectio.\nStudy5: [Comparison of two cesarean techniques: classic versus Misgav Ladach cesarean]. The aim of the study was to compare two cesarean section techniques Methodology. A prospective study was conducted UB 400 cesareans performed at the Gynecological and Obstetric Clinic of the Dakar Teaching Hospital between March 2000 and August 2000. Two hundred patients underwent the classical procedure (CL group) and the other 200 the Misgav Ladach procedure (ML group). Per- and post-operative data were compared between the two groups with Student's test and the Chi(2) test. A p-value less than 0.05 was considered statistically significant. The two groups were similar for socio-demographic and clinical data. The delay between the skin incision and infant delivery was significantly shorter in the ML group (5 minutes 26 seconds versus 6 minutes 20 seconds). The same trend was found for the length of operation (36 minutes 36 seconds versus 54 minutes 38 seconds). Fewer sutures were used in the ML group (2.92 versus 4.14). There is no significant difference for dose of analgesia, post-operative complications and hospital discharge. Cost analysis demonstrated that the Misgav Ladach procedure was 10000 FCFA (15 euros) less costly. Misgav Ladach method is simple, rapid, cost-effective cesarean procedure which appears to be an attractive alternative to traditional cesarean section.\n", + "output": "Conclusions: 'Joel-Cohen based' methods have advantages compared to Pfannenstiel and to traditional (lower midline) CS techniques, which could translate to savings for the health system. However, these trials do not provide information on mortality and serious or long-term morbidity such as morbidly adherent placenta and scar rupture.\n\n[Note: The 19 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]" + }, + { + "input": "Study1: Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial. To evaluate the endpoints of complications (specifically pancreatic fistula and total complications) and death in patients undergoing pancreaticoduodenectomy. Four randomized, placebo-controlled, multicenter trials from Europe have evaluated prophylactic octreotide (the long-acting synthetic analog of native somatostatin) in patients undergoing pancreatic resection. Each trial reported significant decreases in overall complication rates, and two of the four reported significantly lowered rates of pancreatic fistula in patients receiving prophylactic octreotide. However, none of these four trials studied only pancreaticoduodenal resections, and all trials had high pancreatic fistula rates (>19%) in the placebo group. A fifth randomized trial from the United States evaluated the use of prophylactic octreotide in patients undergoing pancreaticoduodenectomy and found no benefit to the use of octreotide. Prophylactic use of octreotide adds more than $75 to the daily hospital charge in the United States. In calendar year 1996, 288 patients received octreotide on the surgical service at the authors' institution, for total billed charges of $74,652. Between February 1998 and February 2000, 383 patients were recruited into this study on the basis of preoperative anticipation of pancreaticoduodenal resection. Patients who gave consent were randomized to saline control versus octreotide 250 microg subcutaneously every 8 hours for 7 days, to start 1 to 2 hours before surgery. The primary postoperative endpoints were pancreatic fistula, total complications, death, and length of hospital stay. Two hundred eleven patients underwent pancreaticoduodenectomy with pancreatic-enteric anastomosis, received appropriate saline/octreotide doses, and were available for endpoint analysis. The two groups were comparable with respect to demographics (54% male, median age 66 years), type of pancreaticoduodenal resection (60% pylorus-preserving), type of pancreatic-enteric anastomosis (87% end-to-side pancreaticojejunostomy), and pathologic diagnosis. The pancreatic fistula rates were 9% in the control group and 11% in the octreotide group. The overall complication rates were 34% in the control group and 40% in the octreotide group; the in-hospital death rates were 0% versus 1%, respectively. The median postoperative length of hospital stay was 9 days in both groups. These data demonstrate that the prophylactic use of perioperative octreotide does not reduce the incidence of pancreatic fistula or total complications after pancreaticoduodenectomy. Prophylactic octreotide use in this setting should be eliminated, at a considerable cost savings.\nStudy2: Prospectively randomized trial using perioperative low-dose octreotide to prevent organ-related and general complications after pancreatic surgery and pancreatico-jejunostomy. The aim of the present study was to evaluate the influence of low-dose perioperative octreotide on the prevention of complications (pancreatic fistula and general complications) in patients undergoing pancreatic surgery followed by pancreaticojejunostomy. A total of 105 patients were randomized to receive either octreotide 0.1 mg subcutaneously 3 times/day for a total of 7 days or no octreotide. The primary endpoints were the occurrence of a pancreatic fistula and or general complications, including extended length of hospital stay. There were 25 surgical draining procedures performed and 80 duodenopancreatectomies with or without preservation of the pylorus. In all, 25 (23.8%) of the patients were treated for chronic pancreatitis, 8 (7.6%) for benign tumoral disease, and 72 (68.6%) for carcinoma. All patients underwent pancreaticojejunostomy.\nStudy3: Randomized controlled multicentre trial of somatostatin infusion after pancreaticoduodenectomy. It remains debatable whether somatostatin can prevent pancreatic fistula and other pancreatic stump-related complications following pancreaticoduodenectomy. This study assessed the effects of somatostatin-14 (S-14) on pancreatic remnant exocrine secretion. This was a double-blind, randomized, placebo-controlled trial in patients undergoing pancreaticoduodenectomy for malignancy. Patients received a continuous infusion of S-14 (n = 38) or placebo (n = 37) for 7 days. Pancreatic juice and peripancreatic drainage fluid was collected and measured, and pancreatic enzymes were monitored daily. Postoperative complications were recorded. S-14 infusion was associated with a decrease in median daily pancreatic juice and pancreatic amylase output. Amylase concentration and output in the peripancreatic drain fluid were significantly lower after S-14 infusion than in the control group (both P < 0.05). The incidence of clinical pancreatic fistula (two of 38 versus eight of 37; P < 0.05) and total pancreatic stump-related complications (five of 38 versus 12 of 37; P < 0.05) was lower in patients treated with S-14. Duration of hospital stay was shorter after S-14 (18 versus 26 days; P = 0.01). Although the effect of S-14 on exocrine secretion remains difficult to demonstrate, it did reduce pancreatic juice leakage from the pancreatic remnant.\nStudy4: Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis. A randomized double-blind placebo-controlled multicentre trial was carried out in 247 patients undergoing major elective surgery for chronic pancreatitis to clarify whether the perioperative application of octreotide prevents postoperative complications. Eleven complications were defined, including death, anastomotic leakage, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency and postoperative pancreatitis. A total of 124 patients underwent pancreatic head resection, 55 left resection, 61 pancreaticojejunostomy and seven had other procedures. The overall mortality rate was 1.2 per cent (octreotide group 1.6 per cent, placebo group 0.8 per cent [corrected] (P not significant)). The postoperative complication rate in the octreotide group was 16.4 per cent (20 of 122 patients) and in the placebo group 29.6 per cent (37 of 125) (P < 0.007). The perioperative application of octreotide substantially reduces the risk of postoperative complications in patients undergoing major pancreatic surgery for chronic pancreatitis.\nStudy5: The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial. Pancreatectomy can be complicated by pancreatic anastomotic leakage, causing major morbidity. Our aim was to determine if vapreotide, a potent long-acting somatostatin analogue, would decrease pancreas-related complications. This prospective, multicenter, randomized, double-blind, placebo-controlled trial involved 275 patients without preexisting chronic pancreatitis undergoing elective proximal, central, or distal pancreatectomy. Complications were defined by objective criteria before beginning the study. One hundred thirty-five patients received vapreotide; 140 patients received placebo. There were no statistically significant differences between vapreotide- and placebo-treated patients in either pancreas-related complications (30.4% versus 26.4%, respectively) or in other complications not directly related to the pancreas (40% versus 42%, respectively). The potent somatostatin analogue vapreotide does not appear to decrease postoperative complications after major pancreatectomy in patients without chronic pancreatitis.\nStudy6: [Somatostatin in duodenocephalopancreatectomy for neoplastic pathology]. nan\nStudy7: Effects of somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy: increased delayed gastric emptying and reduced plasma motilin. Somatostatin inhibits gastroenteropancreatic exocrine secretion and is often used after pancreaticoduodenectomy to reduce pancreatic secretion to minimize tissue damage and pancreatic stump complications. Because our earlier clinical work saw a major increase in delayed gastric emptying (DGE) with somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy (PPPD), this small-group study was designed to confirm or disprove that observation. From August 1997 to December 2000, a total of 23 post-PPPD patients were randomized to receive somatostatin prophylaxis [somatostain (+)] (n = 11) or not [somatostatin] (-) (n = 12). The incidence of DGE, scintographic solid-phase emptying results on day 14 postoperatively, and sequential fasting plasma motilin levels were compared, as motilin levels are related to both gastric motility and somatostatin levels. The somatostatin(+) group exhibited greatly increased patient complaints of DGE: 9 of 11 (82%) versus 3 of 12 (25%) in the somatostatin(-) group. Radiologic scintography showed somatostatin prophylaxis prolonged the half-time (T(1/2)) of solid-phase emptying: 144.5 +/- 51.4 minutes for somatostatin(+) versus 89.0 +/- 59.9 minutes for somatostatin(-) (p < 0.001). Comparing pre-PPPD and post-PPPD plasma motilin levels prior to somatostatin infusion, motilin decreased 80% in reaction to the surgery. For somatostatin(-) patients, motilin levels oscillated, or \"rang,\" postoperatively, reaching a higher level on day 3, declined to a new record minimum on day 7, and by day 21 were 50% of the original and the slope of the recovery curve was increasing well. In somatostatin(+) patients the same ringing pattern was observed but decreased with motilin levels 30% to 70% lower than in the somatostatin(-) patients. By day 21 somatostatin(+) motilin levels were recovering but still only 20% original levels, and the slope of the recovery curve was not optimistic. On postoperative day 14 the plasma motilin levels (below approximately 6 bg/ml) correlated strongly with DGE for both groups. Despite the small sample size, the results indicated that (1) somatostatin prophylaxis significantly decreases fasting plasma motilin; (2) somatostatin prophylaxis produces lingering suppression of plasma motilin; (3) PPPD surgery itself significantly reduces fasting motilin levels with recovery to 50% normal at day 21; (4) the mechanism of somatostatin-induced DGE seems related to reduced fasting plasma motilin levels.\nStudy8: The role of somatostatin in 67 consecutive pancreatectomies: a randomized clinical trial. Somatostatin has been found to be effective in the prevention of postoperative complications in pancreatic surgery. It can inhibit the pancreatic secretions that, quite often, are responsible for complications during the postoperative period. We randomized 67 patients in 2 groups. In the study group (n = 35), somatostatin was administered 30 minutes prior to surgery as well as intraoperatively and postoperatively. No medication was given to the control group (n = 32). Biopsies were taken and processed for electron microscopy and ultrastructural morphometric analysis. Administration of somatostatin reduced the exocrine granule number, and the patients suffered from fewer postoperative complications. Somatostatin reduces granule number and size of pancreatic cells, which can partially explain the prophylactic effect of the drug on early complications of pancreatic surgery, and which is confirmed by the clinical findings.\nStudy9: [Effect of somatostatin on basal and stimulated exocrine pancreatic secretion after partial duodenopancreatectomy. A clinical experimental study]. In a prospective trial 30 patients underwent pancreaticoduodenectomy (Whipple operation) for cancer. They were randomly assigned to receive Somatostatin (SST) (n = 15) or not (n = 15). SST was started at laparotomy with 250 micrograms/h and given over a period of 5 days. A small catheter, which was placed into the duct of the pancreatic remnant, gave access to the pancreatic juice. Volume, amylase, lipase and protein as well as bicarbonate outputs were analyzed. As regards endocrine function, insulin and glucagon plasma levels were measured. The nitrogen balance was calculated. A stimulation test was done on the fifth postoperative day. Six patients (3/3) were assessed as drop-outs. A significant reduction was found for volume, amylase, lipase, protein and bicarbonate with SST, this effect lasting for two days. Lipase however was reduced significantly for 5 days. Pancreatic exocrine function was reduced as well after stimulation, if SST was given. Insulin and glucagon were inhibited with SST, the latter more effectively. We found a positive nitrogen-balance as early as on the second postoperative day in the SST-group, whereas without SST this did not occur before the fourth postoperative day. This findings were significant on the third and fourth postoperative day. The inhibitoric effects of SST, which are demonstrated by our laboratory investigations, conform very well with a more favorable clinical course and a reduction of perioperative morbidity and mortality.\n", + "output": "Conclusions: Somatostatin analogues may reduce perioperative complications but do not reduce perioperative mortality. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in people undergoing pancreatic resection." + }, + { + "input": "Study1: Exit-site care and exit-site infection in continuous ambulatory peritoneal dialysis (CAPD): results of a randomized multicenter trial. A total of 127 patients from 8 hospitals were randomized into 1 of 2 exit-site care regimes to evaluate their effect on rate of exit-site infection (ESI). Group 1 used povidone iodine and nonocclusive dressings changed 2 to 3 times weekly; Group 2 simply cleansed the exit site with nondisinfectant soap and water. Incidence, cause, duration, and treatment of ESI and peritonitis (P) were noted. Groups were analysed for age, sex, end-stage renal disease (ESRD), catheter, and systems. Total cumulative follow up time was 95.6 years. There was a significantly higher rate (p = 0.0183) of ESI in Group 2 (soap and water). The mean rate of ESI was 0.27 episodes/patient year for Group 1 versus 0.71 episodes/patient year for Group 2. Rates of P for the two groups were not significantly different (p greater than 0.50): 0.446 episodes/year for Group 1 versus 0.574 episodes/year for Group 2. S. aureus was responsible for 83% of ESI in Group 1 and 67% of ESI in Group 2. Protective dressing with a disinfectant is associated with significantly less ESI than minimum care. However, further research in exit-site care aimed specifically at reducing S. aureus infection is still required.\nStudy2: Role of preoperative antibiotic prophylaxis in preventing postoperative peritonitis in newly placed peritoneal dialysis catheters. The role of vancomycin and other antibiotics in the treatment of acute peritonitis in peritoneal dialysis (PD) patients is well established. However, the role of preoperative vancomycin or cephalosporins in preventing early infection in newly placed PD catheters remains controversial. We performed a prospective randomized study to examine the role of vancomycin or cefazolin prophylaxis in decreasing the incidence of postoperative peritonitis. Over a 6-year period, 221 patients undergoing 254 permanent peritoneal catheter placement procedures were randomized into three groups. Group I patients (86 procedures) were administered a single intravenous (IV) dose of vancomycin, 1,000 mg, 12 hours before peritoneal catheter placement procedures, whereas group II patients (85 procedures) were administered a single IV dose of cefazolin, 1,000 mg, 3 hours before the procedure. Group III patients (83 procedures) were not administered antibiotics preoperatively for at least 1 week before the procedure. Patients were monitored for peritonitis in the following 14 days. Peritonitis developed in 1 patient (1%) in group I (vancomycin group) and 6 patients (7%) in group II (cefazolin group) compared with 10 patients (12%) in group III (control group); P = 0.02. We conclude that the use of preoperative single-dose IV vancomycin prophylaxis for permanent PD catheter placement reduces the risk for postoperative peritonitis. Single-dose vancomycin is superior to single-dose cefazolin in reducing the risk for postoperative peritonitis. Absence of prophylaxis is associated with a high risk for developing postoperative peritonitis.\nStudy3: A prospective randomized control study of oral nystatin prophylaxis for Candida peritonitis complicating continuous ambulatory peritoneal dialysis. A prospective randomized study of the prevention of candida peritonitis (CP) in continuous ambulatory peritoneal dialysis patients using oral nystatin given concomitantly with antibiotic therapy was carried out for 2 years. Patients were randomized into two groups. Nystatin tablets 500,000 units four times a day were given to group 1 but not group 2 patients whenever antibiotics were prescribed. There were 199 patients at risk (mean follow-up, 18.0 months) in group 1 and 198 patients at risk (mean follow-up, 16.6 months) in group 2. The peritonitis and antibiotic prescription rates were comparable between the two groups. There were four episodes of CP in four patients in group 1 and 12 episodes in 11 patients in group 2. The probability of CP-free survival at 2 years was higher in group 1 compared with group 2 (0.974 v 0.915; P < 0.05). However, only three (75%) CP episodes in group 1 and six (50%) in group 2 were considered \"antibiotics related.\" The incidence of antibiotics-related CP was 1.39 and 3.19 per 100 peritonitis episodes and 0.66 and 1.43 per 100 antibiotic prescriptions in groups 1 and 2, respectively (P = NS). We conclude that oral nystatin prophylaxis with each antibiotic prescription reduced the rate of CP in patients on continuous ambulatory peritoneal dialysis irrespective of its apparent temporal relationship to antibiotic prescription.\n", + "output": "Conclusions: This review demonstrates that nasal mupirocin reduces exit-site/tunnel infection but not peritonitis. Preoperative intravenous prophylaxis reduces early peritonitis but not exit-site/tunnel infection. No other antimicrobial interventions have proven efficacy. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered RCTs to inform decision making about strategies to prevent peritonitis is striking." + }, + { + "input": "Study: The effectiveness of a prenatal education programme for the prevention of congenital toxoplasmosis. A 10 min education programme was developed which, if effective in changing the behaviour of pregnant women, would eliminate or greatly reduce the risk of congenital toxoplasmosis. It was taught in 26 randomly selected (case) prenatal classes offered to women early in their pregnancy. The remaining 26 (control) classes received routine class material which did not mention toxoplasmosis. A questionnaire was administered to all women prior to this early class (pre-test) and again after the last prenatal class, held just prior to delivery (post-test). Changes in pet, food and personal hygiene behaviour between the pre- and post-test were determined and a score calculated by adding points for change towards those behaviours recommended in the programme and subtracting points for change in the opposite direction. Cat owners in case classes had a significantly higher score in pet hygiene behaviour than those in control classes (P less than 0.05). No significant difference was found between the food or personal hygiene scores of women in case and control classes, possibly because of low power. However, although behaviours did not differ on the pre-test, women in case classes had significantly better cooking methods for roast beef and hamburger on the post-test (P less than 0.05 and P less than 0.01 respectively). It is concluded that this programme is effective and should be offered to all women in order to reduce congenital toxoplasmosis incidence.\n", + "output": "Conclusions: Even though primary prevention of congenital toxoplasmosis is considered a desirable intervention, given the lack of related risks compared to secondary and tertiary prevention, its effectiveness has not been adequately evaluated. There is very little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis even though evidence from observational studies suggests it is. Given the lack of good evidence supporting prenatal education for congenital toxoplasmosis prevention, further RCTs are needed to confirm any potential benefits and to further quantify the impact of different sets of educational intervention." + }, + { + "input": "Study1: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. The optimal fractionation schedule for radiotherapy of head and neck cancer has been controversial. The objective of this randomized trial was to test the efficacy of hyperfractionation and two types of accelerated fractionation individually against standard fractionation. Patients with locally advanced head and neck cancer were randomly assigned to receive radiotherapy delivered with: 1) standard fractionation at 2 Gy/fraction/day, 5 days/week, to 70 Gy/35 fractions/7 weeks; 2) hyperfractionation at 1. 2 Gy/fraction, twice daily, 5 days/week to 81.6 Gy/68 fractions/7 weeks; 3) accelerated fractionation with split at 1.6 Gy/fraction, twice daily, 5 days/week, to 67.2 Gy/42 fractions/6 weeks including a 2-week rest after 38.4 Gy; or 4) accelerated fractionation with concomitant boost at 1.8 Gy/fraction/day, 5 days/week and 1.5 Gy/fraction/day to a boost field as a second daily treatment for the last 12 treatment days to 72 Gy/42 fractions/6 weeks. Of the 1113 patients entered, 1073 patients were analyzable for outcome. The median follow-up was 23 months for all analyzable patients and 41.2 months for patients alive. Patients treated with hyperfractionation and accelerated fractionation with concomitant boost had significantly better local-regional control (p = 0.045 and p = 0.050 respectively) than those treated with standard fractionation. There was also a trend toward improved disease-free survival (p = 0.067 and p = 0.054 respectively) although the difference in overall survival was not significant. Patients treated with accelerated fractionation with split had similar outcome to those treated with standard fractionation. All three altered fractionation groups had significantly greater acute side effects compared to standard fractionation. However, there was no significant increase of late effects. Hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally advanced head and neck cancer. Acute but not late effects are also increased.\nStudy2: A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer. To study the effect of accelerated radiation treatment in locally advanced head and neck cancer, a prospective randomised trial was conducted comparing two fractionation schemes which differed only in the overall treatment time; fraction size and total dose were the same in both arms. Eighty-two patients with stage 3 or 4 squamous cell cancer of the oral cavity, oropharynx, hypopharynx or larynx considered suitable for radical radiotherapy as primary treatment were stratified by site and stage and randomised to receive 66 Gy in 33 2 Gy daily fractions in 45-48 days (o.d.) or 66 Gy in 33 2 Gy twice daily fractions in 22-25 days (b.i.d.). An initial improved clinical response in tumour control in the b.i.d. arm was not sustained and the 3 year recurrence free survival and overall survival rates were similar and not significantly different. The actuarial recurrence free survival was 49.1% in the b.i.d. arm and 44.3% in the o.d. arm. The disease free 3 year survival was 59.4% and 56.8%, respectively. The acute and late normal tissue effects were scored using the RTOG scale. As expected the acute effects were much greater in the b.i.d. arm. The combined grade 3 and 4 late effects were similar but the proportion of grade 4 reactions was significantly higher in the b.i.d. arm. The increase in grade 4 toxicity caused the trial to be discontinued after 82 of the planned 226 patients had been randomised. The severity of the normal tissue effects and a failure to demonstrate sustained local control does not support this fractionation scheme in patients with such extensive head and neck cancer.\nStudy3: Randomized clinical trial on 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer - report on 3-year tumour control and normal tissue toxicity. To evaluate tumour and normal tissues 3-year response to 7-day-a-week continuous accelerated irradiation (CAIR) compared to a conventional treatment (5 days per week) in a randomized trial. One hundred patients with squamous cell carcinoma of the head and neck in stage T(2-4)N(0-1)M(0) were entered into the trial between December 1, 1993 and June 30, 1996. Dose per fraction of 2.0 Gy (to the end of 1994), and 1.8 Gy (since January 1, 1995) was the same in both arms and delivered once a day at regular 24-h intervals to total dose in the range of 66-72 Gy (depending on tumour stage). The only difference was overall treatment time being 5 weeks in the CAIR and 7 weeks in control arm. Actuarial 3-year local tumour control was 82% in the CAIR and 37% in the control group (P<0.0001) with reduction in local recurrence rate of 83%. Actuarial 3-year overall survival was 78 and 32% (P<0.0001), respectively. Confluent mucositis was significantly more severe and lasted longer in the CAIR than in control arm. After 2.0 Gy fractions five of 23 patients (22%) in the CAIR developed early necroses over a period of 2-4 months of follow-up which can be considered as a consequential to severe protracted acute mucosal reactions (CLE). For this reason dose per fraction was lowered to 1. 8 Gy and the CLE was not observed again until now. Thus the overall rate of CLE decreased to 10%. The gain in tumour control is likely the effect of shortening of overall treatment time by 14 days and regular continuous dose delivery during the whole course of radiation therapy including weekends. A 7-day schedule produces more severe acute mucosal reactions lasting longer than in conventional fractionation, however tolerable by patients. Relatively high rate (22%) of CLE in the 7-day arm observed during the first year of the study was eliminated by decreasing dose per fraction from 2.0 Gy to 1.8 Gy.\n", + "output": "Conclusions: Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress." + }, + { + "input": "Study1: Introduction of intravenous lipid administration on the first day of life in the very low birth weight neonate. To investigate lipid tolerance in sick, ventilator-dependent, very low birth weight infants from the first day of life and the effects of early introduction of intravenously administered lipid (IVL) on glucose homeostasis. Twenty-nine infants in the neonatal intensive care unit with birth weight less than 1500 gm received isocaloric, isonitrogenous parenteral feedings from day 1 with either IVL, 1 gm/kg from day 1 to 3 gm/kg from day 4 (group I; n = 16), or IVL added only from day 8 (group II; n = 13). Possible adverse clinical effects were monitored. Blood metabolites, nonesterified fatty acids, serum triglycerides, and insulin levels were determined daily. Arterial blood gases were measured and changes in partial pressures of oxygen and of carbon dioxide in arterial blood were compared between the two groups. Early lipid infusion did not appear to have deleterious effects on blood gas tensions or to increase respiratory morbidity. The incidence of other adverse clinical effects that may be associated with IVL was not increased by earlier introduction of lipid. Serum lipid values were comparable to those of preterm infants receiving IVL at a later postnatal age. Blood glucose concentrations were higher in group II (mean, 7.50 (SEM 0.43) mmol/L) than in group I (mean, 6.01 (SEM 0.28) mmol/L; p less than 0.05). There was no evidence of increased gluconeogenesis in infants in group I and no correlation between blood glucose concentrations and serum nonesterified fatty acid concentrations. When given infusion rates not exceeding 0.15 gm/kg/hr, sick, very low birth weight infants can tolerate IVL with stepwise dose increases from the first day of life without an increased incidence of possible adverse effects.\nStudy2: Early elective insulin therapy can reduce hyperglycemia and increase insulin-like growth factor-I levels in very low birth weight infants. To investigate the use of insulin throughout the first week of life in very low birth weight (VLBW) infants (birth weight <1.5 kg) to improve glucose control and increase insulin-like growth factor-I (IGF-I) levels. IGF-I is the dominant hormone involved in fetal growth, and low levels have been implicated in neonatal morbidities, such as retinopathy of prematurity. In this pilot randomized controlled study (n = 16), the intervention group received insulin (0.025 U/kg/hr) on days 1 to 7, with 20% dextrose to maintain normoglycemia. Control infants received standard neonatal care. All infants received continuous glucose monitoring. The intervention and standard care groups had similar mean gestational age (+/- standard deviation), 26.2 (+/- 2.5) vs 26.9 (+/- 2.7) weeks, and birth weight, 0.79 (+/- 0.26) vs 0.73 (+/- 0.16) kg. The standard care infants were hyperglycemic (sensor glucose >10 mmol/L [180 mg/dL]) for 35.9% of the study period, compared with 7.6% for the insulin-treated infants (P = .035). The duration of time with hypoglycemia (<2.6 mmol/L [47 mg/dL]) did not differ between the 2 groups (P = .746). The insulin-treated group had a 2.4-fold increase in mean IGF-I bioactivity (P = .005). Early insulin therapy improves blood glucose control and increases IGF-I bioactivity levels. This could result in less morbidity associated with hyperglycemia and reduced IGF-I levels.\n", + "output": "Conclusions: Glucose infusion rate: There is insufficient evidence from trials comparing lower with higher glucose infusion rates to inform clinical practice. Large randomized trials are needed, powered on clinical outcomes including death, major morbidities and adverse neurodevelopment.\nInsulin infusion: The evidence reviewed does not support the routine use of insulin infusions to prevent hyperglycemia in VLBW neonates. Further randomized trials of insulin infusion may be justified. They should enrol extremely low birth weight neonates at very high risk for hyperglycemia and neonatal death. They might use real time glucose monitors if these are validated for clinical use. Refinement of algorithms to guide insulin infusion is needed to enable tight control of glucose concentrations within the target range." + }, + { + "input": "Study1: Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial. Female-initiated HIV-prevention options, such as microbicides, are urgently needed. We assessed Carraguard, a carrageenan-based compound developed by the Population Council, for its efficacy and long-term safety in prevention of HIV infection in women. We undertook a randomised, placebo-controlled, double-blind trial in three South African sites in sexually-active, HIV-negative women, aged 16 years and older. 6202 participants, who were randomly assigned by a block randomisation scheme to Carraguard (n=3103) or placebo (methylcellulose [n=3099]), were instructed to use one applicator of gel plus a condom during each vaginal sex act. Participants were followed up for up to 2 years. Visits every 3 months included testing for HIV presence and pregnancy, pelvic examinations, risk reduction counselling, and treatment for curable sexually transmitted infections and symptomatic vaginal infections. The primary outcome was time to HIV seroconversion. Analysis was in the efficacy population (a subset of the intention-to-treat population, excluding participants for whom efficacy could not be assessed). This study is registered with ClinicalTrials.gov, number NCT00213083. For the primary outcome (time to HIV seroconversion) we analysed 3011 women in the Carraguard group and 2994 in the placebo group. HIV incidence was 3.3 per 100 woman-years (95% CI 2.8-3.9) in the Carraguard group (134 events) and 3.8 per 100 woman-years (95% CI 3.2-4.4) in the placebo group (151 events), with no significant difference in the distribution of time to seroconversion (p=0.30). The covariate-adjusted hazard ratio was 0.87 (95% CI 0.69-1.09). Rates of self-reported gel use (96.2% Carraguard, 95.9% placebo) and condom use (64.1% in both groups) at last sex acts were similar in both groups. On the basis of applicator testing, however, gel was estimated to have been used in only 42.1% of sex acts, on average (41.1% Carraguard, 43.1% placebo). 1420 (23%) women in the intention-to-treat population had adverse events (713 Carraguard, 707 placebo), and 95 (2%) women had adverse events that were related to gel use (48 Carraguard, 47 placebo). Serious adverse events occurred in 72 (2%) women in the Carraguard group and 78 (3%) in the placebo group, only one of which was considered possibly related to gel use (placebo group). This study did not show Carraguard's efficacy in prevention of vaginal transmission of HIV. No safety concerns were recorded.\nStudy2: Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission. Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed. We performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site. A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08). Cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition. (ClinicalTrials.gov number, NCT00153777; and Current Controlled Trials number, ISRCTN95638385.) 2008 Massachusetts Medical Society\nStudy3: SAVVY (C31G) gel for prevention of HIV infection in women: a Phase 3, double-blind, randomized, placebo-controlled trial in Ghana. The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk. This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between March 2004 and February 2006 in Accra and Kumasi, Ghana. We enrolled 2142 HIV-negative women at high risk of HIV infection, and randomized them to SAVVY or placebo gel. Main outcome measures were the incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies from oral mucosal transudate specimens and adverse events. We accrued 790 person-years of follow-up in the SAVVY group and 772 person-years in the placebo group. No clinically significant differences in the overall frequency of adverse events, abnormal pelvic examination findings, or abnormal laboratory results were seen between treatment groups. However, more participants in the SAVVY group reported reproductive tract adverse events than in the placebo group (13.0% versus 9.4%). Seventeen HIV seroconversions occurred; eight in participants randomized to SAVVY and nine in participants receiving placebo. The Kaplan-Meier estimates of the cumulative probability of HIV infection through 12 months were 0.010 in the SAVVY group and 0.011 in the placebo group (p = 0.731), with a hazard ratio (SAVVY versus placebo) of 0.88 (95% confidence interval 0.33, 2.27). Because of a lower-than-expected HIV incidence, we were unable to achieve the required number of HIV infections (66) to obtain the desired study power. SAVVY was not associated with increased adverse events overall, but was associated with higher reporting of reproductive adverse events. Our data are insufficient to conclude whether SAVVY is effective at preventing HIV infection relative to placebo. ClinicalTrials.gov NCT00129532.\n", + "output": "Conclusions: Limited evidence suggests that vaginal tenofovir microbicides may reduce the risk of acquisition of HIV and HSV-2 infections in women; but other types of topical microbicides have not shown evidence of an effect on HIV or STI acquisition. Therefore, there is not enough evidence to recommend topical microbicides for HIV or STI prevention at present. Further studies are needed to confirm the beneficial effects of tenofovir microbicide gel in vaginal sex. In addition, further research should continue on the development and testing of new microbicides. If the effectiveness of the tenofovir and/or other microbicides is confirmed in further studies, there will need to be a clear pathway to rapid regulatory approval. Successful launch of the effective gel would depend on having in place appropriate mechanisms for distribution to the women who need it, along with a strategy for ensuring that they use it correctly." + }, + { + "input": "Study1: Azithromycin plus artesunate versus artemether-lumefantrine for treatment of uncomplicated malaria in Tanzanian children: a randomized, controlled trial. Acute febrile illness is the most common cause of outpatient attendance and mortality for children in Africa. Malaria and bacterial disease are difficult to differentiate with limited diagnostic facilities. Combinations of antibiotics and antimalarials are potentially attractive for treatment of the syndrome. Azithromycin plus artesunate (AT+AS) is an effective antimalarial combination for adults in Asia. We performed an individually randomized, open-label trial of AZ+AS versus artemether-lumefantrine (AL) involving children (age, 6-59 months) with uncomplicated malaria in Muheza, Tanzania. The primary outcome was parasitological failure by day 28. Parasitological failure by day 42 and failure corrected for reinfection were major secondary outcomes. Of 2497 children screened, 261 were eligible; 129 were randomized to the AZ+AS arm, and 132 were randomized to the AL arm; 92% and 91%, respectively, underwent follow-up to 28 days. Planned interim analysis was performed after 200 patients reached day 28 follow-up and led the Data and Safety Monitoring Board to halt further recruitment. All children had a complete initial response to treatment, but 69 (58%) of 119 children in the AZ+AS arm and 24 (20%) of 120 in the AL arm had asexual parasites at or by day 28 (adjusted odds ratio for failure with AZ+AS treatment, 6.1; 95% confidence interval, 3.3-11.4; P < .001). When analysis was restricted to children with recrudescence, the parasitological failure rate was 32% in the AZ+AS arm and 9% in the AL arm. This difference was maintained at day 42. This trial does not support the use of AZ+AS as treatment for malaria or acute febrile illness in children in areas of Africa with high levels of existing antimalarial drug resistance. ClinicalTrials.gov NCT00694694.\nStudy2: Activity of artemether-azithromycin versus artemether-doxycycline in the treatment of multiple drug resistant falciparum malaria. The efficacy of the combination of artemether with doxycycline or azithromycin was evaluated in 60 patients with acute uncomplicated falciparum malaria who attended malaria clinic in Mae Sot, Tak Province (Thai-Myanmar border). Patients (30 each) were randomized to receive (a) 300 mg artemether together with 100 mg doxycycline as initial doses, followed by 100 mg artemether plus 100 mg doxycycline at 12 hours later, then 100 mg doxycycline every 12 hours for another 4 days, or (b) 300 mg artemether together with 500 mg azithromycin, followed by 250 mg azithromycin at 24 and 48 hours. The follow-up period was 28 days. Patients in either group had a rapid initial response to treatment with comparable PCT and FCT. The cure rate of artemether-azithromycin regimen was significantly lower than that of artemether-doxycycline regimen (14.8 vs 53.3%). Low cure rate from artemether-azithromycin combination in this study was likely to be due to inadequate azithromycin dosage. However, with the low incidence of gastrointestinal adverse effects, the once daily dose of azithromycin could still be increased in order to enhance its clinical efficacy. The simplicity of drug administration and lesser incidence of adverse effects make azithromycin a more proper partner of artemether than doxycycline. Further dose-finding and pharmacokinetic study with the artemether-azithromycin combination is encouraging.\nStudy3: A multicenter study of azithromycin, alone and in combination with chloroquine, for the treatment of acute uncomplicated Plasmodium falciparum malaria in India. Azithromycin has demonstrated in vitro and in vivo activity against Plasmodium falciparum, but small treatment studies have given mixed results. Participants with fever and with both a blood smear and a rapid diagnostic test positive for falciparum malaria were randomly assigned to groups that were treated with either azithromycin or chloroquine or to matched groups receiving a placebo. After an interim analysis, open-label combination therapy with both drugs was initiated. At day 28, 5 (33%) of 15 participants in the azithromycin-treated group had remained free of fever, compared with 4 (27%) of 15 in the chloroquine-treated group. All subsequently enrolled participants then received combination therapy with azithromycin and chloroquine. In 61 (97%) of 67 participants, resolution of fever and parasitemia had occurred by day 7, and, through day 28, no clinical or parasitologic relapse had occurred in them. Resolution of parasitemia was inadequate with monotherapy with either azithromycin or chloroquine, but combination therapy provided substantially improved clinical and parasitologic outcomes. The combination of azithromycin and chloroquine may be an effective alternative treatment for falciparum malaria and deserves further study.\nStudy4: Therapeutic responses to antibacterial drugs in vivax malaria. Some antibacterial drugs have antimalarial activity that can be exploited for the prevention or treatment of malaria. Monotherapy with tetracycline, doxycycline, clindamycin or azithromycin was assessed in 1995-98 in 92 adult patients in Thailand with Plasmodium vivax malaria. All patients recovered following treatment and the early therapeutic responses were similar among the 4 groups. The overall median fever clearance time was 57 h and the mean (SD) overall time to parasite clearance was 134 (48) h. Of 66 patients who completed a 28-day follow-up, reappearances of vivax infection occurred in 27 patients (41%) from all groups; delayed appearances of falciparum malaria occurred in 6 patients (9%), only from the azithromycin group. The overall mean (SD) time to reappearance of P. vivax was 23 (5) days and time taken for detection of falciparum malaria was 13 (4) days after starting treatment for vivax malaria. The 28-day cumulative cure rates of clindamycin (n = 12), tetracycline (n = 18) and doxycycline (n = 18) groups were similar (P > or = 0.14) and all were significantly higher compared to the azithromycin group (n = 18; P < or = 0.04). The intervals until vivax reappearance were also significantly shorter in the azithromycin group [mean (SD) = 21 (6) vs 25 (3) days, P < 0.05] suggesting that some of these were recrudescences. The apparent success rate (no subsequent appearances of either vivax or falciparum infection) was significantly lower for the azithromycin group (11%) compared to the other groups (34-78%; P < 0.01). In current antibacterial treatment regimens, short-course azithromycin has inferior antimalarial activity compared to clindamycin or the tetracyclines.\n", + "output": "Conclusions: Currently, there is no evidence for the superiority or equivalence of azithromycin monotherapy or combination therapy for the treatment of P. falciparum or P. vivax compared with other antimalarials or with the current first-line antimalarial combinations. The available evidence suggests that azithromycin is a weak antimalarial with some appealing safety characteristics. Unless the ongoing dose, formulation and product optimisation process results in a universally efficacious product, or a specific niche application is identified that is complementary to the current scala of more efficacious antimalarial combinations, azithromycin's future for the treatment of malaria does not look promising." + }, + { + "input": "Study1: Schizophrenia--a follow-up study of results of treatment. I. Design and other problems. This is the first of a series of articles on a follow-up study of the results of treatment of schizophrenia, studied over a period of two to five years after first admission and first release. The study compares the follow-up outcome of five different treatment methods given to first-admission male and female schizophrenic patients in the hospital. The design of the study is used as a basis for description and discussion of the practical, ethical, and statistical problems involved. A distinction is made between follow-up and continued treatment design, and it is concluded that both pose massive problems in execution, analysis, presentation, and interpretation.\nStudy2: Group vs individual psychotherapy with schizophrenics. A controlled outcome study. nan\nStudy3: Effects of psychotherapy in schizophrenia: II. Comparative outcome of two forms of treatment. This study compares the effects of exploratory, insight-oriented (EIO) and reality-adaptive, supportive (RAS) forms of psychotherapy on a sample of 95 schizophrenic patients. Analyses of 2-year outcomes revealed a complex interaction between the type of psychotherapy provided and the domain of psychopathology affected. RAS psychotherapy exerted clear preferential effects in the areas of recidivism and role performance. The EIO psychotherapy exerted preferential, albeit more modest, action in the areas of ego functioning and cognition. Overall, however, the magnitude of the differences was low. The results highlighted the need for more focused studies of subgroups, and of process and contextual influences on outcome.\n", + "output": "Conclusions: Current data do not support the use of psychodynamic psychotherapy techniques for hospitalised people with schizophrenia. If psychoanalytic therapy is being used for people with schizophrenia there is an urgent need for trials." + }, + { + "input": "Study1: Increased intravenous fluid intake and the course of labor in nulliparous women. To compare the effect of 2 regimens of intravenous fluid therapy on the course of labor. In a prospective, randomized, double-blind study of 300 nulliparous pregnant women at term conducted at a teaching hospital, 153 women received 125 mL and 147 received 250 mL of intravenous fluid per hour. The groups were matched and analysis was done using the t, chi(2), and Fisher exact tests. P<0.05 was considered statistically significant. In the group that received intravenous fluid at a rate of 250 mL per hour the mean+/-S.D. duration of labor was significantly shorter (253+/-97 vs. 386+/-110 min; P = 0.0001), the frequency of labor lasting both more than 10h and more than 15 h was statistically lower (4.8% vs. 13.8%; P=0.001 and 0% vs. 4.5%; P=0.02, respectively), and the frequency of oxytocin administration was significantly lower (8.1% vs. 20.4%; P=0.001). There was a trend toward a lower frequency of cesarean deliveries in the 250-mL group (16% vs. 22.8%; P=0.1). A greater volume per hour of intravenous fluid than is commonly administered to nulliparous women in active labor is associated with significantly shorter duration of labor and lower frequency of both prolonged labor and oxytocin administration.\nStudy2: Increased intravenous hydration of nulliparas in labor. To assess the effects of intravenous hydration on the duration of active labor in nulliparous women also allowed unrestricted oral consumption of fluids. In a randomized clinical trial 120 nulliparous women with uncomplicated singleton pregnancies at term were randomly assigned to drink fluids at will and receive either no intravenous hydration (group 1) or a Ringer lactate solution at rates of 60 mL, 120 mL, or 240 mL per hour (groups 2-4) throughout active labor. There were differences in duration for the active phase of the first stage of labor (252.3 \u00b1 40.9 min in group 1 vs 206.7\u00b138.3 min in group 4; P<0.001) and for the second stage (64.3 \u00b1 13.9 in group 1 vs 49.8 \u00b1 11.4 min in group 4; P=0.01), but not for the third stage. The percentage of participants who needed labor augmentation with oxytocin was less when intravenous hydration was provided (53.3% in group 1 vs 20.0% in group 4; P=0.02). Intravenous hydration significantly decreased the duration of active labor and reduced the frequency of both prolonged labor and oxytocin administration in nulliparous women. htpp://www.irct.ir registration number: IRCT201105256575N2. Copyright \u00a9 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.\nStudy3: Hyponatraemia and non-electrolyte solutions in labouring primigravida. We performed a prospective randomised study on one hundred primigravid women who required oxytocin to augment labour, comparing dextrose infusion with normal saline. After delivery, the 45 patients whose oxytocin was infused in dextrose had significantly lower serum sodium levels in both mother and baby compared to the 48 patients who had their oxytocin administered in normal saline. This was particularly evident in those cases where epidural analgesia was employed.\n", + "output": "Conclusions: Although the administration of intravenous fluids compared with oral intake alone demonstrated a reduction in the duration of labour, this finding emerged from only two trials. The findings of other trials suggest that if a policy of no oral intake is applied, then the duration of labour in nulliparous women may be shortened by the administration of intravenous fluids at a rate of 250 mL/hour rather than 125 mL/hour. However, it may be possible for women to simply increase their oral intake rather than being attached to a drip and we have to consider whether it is justifiable to persist with a policy of 'nil by mouth'. One trial raised concerns about the safety of dextrose and this needs further exploration.\nNone of the trials reported on the evaluation of maternal views of being attached to a drip during their entire labour. Furthermore, there was no objective assessment of dehydration. The evidence from this review does not provide robust evidence to recommend routine administration of intravenous fluids. Interpreting the results from trials was hampered by the low number of trials contributing data and by variation between trials. In trials where oral fluids were not restricted there was considerable variation in the amount of oral fluid consumed by women in different arms of the same trial, and between different trials. In addition, results from trials were not consistent and risk of bias varied. Some important research questions were addressed by single trials only, and important outcomes relating to maternal and infant morbidity were frequently not reported." + }, + { + "input": "Study1: Propranolol as an adjunct to the treatment of schizophrenia. Propranolol contributed usefully to the practical management of patients with chronic schizophrenia whose florid symptoms had not remitted with major tranquillisers. 14 patients who had received an average equivalent of 954 mg per day of chlorpromazine for 10 years were given, in addition, either propranolol or a placebo for 12 weeks. Both groups had improved by the twelfth week, but the propranolol group had improved significantly more.\nStudy2: Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study. Considerable evidence indicates that the lipophilic beta-blocker propranolol is useful in treating organically based aggression. This study looked at the efficacy of a more hydrophilic beta-blocker, nadolol, to treat aggression in chronic psychiatric inpatients. Forty-one chronic psychiatric inpatients with an average of one aggressive outburst per week (defined by the Overt Aggression Scale [OAS]) were entered into a double-blind, placebo-controlled study lasting 17 weeks. The OAS was used to track aggression on a per-incident basis, while the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions scale (CGI) were used to track clinical status. Nadolol subjects showed a significant decline in frequency of aggression compared with controls (p = .026) and a significant decline in the BPRS total score (p = .007) and in the subfactors \"hostility and suspicion,\" \"negative symptoms,\" and \"signs of hyperarousal/tension.\" There was no significant change in CGI \"severity of illness\" ratings between groups, although the nadolol group was significantly improved from baseline at every subsequent time period while the placebo group was unchanged throughout the study. Nadolol is of significant benefit in the treatment of aggression in chronic psychiatric inpatients. This drug does penetrate the brain over time, but the success of a drug whose primary locus of action is peripheral may implicate a bimodal mechanism of action, i.e., a role for the CNS and the soma in the maintenance of aggression.\nStudy3: Propranolol in schizophrenia: a double blind, placebo controlled trial of propranolol as an adjunct to neuroleptic medication. A double blind, placebo controlled trial was carried out to examine the contribution of propranolol as an adjunct to neuroleptic medication in the treatment of chronic schizophrenic patients whose florid symptoms had not remitted with neuroleptic medication alone. Propranolol was shown to have a more beneficial effect than placebo, but the results were much less dramatic than those which have been described in previous studies. Recent work has shown that there may be a pharmacokinetic interaction between propranolol and neuroleptics, and this should be considered as one possible explanation of our findings.\nStudy4: A placebo-controlled trial of nadolol in the treatment of neuroleptic-induced akathisia. Although propranolol has been documented to be useful in treatment of neuroleptic-induced akathisia, preliminary anecdotal reports on the efficacy of nadolol in treatment of this condition are contradictory. To evaluate the efficacy of nadolol in treatment of this condition, a double-blind, placebo-controlled trial was conducted in 20 psychiatric inpatients. Patients with akathisia of at least moderate severity were randomly assigned to receive nadolol 40 to 80 mg/day or placebo. Patients were rated daily for 4 days, then every other day for 15 days by means of the Extrapyramidal Symptom Rating Scale. No significant differences were found between or within groups in subjective restlessness scores. In objective akathisia scores, there were no significant differences between groups; however, beginning at Day 9, both groups showed significant improvement compared with Day 1. There was no difference between groups in number of responders. The authors' data do not support the efficacy of nadolol in the treatment of neuroleptic-induced akathisia and do not provide support for a peripheral site of action for beta-blockers in treatment of this condition.\nStudy5: A trial of propranolol in chronic schizophrenia. nan\nStudy6: Adjunctive nadolol in the treatment of acutely aggressive schizophrenic patients. This study assessed the safety and efficacy of nadolol 120 mg/day compared with placebo, when administered adjunctively to neuroleptic in a group of acutely aggressive schizophrenic patients. Thirty-four male patients enrolled in this double-blind, placebo-controlled trial. The subjects were evaluated with the Brief Psychiatric Rating Scale (BPRS) and the Simpson Angus Neurologic Rating Scale for extrapyramidal effects. The total BPRS score as well as three factors, thought disturbance, hostility, and activation, was analyzed. Compared with those who received placebo, the patients taking nadolol showed significant improvement on total BPRS score, particularly on the thought disturbance and activation factors, after the first treatment week (p = .05). By the end of the second treatment week, the patients taking placebo also began to show improvement, and the group differences were no longer significant. The patients treated with nadolol showed significantly more improvement on Simpson-Angus scores than those who received placebo (p = .03). However, there was no significant correlation between BPRS and Simpson-Angus changes. In the nadolol group, patients with and without akathisia showed no significant difference in their BPRS scores. These findings suggest that adjunctive nadolol may be useful in the treatment of acutely aggressive schizophrenic patients by inducing a more rapid and consistent decrease of overall psychiatric symptoms and by reducing the extrapyramidal effects. Our results raise the possibility that the mechanism of action of nadolol on psychiatric symptoms in schizophrenic patients may be different from the mechanism of improvement of neuroleptic-induced extrapyramidal symptoms and akathisia. Nadolol may be a helpful adjunctive treatment for schizophrenic patients in general and not just for those with a high hostility level.\n", + "output": "Conclusions: Existing evidence is limited and dated. Any possible benefit of adjunctive beta-blocker therapy is obscured by poor reporting within the studies. Important data on quality of life, satisfaction, healthy days, and cost are not available. Considering the number of people whose symptoms are only partially responsive to antipsychotic medication, well conducted and reported trials in this area could be justified." + }, + { + "input": "Study1: The efficacy of aloe vera gel in the treatment of oral lichen planus: a randomized controlled trial. Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful especially in the atrophic and erosive forms. Several therapies have been tried, with varying results. There is one case report in which aloe vera (AV) was used successfully in the treatment of lichen planus. To compare the efficacy of AV and placebo in the topical management of OLP. A randomized, double-blind, placebo-controlled trial was designed. Fifty-four patients were randomized into two groups to receive AV gel or placebo for 8 weeks. Fifty-four consecutive patients (34 women and 20 men) participated in the study. We found erosive and ulcerative lesions in 83% and 17%, respectively. The most common site of OLP was the lower lip. Twenty-two of 27 patients treated with AV (81%) had a good response after 8 weeks of treatment, while one of 27 placebo-treated patients (4%) had a similar response (P<0.001). Furthermore, two patients treated with AV (7%) had a complete clinical remission. Burning pain completely disappeared in nine patients treated with AV (33%) and in one treated with placebo (4%) (P=0.005). Symptomatology improved by at least 50% (good response) in 17 patients treated with AV (63%) and in two treated with placebo (7%) (P<0.001). No serious side-effects were found in both groups. AV gel is statistically significantly more effective than placebo in inducing clinical and symptomatological improvement of OLP. Therefore, AV gel can be considered a safe alternative treatment for patients with OLP.\nStudy2: Fluticasone propionate spray and betamethasone sodium phosphate mouthrinse: a randomized crossover study for the treatment of symptomatic oral lichen planus. Symptomatic oral lichen planus (OLP) has been palliated with a wide spectrum of topical and systemic therapies. Although the majority of management strategies include corticosteroids, few have been evaluated in randomized controlled trials. We investigated the acceptability and efficacy of topical fluticasone propionate spray (FP) and betamethasone sodium phosphate mouthrinse (BSP) upon the signs and symptoms of OLP, assessing patient quality of life changes as a consequence of these therapies. We implemented a randomized, crossover study in which each drug was administered for a period of 6 weeks with an intervening washout period of 2 weeks at an outpatient oral medicine unit in London, United Kingdom. We treated 48 patients with biopsy-proven symptomatic OLP, and 44 patients (92%) completed the study. The dosage was 50 microg two dose unit sprays and BSP 500 microg, each 4 times daily. Symptomatic improvement was evaluated by means of a visual analogue scale (VAS), the McGill pain score, the Oral Health Impact Profile (OHIP), and Oral Health Quality of Life (OHQoL) questionnaires. The total surface area of the lesions, including all white, erythematous, and ulcerative lesions was measured at each visit. The efficacy, ease of application, and adverse effects associated with each medication were recorded. Both FP and BSP mouthwash caused both a statistically significant reduction in painful symptoms as measured by the VAS and improvement in quality of life as measured by the OHIP and OHoQL indices. There was no significant difference between the two corticosteroids in their efficacy in reducing painful symptoms (measured by the VAS) or in their effect on patient quality of life. Both FP and BSP significantly reduced the surface area of oral lesions. However, FP was statistically significantly better than BSP in reducing lesion surface area. There was no statistically significant difference between the patient-assessed effects of the 2 therapies. FP and BSP are both effective in the short-term clinical management of symptomatic OLP. FP is more acceptable to patients than BSP because of the convenience of the spray form.\nStudy3: Ciclosporin vs. clobetasol in the topical management of atrophic and erosive oral lichen planus: a double-blind, randomized controlled trial. Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, especially in the atrophic and erosive forms. Several drugs have been used with varying results, but most treatments are empirical, and do not have adequate control groups or correct study designs. To compare the effectiveness of clobetasol and ciclosporin in the topical management of OLP and to evaluate which is more cost-effective and which gives the longest remission from signs and symptoms. A randomized, comparative, double-blind study was designed. Forty consecutive patients were divided into two groups to receive clobetasol propionate or ciclosporin for 2 months. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Antimycotic prophylaxis was also given. After the end of therapy, patients underwent a 2-month follow-up. Eighteen of 19 clobetasol-treated patients (95%) improved after 2 months of therapy, while 13 of 20 ciclosporin-treated patients (65%) had a clinical response (P = 0.04). Symptomatology improved in 18 clobetasol-treated patients (95%) and in 17 ciclosporin-treated patients (85%) (not statistically significantly different). Two months after the end of therapy, 33% of clobetasol-treated patients and 77% of ciclosporin-treated patients were stable (P = 0.04). Clobetasol produced significantly more side-effects than ciclosporin (P = 0.04). The daily cost of ciclosporin treatment was 1.82 compared with 0.35 for clobetasol therapy. Clobetasol is more effective than ciclosporin in inducing clinical improvement, but the two drugs have comparable effects on symptoms. Conversely, clobetasol gives less stable results than ciclosporin when therapy ends and has shown a higher incidence of side-effects. The daily cost of ciclosporin is more than five times higher than clobetasol.\nStudy4: A comparative treatment study of topical tacrolimus and clobetasol in oral lichen planus. Existing clinical trials have shown that topical corticosteroids are often effective in the management of oral lichen planus (OLP). However, tacrolimus has recently been shown to be an effective treatment of OLP. To compare the effectiveness of clobetasol and tacrolimus in the topical management of OLP. In this randomized comparative double-blind study, 30 consecutive patients with oral lesions consistent clinically and histologically with OLP were recruited. The patients were divided into 2 groups to receive clobetasol 0.05% or tacrolimus 0.1% ointment and were treated for 6 weeks. The profiles of mean lesion sizes and mean pain measures did not differ between the tacrolimus and clobetasol treatment groups. We found tacrolimus to be as useful as clobetasol in treatment of OLP. We believe that up-to-date evidence indicates the effectiveness of tacrolimus in treating OLP.\nStudy5: Betamethasone oral mini-pulse therapy compared with topical triamcinolone acetonide (0.1%) paste in oral lichen planus: A randomized comparative study. Betamethasone oral mini-pulse (OMP) therapy has been used effectively and safely in vitiligo, alopecia areata, and lichen planus. We sought to evaluate the efficacy and safety of betamethasone OMP in patients with symptomatic moderate to severe oral lichen planus and to compare it with topical triamcinolone acetonide. In all, 49 patients with moderate to severe oral lichen planus were randomly allocated to receive either OMP comprising 5 mg of betamethasone orally on 2 consecutive days per week (group A) or triamcinolone acetonide (0.1%) paste application thrice daily (group B), for 3 months followed by stepwise tapering during the next 3 months. Treatment response was assessed by the change in the score, which was based on the number of sites involved and the area affected. The changes in the symptoms and side effects were also recorded. Patients were followed up after treatment for 3 months to look for relapse. In all, 23 of 25 patients in group A and 23 of 24 patients in group B completed the study. Good to excellent response was seen in 17 of 25 (68.0%) patients in group A as compared with 16 of 24 (66.0%) in group B at 6 months. Symptom-free state was achieved in 13 of 25 (52%) patients in group A and 12 of 24 (50%) in group B. The difference in the mean scores within each group was statistically significant from the fourth week onward in group A and eighth week onward in group B, whereas in patients with erosive disease it was second and twelfth week onward, respectively. The difference in the treatment response between the two groups was statistically significant only at week 24 when reduction in severity score was more in triamcinolone group. Side effects were seen in 14 (56%) patients in group A and 6 (25%) patients in group B, which were mild and reversible. Relapse occurred in 9 of 23 (39.1%) patients in group A after 13.78 +/- 6.96 weeks as compared with 5 of 23 (21.7%) in group B after 19.20 +/- 1.79 weeks. The study was not blinded and the change in the quality of life with treatment was not measured. Betamethasone OMP improves the clinical outcome in patients with moderate to severe oral lichen planus. When compared with topical triamcinolone acetonide it is equally effective but the response is earlier, especially in erosive disease. It may be a useful and convenient alternative either as a monotherapy or to achieve rapid symptomatic relief during periods of exacerbations.\nStudy6: Topical clobetasol in the treatment of atrophic-erosive oral lichen planus: a randomized controlled trial to compare two preparations with different concentrations. Oral lichen planus (OLP) is a chronic inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empirical and do not have adequate control groups or correct study designs. However, to date, the most commonly employed and useful agents for the treatment of LP are topical corticosteroids. A randomized, double-blind, placebo-controlled trial has been designed to compare the efficacy and safety of two different formulations of clobetasol, a very potent topical steroid, in the topical management of OLP and to evaluate which gives the longest remission from signs and symptoms. Thirty-five consecutive patients were divided into two groups: the first received clobetasol propionate 0.025% and the second was given clobetasol propionate 0.05%. Both drugs were placed in 4% hydroxyethyl cellulose bioadhesive gel. Anti-mycotic prophylaxis was also added. After the end of therapy, patients received a 2-month follow-up. In all, 14 of the 15 clobetasol 0.025% patients (93%) and 13 of the 15 clobetasol 0.05% patients (87%), had symptoms improvement after 2 months of therapy (P = 0.001 in both groups). Also, 13 of the 15 clobetasol 0.025% patients (87%) and 11 of the 15 clobetasol 0.05% patients (73%) had clinical improvement after 2 months of therapy (P < 0.05 in both groups). No statistical differences were found in comparing the two different formulations. A larger concentration of the active molecules cannot further improve the therapeutic findings or optimize the obtained results in a significant manner.\nStudy7: Fluocinonide in an adhesive base for treatment of oral lichen planus. A double-blind, placebo-controlled clinical study. Patients with symptomatic oral lichen planus frequently require therapy to reduce signs and symptoms. For this purpose, corticosteroids are often applied topically. In a randomized, double-blind, placebo-controlled study, the efficacy of the topical application of 0.025% fluocinonide was evaluated. Forty consecutive patients with oral lichen planus diagnosed on the basis of histopathologic and immunofluorescence findings participated in this study. All patients were followed for 3 to 17 months. No adverse effects were noted during follow-up period. In the group of 20 patients that received the drug, 4 patients (20%) showed a complete remission, and 12 patients (60%) had a good or partial response to topical treatment. In the placebo-group, these figures were 0 and 6 (30%), respectively. The majority of the placebo-group (70%) did not respond at all with regard to signs (Xt2 = 10.4; p = 0.0013) and symptoms (Xt2 = 6.97, p = 0.008). The results from this study suggest that topical application of fluocinonide in an adhesive base is a safe and effective drug to reduce signs and symptoms in oral lichen planus.\nStudy8: The effectiveness of 1% pimecrolimus cream in the treatment of oral erosive lichen planus. The purpose of this study was to evaluate the efficacy, relative safety, and tolerability of 1% pimecrolimus cream in the treatment of oral erosive lichen planus (OELP). Twenty patients with OELP were randomized into equal groups; group 1 applied 1% pimecrolimus cream twice daily to their oral lesions for 4 weeks, whereas group 2 applied a placebo cream. Photographs of the lesions were taken and analyzed for areas of ulceration, erythema, and reticulation. Discomfort scores were also assessed with a visual analogue scale (VAS). Blood samples were taken at baseline and at study completion; a complete blood count with differential and comprehensive metabolic panel was ordered. The Wilcoxon signed rank test was used. The experimental group showed a decrease in ulceration (alpha = 0.068) and erythema (alpha = 0.005) at the mid-point with continued reduction of erythema at the final (alpha = 0.075) time measurement. The control group demonstrated an increase in reticulation at the mid-point (alpha = 0.017) and final (alpha = 0.007) time measurement. The VAS scores for the experimental group decreased during the study (alpha = 0.022). Blood levels were within the normal range. The OELP lesion size in the 1% pimecrolimus group decreased and the pimecrolimus cream was found to significantly reduce the patient's pain scores. Further study of 1% pimecrolimus as therapy for OELP is warranted since it was shown to be effective, relatively safe, and well tolerated by patients within the limits of this short-term study.\nStudy9: Comparative observation on the effects of Radix tripterygium hypoglaucum tablet and Tripterygium glycosides tablet in treating erosive oral lichen planus. To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus (EOLP). The patients were randomized into two groups, and they were treated with THT (n = 47) or TGT (n = 47), respectively. The therapeutic effects were evaluated after 3 months treatment. For the patients of grade 1, the total efficacy in TGT group was 85.71%, compared with 52.38% in THT group, the efficacy was statistically greater in the group receiving TGT (P = 0.043). However, for the patients of grade 2, the difference was not statistically significant (P = 0.173). TGT is more effective in treating EOLP than THT for grade 1 patients. However, TGT is not suitable for patients of child bearing age.\nStudy10: A new delivery system of clobetasol-17-propionate (lipid-loaded microspheres 0.025%) compared with a conventional formulation (lipophilic ointment in a hydrophilic phase 0.025%) in topical treatment of atrophic/erosive oral lichen planus. A Phase IV, randomized, observer-blinded, parallel group clinical trial. Topical application of clobetasol-17-propionate has been diffusely reported as an efficacious therapy in atrophic/erosive oral lichen planus (OLP), without exposing the patient to systemic side-effects. However, prolonged contact and respective topical effects on the oral mucosa should be avoided. The aim of the present study was to evaluate efficacy and compliance of new lipid microspheres loaded with 0.025% of clobetasol propionate (formulation A) compared with a commonly used formulation (a sort of dispersion of a lipophilic ointment in a hydrophilic phase) with the same amount of drug (formulation B) in the topical treatment of OLP. Fifty patients with symptomatic OLP were enrolled in a controlled single-blind phase IV clinical trial. After a dropout of five patients, a total of 45 patients [12 males and 33 females; mean age 61.1 years (+/- 12.3 SD; range 25-82)] were treated (17 with formulation A and 28 with formulation B, matched for gender and age; P > 0.2) with the same dosage regimen. At times T0, T1 and T2 we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0-100); (ii) clinical score; (iii) clinical resolution; and (iv) patient compliance. Statistical analysis was calculated using S-Plus 4.0 and SPSS 9.0 (Student's t-test, chi(2), Kolmogorov-Smirnow, Friedman, Student-Newman-Keuls, Mann-Whitney U-test and Spearman tests). Both formulations were found to be similar for parameters ii, iii and iv, although with a better general trend for formulation A; a significant difference was registered for formulation A in terms of a reduction in painful symptoms (parameter i) at time T2 (P = 0.02). Our results suggest that the new topical drug delivery system (formulation A) may enhance, at least in terms of symptom remission and compliance, the effectiveness of clobetasol propionate at a dose of 0.025% in OLP therapy.\n", + "output": "Conclusions: This review suggests that there is only weak evidence for the effectiveness of any of the treatments for oral ELP, whilst no evidence was found for genital ELP. More RCTs on a larger scale are needed in the oral and genital ELP populations. We suggest that future studies should have standardised outcome variables that are clinically important to affected individuals. We recommend the measurement of a clinical severity score and a participant-rated symptom score using agreed and validated severity scoring tools. We also recommend the development of a validated combined severity scoring tool for both oral and genital populations." + }, + { + "input": "Study: Home intravenous therapy in cystic fibrosis: a prospective randomized trial examining clinical, quality of life and cost aspects. In this study, we set out to determine if home intravenous (i.v.) antibiotic therapy in adult patients with cystic fibrosis (CF) is a feasible, effective and less costly alternative to hospitalization, and to assess the impact of home therapy on quality of life. The study was a prospective, randomized, two-factor mixed design involving adults presenting with respiratory exacerbations of CF. Patients were randomized such that they were discharged home after 2-4 days, or remained in hospital. Seventeen patients had 31 admissions (13 home and 18 hospital). Following 10 days of therapy, there were no significant differences between home or hospital arms with respect to body weight, 12 minute walking distance, sputum weight, pulse oximetry, or improvement in lung function (forced expiratory volume in one second (FEV1), or forced vital capacity (FVC)). Patients who remained in hospital were less fatigued and noted a greater degree of mastery. Patients discharged early noted less disruption to their family life, personal life and sleeping pattern. The total cost for the home therapy arm was approximately half that of the hospital therapy arm. Home intravenous antibiotic therapy in patients with cystic fibrosis was a feasible, cost-effective alternative to receiving therapy in hospital. Although there was no clinical compromise associated with home therapy, there were advantages and disadvantages in terms of quality of life.\n", + "output": "Conclusions: Current evidence is restricted to a single randomized clinical trial. It suggests that, in the short term, home therapy does not harm individuals, entails fewer investigations, reduces social disruptions and can be cost-effective. There were both advantages and disadvantages in terms of quality of life. The decision to attempt home treatment should be based on the individual situation and appropriate local resources. More research is urgently required." + }, + { + "input": "Study1: Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. To evaluate safety and benefits of feeding preterm infants formulas containing docosahexaenoic acid (DHA) and arachidonic acid (ARA) until 92 weeks postmenstrual age (PMA), with follow-up to 118 weeks PMA. This double-blinded study of 361 preterm infants randomized across three formula groups: (1) control, no supplementation; (2) algal-DHA (DHA from algal oil, ARA from fungal oil); and (3) fish-DHA (DHA from fish oil, ARA from fungal oil). Term infants breast-fed > or =4 months (n = 105) were a reference group. Outcomes included growth, tolerance, adverse events, and Bayley development scores. Weight of the algal-DHA group was significantly greater than the control group from 66 to 118 weeks PMA and the fish-DHA group at 118 weeks PMA but did not differ from term infants at 118 weeks PMA. The algal-DHA group was significantly longer than the control group at 48, 79, and 92 weeks PMA and the fish-DHA group at 57, 79, and 92 weeks PMA but did not differ from term infants from 79 to 118 weeks PMA. Supplemented groups had higher Bayley mental and psychomotor development scores at 118 weeks PMA than did the control group. Supplementation did not increase morbidity or adverse events. Feeding formulas with DHA and ARA from algal and fungal oils resulted in enhanced growth. Both supplemented formulas provided better developmental outcomes than unsupplemented formulas.\nStudy2: Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte membrane lipids. The nutritional requirements of preterm infants for the long chain polyunsaturated essential fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA), have not been clearly defined. The present study evaluated preterm infants of less than 2.3 kg birth weight fed a commercial formula (Preemie SMA) devoid of AA and DHA and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32 to 1.1% AA and 0.24 to 0.76% DHA. An analogous group of infants fed their mothers' breast milk and a breast milk fortifier (when indicated) was also studied. Erythrocyte membrane phospholipids were isolated from blood samples collected at 12 d of age and after a further 4 wk of feeding. Infants fed the formula without AA and DHA showed a reduction in AA level in erythrocyte phosphatidylcholine, and a reduced level of DHA in phosphatidylethanolamine in comparison with infants fed breast milk or infant formula containing AA and DHA. Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the levels of AA and DHA found in erythrocyte membrane phospholipids. From comparison of membrane phospholipid fatty acid composition it appears that a formula level of 0.32-1.1% AA and 0.24-0.76% DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid composition to that of infants fed human milk for most of the lipid fractions examined.\nStudy3: Dietary supplementation of long-chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation. To study the influence of dietary-supplied long-chain polyunsaturated fatty acids on structural brain maturation in preterm infants and to investigate parameters of functional brain development, relating them to structural maturation. Other studies have suggested that dietary supplementation of long-chain polyunsaturated fatty acids in preterm infants may enhance their visual development. The influence on structural brain development has never been evaluated. In a prospective, double-blind study, 42 formula-fed premature infants were randomized to be fed either a standard preterm formula without long-chain polyunsaturated fatty acids or an identical formula supplemented with docosahexaenoic acid (0.015 g/100 ml) and arachidonic acid (0.031 g/100 ml). Infants with significant cerebral damage, retinopathy, chronic disease or feeding problems were excluded. Follow-up was focused on assessment of cerebral myelination by MRI. Psychomotor, mental and visual development was analysed and flash-visual evoked potentials were recorded. It was found that progress of myelination, mental and motor development and latencies of visual evoked potentials were not positively influenced by supplementation of long-chain polyunsaturated fatty acids. At each test age, visual acuity was slightly better in the supplemented infants than in the non-supplemented infants, but the difference never reached significance level Supplementation of long-chain polyunsaturated fatty acids did not have a demonstrable positive influence on structural brain maturation. Related to this finding, in this small cohort of preterm infants without significant neurological damage, sample size being restricted by strict inclusion criteria and MRI procedures, no significant positive effects were found on psychomotor, mental and visual development.\nStudy4: Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age. The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.\nStudy5: The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants. Preterm infants may be born with deficits of both docosahexaenoic acid (DHA) and arachidonic acid (AA), but studies on supplementation of DHA and AA for preterm infants are limited. Preterm infants with a gestational age between 30 and 37 weeks who met all the inclusion criteria were enrolled in this double blind, randomized, comparative study. Infants over 2000 g body weight, over 32 weeks of gestation and in full feeding status would enter into the active intervention period of 6 months. Sixteen infants received Neoangelac Plus with AA and DHA supplementation. Eleven infants received Neoangelac without AA and DHA supplementation. The babies had scheduled physical examinations and their cognitive development, visual acuity, and vital signs to be checked. Adverse events were also recorded. The mean Mental Development Index (MDI) scores for the supplementation and non-supplementation groups were 96.1 +/- 8.6 and 91.7 +/- 10.4 respectively at 6 months and 98.7 +/- 8.0 and 90.5 +/- 6.9 respectively at 1 year. The mean Physical Development Index (PDI) scores of these two groups were 102.2 +/- 10.5 and 95.4 +/- 13.2 respectively at 6 months and 98.0 +/- 5.8 and 86.7 +/- 11.1 respectively at 1 year. By repeated measures ANOVA, significant differences existed between groups for MDI and PDI (p = 0.020 and 0.008). However, there were no differences in visual acuity, physical examination variables or vital signs between these two groups. No obvious adverse effects were observed during the study period. These results showed possible benefits in the neurodevelopment of larger preterm infants given formula supplemented with DHA and AA.\n", + "output": "Conclusions: Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. On pooling of results, no clear long-term benefits or harms were demonstrated for preterm infants receiving LCPUFA-supplemented formula." + }, + { + "input": "Study: Efficacy of metoclopramide as an adjunct to duodenal placement of small-bore feeding tubes: a randomized, placebo-controlled, double-blind study. We examined whether metoclopramide would improve the success rate of transpyloric intubation of a weighted Corpak feeding tube when fluoroscopic guidance is not used. Seventy patients were randomized in a prospective, double-blind fashion to receive either placebo (n = 35) or metoclopramide, 10 mg (n = 35) parenterally, administered immediately after the feeding tube was inserted. Tube location was determined independently by two observers who examined radiographs obtained after barium was instilled via the tube. There was no significant increase in the success rate of duodenal intubation in the total group following metoclopramide, 60%, compared to placebo, 49%. However, analysis of subgroups among the placebo-treated patients revealed that diabetes mellitus, but not other medical conditions, decreased the success rate for duodenal intubation, 20 vs 60% (p less than 0.05). Among diabetic patients, metoclopramide resulted in a significant increase in duodenal placement compared to placebo (p less than 0.05). We conclude that parenteral metoclopramide significantly increases the frequency of transpyloric intubation with small feeding tubes without fluoroscopic guidance in diabetic patients but not in nondiabetic patients.\n", + "output": "Conclusions: Metoclopramide enhanced the migration of naso-enteral tubes, but the results did not reach conventional statistical significance. The reasons may include: small studies, underpowered, varying doses, etc. In clinical practice, clinicians should no longer use metoclopramide for this purpose. However, more randomised clinical trials should be performed with a significant sample size, administering metoclopramide or not. The use of metoclopramide may include adverse reactions, such as depression, high blood pressure, decrease of libido, headache, skin rash, fatigue, fever, hyperactivity, insomnia, nausea, sedation, drowsiness, agitation, extrapyramidal reactions (impaired speech or impaired swallowing, unsteady gait, inflexibility of upper and lower members, tremor)." + }, + { + "input": "Study: High and low dose oxytocin in augmentation of labor. To compare the efficacy and safety of high dose oxytocin in the augmentation of labor. Two hundred pregnant women requiring augmentation of labor were randomly assigned to receive oxytocin by either a low dose protocol (1.5 microm/min initially, increased by 1.5 microm/min every 30 min) or a high dose protocol (4.5 microm/min initially, increased by 4.5 microm/min every 30 min). High dose of oxytocin was associated with a significant shortening of labor 4 (1.10-10) vs. 6 (1-10) h, p<0.0001 without a significant difference in cesarean delivery rate, neonatal and maternal outcome. The use of high dose oxytocin is associated with significantly shorter labor without any adverse fetal and maternal effects.\n", + "output": "Conclusions: Higher dose of oxytocin starting and increment dose (4 mU per minute or more) was associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence. The number of studies and the quality of the available evidence is of concern. Additionally, there is insufficient evidence for other maternal and neonatal outcomes, and how women feel about the higher doses of oxytocin. Therefore, no firm recommendation can be made. Further research should evaluate the effect of high dose oxytocin for women delayed in labour and should include these outcomes." + }, + { + "input": "Study1: Randomised controlled trial of plasma protein fraction versus dopamine in hypotensive very low birthweight infants. Around 20% of very low birthweight infants admitted to a neonatal intensive care unit become hypotensive within 24 hours of their admission. Standard treatment is either expansion of the circulating volume by the infusion of plasma protein fraction or by using dopamine to improve cardiac function. The purpose of this study was to investigate by a randomised controlled trial which was the most appropriate treatment. Thirty nine infants were randomised to receive either plasma protein fraction or dopamine as first line treatment if they became hypotensive within 24 hours of admission to the neonatal intensive care unit. Seventeen of 19 (89%) infants responded to dopamine, whereas only 9/20 (45%) responded to plasma protein fraction. The median dose of dopamine needed to increase the blood pressure to at least the 10th centile was 7.5 micrograms/kg/min and was infused for a median duration of 18 hours. These observations suggest that dopamine should be used earlier in the treatment of these infants than has previously been recommended.\nStudy2: The haemodynamic effects of dopamine and volume expansion in sick preterm infants. To determine the haemodynamic effects of dopamine and volume expansion in preterm neonates. Effect parameters were mean arterial blood pressure (MABP), left ventricular output (LVO) and global cerebral blood flow (CBF). In a randomised, clinical control trial 36 preterm neonates were randomised to receive either dopamine 5 microg/kg per min, volume expansion with albumin 20% 15 ml/kg or no treatment. Parameters were measured before and 2 h after initiation of treatment. Dopamine was effective in increasing MABP; both treatments increased LVO, whereas no significant difference between the treatment groups and the control group could be demonstrated with regard to CBF. No effect on global cerebral blood flow could be demonstrated in this study, despite significant effects on systemic circulatory parameters. However, the variance on the measurement of cerebral blood flow indicates that a small but clinically significant effect may have been overlooked.\n", + "output": "Conclusions: Dopamine was more successful than albumin at correcting low BP in hypotensive preterm infants, many of whom had already received volume. Neither intervention has been shown to be superior at improving blood flow or in improving mortality and morbidity in preterm infants. The trials do not allow any firm conclusions to be made as to whether or when volume or dopamine should be used in preterm infants." + }, + { + "input": "Study1: Effect of cataract surgery on the corneal endothelium: modern phacoemulsification compared with extracapsular cataract surgery. To investigate whether modern phacoemulsification surgery results in more damage to the corneal endothelium than extracapsular cataract extraction (ECCE), and to examine which preoperative, operative, and postoperative factors influence the effect of cataract surgery on the endothelium. Randomized controlled trial. Five hundred patients 40 years or older were randomized into 2 groups (ECCE, 249; phacoemulsification, 251). Central corneal endothelial cell counts, coefficient of variation of cell size, and hexagonality were assessed before surgery and up to 1 year postoperatively. Endothelial cell count. Four hundred thirty-three patients completed the trial. The initial preoperative mean cell count for the entire sample was 2481 (standard error [SE]: 18.6), reduced at 1 year postoperatively to 2239 (SE: 23.5). An average 10% reduction in cell count was recorded by 1 year postoperatively. There was no such change in hexagonality or in the coefficient of variation. There was no significant difference in overall percentage cell loss between the 2 treatment groups. Factors associated with excessive cell loss (> or =15% by 1 year) were a hard cataract (odds ratio [OR]: 2.1, 95% confidence limits: 1.1-4.1; P = 0.036), age (OR: 1.04, P = 0.005), and capsule or vitreous loss at surgery (OR: 2.38, P = 0.106). Phacoemulsification carried a significantly higher risk (OR: 3.7, P = 0.045) of severe cell loss in the 45 patients with hard cataracts relative to ECCE (52.6% vs. 23.1%; chi-square test, P = 0.041), with both procedures achieving similar postoperative visual acuity outcomes. No significant difference in overall corneal endothelial cell loss was found between these 2 operative techniques. The increased risk of severe cell loss with phacoemulsification in patients with hard cataracts suggests that phacoemulsification may not be the optimal procedure in these cases, and that ECCE should be preferred.\nStudy2: The Madurai Intraocular Lens Study. II: Clinical outcomes. To evaluate the safety and efficacy of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) compared with intracapsular cataract extraction with aphakic glasses (ICCE-AG). In a nonmasked randomized controlled clinical trial, 3,400 bilaterally vision-impaired patients aged 40 to 75 years with operable cataract were randomly assigned to receive either ICCE-AG or ECCE/PC-IOL at the Aravind Eye Hospital in India. The surgery was performed by one of four study surgeons. Patients were hospitalized for 5 postoperative days, with follow-up visits at 2, 6, and 12 months after discharge. Postsurgery evaluations were conducted by two independent study ophthalmologists. At any single postoperative follow-up time point, there were no statistically significant differences of clinical relevance between treatment groups for any complication of a serious nature except cystoid macular edema, which was more common with ICCE (4.2% vs 1.6%). In general, whether of a trivial, intermediate, or serious nature, complication rates were low at each evaluation time point. Cumulatively, the incidence of serious complications of all types throughout the 1-year study period was 14.5% for patients in the ICCE-AG group and 7.7% in the ECCE group (P < .001). Best-corrected visual acuity of 20/40 or better at 12 months was attained by 90.7% of ICCE-AG patients and 96.3% of ECCE/PC-IOL patients (P < .001). Although both operative procedures are safe and effective for cataract patients with bilateral impairment, ECCE/PC-IOL is superior to ICCE-AG in terms of both visual acuity restoration and safety.\nStudy3: Comparison of endothelial cell loss and surgically induced astigmatism following conventional extracapsular cataract surgery, manual small-incision surgery and phacoemulsification. To compare the surgically induced astigmatism (SIA) and endothelial cell loss following conventional extracapsular cataract surgery (ECCE), manual small-incision cataract surgery (Blumenthal technique)(SICS) and phacoemulsification (PE) with non-foldable intraocular lens implantation. 186 cataractous eyes with nuclear sclerosis grade 3 or less were randomized to undergo ECCE, SICS or PE with intraocular lens (non-foldable) implantation after a detailed pre-operative assessment. Keratometry and specular microscopy were performed pre-operatively and 6 weeks postoperatively. Surgically induced astigmatism was calculated using the rectangular coordinate method (Holladay et al.). Mean endothelial cell loss was similar for all three groups (p = 0.855); ECCE induced a loss of 4.72% (SD: 13.07); SICS 4.21% (SD: 10.29) and PE 5.41% (SD: 10.99). Mean SIA was 1.77D (1.61D) for the ECCE group, 1.17D (0.95D) for the SICS group and 0.77D (0.65D) for the PE group (p = 0.001). The magnitude of the difference between the SICS and the PE group was 0.4D. PE induced less astigmatism than SICS and ECCE in this study but the magnitude of the difference between SICS and PE was small. There was no significant difference in endothelial cell loss between the three groups.\n", + "output": "Conclusions: This review provides evidence from seven RCTs that phacoemulsification gives a better outcome than ECCE with sutures. We also found evidence that ECCE with a posterior chamber lens implant provides better visual outcome than ICCE with aphakic glasses. The long term effect of posterior capsular opacification (PCO) needs to be assessed in larger populations. The data also suggests that ICCE with an anterior chamber lens implant is an effective alternative to ICCE with aphakic glasses, with similar safety. Phacoemulsification provides the best visual outcomes but will only be accessible to the poorer countries if the cost of phacoemulsification and foldable IOLs decrease. Manual small incision cataract surgery provides early visual rehabilitation and comparable visual outcome to PHACO. It has better visual outcomes than ECCE and can be used in any clinic that is currently carrying out ECCE with IOL. Further research from developing regions are needed to compare the cost and longer term outcomes of these procedures e.g. PCO and corneal endothelial cell damage." + }, + { + "input": "Study1: [Clinical evaluation of Foley catheters]. nan\nStudy2: Single-blind, randomised, parallel group study of the Bard Biocath catheter and a silicone elastomer coated catheter. A group of 69 community patients undergoing long-term urethral catheterisation for urinary incontinence took part in this study; 33 patients with a mean age of 70.03 years (+/- 16.6) received the Dow Corning Silastic catheter (16 F 10-ml balloon) and 36 patients with a mean age of 75.61 years (+/- 12.6) received the Bard Biocath catheter (16 F 10-ml balloon). Over a 16-week period catheters were monitored every 2 weeks and changed as necessary. The Bard Biocath catheter remained in situ for an average of 89.61 days (+/- 35.31) and the Silastic catheter remained in situ for an average of 56.7 days (+/- 38.8); this difference was statistically significant. Used catheters were analysed for encrustation using scanning electron microscopy (SEM). The average time in situ for non-encrusted Biocath catheters was 83.7 days and 25.28 days for non-encrusted Silastic catheters. It was found that 70% of patients who received Biocath catheters preferred them to their previous catheters whereas only 30% of patients in the Silastic group preferred the trial catheter. The incidence of bypassing was 28% in the Biocath group and 52.8% in the Silastic group.\n", + "output": "Conclusions: The updated search could not reveal any additional evidence. Very few trials have compared different types of catheter for long-term bladder drainage. All trials were small and showed methodological weaknesses. Therefore, the evidence was not sufficient as a reliable basis for practical conclusions. Further, better quality trials are needed to address the current lack of evidence in this clinically important area." + }, + { + "input": "Study1: A multicenter, randomized, double-blind, controlled dose finding study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Postherpetic neuralgia (PHN) is a painful complication of acute herpes zoster. This multicenter, double-blind, controlled study randomized 299 PHN patients to receive either NGX-4010, a high-concentration capsaicin (8%) patch, or a low-concentration capsaicin (0.04%) control patch for 30, 60, or 90 minutes. The mean percent reductions in NPRS score from baseline to weeks 2 through 8 were significantly greater in the total NGX-4010 group (26.5%, P = .0286) and the 90-minute NGX-4010 group (27.8%, P = .0438) compared to the pooled control group (17.3%). After review of the data suggested a difference between genders in reporting of pain scores and a higher proportion of males (61%) in the 60-minute NGX-4010 group, post hoc gender-stratified analyses were performed and showed that the 60-minute NGX-4010 group also had a significantly larger mean percent reduction in average pain scores (28.0%, P = .0331). Pain reduction in the 30-minute NGX-4010 group, although similar in magnitude to the other doses, was not significantly different from control in either of these analyses. Similar results were observed during weeks 2\u00a0through 12. Most treatment-emergent adverse events were application-site specific, transient and mostly mild to moderate in severity. This article reports the safety and efficacy of NGX-4010 applied for 3 different durations (30, 60, or 90 minutes) in patients with PHN. The results identified the 60-minute duration as the dose to be evaluated in subsequent studies and identified a gender effect on reported changes in pain. Copyright \u00a9 2010. Published by Elsevier Inc.\nStudy2: A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. To confirm the efficacy, tolerability, and safety of NGX-4010, an 8% capsaicin dermal patch (capsaicin 640 \u00b5g/cm(2) ), in patients with postherpetic neuralgia (PHN). PHN is a chronic pain disorder that can be difficult to treat and for which current treatment options are often limited by poor tolerability. A total of 418 patients were randomized to receive a single 60-minute application of NGX-4010 or a 0.04% capsaicin control patch (3.2 \u00b5g/cm(2) ) in a multicenter, double-blind, confirmatory, phase 3 study. Patients were 18-90 years old with a diagnosis of PHN, pain for at least 6 months, and an average baseline Numeric Pain Rating Scale (NPRS) score of 3-9. The primary efficacy end point was the percentage change in NPRS score from baseline to weeks 2-8. NGX-4010 recipients had a significantly greater mean reduction from baseline in pain during weeks 2-8 compared with the control group (32.0% vs 24.4%; P=0.011). A \u2265 30% reduction in mean NPRS scores was achieved in 46% of NGX-4010 recipients compared with 34% of controls (P=0.02). Pain was significantly lower in NGX-4010 recipients than controls by week 2, and greater pain reduction was maintained throughout the remaining 12-week study period. Most treatment-emergent adverse events were application site specific (notably erythema and pain), transient, and generally mild to moderate in severity. In patients with PHN, a single 60-minute application of NGX-4010 produced significant reduction in pain that was maintained over a 12-week period. Wiley Periodicals, Inc.\n", + "output": "Conclusions: High-concentration topical capsaicin used to treat postherpetic neuralgia and HIV-neuropathy generates more participants with high levels of pain relief than does control treatment using a much lower concentration of capsaicin. The additional proportion who benefit over control is not large, but for those who do obtain high levels of pain relief there are additional improvements in sleep, fatigue, depression and an improved quality of life. High-concentration topical capsaicin is therefore similar to other therapies for chronic pain. In this case, the high cost of single and repeated applications suggest that high-concentration topical capsaicin is likely to be used when other available therapies have failed, and that it should probably not be used repeatedly without substantial documented pain relief. Even when efficacy is established, there are unknown risks, especially on epidermal innervation, of repeated application of long periods." + }, + { + "input": "Study1: Improved glycemic control without hypoglycemia in elderly diabetic patients using the ubiquitous healthcare service, a new medical information system. To improve quality and efficiency of care for elderly patients with type 2 diabetes, we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare (u-healthcare) service, which is an individualized health management system using advanced medical information technology. We conducted a 6-month randomized, controlled clinical trial involving 144 patients aged >60 years. Participants were randomly assigned to receive routine care (control, n = 48), to the self-monitored blood glucose (SMBG, n = 47) group, or to the u-healthcare group (n = 49). The primary end point was the proportion of patients achieving A1C <7% without hypoglycemia at 6 months. U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient's mobile phone. Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server. Once the data are transferred to the server, an automated system, the CDSS rule engine, generates and sends patient-specific messages by mobile phone. After 6 months of follow-up, the mean A1C level was significantly decreased from 7.8 \u00b1 1.3% to 7.4 \u00b1 1.0% (P < 0.001) in the u-healthcare group and from 7.9 \u00b1 1.0% to 7.7 \u00b1 1.0% (P = 0.020) in the SMBG group, compared with 7.9 \u00b1 0.8% to 7.8 \u00b1 1.0% (P = 0.274) in the control group. The proportion of patients with A1C <7% without hypoglycemia was 30.6% in the u-healthcare group, 23.4% in the SMBG group (23.4%), and 14.0% in the control group (P < 0.05). The CDSS-based u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients.\nStudy2: Effect of computer-based learning on diabetes knowledge and control. Two interactive computer-based systems have been evaluated: a teaching program with text and animated graphics and a multiple-choice knowledge-assessment program (KAP) with optional prescriptive feedback. One hundred seventy-four routine-attending insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients were allocated to active and control groups to determine the effect of these programs on knowledge and control after a 4- to 6-mo follow-up period. Interactive computer teaching (ICT) resulted in a significant knowledge increment in both IDDM and NIDDM patients (P less than .05), together with a mean fall of 0.8 and 0.7%, respectively, in HbA1c (P less than .05 and P greater than .1), but no changes were observed in respective control groups. The KAP with feedback also produced a significant knowledge increment in both IDDM and NIDDM patients (P less than .05), of similar magnitude to the ICT program, and a mean fall in HbA1c of 1.2 and 1.3%, respectively (P less than .05), with no changes in the corresponding control groups. Even when KAP was used without prescriptive feedback, smaller but significant mean falls in HbA1c of 0.7 and 0.8% (P less than .05) were seen in IDDM and NIDDM patients, respectively, suggesting a motivational effect resulting from program participation.(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy3: The development and evaluation of a computer-aided diabetes education program. This paper describes the development and evaluation of a computer-aided learning (CAL) program. The program was tested in a trial that involved 36 people with diabetes; 20 received CAL lessons in diabetes management and 16 attended conventional diabetes classes conducted by diabetes educators. When measurements taken before and three months after the education were compared, both groups showed significant improvement in their knowledge; the blood glucose levels of the CAL group were significantly lower but those of the conventional education group were higher. This means that the CAL program was as effective as conventional education in imparting knowledge but it was more likely to motivate people to control their glucose levels. The CAL program allows diabetes educators to spend less time on education in basic knowledge and to concentrate more on motivational and social factors that are important determinants of patient compliance. It can also benefit people with diabetes whose access to health professionals and/or conventional diabetes education is restricted.\nStudy4: The D-Net diabetes self-management program: long-term implementation, outcomes, and generalization results. A prerequisite to translating research findings into practice is information on consistency of implementation, maintenance of results, and generalization of effects. This follow-up report is one of the few experimental studies to provide such information on Internet-based health education. We present follow-up data 10 months following randomization on the \"Diabetes Network (D-Net)\" Internet-based self-management project, a randomized trial evaluating the incremental effects of adding (1) tailored self-management training or (2) peer support components to a basic Internet-based, information-focused comparison intervention. Participants were 320 adult type 2 diabetes patients from participating primary care offices, mean age 59 (SD = 9.2), who were relatively novice Internet users. All intervention components were consistently implemented by staff, but participant website usage decreased over time. All conditions were significantly improved from baseline on behavioral, psychosocial, and some biological outcomes; and there were few differences between conditions. Results were robust across on-line coaches, patient characteristics, and participating clinics. The basic D-Net intervention was implemented well and improvements were observed across a variety of patients, interventionists, and clinics. There were, however, difficulties in maintaining usage over time and additions of tailored self-management and peer support components generally did not significantly improve results.\nStudy5: [Computer assisted nutrition therapy for patients with type 2 diabetes]. To evaluate the efficacy of the\" Diabetes Diet Advisor\"(PC-DR vision 1.0)\" for type 2 diabetes. One hundred and fifty type 2 diabetic patients were divided in the 2 groups. The study group included 88 type 2 diabetic patients managed by \"Diabetes Diet Advisor(PC-DR vision 1.0)\"; the control group included 62 cases with a fixed carbohydrate content. All patients were followed up for 8 weeks. After 8 weeks dietary therapy, the fasting blood glucose (FBG), cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL- C) and body mass index (BMI) in study group were all significantly less than those in the control group (P<0.05). In the study group,the significant decrease were achieved in all indicates and FBG and 2hPBG decreased persistently. Twenty-five patients (28.41%) in study group and 6 patients (9.68%) in control group reduced their dosage of hypoglycemic agents or stopped drug therapy (P=0.007). The software \"Diabetes Diet Advisor (PC-DR vision 1.0)\" is a useful tool of dietary management for patients with type 2 diabetes.\nStudy6: Online diabetes self-management program: a randomized study. We hypothesized that people with type 2 diabetes in an online diabetes self-management program, compared with usual-care control subjects, would 1) demonstrate reduced A1C at 6 and 18 months, 2) have fewer symptoms, 3) demonstrate increased exercise, and 4) have improved self-efficacy and patient activation. In addition, participants randomized to listserve reinforcement would have better 18-month outcomes than participants receiving no reinforcement. A total of 761 participants were randomized to 1) the program, 2) the program with e-mail reinforcement, or 3) were usual-care control subjects (no treatment). This sample included 110 American Indians/Alaska Natives (AI/ANs). Analyses of covariance models were used at the 6- and 18-month follow-up to compare groups. At 6 months, A1C, patient activation, and self-efficacy were improved for program participants compared with usual care control subjects (P < 0.05). There were no changes in other health or behavioral indicators. The AI/AN program participants demonstrated improvements in health distress and activity limitation compared with usual-care control subjects. The subgroup with initial A1C >7% demonstrated stronger improvement in A1C (P = 0.01). At 18 months, self-efficacy and patient activation were improved for program participants. A1C was not measured. Reinforcement showed no improvement. An online diabetes self-management program is acceptable for people with type 2 diabetes. Although the results were mixed they suggest 1) that the program may have beneficial effects in reducing A1C, 2) AI/AN populations can be engaged in and benefit from online interventions, and 3) our follow-up reinforcement appeared to have no value.\nStudy7: Telecommunication support for rural women with diabetes. The Women to Women Diabetes Project tested the use of telecommunication technology to deliver diabetes education and social support to rural women with diabetes. The aims were to (1) test the effects of the computer intervention in providing support, information, and education on selected outcomes, and (2) evaluate the women's attitudes toward and satisfaction with the intervention and the support provided. Thirty women were randomized into computer and noncomputer groups and participated for 10 months. For 5 months, one group participated in a self-help support and educational group via the computer; the other group continued to use their usual modes of support and communication. Psychosocial well-being scales were administered and attitudes were surveyed. Improving health and higher educational levels positively influenced measures of social support and quality of life. Women who were married or who reported greater support had higher scores on the Personal Resource Questionnaire. The women expressed positive effects of the computer-based support group on their lives. The intervention was enthusiastically accepted, and could be conducted effectively in isolated rural areas.\nStudy8: Effects of a brief computer-assisted diabetes self-management intervention on dietary, biological and quality-of-life outcomes. There is a need for practical, efficient and broad-reaching diabetes self-management interventions that can produce changes in lifestyle behaviours such as healthy eating and weight loss. The objective of this study was to evaluate such a computer-assisted intervention. Type 2 diabetes primary care patients (n=335) from fee-for-service and health maintenance organization settings were randomized to social cognitive theory-based tailored self-management (TSM) or computer-aided enhanced usual care (UC). Intervention consisted of computer-assisted self-management assessment and feedback, tailored goal-setting, barrier identification, and problem-solving, followed by health counsellor interaction and follow-up calls. Outcomes were changes in dietary behaviours (fat and fruit/vegetable intake), haemoglobin Alc (HbA1c), lipids, weight, quality of life, and depression. TSM patients reduced dietary fat intake and weight significantly more than UC patients at the 2-month follow-up. Among patients having elevated levels of HbA1c, lipids or depression at baseline, there were consistent directional trends favouring intervention, but these differences did not reach significance. The intervention proved feasible and was implemented successfully by a variety of staff. This relatively low-intensity intervention appealed to a large, generally representative sample of patients, was well implemented, and produced improvement in targeted behaviours. Implications of this practical clinical trial for dissemination are discussed.\nStudy9: Clinic-based support to help overweight patients with type 2 diabetes increase physical activity and lose weight. Our objective was to test the effect of physicians providing brief health lifestyle counseling to patients with type 2 diabetes mellitus during usual care visits. We conducted a randomized controlled trial of a 12-month intervention at 2 large community health centers, enrolling 310 patients with a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater. In the intervention group, self-management goals for nutrition and physical activity were set using a tailored computer program. Goals were then reviewed at each clinic visit by physicians. The control group received only printed health education materials. The main outcome measures included change in physical activity and body weight. In the intervention group, recommended levels of physical activity increased from 26% at baseline to 53% at 12 months (P< .001) compared with controls (30% to 37%; P= .27), and 32% of patients in the intervention group lost 6 or more pounds at 12 months compared with 18.9% of controls (odds ratio, 2.2; P= .006). A brief intervention to increase the dialogue between patients and health care providers about behavioral goals can lead to increased physical activity and weight loss.\n", + "output": "Conclusions: Computer-based diabetes self-management interventions to manage type 2 diabetes appear to have a small beneficial effect on blood glucose control and the effect was larger in the mobile phone subgroup. There is no evidence to show benefits in other biological outcomes or any cognitive, behavioural or emotional outcomes." + }, + { + "input": "Study1: Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy. A double-blind, placebo-controlled trial is reported of lamotrigine as add-on treatment in therapy-resistant epilepsy. A within-patients serial design was used, with two 3-month treatment periods and an intervening 6-week washout/crossover period. An unblinded investigator adjusted lamotrigine dosage to achieve a plasma concentration within a previously predicted therapeutic range. All patients had therapy-resistant partial seizures, some in combination with other seizure types and were without serious neurological or intellectual deficit. Of 34 patients recruited only one was withdrawn because of an adverse experience (maculo-papular rash) probably related to the experimental drug and 30 completed the trial. The other 3 withdrawals were due to default during baseline, dispensing error and cholecystectomy. There was a modest statistically significant reduction in total and partial seizures on lamotrigine compared to placebo treatment. There was no difference in adverse experiences or abnormal biochemical or haematological findings between the lamotrigine and placebo periods. The plasma concentrations of concomitantly administered antiepileptic drugs were not affected by lamotrigine treatment. It is concluded that lamotrigine shows promise as an antiepileptic drug with low toxicity.\nStudy2: Controlled trial of lamotrigine (Lamictal) for treatment-resistant partial seizures. The antiepileptic effect of lamotrigine (Lamictal) was assessed in a double-blind, placebo-controlled, crossover trial in 56 adult patients with refractory partial seizures. Lamotrigine or placebo was added to the patients' existing antiepileptic drugs (AEDs). The dose of lamotrigine varied from 75 to 400 mg daily. Thirty-eight patients completed the trial and 7 withdrew because of adverse experiences. There was a statistically significant reduction in seizure counts on lamotrigine compared with placebo for total seizures (30.3% reduction, 95% CI 8.4%, 47.0%), complex partial seizures (29.2% reduction, 95% CI 3.8%, 47.9%) and secondary generalised seizures (37.9%, CI 18.9%, 52.4%). The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories. There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo. There were no differences in abnormal haematological or biochemical findings between lamotrigine and placebo, and lamotrigine had no effect on plasma concentrations of concomitant AEDs.\n", + "output": "Conclusions: Lamotrigine add-on therapy is effective in reducing the seizure frequency, in people with drug-resistant partial epilepsy. Further trials are needed to assess the long-term effects of lamotrigine, and to compare it with other add-on drugs.Two new trials have been included in this update, but the conclusions are unchanged." + }, + { + "input": "Study: Randomised controlled trial of topical ciclosporin A in steroid dependent allergic conjunctivitis. To evaluate the efficacy, safety, and therapeutic effect of topical ciclosporin A 0.05% as a steroid sparing agent in steroid dependent allergic conjunctivitis. Prospective, randomised, double masked, placebo controlled trial comparing signs, symptoms, and the ability to reduce or stop concurrent steroid in steroid dependent atopic keratoconjunctivitis and vernal keratoconjunctivitis using 0.05% topical ciclosporin A compared to placebo. Steroid drop usage per week (drug score), symptoms, and clinical signs scores were the main outcome measures. The study included an enrolment of 40 patients, 18 with atopic keratoconjunctivitis and 22 with vernal keratoconjunctivitis. There was no statistical significant difference in drug score, symptoms, or clinical signs scores between the placebo and ciclosporin group at the end of the treatment period. No adverse reactions to any of the study formulations were encountered. Topical ciclosporin A 0.05% was not shown to be of any benefit over placebo as a steroid sparing agent in steroid dependent allergic eye disease.\n", + "output": "Conclusions: This systematic review highlights the relative scarcity of controlled clinical trials assessing the efficacy of topical CsA therapy in AKC and suggests that evidence on the efficacy and safety of topical CsA treatment in patients with CsA remains limited. However, the data suggest that topical CsA may provide clinical and symptomatic relief in AKC and may help to reduce topical steroid use in patients with steroid-dependent or steroid-resistant AKC. No serious adverse events were reported. Reported adverse events in patients treated with topical CsA include intense stinging and eyelid skin maceration. One patient in the placebo group developed a severe allergic response to maize antigens. However, the total number of patients in the trials was too small to assess the safety of this treatment.\nAdditional well-designed and powered RCTs of topical CsA in AKC are needed. Ideal study designs should include adequate randomisation and concealment of allocation; masking of participants, personnel and outcome assessors; adequate follow-up periods and minimisation of attrition bias; and comparison groups with similar clinical and epidemiologic characteristics. Samples should be large enough to provide sufficient statistical power to assess the safety of CsA and to detect clinically relevant treatment effect sizes of the primary outcomes. Analyses should be appropriate to the study\u2019s design and outcome measures. Moreover, standardisation of outcome measures and follow-up periods across studies would be beneficial to maximise study comparability." + }, + { + "input": "Study1: The use of breast stimulation to prevent postdate pregnancy. Postdate pregnancy is estimated to occur in 3% to 12% of all gestations. Morbidity and mortality rates associated with this common obstetric problem are higher than those with term gestation. The incidence of fetal distress, birth injury, meconium aspiration, congenital malformations, macrosomia, and oligohydramnios is also greater in postdate pregnancy. We prospectively evaluated breast self-stimulation to determine its effect on the incidence of postdate pregnancy. Two hundred low-risk patients at 39 weeks' gestation were randomly assigned to either a control group or a breast-stimulation group. Results showed that breast stimulation reduced the number of pregnancies managed as postdates from 17 per 100 (17%) to five per 100 (5%) (p less than 0.01), a 70% reduction. It is concluded that breast stimulation in postdates pregnancies can decrease significantly the number of patients that must be monitored by biochemical or biophysical means.\nStudy2: Induction of labor with an electric breast pump. Nipple stimulation with an electric breast pump was compared with oxytocin infusion as a means of labor induction. The time from stimulation to the onset of regular uterine activity and to 200 Montevideo units of uterine activity and the time until entrance into the active phase of labor were significantly shorter in the nipple stimulation group. Once the women were in active labor, there was no difference between the groups in the length of labor or mode of delivery.\nStudy3: Cervical ripening by breast stimulation. The effect of breast stimulation on cervical ripening was studied. One hundred patients who had completed 38 weeks' gestation and had uncomplicated antenatal courses were recruited and divided into two groups: treatment and control. In the treatment group, gentle breast stimulation of alternate breasts was performed first for 1.5 hours under monitoring in the hospital and then for three hours daily for three days at home. No uterine hypertonus was detected. It was found that there was a significant change in the Bishop score of 3.96 +/- 1.34 points in the stimulated group as compared with the control group 1.04 +/- 1.03 points. After three days, a cross-over trial was performed with the extreatment group becoming the control and the excontrol group undergoing breast stimulation for the same period of time and under the same conditions. Again, the excontrol group was found to have a better mean cervical score (3.11 +/- 1.42 points) than the extreatment group (0.76 +/- 0.97 points) during breast stimulation. It is stressed that no uterine hypertonus was detected with gentle, unilateral breast stimulation, and there were no maternal or fetal complications as a result of this modality of cervical ripening.\nStudy4: Cervical ripening and induction of labour by breast stimulation. The value of gentle, unilateral breast stimulation in the ripening of cervix and induction of labour was studied. Three hundred patients with uncomplicated term pregnancies, (38-42 weeks) were recruited into the study, consisting of three separate randomised double blind prospective trials. The first trial was to evaluate the effectiveness of breast stimulation in ripening the cervices of 200 term primigravid patients. There was a mean change of 3.90 +/- 2.39 points in cervical score among the study group compared to 0.50 +/- 0.67 among the control group. Thirty-three per cent of the study group went into labour when compared with 4% among the control group. In a second study of cross-over trial involving 78 of the original 200 patients, the study (ex-control) group had a mean change in cervical score of 3.84 +/- 2.24 when compared with the control (ex-study) group, (1.43 +/- 1.08). In a third study involving 100 multiparous patients, a mean change in cervical score of 2.74 +/- 1.16 was observed in the study group when compared with the control group, 0.92 +/- 1.07. Forty-six per cent of the patients went into labour compared with 12% in the control group. All findings were highly significant and there were no maternal or fetal side-effects. The study confirmed the efficacy of breast stimulation in cervical ripening and induction of labour.\n", + "output": "Conclusions: Breast stimulation appears beneficial in relation to the number of women not in labour after 72 hours, and reduced postpartum haemorrhage rates. Until safety issues have been fully evaluated it should not be used in high-risk women. Further research is required to evaluate its safety, and should seek data on postpartum haemorrhage rates, number of women not in labour at 72 hours and maternal satisfaction." + }, + { + "input": "Study1: Experience with two different medicated intrauterine devices: a comparative study of the Progestasert and Nova-T. A comparative study of the Progestasert (UPS) and the Nova-T in 326 randomly selected women was carried out. The observation period was 1 year. The over-all continuation rates for the two types of intrauterine devices (IUDs) were similar. The expulsion rate for the Nova-T (9.2%) was considerably higher (P = 0.001) than that for the UPS (1.2%). Medical removals for bleeding/pain were more frequent (P = 0.028) for the UPS (15.4%) as compared with the Nova-T (6.1%). The pregnancy rate for the UPS (Pearl index = 4.8) was insignificantly higher than that for the Nova-T (Pearl index = 2.8). Two of the pregnancies in the UPS group were ectopic. No significant changes in the reactive immunoglobulins (IgA, IgG, or IgM) were observed in either of the groups. Our results indicate that neither of these two IUDs is preferable to the already existing medicated IUDs, such as the Copper T or the Copper 7.\nStudy2: A comparative study of the levonorgestrel-releasing intrauterine system Mirena versus the Copper T380A intrauterine device during lactation: breast-feeding performance, infant growth and infant development. Mirena is a levonorgestrel-releasing intrauterine system (LNG-IUS) that provides highly effective and long-acting progestogen-only contraception. The objective of this study was to analyze the possible effects of using LNG-20 microg IUS on breast-feeding performance, infant growth and infant development during the first postpartum year as compared with the Copper T380A intrauterine device (Cu T380A IUD). This study is a prospective, controlled and randomized trial. The study was conducted at the Department of Obstetrics and Gynecology, Assiut University Hospital, Egypt. Three hundred twenty lactating women asking for initiation of contraception during the early postpartum stage were assigned randomly into two groups, the LNG-20 microg IUS group (n=163) and the Cu T380A group (n=157). The insertions were done 6-8 weeks postpartum. Each participant was followed up at three monthly intervals after insertion and until the first birthday of her baby. During these visits, the breast-feeding pattern was assessed, certain infant physical growth parameters were measured and a set of infant development tests was performed. No pregnancy occurred in both groups. There were no significant differences in the net continuation rates between the two groups (89.3 for LNG-IUS vs. 90.9 for Cu T380A). The LNG-20 microg IUS group had comparable rates of breast-feeding continuation, complete weaning, full breast-feeding and partial breast-feeding, with the Cu-IUD group. No statistically significant differences were found between groups with regard to all infant physical growth parameters and various infant development tests. The findings of the current study confirm that the use of LNG-20 microg IUS during the first postpartum year in lactating women provides highly effective and acceptable contraception and does not negatively influence breast-feeding or the growth and development of breast-fed infants.\nStudy3: Five years' experience with levonorgestrel-releasing IUDs. Two levonorgestrel-releasing IUDs and a copper-releasing IUD of the same shape were studied in a randomized comparative study over five years. The levonorgestrel-releasing IUDs released 20 micrograms or 30 micrograms per day. The Pearl index during the 10,600 woman-months of LNG-IUD use was 0.11. The control device releasing copper had a Pearl index of 1.6. The amount and duration of menstrual bleeding was greatly reduced, leading to a high incidence of oligo- or amenorrhea. The continuation rate in this pioneer trial was 53 per 100 users for the levonorgestrel-releasing IUD (LNG-IUDs) and 50 per 100 users for the copper-releasing IUD (Nova T). The removal rates for reasons other than amenorrhea were not significantly different. Discontinuation because of amenorrhea occurred during the first two years, the cumulative termination rate for this reason was 11.6 per 100 users at five years. The LNG-IUDs removed for investigation after five years of use revealed that the devices contained about 40 percent of the original load. The effective lifespan of the device has been demonstrated by this study to be five years; the residual steroid gives an additional safety period of two more years. The LNG-IUD is a highly effective reversible contraceptive method, which strongly reduced the amount and duration of bleeding. During the first two months there is scanty but frequent spotting which, like the high incidence of oligo- and/or amenorrhea, requires counselling of health personnel and women using LNG-IUDs.\nStudy4: Effect of a levonorgestrel intrauterine system on women with type 1 diabetes: a randomized trial. Women with diabetes need safe, effective contraception. Although intrauterine devices provide superior contraception, concerns remain that progestin absorbed systemically from the levonorgestrel-releasing device may impair carbohydrate metabolism. To examine the effect of the levonorgestrel-releasing intrauterine system on glucose metabolism in diabetic women. We randomly assigned 62 women with uncomplicated insulin-dependent diabetes mellitus to either a levonorgestrel-releasing or a copper T 380A intrauterine device. The primary outcome to assess glucose metabolism was glycosylated hemoglobin; fasting serum-glucose levels and daily insulin dose requirements over 12 months of observation were examined as well. Outcome data were available for 29 women using the levonorgestrel-releasing and 30 using the copper device. At 12 months, mean glycosylated levels were similar for women of the 2 groups (6.3%, standard deviation [SD] +/- 1.5 compared with 6.3%, SD +/- 1.3, respectively). The same was true for mean fasting-serum glucose levels (7.4 mM, SD +/- 4.2 compared with 7.5 mM, SD +/- 4.2) and daily insulin doses (35.1 units, SD +/- 12.8 compared with 36.4 units, SD +/- 9.0). No important differences were noted at either 6 weeks or 6 months. The levonorgestrel-releasing device had no adverse effect on glucose metabolism, even at the 6-week observation when systemic levels of levonorgestrel would have been higher than at later observations. Concern about a potential adverse effect of this contraceptive on glucose control is unwarranted, and its use in women with diabetes should be liberalized. I.\nStudy5: Randomized clinical trial with intrauterine devices (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B). A 36-month study. Indian Council of Medical Research Task Force on IUD. A total of 1905 subjects were randomly allocated to four types of intrauterine devices (IUDs) and were observed for 45,683 woman-months of use. While no method failure was observed with levonorgestrel (LNG) IUD, 11 women became pregnant with other devices; 4 with Copper T 380Ag, 1 with Copper T 220C, and 6 while using Copper T 200B, indicating method failure rates of 1.0, 0.3 and 1.6, respectively, at 36 months of use. These rates were within acceptable range. Continuation rates were significantly lower with LNG IUD (74.5, 58.7, 38.8 at 1 year, 2 years and 3 years, respectively) as compared to other copper devices, which ranged between 82.4 to 84.4 at 1 year, 66.6 to 69.9 at 2 years and 45.4 to 50.4 at 3 years. The difference in continuation rates was mainly due to menstrual disturbances (e.g. amenorrhoea, irregular bleeding) which were higher with LNG IUD (27.9 per 100 users) as compared to the copper devices (13.4-15.4 per 100 users) at 36 months of use. The risk of expulsion ranged between 8.3 to 10.6 per 100 users and was comparable for all the devices. The observations from the present study based on 36 months of experience with different intrauterine devices do not indicate the need to replace CuT 200, the device currently in use in the National Programme.\nStudy6: The effect of low-dose 3-keto-desogestrel added to a copper-releasing intrauterine contraceptive device on menstrual blood loss: a double-blind, dose-finding, placebo-controlled study. We sought to establish the lowest dose of 3-keto-desogestrel, when added to a copper-releasing intrauterine contraceptive device, that is needed to reduce menstrual blood loss to a very low level and to treat (essential) menorrhagia successfully. A double-blind group comparative study was designed in which 203 healthy women with or without menorrhagia were enrolled and randomized to four different Multiload Cu250 intrauterine contraceptive devices, releasing 0 (control), 1.5, 3, or 6 microg of 3-keto-desogestrel daily. Menstrual blood loss, hemoglobin, and serum ferritin levels were determined before and during treatment. All 3-keto-desogestrel-copper intrauterine contraceptive devices reduced menstrual blood loss significantly, causing a reduction of up to 30 to 40 mL after 12 months of use. All women with essential menorrhagia were considered to have been successfully treated after 6 months of use. Serum ferritin levels rose with all three 3-keto-desogestrel-loaded devices. A Multiload Cu250 intrauterine contraceptive device releasing 1.5 microg of 3-keto-desogestrel daily is able to reduce menstrual blood loss to a very low level and to replete body iron stores in women with or without menorrhagia. Higher doses have no superior effect.\nStudy7: Recovery of fertility after use of the levonorgestrel 20 mcg/d or Copper T 380 Ag intrauterine device. Following use of either the Levonorgestrel 20 mcg/day or the TCu 380 Ag IUD in a randomized comparative study, 110 women stopped contracepting to have planned pregnancies. Pregnancy rates and recovery of fertility have been assessed. Age at acceptance, duration of use, parity and intervals between last pregnancy and IUD insertion or removal were similar for both groups. Life table pregnancy rates at one year were higher than 90 per cent for both device groups; but because some women quickly changed their minds or had been at risk of pregnancy only a short time before the analysis date, only 60.9 percent had actually become pregnant. Median time to planned pregnancy was 3 months for the TCu 380 Ag group and 4 months for the Levonorgestrel 20 group. Neither duration of use nor age at insertion or age at termination affected the pregnancy rates significantly.\n", + "output": "Conclusions: Evidence suggests there is no difference in pregnancy rates among LNG-20 IUS, IUD >250mm2 and Norplant-2 users. The LNG-20 IUS more effectively prevented intrauterine and extrauterine pregnancies than IUDs \u2264250mm2. P4-IUS was significantly more effective than non-medicated IUDs, but no difference was observed when compared to IUDs \u2264250mm2. Continuation rates for LNG-20 IUS, non-hormonal IUDs and Norplant-2 were similar. Lack of menstrual bleeding was the main reason for discontinuation of LNG-20 IUS.\nRecent evidence, from studies meeting the review inclusion criteria for the update conducted in July 2009, suggests that the LNG-20 IUS does not impact upon breastfeeding performance or the growth and development of breastfed infants in lactating women nor did the device have an adverse effect on glucose metabolism among insulin-dependent diabetic women." + }, + { + "input": "Study1: Adjunctive magnesium infusion therapy in acute myocardial infarction. Intravenous magnesium therapy in acute myocardial infarction (MI) has been shown to be beneficial in many studies. However, these effects are not consistent from one trial to another, and their clinical significance is often questionable. A total of 78 consecutive patients were included in a prospective placebo controlled, randomized study of the effects of intravenous magnesium sulfate infusion in acute MI. Of these, 52 (66%) received intravenous streptokinase and the rest belonged to a non-thrombolysed group. These patients were randomized to receive magnesium sulfate infusion (8 mmol over 5 min followed by 65 mmol over 24 h) or placebo. The end points were serious arrhythmias, left ventricular ejection fraction (LVEF) and death during hospital stay and at the end of 28 days. LVEF measured by radionuclide ventriculography at discharge (9 +/- 5 days) was similar in two groups (41 +/- 11 vs. 39 +/- 10; magnesium vs. placebo respectively, P = 0.40). However, the LVEF of the placebo-treated thrombolysed group was higher than the non-thrombolysed group (42 +/- 10 vs. 37 +/- 0, P = 0.02). Incidence of nonsustained ventricular tachycardia (NSVT) was higher with placebo than with magnesium (50% vs. 23% respectively, P < 0.02, odds ratio = 0.29; 95% confidence intervals (CI) 0.1-0.85). Mortality during hospital stay and at the end of 28 days was also similar in both the groups. Thus, the administration of magnesium infusion as an adjunct to thrombolytic therapy remains to be of questionable benefit.\nStudy2: A randomized study of intravenous magnesium in acute myocardial infarction treated with direct coronary angioplasty. Notwithstanding the negative result of the International Study of Infarct Survival-4 (ISIS-4), the controversy about the role of magnesium in acute myocardial infarction is still open because, according to experimental data, magnesium could decrease myocardial damage and mortality only if infusion is started before reperfusion. This randomized placebo-controlled trial was designed to evaluate the effect of intravenous magnesium, delivered before, during, and after direct coronary angioplasty, in patients with acute myocardial infarction. One-hundred fifty patients were randomized to intravenous magnesium sulfate or placebo. The primary end point was an infarct zone wall motion score index at 30 days, as a measure of infarct size. The secondary end points included creatine kinase peak, ventricular fibrillation/tachycardia within the first 24 hours, death and congestive heart failure within the 30-day follow-up, and 30-day left ventricular ejection fraction. Analysis was by intention to treat. There were no significant differences between the magnesium and placebo groups in the 30-day infarct zone wall motion score index (1.93 +/- 0.61 vs 1.85 +/- 0.51, P =.39), ventricular arrhythmias (24% vs 15%, P =.15), death (0 vs 1%, P =.32), heart failure (8% vs 7%, P =.75), and 30-day left ventricular ejection fraction (49% +/- 11% vs 50% +/- 9%, P = 0.55). There was a trend toward a higher creatine kinase peak in the magnesium group (3059 +/- 2359 vs 2404 +/- 1673,P =.052). Intravenous magnesium delivered before, during, and after reperfusion did not decrease myocardial damage and did not improve the short-term clinical outcome in patients with acute myocardial infarction treated with direct angioplasty.\nStudy3: Magnesium therapy in acute myocardial infarction--a double-blind study. Various methods have been proposed and tried to limit the extent of myocardial damage at the time of infarction. We chose to assess the usefulness of intravenous magnesium in this regard because of its important role in myocardial metabolism and function and the suggestion of its deficiency in ischemic hearts. A double-blind randomized trial was carried out and results analyzed in 76 patients. At the end of the infusion period the mean serum Mg++ level for the treated group was 3.6 versus 1.9 mg/dl for the control group. The estimated size of infarction (as measured by MB-CK release) was not significantly smaller overall in the treated group (37.4 +/- 4.3 vs. 45.6 +/- 4.6 MB-CK g/Eq), but was significantly smaller in the treated subgroup without heart failure (31.6 +/- 5.8 vs. 44.7 +/- 4.8 MB-CK g/Eq). A trend toward less ventricular ectopy was seen in the group treated with magnesium. There was significantly less lidocaine used for the treatment of ventricular dysrhythmias in this group. Magnesium supplementation in patients undergoing acute coronary events is promising and deserves further study.\nStudy4: Benefits of magnesium in acute myocardial infarction: timing is crucial. To evaluate magnesium deficiency during and after acute myocardial infarction (AMI) and the role of intravenous magnesium therapy given in the early postinfarction period. One hundred patients with AMI were randomly assigned to 2 equal groups and monitored over a 4-week period. The placebo group received intravenous dextrose solution and the trial group was given 15 g intravenous magnesium (62 mmol) over a 48-hour period. Serum magnesium levels were measured on days 1, 2, 4, and 6 after admission by calorimetry with methyl thymol blue. The groups were comparable in prevalence of risk factors for coronary artery disease and other acute parameters of AMI. The serum magnesium levels of a group of 50 controls were higher (1.61 +/- 0. 21 vs 1.23 +/- 0.27mEq/L) than in patients with AMI (P <.001). There was an increase in serum magnesium levels in the trial group on day 2 (1.73 +/- 0.27 vs 1.29 +/- 0.28 mEq/L; P <.001) as well as on day 4 (1.62 +/- 0.25 vs 1.38 +/- 0.36 mEq/L; P <.001). The trial group also showed significantly lower incidence of arrhythmias (8% vs 34%) and death (4% vs 20%). The mortality rate from pump failure was reduced in the trial group (4% vs 14%). The serum magnesium levels in patients with AMI were lower compared with controls. The administration of intravenous magnesium to patients in the immediate postinfarction period is cardioprotective and decreases the incidence of arrhythmia, pump dysfunction, and death. Thus intravenous magnesium is a safe, effective, and inexpensive modality of treatment in AMI.\nStudy5: Effects of intravenous magnesium sulphate in suspected acute myocardial infarction on acute arrhythmias and long-term outcome. A total of 252 patients with suspected acute myocardial infarction were included in a double blind study and randomised to 50 mmol magnesium sulfate infusion under 20 h or corresponding placebo. Acute myocardial infarction was verified in 117 patients and 59% of these had concomitant treatment with thrombolysis. One-hundred ninety-four patients had Holter registrations during the first day in the coronary care unit. Intention-to-treat analysis showed an increase in long RR-intervals (> 3 s) in the magnesium treated group (P = 0.006) and a tendency toward a reduction in episodes of ventricular premature complexes in triplets (P = 0.09). During hospital stay and a mean of 22 months follow-up, 23 fatal events occurred in the magnesium allocated group and 31 fatal events among the placebo allocated group (P = 0.1). Mortality rate from cardiac disease was reduced by 54% (95% C.I. 30-99%, P < 0.05). Subgroup analysis on acute myocardial infarction patients showed a 48% mortality risk reduction in the magnesium treated acute myocardial infarction group compared to the placebo treated acute myocardial infarction group (95% C.I. 23-104%, P = 0.06). There was no significant interaction between the effects of magnesium and thrombolytic treatment on total mortality or cardiac events. This study supports the results of other small double blind placebo controlled studies regarding effects of magnesium therapy on mortality in acute myocardial infarction, but are in discordance to the conclusion from the ISIS-4 study. The reasons for these discrepancies cannot be elucidated by our data.\nStudy6: [Intravenous magnesium in acute myocardial infarct]. The effects of magnesium (Mg) on the incidence of arrhythmias and on mortality were evaluated in 61 patients with documented acute myocardial infarction (AMI), in a randomized, double blind placebo controlled study. During the first 24 hours 31 patients received infusion of 1000 ml isotonic saline with 17 g MgSO4 and 30 ones received only equal volumes of saline as placebo. The baseline characteristics of the population including serum Mg and potassium were similar in the two groups. Severe arrhythmias were not as frequent in the Mg group (22%) as in the placebo one (36%), but the difference was not statistically significant (p = 0.05). There is no significant difference between the groups neither in mortality (3.2%; 0%) nor in conduction disturbances (3.2%; 3%). The adverse effects of Mg therapy were transient and therapy interruption was not required. Although the trial is not an extensive one, and the results are nonsignificant, we consider intravenous Mg therapy to be simple and cheap with its place in the treatment of AMI in properly selected patients. According to available data it should be administered as soon as possible after the onset of AMI symptoms, before thrombolytic therapy, in 24-hrs. dose not exceeding 50-65 mmol probably through several days, but the optimal duration of therapy should be further investigated.\nStudy7: Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality. Two hundred patients with acute myocardial infarction were entered into a randomised double-blind trial where they received either intravenous magnesium sulphate or saline for 24 hours after admission to hospital. The incidence of ventricular arrhythmias necessitating treatment was reduced by more than half in the group receiving magnesium sulphate. There were two deaths in the group receiving magnesium sulphate and seven receiving saline placebo. Total cardiac events were significantly reduced in the magnesium treated group. These reductions cannot be attributed to differences in risk factors or therapy between the two groups, either before or during the period of study. These results suggest that magnesium administration reduces the incidence of serious tachyarrhythmias and death after acute myocardial infarction and that this simple regime warrants further study.\nStudy8: Threatening arrhythmias in acute myocardial infarction are prevented by intravenous magnesium sulfate. nan\nStudy9: ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. 58,050 patients entering 1086 hospitals up to 24 h (median 8 h) after the onset of suspected acute myocardial infarction (MI) with no clear contraindications to the study treatments (in particular, no cardiogenic shock or persistent severe hypotension) were randomised in a \"2 x 2 x 2 factorial\" study. The treatment comparisons were: (i) 1 month of oral captopril (6.25 mg initial dose titrated up to 50 mg twice daily) versus matching placebo; (ii) 1 month of oral controlled-release mononitrate (30 mg initial dose titrated up to 60 mg once daily) versus matching placebo; and (iii) 24 h of intravenous magnesium sulphate (8 mmol initial bolus followed by 72 mmol) versus open control. There were no significant \"interactions\" between the effects of these three treatments, and the results for each are based on the randomised comparison of about 29,000 active versus 29,000 control allocated patients. Captopril There was a significant 7% (SD 3) proportional reduction in 5-week mortality (2088 [7.19%] captopril-allocated deaths vs 2231 [7.69%] placebo; 2p = 0.02), which corresponds to an absolute difference of 4.9 SD 2.2 fewer deaths per 1000 patients treated for 1 month. The absolute benefits appeared to be larger (perhaps about 10 fewer deaths per 1000) in certain higher-risk groups, such as those presenting with a history of previous MI or with heart failure. The survival advantage appeared to be maintained in the longer term (5.4 [SD 2.8] fewer deaths per 1000 at 12 months). Captopril was associated with an increase of 52 (SD 2) patients per 1000 in hypotension considered severe enough to require termination of study treatment, of 5 (SD 2) per 1000 in reported cardiogenic shock, and of 5 (SD 1) per 1000 in some degree of renal dysfunction. It produced no excess of deaths on days 0-1, even among patients with low blood pressure at entry. Mononitrate There was no significant reduction in 5-week mortality, either overall (2129 [7.34%] mononitrate-allocated deaths vs 2190 [7.54%] placebo) or in any subgroup examined (including those receiving short-term non-study intravenous or oral nitrates at entry). Further follow-up did not indicate any later survival advantage. The only significant side-effect of the mononitrate regimen studied was an increase of 15 (SD 2) per 1000 in hypotension. Those allocated active treatment had somewhat fewer deaths on days 0-1, which is reassuring a bout the safety of using nitrates early in acute MI.(ABSTRACT TRUNCATED AT 400 WORDS)\nStudy10: Magnesium in the prevention of lethal arrhythmias in acute myocardial infarction. Seven of 48 patients (14.6%) with acute myocardial infarction who were given 2.4 g of magnesium sulfate as a single intravenous dose had potentially lethal arrhythmias during the first 24 hours after admission, whereas 16 (34.8%) of 46 patients receiving placebo had similar arrhythmias. In addition, 14 of these 16 patients in the placebo group had their first arrhythmia (in the intensive coronary-care unit) within two hours after the start of the study, whereas in the magnesium-treated group, there were no such arrhythmias until some four hours later. The higher the lymphocyte potassium concentration, the greater the reduction in the incidence of arrhythmias. Serum magnesium levels increased by 16.5% and lymphocyte magnesium concentrations by 72% in the magnesium treated group. Intravenous magnesium reduces the incidence of serious arrhythmias after acute myocardial infarction.\n", + "output": "Conclusions: Owing to the likelihood of publication bias and marked heterogeneity of treatment effects, it is essential that the findings are interpreted cautiously. From the evidence reviewed here, we consider that: (1) it is unlikely that magnesium is beneficial in reducing mortality both in patients treated early and in patients treated late, and in patients already receiving thrombolytic therapy; (2) it is unlikely that magnesium will reduce mortality when used at high dose (>=75 mmol); (3) magnesium treatment may reduce the incidence of ventricular fibrillation, ventricular tachycardia, severe arrhythmia needing treatment or Lown 2-5, but it may increase the incidence of profound hypotension, bradycardia and flushing; and (4) the areas of uncertainty regarding the effect of magnesium on mortality remain the effect of low dose treatment (< 75 mmol) and in patients not treated with thrombolysis." + }, + { + "input": "Study1: Discontinuation of antistreptococcal prophylaxis. A double-blind study in rheumatic patients free of heart disease. nan\nStudy2: Prophylaxis of recurrences of rheumatic fever with penicillin given orally; final report of a five year study. nan\nStudy3: Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four-week regimens: comparison of two brands of BPG. This prospective study was aimed at answering two important questions: 1) Is a biweekly schedule of 1.2 million U intramuscular benzathine penicillin G (BPG) superior to a 4-week one in the prevention of upper respiratory Group A beta-hemolytic streptococcal (GABHS) infections and rheumatic fever (RF) recurrences? 2) Is there a difference in the bioavailability of BPG obtained from different manufacturers? Three hundred sixty rheumatic patients aged 4 to 20 years were randomly assigned to either a biweekly (190 patients) or 4-week (160 patients) BPG prophylactic schedule and were followed-up monthly for 2 years by clinical examination, throat swab culture for GABHS and measurement of antistreptolysin O titer to detect GABHS infection and/or recurrences of RF (according to revised Jones' Criteria). Thereafter, 34 rheumatic subjects, aged 8 to 16 years were randomly assigned to receive a 4-week injection of 1.2 million U of either a locally manufactured BPG brand (22 patients) or an imported one (12 patients). Sera of all patients were tested for penicillin level by plate diffusion method on days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 after the intramuscular injection of BPG. The GABHS infection rate was found to be 0.2% and 0.3% for patients on the biweekly and 4-week BPG schedules, respectively, with no significant differences between them. However, the RF recurrence rate/patient/year for the 4-week schedule patients (0.12) was double that for the biweekly schedule ones (0.06). Estimation of the bioavailability of the two different brands of BPG demonstrated a difference in their pharmacokinetics and a decrease in the serum penicillin concentration below the minimum inhibitory concentration 3 weeks after the injection of either brand. Although a biweekly schedule may not be superior in preventing upper respiratory GABHS infection, it may play a role in preventing the sequelae of such infections. The short duration of penicillinemia explains the superiority of the 2-week schedule in RF prophylais. The difference in the pharmacokinetics of penicillin brands might contribute to the high recurrence rate of RF reported in Egypt.\nStudy4: Prophylaxis of recurrent rheumatic fever. Therapeutic-continuous oral penicillin vs monthly injections. nan\nStudy5: Epidemiology and prophylaxis of rheumatic fever in Delhi--a five year follow-up. nan\n", + "output": "Conclusions: Intramuscular penicillin seemed to be more effective than oral penicillin in preventing rheumatic fever recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor quality of trials." + }, + { + "input": "Study1: Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke. To determine the effect of intravenous recombinant tissue plasminogen activator (rt-PA) on vascular and neurologic outcomes, we enrolled 31 patients with acute carotid artery-territory ischemic stroke within 6 hours from symptom onset in a randomized, double-blind, placebo-controlled study. We gave either rt-PA (duteplase at the dose of 20 or 30 mega-international units [MIU]) or placebo intravenously for 60 minutes in patients randomly assigned to the three groups. A comparison between the baseline and postinfusion angiograms showed that complete or partial reperfusion occurred in 50% (5/10) of patients treated with 30 MIU rt-PA, 44% (4/9) of those treated with 20 MIU rt-PA, and 17% (2/12) in the control group. In patients with middle cerebral artery occlusions, reperfusion occurred in 71% (5/7) of the 30-MIU group, in 67% (4/6) of the 20-MIU group, and in 13% (1/8) of the control group. Patients treated with 30 MIU rt-PA showed a significantly early and better clinical improvement, as measured by the neurologic scale, than did those treated with placebo. Parenchymal hemorrhage occurred in one patient in each group, and frequency of clinically insignificant hemorrhagic infarction was comparable among the treatment groups. No major systemic complications occurred in any group. These results support the efficacy of intravenous infusion of rt-PA soon after the onset of stroke in producing rapid thrombolysis and neurologic recovery; it may be of particular value in patients with thromboembolic occlusion in the middle cerebral artery.\nStudy2: Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group. To determine whether the administration of 1.5 million units of streptokinase intravenously within 4 hours of the onset of acute ischemic stroke would reduce morbidity and mortality at 3 months and whether outcomes may be better for those receiving therapy within 3 hours of stroke onset compared with those receiving it after 3 hours. Randomized, double-blind, placebo-controlled trial with 3-month follow-up. A total of 340 patients, aged 18 to 85 years, with moderate to severe strokes were randomized from 40 centers throughout Australia from June 1992 to November 1994. Administration of 1.5 million units of streptokinase or placebo intravenously in 100 mL of normal saline over 1 hour. Combined death and disability score (Barthel index <60) 3 months after the stroke. Using an intention-to-treat analysis with a combined death and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outcomes for streptokinase vs placebo (relative risk [RR] of unfavorable outcome, 1.08; 95% confidence interval [CI], 0.74-1.58) and an excess of hematomas (13.2%[12.6% symptomatic] in the treated group, 3% [2.4% symptomatic] for placebo [P<.01]). However, poor outcomes were confined to patients receiving therapy more than 3 hours after stroke onset (RR of unfavorable outcome, 1.22; 95% CI, 0.80-1.86). In contrast, among the 70 patients who were entered into the trial within 3 hours of stroke onset, there was a trend toward improved outcomes for those who received streptokinase (RR of unfavorable outcome, 0.66; 95% CI, 0.28-1.58), and this outcome pattern was significantly better than for those receiving therapy after 3 hours (P=.04). Streptokinase administration resulted in excess deaths in the group treated after 3 hours (RR, 1.98; 95% CI, 1.18-3.35), but not among those treated within 3 hours (RR, 1.11; 95% CI, 0.38-3.21). The administration of streptokinase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was safer and associated with significantly better outcomes than later treatment, it showed no significant benefit over placebo. The timing of thrombolytic therapy for acute stroke is critical.\nStudy3: Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events. As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.) 2008 Massachusetts Medical Society\nStudy4: Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan. The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase (UK) in patients with stroke within 6 hours of onset. Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were randomized to the UK or control groups. Clinical outcome was assessed by the modified Rankin Scale, National Institutes of Health Stroke Scale, and Barthel Index. The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan. A total of 114 patients underwent randomization, 57 patients in each group. Background characteristics were comparable between the 2 groups. The primary end point of favorable outcome (modified Rankin Scale 0 to 2) at 90 days was somewhat more frequent in the UK group than in the control group (49.1% and 38.6%, OR: 1.54, 95% CI: 0.73 to 3.23) but did not reach a significant level (P=0.345). However, excellent functional outcome (modified Rankin Scale 0 to 1) at 90 days, a preplanned secondary end point, was more frequent in the UK group than in the control group (42.1% and 22.8%, P=0.045, OR: 2.46, 95% CI: 1.09 to 5.54). There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group (P=0.017). The 90-day cumulative mortality was 5.3% in the UK group and 3.5% in the control group (P=1.000), and intracerebral hemorrhage within 24 hours of treatment occurred in 9% and 2%, respectively (P=0.206). The trial was aborted prematurely and the primary end point did not reach statistical significance. Nevertheless, the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome.\nStudy5: A pilot study of streptokinase for acute cerebral infarction. We evaluated intravenous streptokinase in the treatment of cerebral infarction. Following neurological assessment and cerebral computed tomography (CT), patients aged 40-80 years with symptoms of anterior circulation acute ischaemic stroke were given 1.5 M units streptokinase or saline placebo in a double-blind randomized study. Twenty patients (10 streptokinase, 10 placebo), 11 males, 9 females, aged 57-79 years, were treated out of 512 consecutive admissions to the acute stroke unit over a 2-year period. Initial CT was normal in 11 (6 placebo, 5 streptokinase) and showed early signs of cerebral infarction in nine (4 placebo, 5 streptokinase). Median times from symptom onset to treatment were 5.2 h (placebo) and 5.8 h (streptokinase). Streptokinase treatment was associated with symptomatic hypotension in one patient. Repeat CT at 72 h demonstrated intracerebral haematoma in two patients and haemorrhagic infarction in one patient in the streptokinase group; the two cases of haematoma formation were associated with neurological deterioration and death. One patient in the placebo group had evidence of haemorrhagic infarction at 72 h. There were three deaths in each treatment group, all within the first 14 days. Patients with acute stroke can be evaluated with CT and treated with streptokinase within 6 h, but the opportunity for treatment is currently limited to few patients. Streptokinase treatment is not without risk, but potential clinical benefit justifies ongoing multicentre randomized trials.\nStudy6: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS) To evaluate the efficacy and safety of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke. Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. A total of 75 hospitals in 14 European countries. A total of 620 patients with acute ischemic hemispheric stroke and moderate to severe neurologic deficit and without major early infarct signs on initial computed tomography (CT). Patients were randomized to treatment with 1.1 mg per kilogram of body weight of rt-PA (alteplase) or placebo within 6 hours from the onset of symptoms. Primary end points included Barthel Index (BI) and modified Rankin Scale (RS) at 90 days. Secondary end points included combined BI and RS, Scandinavian Stroke Scale (SSS) at 90 days, and 30-day mortality. Tertiary end points included early neurologic recovery (SSS) and duration of in-hospital stay. Safety parameters included mortality and incidence of intracranial or extracranial hemorrhage. The distribution of demographic variables was similar among patients in the rt-PA and placebo treatment arms in both the intention-to-treat (ITT) analysis and the explanatory analysis for the target population (TP). A total of 109 patients (17.4%) were included in the trial despite major protocol violations but excluded from the TP. There was no difference in the primary end points in the ITT analysis, while the TP analysis revealed a significant difference in the RS in favor of rt-PA-treated patients (P = .035). Of the secondary end points, the combined BI and RS showed a difference in favor of rt-PA-treated patients in both analyses (P < .001). Neurologic recovery at 90 days was significantly better for rt-PA-treated patients in the TP (P = .03). The speed of neurologic recovery assessed by the SSS was significantly better up to 7 days in the ITT analysis and up to 30 days for the TP in the rt-PA treatment arm. In-hospital stay was significantly shorter in the rt-PA treatment arm in both analyses. There were no statistically significant differences in the mortality rate at 30 days or in the overall incidence of intracerebral hemorrhages among the rt-PA and placebo treatment arms in either analysis. However, the occurrence of large parenchymal hemorrhages was significantly more frequent in the rt-PA-treated patients. Intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan. However, the identification of this subgroup is difficult and depends on recognition of early major CT signs of early infarction. Therefore, since treating ineligible patients is associated with an unacceptable increase of hemorrhagic complications and death, intravenous thrombolysis cannot currently be recommended for use in an unselected population of acute ischemic stroke patients.\nStudy7: Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion. Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.\nStudy8: Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial--Italy (MAST-I) Group. In ischaemic stroke, thrombolytic drugs speed the recanalisation of intracerebral arteries. The effects of aspirin are not known. A trial was conducted to determine whether, separately or together, streptokinase and aspirin have clinical benefits in acute ischaemic stroke similar to those in acute myocardial infarction. 622 patients with acute ischaemic stroke within 6 hours of symptom onset were randomised with a 2 x 2 factorial design to (i) a 1-hour intravenous infusion of 1.5 MU streptokinase, (ii) 300 mg/day buffered aspirin for 10 days, (iii) both active treatments, or (iv) neither. Early results raised a question whether the trial should be continued. Streptokinase (alone or with aspirin) was associated with an excess of 10-day case fatality (odds ratio 2.7; 95% confidence interval 1.7-4.3; 2p < 0.00001). Of the four groups randomised, only patients allocated to streptokinase plus aspirin had a significantly higher risk of early death than those given neither streptokinase nor aspirin (odds ratio 3.5; 95% CI 1.9-6.5; 2p < 0.00001). Streptokinase (alone or with aspirin) and aspirin (alone or with streptokinase) reduced, albeit not significantly, the incidence of combined six-month case fatality and severe disability: odds ratio for streptokinase 0.9 (95% CI 0.7-1.3) and odds ratio for aspirin 0.9 (95% CI 0.6-1.3). The risk of early death with thrombolytic treatments should be weighed against the potential benefit of a marginal reduction of severe disability after the first six months.\nStudy9: Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Previous studies have suggested that desmoteplase, a novel plasminogen activator, has clinical benefit when given 3-9 h after the onset of the symptoms of stroke in patients with presumptive tissue at risk that is identified by magnetic resonance perfusion imaging (PI) and diffusion-weighted imaging (DWI). In this randomised, placebo-controlled, double-blind, dose-ranging study, patients with acute ischaemic stroke and tissue at risk seen on either MRI or CT imaging were randomly assigned (1:1:1) to 90 microg/kg desmoteplase, 125 microg/kg desmoteplase, or placebo within 3-9 h after the onset of symptoms of stroke. The primary endpoint was clinical response rates at day 90, defined as a composite of improvement in National Institutes of Health stroke scale (NIHSS) score of 8 points or more or an NIHSS score of 1 point or less, a modified Rankin scale score of 0-2 points, and a Barthel index of 75-100. Secondary endpoints included change in lesion volume between baseline and day 30, rates of symptomatic intracranial haemorrhage, and mortality rates. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT00111852. Between June, 2005, and March, 2007, 193 patients were randomised, and 186 patients received treatment: 57 received 90 microg/kg desmoteplase; 66 received 125 microg/kg desmoteplase; and 63 received placebo. 158 patients completed the study. The median baseline NIHSS score was 9 (IQR 6-14) points, and 30% (53 of 179) of the patients had a visible occlusion of a vessel at presentation. The core lesion and the mismatch volumes were small (median volumes were 10.6 cm(3) and 52.5 cm(3), respectively). The clinical response rates at day 90 were 47% (27 of 57) for 90 microg/kg desmoteplase, 36% (24 of 66) for 125 microg/kg desmoteplase, and 46% (29 of 63) for placebo. The median changes in lesion volume were: 90 microg/kg desmoteplase 14.0% (0.5 cm(3)); 125 microg/kg desmoteplase 10.8% (0.3 cm(3)); placebo -10.0% (-0.9 cm(3)). The rates of symptomatic intracranial haemorrhage were 3.5% (2 of 57) for 90 microg/kg desmoteplase, 4.5% (3 of 66) for 125 microg/kg desmoteplase, and 0% for placebo. The overall mortality rate was 11% (5% [3 of 57] for 90 microg/kg desmoteplase; 21% [14 of 66] for 125 microg/kg desmoteplase; and 6% [4 of 63] for placebo). The DIAS-2 study did not show a benefit of desmoteplase given 3-9 h after the onset of stroke. The high response rate in the placebo group could be explained by the mild strokes recorded (low baseline NIHSS scores, small core lesions, and small mismatch volumes that were associated with no vessel occlusions), which possibly reduced the potential to detect any effect of desmoteplase. PAION Deutschland GmbH; Forest Laboratories.\nStudy10: The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g) : results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators. The Thrombolytic Therapy in Acute Ischemic Stroke Study, which started in August of 1991, was designed to assess the efficacy and safety of intravenous rtPA (alteplase) in patients with acute (0 to 6 hours) ischemic stroke. In October 1993 enrollment was halted because of Safety Committee (DMSB) concerns. In December 1993 the time window was changed to 0 to 5 hours, and it was decided to restart enrollment as a separate study (part B). We report here the results of the original study (part A), focusing on evaluating the safety and efficacy of rtPA given between 0 and 6 hours after stroke onset. This investigation was a phase II, placebo-controlled, double-blind, randomized study utilizing 0.9 mg/kg IV rtPA or placebo over 1 hour, which was conducted at university and community sites in North America. Except for time to treatment, enrollment criteria were very similar to those of the NINDS rtPA stroke study. Primary efficacy end points were the number of patients with a decrease of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) at 24 hours and day 30, along with infarct volume at day 30. Secondary end points included mortality and functional recoveries on the Barthel Index and Modified Rankin scale at days 30 and 90. A total of 142 patients were enrolled at 42 sites in North America, including 22 <3 hours (15%) and 46 between 5 and 6 hours (32%). The groups were well matched on baseline characteristics, including NIHSS (mean of 13 for both). For the primary end points, a higher percentage of rtPA patients had a 4-point improvement at 24 hours (placebo 21%, rtPA 40%; P=0.02); however, this early effect was reversed by 30 days, with more placebo patients having a 4-point improvement (75%) than patients treated with rtPA (60%, P=0.05). Treatment with rtPA significantly increased the rate of symptomatic intracerebral hemorrhage within 10 days (11% versus 0%, P<0.01) and mortality at 90 days (23% versus 7%, P<0.01). This study found no significant rtPA benefit on any of the planned efficacy end points at 30 and 90 days in patients treated between 0 and 6 hours after stroke onset. These negative results apply to patients treated after 3 hours, because only 15% of the patients were enrolled before 3 hours. The risk of symptomatic intracerebral hemorrhage was increased with rtPA treatment, particularly in patients treated between 5 and 6 hours after onset. These results do not support the use of intravenous rtPA for stroke treatment >3 hours after onset.\n", + "output": "Conclusions: Overall, thrombolytic therapy appears to result in a significant net reduction in the proportion of patients dead or dependent in activities of daily living. This overall benefit was apparent despite an increase both in deaths (evident at seven to 10 days and at final follow up) and in symptomatic intracranial haemorrhages. Further trials are needed to identify which patients are most likely to benefit from treatment and the environment in which thrombolysis may best be given in routine practice." + }, + { + "input": "Study1: Antimicrobial therapy in preterm premature rupture of membranes: results of a prospective, double-blind, placebo-controlled trial of erythromycin. This study was conducted to evaluate the effectiveness of oral erythromycin treatment in safely prolonging pregnancy among women experiencing preterm premature rupture of membranes. Sixty-five women were randomly assigned to receive double-blind treatment with either erythromycin base or an identical-appearing placebo three times daily for 7 days. Only women between 23 and 34 completed weeks' gestation who did not have an indication for delivery were enrolled in the study. Pretreatment microbiologic tests were obtained and women were followed expectantly. Fifty-five women and their newborns completed the protocol and were fully evaluated. Overall, time from rupture of membranes to onset of labor and to delivery was longer, although not significantly, for erythromycin-treated women. Similarly, there was a trend for reduced neonatal intensive care (level II, p = 0.07). When gestational age at enrollment was controlled, erythromycin treatment of women between 28 to 32 weeks' gestation was associated with a prolonged interval from enrollment to delivery [erythromycin: 292 hours (5 to 679); placebo: 54 (12 to 323); p less than 0.044]. Fifty percent of erythromycin-treated women between 28 to 32 weeks' gestation continued their pregnancies at least 13 days after premature rupture of membranes, whereas 50% of placebo-treated women were delivered of infants within 4 days (p = 0.02). Erythromycin treatment among women less than 28 and between 33 to 34 weeks' gestation was not associated with prolonged latency or other changes. There were no differences between erythromycin- and placebo-treated women in the occurrence of clinically recognized chorioamnionitis, postpartum endometritis, or neonatal infectious morbidity. In this double-blind, placebo-controlled trial, erythromycin treatment was well tolerated, safe, and associated with prolongation of pregnancy and reduced intensive neonatal care requirements for selected mother-newborn pairs with preterm premature rupture of membranes.\nStudy2: Use of ampicillin and corticosteroids in premature rupture of membranes: a randomized study. A randomized study was conducted to investigate the effects of antenatal corticosteroids and ampicillin in the management of preterm pregnancies under 34 weeks complicated by premature rupture of membranes. Patients with documented lecithin/sphingomyelin (L/S) ratios of less than 2.0 and a singleton gestation were eligible to participate in the study. One hundred sixty-five patients qualified and were randomized, using sealed envelopes, to four study groups. All patients were followed expectantly. Group I (41 patients) received neither ampicillin nor corticosteroids. Group II (43 patients) received 24 mg of antenatal betamethasone. Group III (37 patients) received 2 g of intravenous ampicillin every 6 hours, with discontinuation of antibiotic therapy if cultures were negative for pathogenic bacteria. Group IV (44 patients) received both corticosteroids and ampicillin as described for groups II and III, respectively. Compared with patients not receiving corticosteroids, those administered antenatal corticosteroids experienced a reduction in the incidences of respiratory distress syndrome (53 versus 26%), bronchopulmonary dysplasia (23 versus 9%), severe grades of intracranial hemorrhage (15 versus 3%), and patent ductus arteriosus (18 versus 6%), with no difference in the incidence of maternal or neonatal infection. Compared with patients not receiving antenatal antibiotics, the group of patients treated with ampicillin on admission had a lower incidence of clinical chorioamnionitis (4 versus 26%) and neonatal sepsis (5 versus 10%). This reduction in infectious morbidity by antenatal ampicillin was restricted to those patients (28.4% of the study population) colonized with group B streptococci.(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy3: Duration of antibiotic therapy after preterm premature rupture of fetal membranes. This study was undertaken to compare the efficacy of 3 days versus 7 days of ampicillin in prolonging gestation for at least 7 days in women with preterm premature rupture of membranes (PPROM). We performed a randomized clinical trial comparing 3 days of ampicillin with 7 days ampicillin in patients with PPROM. Our primary outcome was the prolongation of pregnancy for at least 7 days. Secondary outcomes included rates of chorioamnionitis, postpartum endometritis, and neonatal morbidity and mortality. Forty-eight patients were randomly selected. There was no statistically significant difference in the ability to achieve a 7-day latency (relative risk 0.83, 95% CI 0.51-1.38). In addition, there was no statistically significant difference in the rates of chorioamnionitis, endometritis, and our composite neonatal morbidity. In patients with PPROM, length of antibiotic therapy does not change the rate of a 7-day latency or affect the rate of chorioamnionitis, postpartum endometritis, or neonatal morbidity.\nStudy4: Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. We did a randomised multicentre trial to try to resolve this issue. 4826 women with pPROM were randomly assigned 250 mg erythromycin (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. Two women were lost to follow-up, and there were 15 protocol violations. Among all 2415 infants born to women allocated erythromycin only or placebo, fewer had the primary composite outcome in the erythromycin group (151 of 1190 [12.7%] vs 186 of 1225 [15.2%], p=0.08) than in the placebo group. Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 [11.2%] vs 166 of 1149 [14.4%], p=0.02). Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only. Use of erythromycin was also associated with prolongation of pregnancy, reductions in neonatal treatment with surfactant, decreases in oxygen dependence at 28 days of age and older, fewer major cerebral abnormalities on ultrasonography before discharge, and fewer positive blood cultures. Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy, they were also associated with a significantly higher rate of neonatal necrotising enterocolitis. Erythromycin for women with pPROM is associated with a range of health benefits for the neonate, and thus a probable reduction in childhood disability. However, co-amoxiclav cannot be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis. A follow-up study of childhood development and disability after pPROM is planned.\nStudy5: Erythromycin therapy in preterm premature rupture of the membranes: a prospective, randomized trial of 220 patients. The use of prophylactic antibiotics in the management of preterm premature rupture of the membranes has not been adequately studied. The purpose of this study was to evaluate the efficacy of oral erythromycin therapy in the prolongation of latency and reduction of infectious morbidity after preterm premature rupture of membranes. In this randomized, prospective, double-blind, placebo-controlled study, 220 women at 20 to 35 weeks' gestation were evaluated. Subjects received oral erythromycin 333 mg (n = 106) or indistinguishable placebo (n = 114) every 8 hours from randomization to delivery. Prolongation of latency was identified with erythromycin therapy (p = 0.02), particularly for those destined to have chorioamnionitis (p = 0.003) and those with oligohydramnios (p = 0.01). No decrease in the incidence of maternal or neonatal infectious morbidity was seen. Oral erythromycin delays, but does not prevent, the onset of clinical infection when administered to women with preterm premature rupture of membranes. This regimen does not decrease neonatal morbidity and mortality.\nStudy6: Antibiotic therapy in preterm premature rupture of membranes: Are seven days necessary? A preliminary, randomized clinical trial. The purpose of this study was to determine whether 3 days of broad-spectrum antibiotic therapy, which is intended to prolong latency in patients with preterm premature rupture of membranes, is comparable to 7 days of therapy. Patients with preterm premature rupture of membranes at three separate study sites were asked to participate in this intent-to-treat, prospective, randomized trial. They were assigned randomly to either 3 or 7 days of ampicillin-sulbactam (3 g intravenously every 6 hours). The primary outcome of interest was the latency period from membrane rupture to delivery. Forty-two individuals were enrolled in each group. No difference was noted in the latency interval between the two groups (3 days, 214 +/- 225 hours, vs 7 days, 229 +/- 218 hours). A significantly higher number of patients in the 3-day group completed therapy (80.1% vs 47.6%, P =.003). No other parameters were significantly different between the two groups. No adverse events or trends were noted in either group. There appears to be no difference in the latency period between 3 and 7 days of ampicillin-sulbactam antibiotic therapy. More patients are needed to exclude a type II error.\nStudy7: Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial. The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial. By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age. In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery. In the control group 45 patients received intravenous and oral placebo. Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05). Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05). The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001). These infants also had higher 1- and 5-minute Apgar scores. Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group.\nStudy8: Expectant management of preterm ruptured membranes: effects of antimicrobial therapy. To determine whether the addition of broad-spectrum antimicrobial therapy to traditional expectant management improves pregnancy outcome in patients with premature rupture of membranes (PROM) remote from term. Patients with preterm PROM before 34 weeks' gestation who were not in labor and had no signs of infection or fetal distress were randomized to one of two study groups: 1) expectant management alone and 2) expectant management plus antimicrobial therapy. Women in the latter group received intravenous ampicillin, gentamicin, and clindamycin for 24 hours, followed by amoxicillin plus clavulanic acid orally for 7 days. Other than antibiotic use, management of the two groups was identical. Significantly more women (P < .01) treated with antibiotics (20 of 48, 42%) remained undelivered 7 days after admission compared with those managed expectantly without antibiotics (seven of 46, 15%). In addition, more neonates in the group managed with antibiotics were admitted to the routine nursery (nine of 48 versus two of 45; P = .03). However, there was no difference between the groups in the frequency of serious maternal or neonatal morbidity. The addition of broad-spectrum antimicrobial therapy to traditional expectant management of pregnancy complicated by preterm PROM may increase the number of gestations undelivered 7 days after admission. It may also decrease the proportion of infants admitted to special care nurseries. Whether these effects result in significant short- or long-term maternal or neonatal benefit remains to be determined.\nStudy9: Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture. Our purpose was to determine whether maternal administration of prophylactic ampicillin or erythromycin after preterm amnion rupture is associated with maternal or neonatal benefits. Women with singleton pregnancies between 24 and 33 weeks 6 days of gestation were eligible if they had no immediate indication for delivery. After giving informed consent, patients were randomized either to receive ampicillin (erythromycin if penicillin allergic) until delivery or to enter a control group. Women whose cervical cultures were positive for either group B streptococci or Neisseria gonorrhoeae received treatment. Tocolytics and corticosteroids were not used. From January 1990 to February 1992 117 patients (antibiotics 59, control 58) were recruited and analyzed. Prophylactic antibiotics were associated with a longer latent phase (mean 12 vs 7.0 days, p = 0.004) and fewer maternal infectious complications (29% vs 60%, p = 0.001). A higher incidence of neonatal necrotizing enterocolitis was observed in the treatment group (14% vs 3.5%, p = 0.05). Other neonatal complications, including death, were lower in the treatment group, but none attained statistical significance (p = 0.09 to 0.33). The use of prophylactic antibiotics in selected patients after preterm amnion rupture appears to have a demonstrable maternal benefit. Large, multicenter trials may demonstrate a significant neonatal benefit or confirm any adverse outcomes.\nStudy10: Premature rupture of the membranes: effect of penicillin prophylaxis and long-term outcome of the children. To assess the value of prophylaxis with penicillin in women with premature rupture of membranes (PROM) and the long-term outcome of children born after prolonged PROM, we studied 221 women with this condition. Penicillin (5 mu twice, 6 hours apart) was given intravenously to 50 women and placebo to 51 women, whereas 76 comparable patients were treated without penicillin or placebo. The time interval between PROM and delivery ranged from 14 hours to 56 days. Chorioamnionitis occurred more frequently (p less than 0.05) among patients with placebo (14%) than among those treated with penicillin (2%). One puerperal endometritis appeared in the placebo group compared with none in the penicillin group. One newborn (1.7%) born to a mother with placebo prophylaxis developed septicemia, compared with none in the penicillin group. The outcomes of pregnancies complicated with PROM treated without penicillin or placebo were comparable with those in the placebo group. In addition, we compared somatic and psychomotor development of 159 children born to mothers with prolonged PROM (more than 12 hours; mean, 5.6 days; range, 14 to 1344 hours) with those of 43 children born at similar gestational age within 5 hours after PROM. No pulmonary sequelae could be linked to the long time period between PROM and delivery, but infants born soon after PROM more often (p less than 0.05) had cerebral palsy (8 of 43, 18.6%) than did infants born after prolonged PROM (7 of 159; 4.4%). We conclude that, in cases with PROM, penicillin prophylaxis decreases maternal and neonatal infectious morbidity and that the long interval between PROM and delivery does not impair the long-term outcome for these children.\n", + "output": "Conclusions: The decision to prescribe antibiotics for women with PROM is not clearcut. Benefits in some short-term outcomes (prolongation of pregnancy, infection, less abnormal cerebral ultrasound before discharge from hospital) should be balanced against a lack of evidence of benefit for others, including perinatal mortality, and longer term outcomes. If antibiotics are prescribed it is unclear which would be the antibiotic of choice.\nCo-amoxiclav should be avoided in women at risk of preterm delivery due to increased risk of neonatal necrotising enterocolitis." + }, + { + "input": "Study1: Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations. This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 microg/day) received budesonide/formoterol 160/4.5 microg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 microg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 microg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation, emergency room treatment or oral steroids (primary variable) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol (p=0.0034 and p=0.023 respectively; log-rank test). Exacerbation rates were 19, 16 and 12 events/100 patients/6 months for salmeterol/fluticasone, fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief, respectively, [rate reduction vs. fixed-dose salmeterol/fluticasone (0.61; 95% CI 0.49-0.76, p<0.001) and vs. fixed-dose budesonide/formoterol (0.72; 95% CI 0.57-0.90, p=0.0048)]. Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients. All treatments provided similar marked improvements in lung function, asthma control days and asthma-related quality of life. Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol.\nStudy2: Comparison of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler and fixed-dose fluticasone propionate/salmeterol dry powder inhaler in asthma patients. The adjustable-dose budesonide/formoterol dry powder inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI. We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized metered-dose inhaler versus the fixed-dose budesonide/formoterol pressurized metered-dose inhaler and the fixed-dose fluticasone propionate/salmeterol DPI. This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 microg x 2 inhalations [320/9 microg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 microg x 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 microg] twice daily to 2 inhalations [320/9 microg] once daily or 4 inhalations [640/18 microg] twice daily) for 6 months (treatment period 2). There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P < .001) was used with adjustable-dose versus fixed-dose budesonide/formoterol. All treatments were well tolerated. Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.\nStudy3: EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma. This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids. The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group. The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated. Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.\n", + "output": "Conclusions: Statistical imprecision in the effect estimates for exacerbations and serious adverse events do not enable us to conclude that either therapy is superior. The uncertainty around the effect estimates justify further trials to provide more definitive conclusions; the overall quality of evidence based on GRADE recommendations for the three primary outcomes and withdrawals due to serious adverse events was moderate. We rated the quality of evidence for mortality to be low. Results for lung function outcomes showed that the drugs were sufficiently similar that further research is unlikely to change the effects. No trials were identified in the under-12s and research in this population is a high priority. Evaluation of quality of life is a priority for future research." + }, + { + "input": "Study1: Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers. Hyperbaric oxygen therapy can be used as an adjunct to standard wound care in the treatment of diabetic patients with foot ulcers. We undertook a prospective, randomized investigation of the use of hyperbaric oxygen therapy versus standard therapy for the treatment of foot ulcers in diabetic patients. A number of demographic variables were analyzed in regard to wound healing. We noted that foot ulcers in patients in the hyperbaric oxygen therapy group were more likely to heal, and were more likely to undergo amputation distal to the metatarsophalangeal joint compared with those patients receiving standard therapy without hyperbaric oxygen. We feel that hyperbaric oxygen therapy should be considered a useful adjunct in the management of foot ulcers in diabetic patients.\nStudy2: Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. To evaluate the effectiveness of systemic hyperbaric oxygen therapy (s HBOT) in addition to a comprehensive protocol in decreasing major amputation rate in diabetic patients hospitalized for severe foot ulcer. From August 1993 to August 1995, 70 diabetic subjects were consecutively admitted into our diabetologic unit for foot ulcers. All the subjects underwent our diagnostic-therapeutic protocol and were randomized to undergo s-HBOT. Two subjects, one in the arm of the treated group and one in the arm of nontreated group, did not complete the protocol and were therefore excluded from the analysis of the results. Finally, 35 subjects received s-HBOT and another 33 did not. Of the treated group (mean session = 38.8 +/- 8), three subjects (8.6%) underwent major amputation: two below the knee and one above the knee. In the nontreated group, 11 subjects (33.3%) underwent major amputation: 7 below the knee and 4 above the knee. The difference is statistically significant (P = 0.016). The relative risk for the treated group was 0.26 (95% CI 0.08-0.84). The transcutaneous oxygen tension measured on the dorsum of the foot significantly increased in subjects treated with hyperbaric oxygen therapy: 14.0 +/- 11.8 mmHg in treated group, 5.0 +/- 5.4 mmHg in nontreated group (P = 0.0002). Multivariate analysis of major amputation on all the considered variables confirmed the protective role of s-HBOT (odds ratio 0.084, P = 0.033, 95% CI 0.008-0.821) and indicated as negative prognostic determinants low ankle-brachial index values (odds ratio 1.715, P = 0.013, 95% CI 1.121-2.626) and high Wagner grade (odds ratio 11.199, P = 0.022, 95% CI 1.406-89.146). s-HBOT, in conjunction with an aggressive multidisciplinary therapeutic protocol, is effective in decreasing major amputations in diabetic patients with severe prevalently ischemic foot ulcers.\nStudy3: Treatment of diabetic foot ulcers: a comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy. This study compared the effectiveness of extracorporeal shockwave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) in chronic diabetic foot ulcers. The ESWT group (39 patients/44 feet) received shockwave therapy twice per week for total six treatments. The HBOT group (38 patients/40 feet) received hyperbaric oxygen therapy daily for total 20 treatments. Evaluations included clinical assessment, blood flow perfusion scan and histopathological examination. The overall clinical results showed completely healed ulcers in 57% and 25% (P = 0.003); \u2265 50% improved ulcers in 32% and 15% (P = 0.071); unchanged ulcers in 11% and 60% (P < 0.001) and none worsened for the ESWT and the HBOT group respectively. The blood flow perfusion rates were comparable between the two groups before treatment (P = 0.245), however, significant differences were noted after treatment favoring the ESWT group (P = 0.002). Histopathological examination revealed considerable increases in cell proliferation and decreases in cell apoptosis in the ESWT group as compared to the HBOT group. ESWT is more effective than HBOT in chronic diabetic foot ulcers. ESWT-treated ulcers showed significant improvement in blood flow perfusion rate and cell activity leading to better healing of the ulcers relative to HBOT in chronic diabetic foot ulcers. Copyright \u00a9 2011 Elsevier Ireland Ltd. All rights reserved.\nStudy4: The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications. The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers. eighteen diabetic patients with ischaemic, non-healing lower-extremity ulcers were recruited in a double-blind study. Patients were randomly assigned either to receive 100% oxygen (treatment group) or air (control group), at 2.4 atmospheres of absolute pressure for 90 min daily (total of 30 treatments). healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group. The median decrease of the wound areas in the treatment group was 100% and in the control group was 52% (p=0.027). Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen, there was a potential saving in the total cost of treatment for each patient during the study. hyperbaric oxygen enhanced the healing of ischaemic, non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible.\nStudy5: Hyperbaric oxygen reduced size of chronic leg ulcers: a randomized double-blind study. To evaluate the effect of hyperbaric oxygen therapy on chronic wound healing, 16 otherwise healthy patients who had nondiabetic, chronic leg ulcers with no large vessel disease were included in a double-blind study. Patients were grouped according to age and then randomly assigned to two groups breathing either air or oxygen at 2.5 atmospheres of absolute pressure for 90 minutes 5 days per week for a total of 30 treatments. The wound area was copied onto transparent film covering the wound and then measured using only one matching wound from each patient. The mean decrease of the wound areas at weeks 2, 4, and 6 in the oxygen group were 6 percent (SD +/- 14), 22 percent (SD +/- 13), and 35.7 percent (SD +/- 17), respectively, and in the air group, 2.8 percent (SD +/- 11), 3.7 percent (SD +/- 11), and 2.7 percent (SD +/- 11), respectively, giving a p value less than 0.05 at week 4, and a p value less than 0.001 at week 6 between the groups using the Mann-Whitney U test. These data indicate that hyperbaric oxygen therapy may be used as a valuable adjunct to conventional therapies when nondiabetic wounds do not heal.\nStudy6: Hyperbaric oxygen therapy in diabetic foot. To study the effect of hyperbaric oxygen therapy in chronic diabetic foot lesions, a prospective controlled study was undertaken. Thirty diabetics with chronic foot lesions were randomised to study group (conventional management and 4 sessions of hyperbaric oxygen therapy) and control group (conventional management). The patients were assessed for average hospital stay, control of infection and wound healing. The control of infection spread was quicker. Positive cultures decreased from initial 19 to 3 in study group as against from 16 to 12 in the control group. (p < 0.05). This difference was most pronounced for Escherichia coli. Also, the need for major amputation was significantly less in the study group (n = 2) as against the control group (n = 7) (p < 0.05). The average hospital stay was not affected. We conclude that hyperbaric oxygen therapy can be safely used and is beneficial as an adjuvant therapy in chronic diabetic foot lesions.\nStudy7: Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers. From 1999 to 2000, 28 patients (average age 60.2 +/- 9.7 years, diabetes duration 18.2 +/- 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline. HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO(2)) measured on the dorsum of the feet of the patients was 45.6 +/- 18.1 mmHg (room air). During HBO, the TcPO(2) measured around the ulcer increased significantly from 21.9 +/- 12.1 to 454.2 +/- 128.1 mmHg (P < 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control group [P = 0.037]). Such a difference could no longer be observed at day 30 (48.1 +/- 30.3 vs. 41.7 +/- 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group. In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations.\nStudy8: Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Chronic diabetic foot ulcers are a source of major concern for both patients and health care systems. The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) in the management of chronic diabetic foot ulcers. The Hyperbaric Oxygen Therapy in Diabetics with Chronic Foot Ulcers (HODFU) study was a randomized, single-center, double-blinded, placebo-controlled clinical trial. The outcomes for the group receiving HBOT were compared with those of the group receiving treatment with hyperbaric air. Treatments were given in a multi-place hyperbaric chamber for 85-min daily (session duration 95 min), five days a week for eight weeks (40 treatment sessions). The study was performed in an ambulatory setting. Ninety-four patients with Wagner grade 2, 3, or 4 ulcers, which had been present for >3 months, were studied. In the intention-to-treat analysis, complete healing of the index ulcer was achieved in 37 patients at 1-year of follow-up: 25/48 (52%) in the HBOT group and 12/42 (29%) in the placebo group (P = 0.03). In a sub-analysis of those patients completing >35 HBOT sessions, healing of the index ulcer occurred in 23/38 (61%) in the HBOT group and 10/37 (27%) in the placebo group (P = 0.009). The frequency of adverse events was low. The HODFU study showed that adjunctive treatment with HBOT facilitates healing of chronic foot ulcers in selected patients with diabetes.\n", + "output": "Conclusions: In people with foot ulcers due to diabetes, HBOT significantly improved the ulcers healed in the short term but not the long term and the trials had various flaws in design and/or reporting that means we are not confident in the results. More trials are needed to properly evaluate HBOT in people with chronic wounds; these trials must be adequately powered and designed to minimise all kinds of bias." + }, + { + "input": "Study1: De-functioning stomas: a prospective controlled trial comparing loop ileostomy with loop transverse colostomy. Patients undergoing colorectal surgery who required a defunctioning stoma were randomly allocated to receive either a loop ileostomy (n = 23) or transverse loop colostomy (n = 24). Assessment was made during construction, immediately postoperatively, during the period of outpatient supervision and before and after stoma closure. The ileostomy was associated with significantly less odour than the colostomy (P less than 0.01) and required significantly less appliance changes (P less than 0.05). Furthermore eleven patients (58 per cent) with a colostomy experienced three or more problems with stoma management compared with only three patients (18 per cent) with an ileostomy (P less than 0.05). Wound infection was also significantly more common after closure of the colostomy compared with the ileostomy. Both types of stoma were demonstrated objectively to defunction the distal bowel almost completely. These results indicate that a loop ileostomy is the procedure of first choice when a stoma is needed to defunction the distal colorectum.\nStudy2: Randomized clinical trial comparing loop ileostomy and loop transverse colostomy for faecal diversion following total mesorectal excision. The aim of this study was to compare loop ileostomy and loop transverse colostomy as the preferred mode of faecal diversion following low anterior resection with total mesorectal excision for rectal cancer. Patients who required proximal diversion after low anterior resection with total mesorectal excision were randomized to have either a loop ileostomy or a loop transverse colostomy. Postoperative morbidity, stoma-related problems and morbidity following closure were compared. From April 1999 to November 2000, 42 patients had a loop ileostomy and 38 had a loop transverse colostomy constructed following low anterior resection. Postoperative intestinal obstruction and prolonged ileus occurred more commonly in patients with an ileostomy (P = 0.037). There was no difference in time to resumption of diet, length of hospital stay following stoma closure and incidence of stoma-related complications after discharge from hospital. A total of seven patients had intestinal obstruction from the time of stoma creation to stoma closure (six following ileostomy and one following colostomy; P = 0.01). Intestinal obstruction and ileus are more common after loop ileostomy than loop colostomy. Loop transverse colostomy should be recommended as the preferred method of proximal faecal diversion.\nStudy3: Temporary decompression after colorectal surgery: randomized comparison of loop ileostomy and loop colostomy. Loop ileostomy or loop transverse colostomy for temporary decompression of a left colonic anastomosis represents an important issue in abdominal surgery. A randomized study, comparing loop ileostomy (n = 37; group 1) or loop transverse colostomy (n = 39; group 2), was conducted. Patients were followed from construction to closure of the stoma. Age, weight, sex and indication for surgery were similar in both groups. After stoma construction complications were reported in nine of 37 patients in group 1 and in one of 39 in group 2 (P < 0.01), leading to postoperative death in five of 37 in group 1 and one of 39 in group 2. In the period between stoma construction and closure significant differences were observed only in prolapse rate (one of 32 group 1, 16 of 38 group 2; P < 0.01), need for temporary adaptation of clothing (eight of 32 group 1, 22 of 38 group 2; P < 0.01) and dietary guidelines (23 of 32 group 1, four of 38 group 2; P < 0.01). One patient died in group 1 and four in group 2; the deaths were not stoma related. After stoma closure eight of 29 patients in group 1 had complications and there were two deaths compared with three of 32 and no deaths in group 2. Both types of stoma carry a high complication rate with a considerable associated mortality rate. The interval between stoma construction and closure has substantial impact on social and economic status. Based on all three phases studied, routine use of transverse colostomy is advised if decompression of the left colon is indicated.\n", + "output": "Conclusions: The best available evidence for decompression of colorectal anastomosis, either use of loop ileostomy or loop colostomy, could not be clarified from this review. So far, the results in terms of occurrence of postoperative stoma prolapse support the choice of loop ileostomy as a technique for fecal diversion for colorectal anastomosis, but large scale RCT's is needed to verify this." + }, + { + "input": "Study: Prospectively randomized trial comparing the pseudoaccommodation of the AMO ARRAY multifocal lens and a monofocal lens. A prospective trial was set up to compare pseudoaccommodation. Fifty patients were randomized into two groups. Group 1 comprised 25 patients who had a monofocal implant and a postoperative refractive aim of -0.3 to -1.3 diopter (D) spherical equivalent and an astigmatic component between 1.0 and 1.75 D cylinder. Group 2 comprised 25 patients who had a new multizone refraction style multifocal implant and a postoperative refractive aim of -0.5 to +0.5 D spherical equivalent and an astigmatic component of less than 1.0 D cylinder. Eighty percent of postoperative refractions in Group 1 and 88% in Group 2 were within 0.5 D either side of the refractive aim. Forty-eight percent of Group 1 and 72% of Group 2 could see both 20/40 and J3 unaided. Four percent of Group 1 and 84% of Group 2 could read J2 with the distance correction. Sixteen percent of Group 1 and 48% of Group 2 could read J2 at 25 cm unaided (P = .03). Sixty-four percent of Group 1 and 88% of Group 2 stated they could manage daily activities without glasses. However, 88% of Group 1 and 52% of Group 2 requested reading glasses to improve clarity of the smallest print.\n", + "output": "Conclusions: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs. Whether that improvement outweighs the adverse effects of multifocal IOLs will vary between patients. Motivation to achieve spectacle independence is likely to be the deciding factor." + }, + { + "input": "Study1: Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently, no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction; however, over the past years, procalcitonin (PCT) is the first among a large array of inflammatory variables that offers this possibility. The present study aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients. All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible. Patients were randomly assigned to either a PCT-guided (study group) or a standard (control group) antibiotic regimen. Antibiotic therapy in the PCT-guided group was discontinued, if clinical signs and symptoms of infection improved and PCT decreased to <1 ng/ml or the PCT value was >1 ng/ml, but had dropped to 25 to 35% of the initial value over three days. In the control group antibiotic treatment was applied as standard regimen over eight days. A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high-grade suspected infections were enrolled in this study. In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly. The control group comprised 53 patients with a standardized duration of antibiotic therapy over eight days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls (5.9 +/- 1.7 versus 7.9 +/- 0.5 days, P < 0.001) without negative effects on clinical outcome. Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine. ANNOTATION: Results were previously published in German in Anaesthesist 2008; 57: 571-577 (PMID: 18463831). ISRCTN10288268.\nStudy2: Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay. 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat. Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%). Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.\nStudy3: [The value of serum procalcitonin in treatment of community acquired pneumonia in outpatient]. To evaluate the value of serum procalcitonin (PCT) on antibiotic use in treatment of community acquired pneumonia (CAP) in outpatient. From November 2006 to February 2008, a total of 127 patients with CAP in outpatient were randomly assigned into two groups: PCT group (n = 63) and control group (n = 64). PCT levels of all patients were measured after study admission. On the base of similarly normal treatment, the control group received antibiotics according to the attending physicians and the PCT group were treated with antibiotics according to serum PCT levels: antibiotic treatment was applied with PCT level > or = 0.25 microg/L and was discouraged with PCT level < 0.25 microg/L. Clinical efficacy, rate of antibiotics use, duration courses and costs of antibiotics were observed. Clinical efficacy of the PCT group was similar with the control group (92.1% vs 87.5%, P > 0.05); rate and costs of antibiotics use was lower, antibiotic duration of the PCT group was shorter than that of the control group (P < 0.05, P < 0.001, P < 0.001). PCT could be used in treatment of CAP for antibiotic use in outpatient, which may reduce antibiotic use, shorten antibiotic duration and lower costs of antibiotic.\nStudy4: Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules. Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03). Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.\nStudy5: Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine. The biochemical variable procalcitonin (PCT) is known to indicate systemically relevant bacterial infections with high accuracy. In the present study, we aimed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. Patients were randomly assigned to a PCT-guided or a control group requiring antibiotic treatment. All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum. In the PCT-guided group, antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either <1 ng/ml or decreased to <35% of the initial concentration within three consecutive days. In the control group, antibiotic treatment was directed by empirical rules. The PCT-guided group (n = 14 patients) and the control group (n = 13 patients) did not differ in terms of biological variables, underlying diseases, and overall disease severity. PCT guidance led to a significant reduction of antibiotic treatment from 6.6 +/- 1.1 days (mean +/- SD) compared with 8.3 +/- 0.7 days in control patients (p < 0.001) along with a reduction of antibiotic treatment costs of 17.8% (p < 0.01) without any adverse effects on outcome. Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine.\nStudy6: Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.\n", + "output": "Conclusions: Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARI was not associated with higher mortality rates or treatment failure. Antibiotic consumption was significantly reduced across different clinical settings and ARI diagnoses. Further high-quality research is needed to confirm the safety of this approach for non-European countries and patients in intensive care. Moreover, future studies should also establish cost-effectiveness by considering country-specific costs of procalcitonin measurement and potential savings in consumption of antibiotics and other healthcare resources, as well as secondary cost savings due to lower risk of side effects and reduced antimicrobial resistance." + }, + { + "input": "Study: Safety and therapeutical benefit of hemicraniectomy combined with mild hypothermia in comparison with hemicraniectomy alone in patients with malignant ischemic stroke. Both for hemicraniectomy and for hypothermia, several reports describe a beneficial effect in patients with malignant supratentorial cerebral ischemia. We compared the safety and the clinical outcome in patients with a malignant supratentorial infarction who were treated with hemicraniectomy alone (HA) or received a combination therapy with hemicraniectomy and hypothermia of 35 degrees C (HH), respectively. In a prospective and randomized study, 25 consecutive patients were treated after an ischemic infarction of more than two thirds of one hemisphere by HA (n=13 patients) or the HH combination therapy (n=12 patients). Safety parameters were compared between both treatment groups, the clinical outcome was assessed during treatment and after 6 months. Age, cranial CT or MRI findings, initial National institutes of Health Stroke Scale Score (NIHSSS) and level of consciousness were not significantly different between both groups. Hemicraniectomy was performed within 15+/- 6 h after the ischemic event. Hypothermia was induced immediately after surgery. Overall mortality was 12% (2/13 vs. 1/12 in the two groups), but none of these 3 patients died due to treatment-related complications. There were no severe side effects of hypothermia. Duration of need for intensive care or for mechanical ventilation and infectious status did not differ significantly between both groups, but the need for catecholamine application was increased in the HH group. The clinical outcome showed a tendency for a better outcome in the HH compared with the HA group with respect to status after 6 months, as assessed by the NIHSSS (10+/-1 vs. 11+/-3, p<0.08). The present study suggests that a combined therapy of mild hypothermia and hemicraniectomy in malignant brain infarction does not imply additional risks by side effects and improves functional outcome as compared with hemicraniectomy alone. Copyright (c) 2006 S. Karger AG, Basel.\n", + "output": "Conclusions: Although there is some evidence that mild hypothermia is safe, its effectiveness is not clear when compared with normothermia. We need to perform more clinical trials in order to establish the benefit, if any, of hypothermia for cerebral protection during brain surgery before making firm recommendations for the routine use of this intervention." + }, + { + "input": "Study1: Levodopa or dopamine agonists, or deprenyl as initial treatment for Parkinson's disease. A randomized multicenter study. Objectives: levodopa improves the quality of life in parkinsonian patients, however long term response is compromised by the emergence of motor fluctuations and dyskinesias. The aim of this study was to compare the occurrence of motor fluctuations and dyskinesias in previously untreated patients assigned to receive levodopa, a dopamine agonist or deprenyl.Thirty-five neurological departments in Italian hospitals participated in this randomized open trial. Patients with Parkinson's disease, who required the initiation of an effective antiparkinsonian treatment, were randomly assigned to receive levodopa, dopamine agonists or deprenyl. The end-points were motor dyskinesias and motor fluctuations occurring in a median follow-up period of about 3years.After a median follow-up of 34months, motor fluctuations and dyskinesias were less frequent in patients assigned to a dopamine agonist or deprenyl than in patients assigned to levodopa (relative risk [RR] 0.5, 95% confidence interval [95% CI] 0.3-0.8, and RR=0.6, 95% CI 0.3-0.9, respectively), but dopamine agonists were less effective and less well tolerated than levodopa. The lower frequency of motor fluctuations in patients assigned to deprenyl was no longer statistically significant when prognostic predictors were considered in a multivariable analysis. Long-term mortality did not differ in the three arms of the study. Dopamine agonists and deprenyl can be considered as an alternative to levodopa for starting treatment in Parkinson's disease patients. However, on clinical grounds, only small advantages are expected over the traditional therapy initiation with levodopa.\nStudy2: Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease: a two-year follow-up study of previously untreated patients. The cognitive effects of dopaminergic treatment in Parkinson's disease (PD) are still controversial. To evaluate, in previously untreated patients with PD, whether chronic dopaminergic stimulation produces significant cognitive changes; whether they are sustained beyond the period of a few months; and whether the cognitive status of two motor-comparable groups is differently affected by levodopa and pergolide. Parallel, randomized open study with blind neuropsychologic evaluation of 20 consecutive de novo patients with PD before and 3, 6, 12, 18, and 24 months after monotherapy with levodopa (n = 10) or pergolide (n = 10; 6-month monotherapy; pergolide + levodopa thereafter). Both treatments were associated with a significant improvement in motor scores and in tests assessing learning and long-term verbal and visual memory, visuospatial abilities, and various frontal tasks. While improvement in motor scores persisted, improvement in activities of daily living and in semantic fluency, Luria's rhythm and motor and long-term memory tests was not sustained at the 24-month examination. Further, performance on attentional, short-term memory, and the Stroop tests did not change over the course of the study. Both treatments were associated with incomplete but long-lasting (18 mos) improvement in many cognitive tasks which declined thereafter, suggesting that dopaminergic replacement is not enough to compensate for all cognitive deficits of PD.\nStudy3: Trial of subtherapeutic pergolide in de novo Parkinson's disease. The effect of pergolide 25 mug twice daily on levodopa initiation was assessed in a randomized, placebo-controlled, parallel group, double-blind multicenter trial in 106 untreated early Parkinson's disease patients. The primary endpoint of mean time until levodopa was 520 days (95% confidence interval [CI], 422-618 days) for pergolide versus 434 days (95% CI, 358-609 days) for placebo. However, this increase of 86 days for pergolide was not statistically significant. The wash-in effect of pergolide was significant at 6 weeks (change in mean Unified Parkinson's Disease Rating Scale [UPDRS] 2 and 3 was -0.1 [95% CI, -1.4 to 1.3] for pergolide vs. 2.2 [95% CI, 1.1-3.3] for placebo). At termination, the change from baseline in mean UPDRS 2 and 3 score was 11.4 (95% CI, 8.8-14) for pergolide and 14.6 (95% CI, 12-17.2) for placebo (P=0.08). There was no significant change in UPDRS 2 and 3 for the 83 patients achieving the planned 4-week washout at termination (pergolide 1.2 [95% CI, -0.8 to 3.2] vs. placebo 0.0 [95% CI, -1.6 to 1.6]. Adverse events were infrequent and occurred equally for pergolide and placebo. The study shows no evidence of a neuroprotective effect but indicates a mild symptomatic benefit from pergolide at a dose normally considered subtherapeutic.\nStudy4: A double-blind study of bromocriptine and L-dopa in de novo Parkinson's disease. Short-term results. The first phase of a longitudinal multicenter study comparing bromocriptine and L-dopa (as Sinemet) as de novo therapy for Parkinson's disease using a double-blind randomized design has recently been completed. Over a period of 5.5 months, bromocriptine and L-dopa were equipotent in reducing functional and neurological disability. These observations complement and extend earlier studies and suggest a role for bromocriptine as de novo therapy of Parkinson's disease.\nStudy5: Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. Multicenter, parallel-group, double-blind, randomized controlled trial. Academic movement disorders clinics at 22 sites in the United States and Canada. Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.\nStudy6: Efficacy of piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study. Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on alpha2A and alpha2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: -10.0 points in the piribedil group vs. -6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients. Copyright 2003 Movement Disorder Society\n", + "output": "Conclusions: This meta-analysis confirms that motor complications are reduced with dopamine agonists compared to levodopa, but also establishes that other important side-effects are increased and symptom control is poorer with agonists. Larger, long-term comparative trials assessing patient-rated quality of life are needed to assess more reliably the balance of benefits and risks of dopamine agonists compared to levodopa." + }, + { + "input": "Study1: Optimal weekly frequency of 308-nm excimer laser treatment in vitiligo patients. Recently the beneficial effect of excimer laser treatment has been reported for patients with vitiligo. The influence of treatment frequency on this effect is not clear. To determine the optimal frequency of 308-nm excimer laser therapy for vitiligo. In this prospective, university-based hospital study over 12 weeks we enrolled 14 patients. Each had at least three stable vitiligo lesions in the same body area. The three stable vitiligo lesions in each subject were randomly assigned to receive excimer laser treatment once (1 x), twice (2 x) and three times (3 x) weekly, respectively. The initial ultraviolet (UV) dose was 50 mJ cm(-2) less than the 308-nm minimal erythematous dose in vitiligo skin. The UV dose was increased at each treatment session according to the erythematous response to the previous treatment. Thirteen subjects were treated for at least 6 weeks; seven were treated for all 12 weeks. At 6 weeks, the repigmentation rates for treated lesions were 8% (1/13) after 1 x weekly treatment, 23% (3/13) after 2 x weekly treatment and 62% (8/13) after 3 x weekly treatment (P = 0.0134; 3 x vs. 1 x weekly); at 12 weeks, these rates were 46% (6/13), 62% (8/13) and 69% (9/13), respectively (P = NS; 3 x vs. 1 x weekly). Repigmentation initiation correlated with treatment number, regardless of frequency (P = NS). As shown by Kaplan-Meier analysis, repigmentation occurred earliest in the most frequently treated lesions (P = 0.0336). At 12 weeks, the projected repigmentation rates for 1 x, 2 x and 3 x weekly treatment approached each other (60%, 79% and 82%, respectively); the mean repigmentation grades (on a scale of 0-5) for 1 x, 2 x and 3 x weekly treatment were 1.7, 2.4 and 3.3, respectively (P = 0.018; 3 x vs. 1 x weekly). Laser-induced repigmentation persisted in most cases over the entire follow-up of 12 months after the end of treatment. 308-nm excimer laser therapy is effective against vitiligo. Although repigmentation occurs fastest with 3 x weekly treatment, the ultimate repigmentation initiation seems to depend entirely on the total number of treatments, not their frequency. However, treatment periods of more than 12 weeks may be necessary to obtain a satisfactory clinical repigmentation, particularly when vitiligo lesions are treated only 1 x or 2 x compared with 3 x weekly.\nStudy2: Targeted broadband ultraviolet b phototherapy produces similar responses to targeted narrowband ultraviolet B phototherapy for vitiligo: a randomized, double-blind study. Narrowband ultraviolet B (NB-UVB) phototherapy, with a 308-nm xenon chloride excimer laser, and targeted UVB phototherapy have produced encouraging therapeutic results for vitiligo. However, very few studies employing broadband UVB exist. Moreover, there has been no direct comparison study between broadband UVB and NB-UVB for the treatment of vitiligo. The aims of this study were to compare the repigmenting efficacy of targeted broadband UVB phototherapy with that of NB-UVB in an equi-erythemogenic manner. Twenty identical vitiliginous lesions from 10 patients were randomly allocated to receive either targeted broadband UVB or targeted NB-UVB phototherapy. UV fluences were started at 50% of the minimal erythema dose detected within the vitiliginous patches, then increased gradually, in the same manner, to ensure equi-erythemogenic comparison. Treatments were carried out twice weekly for 12 weeks. The results show that grade 1, i.e. 1-25% repigmentation, to grade 2, 26-50% repigmentation, occurred in 6 of 10 subjects. Responses in terms of repigmentation, de-pigmentation, or lack thereof, were similar between lesions receiving broadband and NB-UVB phototherapy. Onset of repigmentation occurred as early as 4 weeks of treatment in most subjects. Treatments were well tolerated, with only minimal erythema and hyperpigmentation. The study was carried out in a small number of patients with skin types III, IV and V. The irradiation device was a targeted UVB device and thus the results may not be applicable to other light sources, such as the excimer laser or total-body irradiation cabinets. In conclusion, targeted broadband UVB produces similar clinical responses to targeted NB-UVB in the treatment of the non-segmental type of vitiligo.\nStudy3: Comparison of 0.05% clobetasol propionate cream and topical Puvasol in childhood vitiligo. nan\nStudy4: Combination of PUVAsol and topical calcipotriol in vitiligo. A large variety of therapeutic agents are being tried for the treatment of vitiligo, but psoralens continue to be mainstay of treatment although they are not uniformly effective. Recent advances in pathophysiology have established a perturbed calcium homeostasis in affected skin, and melanocytes were shown to express vitamin D3 receptors. The purpose of present study was to determine the efficacy of the combination of PUVAsol with topical calcipotriol in the treatment of vitiligo. Nineteen patients with essentially bilateral symmetrical lesions were enrolled in a randomized, double-blind, right/left comparative study of 18 months duration. An oral dose of 0.6 mg/kg 8-methoxypsoralen was given 2 h before exposure to sunlight thrice weekly to all patients. The patients were advised to apply calcipotriol (50 microgram/g) on one side of the body and placebo ointment over the lesions on the other side twice daily. At the end of 6 months, 12 patients (70%) showed marked to complete improvement on calcipotriol-treated sides as compared to 6 patients (35%) showing similar improvement on placebo-treated sides (p <0.05). At the end of treatment, 13 patients (76%) showed marked improvement in calcipotriol-treated lesions whereas 9 patients (53%) showed moderate to marked improvement in placebo-treated lesions. The repigmentation of hands and feet was much better with the combination of PUVAsol and calcipotriol. The combination of PUVA and calcipotriol is highly effective and works faster and may be used for shortening the therapy with PUVA in the treatment of vitiligo.\nStudy5: The efficacy of pimecrolimus 1% cream plus narrow-band ultraviolet B in the treatment of vitiligo: a double-blind, placebo-controlled clinical trial. Recently, narrow-band ultraviolet B (NB-UVB) and topical immunomodulators have been successfully used in the treatment of vitiligo. To determine whether the combination of pimecrolimus with NB-UVB accelerates the response time and/or improves the degree of response in patients with vitiligo. Sixty-eight patients with vitiligo enrolled in this randomized, double-blind, placebo-controlled study. The patients were randomized into two groups and treated with NB-UVB plus either pimecrolimus or placebo for 3 months. Tri-weekly radiation was started at 280 mJ/cm(2), with 15% increments for each subsequent treatment until erythema was reported or a maximum of 800 mJ/cm was achieved. At baseline and 6 and 12 weeks after commencement of therapy, vitiliginous patches were measured. Fifty patients completed the 3-month study. No significant side effects except self-limited erythema and pruritus were observed. After 12 weeks of treatment, repigmentation of the facial lesions was higher in patients treated with combined pimecrolimus and NB-UVB compared with the placebo plus NB-UVB group (64.3 vs 25.1%) (p < 0.05%). There was no statistically significant difference in the repigmentation rate between the two groups on other body areas. On the face, NB-UVB works better if combined with pimecrolimus 1% cream rather than used alone.\nStudy6: Comparison of systemic PUVA and NB-UVB in the treatment of vitiligo: an open prospective study. Vitiligo is a common pigmentary disorder with great cosmetic and psychological morbidity. No treatment available is a definitive cure. Systemic psoralen and ultraviolet A (PUVA) has been the mainstay of treatment. Narrow-band ultraviolet B (NB-UVB) has been recently introduced. Although retrospective comparative study of systemic PUVA and NB-UVB has been published from our centre, no prospective study has been reported to date. To investigate the position of NB-UVB vis-\u00e0-vis PUVA in terms of efficacy, time to repigment and adverse effects and to help decide if one therapy has an advantage over another in the treatment of vitiligo. It was a randomized, open, prospective study of 50 patients divided equally in TMP PUVA and NB-UVB groups. The study period was from January 2004 to June 2005. The mean degree of repigmentation attained in the NB-UVB group was 52.24% over a mean treatment period of 6.3 months, whereas in the PUVA group it was 44.7% in a mean period of 5.6 months (P=0.144). After excluding the results of therapy-resistant sites, that is, hands and feet, the mean degree of repigmentation in the NB-UVB group was 67.57%, whereas in the PUVA group it was 54.2% (P=0.007). NB-UVB performed better in comparison to TMP PUVA in terms of mean total repigmentation when traditionally considered therapy-resistant sites were excluded.\nStudy7: Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study. Vitiligo is an acquired skin disorder that is characterized by well-defined, often symmetric white patches. Although current therapeutic modalities are directed toward increasing melanocyte melanin production, few treatment modalities address the immunologic nature of the disease. To determine whether excimer laser, a known therapeutic modality, in combination with tacrolimus, a topical immunomodulator, accelerate response time and/or improve the degree of response in patients with this disorder. Eight subjects diagnosed with vitiligo were recruited to participate in this institutional review board-approved double-blind, placebo-controlled study. Twenty-four symmetric vitiliginous patches (elbows, knees) from eight subjects received excimer laser treatment three times per week for 24 treatments or 10 weeks. Additionally, topical tacrolimus 0.1% ointment (Protopic) and placebo (Aquaphor) were applied to randomized patches (left or right) twice daily throughout the length of the trial. Vitiliginous patches were monitored with photographs at baseline, every 2 weeks, and 6 months after treatment. Biopsies were performed on subjects with significant results. Twenty vitiliginous patches from six subjects qualified for evaluation. Fifty percent of patches treated with combination excimer laser and tacrolimus achieved a successful response (75% repigmentation) compared with 20% for the placebo group. Subjects who responded successfully repigmented faster (19%) with combination therapy compared with excimer laser alone. Additionally, three subjects experienced transient hyperpigmentation in lesions treated with combination therapy. Combining topical immunomodulators with known phototherapeutic modalities may represent a key advancement in the treatment of disease.\nStudy8: Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract: a randomized double-blind placebo-controlled study. The first choice treatment for vitiligo vulgaris is narrow-band UVB (NB-UVB), but no satisfactory treatment exists. To investigate if Polypodium leucotomos, an antioxidative and immunomodulatory plant extract, improves NB-UVB-induced repigmentation. Fifty patients with vitiligo vulgaris randomly received 250 mg oral P. leucotomos or placebo three times daily, combined with NB-UVB twice weekly for 25-26 weeks. Repigmentation was higher in the P. leucotomos group vs. placebo in the head and neck area (44% vs. 27%, P = 0.06). Small repigmentation increases (P = n.s.) were observed for the trunk (6% increased repigmentation), extremities (4%), and hands and feet (5%) in the P. leucotomos group vs. placebo. Patients attending more than 80% of required NB-UVB sessions showed increased repigmentation in the head and neck area in the P. leucotomos group vs. placebo (50% vs. 19%, P < 0.002); no significant differences were seen in the other body areas. Patients with skin types 2 and 3 showed more repigmentation in the head and neck area in the P. leucotomos group vs. placebo (47% vs. 21%, P = 0.01), and no significant differences were seen in the other body areas. No conclusions could be drawn on skin types 4 and 5 due to low patient numbers. There is a clear trend towards an increase in repigmentation of vitiligo vulgaris affecting the head and neck area when NB-UVB phototherapy is combined with oral P. leucotomos. This effect may be more pronounced in light skin types.\nStudy9: Narrow-band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of vitiligo. Vitiligo is a common, idiopathic, acquired, depigmenting disease characterized by loss of normal melanin pigments in the skin. The most interesting treatment methods for extensive vitiligo involve psoralen plus ultraviolet A (PUVA) therapy and ultraviolet (UV)-B phototherapy, particularly narrow-band UV-B. In this randomized and comparative study, we investigated the safety and efficacy of narrow band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of generalized vitiligo. Of the 40 vitiligo patients enrolled in the study, 15 were treated with the calcipotriol plus narrow-band UV-B (NBUVB) and 25 with narrow band UV-B alone. The patients were randomized into two NBUVB treatment groups. The first group, consisting of 24 patients (all male), received only NBUVB treatment; the second group, consisting of 13 patients (all male) applied 0.05% topical calcipotriol ointments twice daily. Both groups were irradiated with NBUVB (311 nm). In the NBUVB group, the percentage of the body surface affected was reduced from 27.21 +/- 10.41% to 16.25 +/- 8.54% after a mean of 30 treatment sessions. The mean repigmentation percentage was 41.6 +/- 19.4%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 19 patients (19/24; 79.17%) had clinically good results. In the NBUVB plus calcipotriol group, the percentage of the body surface affected was reduced from 23.35 +/- 6.5% to 13.23 +/- 7.05% after a mean of 30 treatment sessions. The mean repigmentation percentage was 45.01 +/- 19.15%. In clinical evaluation (moderate and marked/complete response was accepted as an effective treatment), 10 patients (10/13; 76.92%) had clinically good results. Statistically significant intragroup reductions from the baseline percentage of the body surface affected were seen at the endpoint of treatment for the two treatment groups (P < 0.001). However, there was no statistically significant difference between the two treatment groups at the end of therapy with respect to the reduction of repigmentation rates (P > 0.05). The present study reconfirmed the efficacy of NBUVB phototherapy in vitiligo. It can be a therapeutic option considered in the management of patients with vitiligo. However, addition of topical calcipotriol to NBUVB did not show any advantage.\nStudy10: Ultraviolet A in vitiligo. Both types of Ultraviolet (UV), UVB (290-320 nm) and UVA (320-400 nm), produce increased pigmentation or tanning. However, no evaluation of UVA alone in the treatment of vitiligo has been reported. Therefore, it was the purpose of this work to study the pigmentogenic effect of UVA (5 and 15 J/cm(2)) in vitiligo. The study included 20 randomly selected patients with vitiligo involving more than 30% of the body surface area with a bilateral/symmetrical distribution. They were equally divided into two groups each of 10 patients. All patients received three weekly sessions of UVA, 15 J/cm(2) in group I and 5 J/cm(2) in group II, a total of 48 sessions over 16 weeks. Overall pigmentation of 60% and above was recorded in 50% and 10% of patients in groups I and II, respectively. We conclude that broadband UVA alone, without psoralens, and in appropriate doses may be of important therapeutic value in vitiligo.\n", + "output": "Conclusions: This review has found some evidence from individual studies to support existing therapies for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures. There is a need for follow-up studies to assess permanence of repigmentation as well as high quality randomised trials using standardised measures and which also address quality of life." + }, + { + "input": "Study1: Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. Chronic reflex sympathetic dystrophy (also called the complex regional pain syndrome) is a painful, disabling disorder for which there is no proven treatment. In observational studies, spinal cord stimulation has reduced the pain associated with the disorder. We performed a randomized trial involving patients who had had reflex sympathetic dystrophy for at least six months. Thirty-six patients were assigned to receive treatment with spinal cord stimulation plus physical therapy, and 18 were assigned to receive physical therapy alone. The spinal cord stimulator was implanted only if a test stimulation was successful. We assessed the intensity of pain (on a visual-analogue scale from 0 cm [no pain] to 10 cm [very severe pain]), the global perceived effect (on a scale from 1 [worst ever] to 7 [best ever]), functional status, and the health-related quality of life. The test stimulation of the spinal cord was successful in 24 patients; the other 12 patients did not receive implanted stimulators. In an intention-to-treat analysis, the group assigned to receive spinal cord stimulation plus physical therapy had a mean reduction of 2.4 cm in the intensity of pain at six months, as compared with an increase of 0.2 cm in the group assigned to receive physical therapy alone (P<0.001 for the comparison between the two groups). In addition, the proportion of patients with a score of 6 (\"much improved\") for the global perceived effect was much higher in the spinal cord stimulation group than in the control group (39 percent vs. 6 percent, P=0.01). There was no clinically important improvement in functional status. The health-related quality of life improved only in the 24 patients who actually underwent implantation of a spinal cord stimulator. Six of the 24 patients had complications that required additional procedures, including removal of the device in 1 patient. In carefully selected patients with chronic reflex sympathetic dystrophy, electrical stimulation of the spinal cord can reduce pain and improve the health-related quality of life.\nStudy2: Spinal cord stimulation versus reoperation for failed back surgery syndrome: a prospective, randomized study design. Retrospectively reported results of spinal cord stimulation compare favorably with those of neurosurgical treatment alternatives for the treatment of failed back surgery syndrome, including reoperation and ablative procedures. There has been no direct prospective comparison, however, between SCS and other techniques for pain management. Therefore, we have designed a prospective, randomized comparison of spinal cord stimulation and reoperation in patients with persistent radicular pain, with and without low back pain, after lumbosacral spine surgery. Patients selected for reoperation by standard criteria are randomly assigned to initial treatment by one or the other technique. The primary outcome measure is the frequency of crossover to the alternative procedure, if the results of the first have been unsatisfactory after 6 months. Results for the first 27 patients reaching the 6-month crossover point show a statistically significant (p = 0.018) advantage for spinal cord stimulation over reoperation. Many other potentially important outcome measures will now be followed long-term as a larger overall study population accumulates.\n", + "output": "Conclusions: Although there is limited evidence in favour of SCS for Failed Back Surgery Syndrome and Complex Regional Pain Syndrome Type I, more trials are needed to confirm whether SCS is an effective treatment for certain types of chronic pain. In addition, there needs to be a debate about trial designs that will provide the best evidence for assessing this type of intervention." + }, + { + "input": "Study1: Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease. Patients with symptomatic peripheral arterial occlusive disease have a claudication-limited peak exercise performance that is improved with exercise training. The effects of training on skeletal muscle metabolism were evaluated in 26 patients with claudication, randomized into a 12-wk program of treadmill training (enhances muscle metabolic activity in normal subjects), strength training (stimulates muscle hypertrophy in normal subjects), or a nonexercising control group. Gastrocnemius muscle biopsies were performed at rest and before and after training. After 12 wk, only treadmill training improved peak exercise performance and peak oxygen consumption. Treadmill training did not alter type I or type II fiber area and did not increase citrate synthase activity but was associated with an increase in the percentage of denervated fibers (from 7.6 +/- 5.4 to 15.6 +/- 7.5%, P < 0.05). Improvement in exercise performance with treadmill training was associated with a correlative decrease in the plasma (r = -0.67) and muscle (r = -0.59) short-chain acylcarnitine concentrations (intermediates of oxidative metabolism). Patients in the strength and control groups had no changes in muscle histology or carnitine metabolism, but strength-trained subjects had a decrease in citrate synthase activity. Thus treadmill training increased peak exercise performance, but this benefit was associated with skeletal muscle denervation and the absence of a \"classic\" mitochondrial training response (increase in citrate synthase activity). The present study confirms the relationship between skeletal muscle acylcarnitine content and function in peripheral arterial occlusive disease, demonstrating that the response to treadmill training was associated with parallel improvements in intermediary metabolism.\nStudy2: Short-term effects of cycle and treadmill training on exercise tolerance in peripheral arterial disease. To explore the efficacy of cycle training in the treatment of intermittent claudication, the present study compared performance and physiologic effects of cycle training with more conventional treadmill walking training in a group of patients with claudication. Forty-two individuals with peripheral arterial disease and intermittent claudication (24 men, 18 women) were stratified by gender and the presence or absence of type 2 diabetes mellitus and then randomized to a treadmill (n = 13), cycle (n = 15), or control group (n = 14). Treadmill and cycle groups trained three times a week for 6 weeks, whereas the control group did not train during this period. Maximal and pain-free exercise times were measured on graded treadmill and cycle tests before and after training. Treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance. Cycle training significantly improved maximal cycle time but did not improve treadmill performance. However, there was evidence of a stronger cross-transfer effect between the training modes for patients who reported a common limiting symptom during cycling and walking at baseline. There was also considerable variation in the training response to cycling, and a subgroup of responsive patients in the cycle group improved their walking performance by more than the average response observed in the treadmill group. These findings suggest that cycle exercise is not effective in improving walking performance in all claudication patients but might be an effective alternative to walking in those who exhibit similar limiting symptoms during both types of exercise.\nStudy3: [Effect of a 2-year ambulatory vascular sports program on walking distance in claudication patients--a controlled study]. nan\nStudy4: Improvement of the walking ability in intermittent claudication due to superficial femoral artery occlusion with supervised exercise and pneumatic foot and calf compression: a randomised controlled trial. To compare the effect of unsupervised exercise, supervised exercise and intermittent pneumatic foot and calf compression (IPC) on the claudication distance, lower limb arterial haemodynamics and quality of life of patients with intermittent claudication. Thirty-four eligible patients with stable intermittent claudication were randomised to IPC (n = 13, 3h/d for 6 months), supervised exercise (n = 12, three hourly sessions/week for 6 months) or unsupervised exercise (n = 9). In each patient, initial claudication distance (ICD), absolute claudication distance (ACD), resting ankle brachial pressure index (ABPI), and resting hyperaemic calf arterial inflow were measured before, 6 weeks, 6 months and 1 year after randomisation. Quality of life was assessed with the short form (SF)-36, walking impairment (WIQ) and intermittent claudication questionnaires (ICQ). Compared with unsupervised exercise, both IPC and supervised exercise, increased ICD and ACD, up to 2.83 times. IPC increased arterial inflow (p < 0.05 at 6 weeks) and ABPI. Supervised exercise decreased arterial inflow and increased ABPI (p < 0.05 at 6 months). Unsupervised exercise had no effect on arterial inflow or ABPI. IPC improved significantly the ICQ score and the speed score of the WIQ, while supervised exercise improved the WIQ claudication severity score. At 1 year clinical effectiveness of supervised exercise and IPC was largely preserved. IPC, by augmenting leg perfusion, achieved improvement in walking distance comparable with supervised exercise. Long-term results in a larger number of patients will provide valuable information on the optimal treatment modality of intermittent claudication.\nStudy5: Effect of daily muscular exercise in patients with intermittent claudication. nan\nStudy6: Physical training and antiplatelet treatment in stage II peripheral arterial occlusive disease: alone or combined? The efficacy of physical training alone or combined with antiplatelet therapy (dipyridamole and aspirin) was studied in 30 patients with stage II peripheral arterial occlusive disease (PAOD). Patients were randomly allocated to one of the following groups: Group A--dipyridamole 75 mg three times daily and aspirin 330 mg once daily: Group B--physical exercise; Group C--physical exercise and dipyridamole 75 mg three time daily and aspirin 330 mg once daily. After six months' treatment the pain-free walking time (PFWT) and the maximum walking time (MWT) improved significantly (p less than 0.05) in all three groups. In group A the PFWT lengthened by 35% (from 101.00 +/- 34.56 to 137.32 +/- 40.50 s) and the MWT by 38% (from 150.34 +/- 55.60 to 207.26 +/- 60.67 s); in group B the PFWT lengthened by 90% (from 90.65 +/- 40.54 to 171.45 +/- 55.60 s) and the MWT by 86% (from 145.39 +/- 60.50 to 270.63 +/- 63.61 s). When physical exercise was associated with drugs as in group C, the PFWT lengthened by 120% (from 89.51 +/- 43.89 to 196.72 +/- 51.73 s) and the MWT by 105% (from 160.43 +/- 59.84 to 329.05 +/- 63.96 s). No significant variations were observed at any stage of the study in the ankle/arm pressure ratio at rest and after standard treadmill exercise, in the plethysmographic rest and peak flows, or in the transcutaneous oxygen pressure in basal conditions and in its half recovery time after an induced ischemia. The results confirm the benefits of regular exercise in stage II PAOD patients but suggest they may be enhanced by antiplatelet therapy.\nStudy7: Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease. Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6 h/day) or a 2 weeks supervised physical training, randomly assigned. Patients were studied before (T0) and after (T14) treatments and 10 days later (T24). The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM; p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to human plasma coated microwells was reduced only after treatment with iloprost (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1); p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion, whereas only iloprost reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function.\nStudy8: Exercise rehabilitation improves functional outcomes and peripheral circulation in patients with intermittent claudication: a randomized controlled trial. To determine the effects of a 6-month exercise program on ambulatory function, free-living daily physical activity, peripheral circulation, and health-related quality of life (QOL) in disabled older patients with intermittent claudication. Prospective, randomized controlled trial. University Medical (Center and Veterans Affairs Medical Center, Baltimore, Maryland. Thirty-one of 61 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise rehabilitation and 30 to usual-care control. Three patients from the exercise group and six patients from the control group dropped out, leaving 28 and 24 patients, respectively, completing the study in each group. Six months of exercise rehabilitation. Treadmill distance walked to onset of claudication and to maximal claudication, ambulatory function, peripheral circulation, perceived QOL, and daily physical activity. Compliance with the exercise program was 73% of the possible sessions. Exercise rehabilitation increased treadmill distance walked to onset of claudication by 134% (P < .001) and to maximal claudication by 77% (P < .001), walking economy by 12% (P = .003), 6-minute walk distance by 12% (P < .001), and maximal calf blood flow by 30% (P < .001). Changes in distance walked to maximal pain correlated with changes in walking economy (r = -.50, P = .013) and changes in maximal calf blood flow (r = .38, P = .047). Exercise rehabilitation increased accelerometer-derived daily physical activity by 38% (P < .001); this change correlated with the change in distance walked to maximal pain (r = .45, P = .020). These improvements were significantly better than the changes in the control group (P < .05). Improvements in claudication following exercise rehabilitation in older PAOD patients are dependent on improvements in peripheral circulation and walking economy. Improvement in treadmill claudication distances in these patients translated into increased accelerometer-derived physical activity in the community, which enabled the patients to become more functionally independent.\nStudy9: Exercise training for intermittent claudication: does it adversely affect biochemical markers of the exercise-induced inflammatory response? To identify a stable biochemical marker of disease severity in patients with intermittent claudication and to use these findings to assess the effect of therapeutic exercise training. Case-control study: prospective randomised-controlled trial of exercise training. Plasma fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP) and urinary albumin-creatinine ratio (ACR) were measured in 67 claudicants and 15 controls. Twenty-two patients were randomised to supervised exercise training and 17 randomised to observation. Subjects were reviewed at 3, 6 and 12 months. The median (interquartile range) baseline fibrinogen was 3.7 g/l (3.3-4.25) in claudicants and 3.5 g/l (2.9-3.95) in controls (p = 0.045); CRP was 4.7 mg/l (2.2-9.0) and 2.1 mg/l (1.0-2.8), respectively (p < 0.0001); SAA was 72 mg/l (35-132) and 30 mg/l (20-89) (p = 0.0009). Claudicants showed an increased urinary ACR following treadmill exercise (Wilcoxon, p < 0.0001) with no change in controls. Exercise training reduced SAA at 6 months, CRP at 3 months and progressively attenuated the post-exercise increase in ACR. No similar changes were found in controls. Repetitive low-grade inflammatory events in claudicants lead to elevation of serum acute-phase proteins. Exercise training is associated with symptomatic improvement and reduction inflammatory markers. The concern that exercise has adverse systemic effects therefore seems to be unjustified.\nStudy10: Benefit of exercise conditioning for patients with peripheral arterial disease. Patients with atherosclerotic peripheral arterial disease (PAD) of the lower extremities have impaired walking ability due to exercise-induced muscle ischemia and the resultant pain of intermittent claudication. To evaluate the benefit of exercise training as a treatment for patients with PAD, as well as possible mechanisms associated with improvement, we randomly assigned 19 men with disabling claudication to treated and control groups. Treatment consisted of supervised treadmill walking (1 hr/day, 3 days/wk, for 12 weeks) with progressive increases in speed and grade as tolerated. Graded treadmill testing was performed to maximal toleration of claudication pain on entry and after 12 weeks of training to define changes in peak exercise performance. After 12 weeks, treated subjects had increased their peak walking time 123%, peak oxygen consumption 30%, and pain-free walking time 165% (all p less than 0.05). Control subjects had no change in peak oxygen consumption, but after 12 weeks, peak walking time increased 20% (p less than 0.05). In treated subjects, maximal calf blood flow (measured by a plethysmograph) increased 38 +/- 45% (p less than 0.05), but the change in flow was not correlated to the increase in peak walking time. Elevated plasma concentrations of acylcarnitines have been associated with the functional impairment of PAD and may reflect the metabolic state of ischemic skeletal muscle. In treated subjects, a 26% decrease in resting plasma short-chain acylcarnitine concentration was correlated with improvement in peak walking time (r = -0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)\n", + "output": "Conclusions: Exercise programmes were of significant benefit compared with placebo or usual care in improving walking time and distance in selected patients with leg pain from IC." + }, + { + "input": "Study1: Prospective randomized blind controlled trial comparing sutures, tape, and octylcyanoacrylate tissue adhesive for skin closure after phlebectomy. The patient's view of the outcome after phlebectomy is mainly dependent on the cosmetic result. To compare 5-0 monofilament sutures with tapes and tissue adhesive for wound closure after varicose vein surgery. Seventy-nine patients undergoing varicose vein surgery were prospectively randomized in three groups (tissue adhesive, sutures, tape) for skin closure and compared. The follow-up 1 year postoperatively was done by a senior dermatologist who was blinded in the method of skin closure. The cosmetic outcome showed little advantage for the suture group. Taping the incisions is faster than suturing them but without significance; closure with tissue adhesive takes nearly the double of time. The closure for one incision with tissue adhesive is 40 times more expensive than with tapes and 14 times more expensive than with sutures. This study failed to demonstrate an advantage of tissue adhesive and tapes over monofilament sutures for skin closure after phlebectomy.\nStudy2: Randomized study of the effectiveness of closing laparoscopic trocar wounds with octylcyanoacrylate, adhesive papertape or poliglecaprone. Several methods for skin closure are used, i.e. sutures, adhesive papertape and tissue adhesives. Little is known about the efficacy of these techniques in laparoscopic surgery. This study was performed to analyse the efficacy of octylcyanoacrylate, a new tissue adhesive, adhesive papertape and poliglecaprone for wound closure in laparoscopy. From May 2000 to September 2001, 140 patients were included in a prospective randomized trial. Wounds were closed with octylcyanoacrylate (n = 48), adhesive papertape (n = 42) or poliglecaprone (n = 50). Closing time, wound infection, cosmetic results and costs were evaluated. A time-motion analysis was also performed. The patients in the three groups were well matched for age, gender and body mass index. Closing times per wound were 26, 33 and 65 s respectively for adhesive papertape, octylcyanoacrylate and poliglecaprone (P < 0.001). Cosmetic results, as scored by the patients, were no different. The number of actions required to close each wound was 5.7, 8.3 and 21.0 for octylcyanoacrylate, adhesive papertape (P = 0.05 versus octylcyanoacrylate) and poliglecaprone (P < 0.01 versus octylcyanoacrylate and adhesive papertape) respectively. Octylcyanoacrylate was significantly more expensive than poliglecaprone and adhesive papertape. Closure with adhesive papertape was the fastest method. The smallest number of actions required to close a wound was with octylcyanoacrylate. Adhesive papertape was the most cost-effective.\nStudy3: A blinded, randomised, controlled trial of stapled versus tissue glue closure of neck surgery incisions. Cosmetic acceptability of scar and neck mobility are important outcomes after collar line incision for neck surgery. This randomised, controlled trial compares these parameters in closures using tissue glue (Dermabond, Ethicon, UK) and skin staples. Patients requiring a collar line incision were randomised to receiving tissue glue or staples for skin closure. Time for closure to be completed was recorded. Mobility of the neck was assessed using a visual analogue scale at 48 h and 1 week after surgery. At 6 weeks, cosmetic appearance was assessed using a linear 1-10 visual analogue scale by the patient, surgeon and an independent blinded assessor. Results were compared using appropriate statistical tests. Glued (n = 14) and stapled (n = 15) closures were performed for hemithyroidectomy (n = 8 versus 6), sub-total thyroidectomy (n = 2 versus 4), total thyroidectomy (n = 1 versus 4) and parathyroidectomy (n = 3 versus 1). Closure with tissue glue took significantly longer than with staples (mean, 95 versus 28 s; P < 0.001). Neck mobility scores were comparable at 48 h and 1 week (mean, 4.8 versus 4.4; P = 0.552: and 2.7 versus 2.6; P = 0.886). Cosmetic appearance at 6 weeks was comparable when patient (mean, 1.7 versus 1.8; P = 0.898), surgeon (mean, 2.6 versus 2.3; P = 0.633) and independent assessment (mean, 1.4 versus 1.9; P = 0.365) was performed. The use of glued skin closure may increase the duration of surgery but acceptable neck mobility and wound cosmesis can be achieved by the more rapid application of stapled skin closure in cervicotomy incisions.\nStudy4: Use of octyl-2-cyanoacrylate for skin closure in facial plastic surgery. Octyl-2-cyanoacrylate is a long carbon chain cyanoacrylate derivative that is stronger and more pliable than its shorter chain derivatives. One hundred and eleven patients underwent elective surgical procedures by the same surgeon using either octyl-2-cyanoacrylate or sutures for skin closure at the University of Illinois at Chicago. Most patients underwent excision of benign skin lesions with a mean wound size of 112 mm3. Patients were randomized into either control (vertical mattress suture closure) or test groups (closure with octyl-2-cyanoacrylate). Surgical judgment was used to determine which wounds in each group required application of subcutaneous sutures to relieve tension and aid in skin edge eversion. Generally, full-thickness (through dermis) wounds larger than 1 cm3 required the use of subcutaneous sutures. The time required to close the epidermis with suture (mean, 3 minutes and 47 seconds) was about four times that of octyl-2-cyanoacrylate (mean, 55 seconds). Wounds were evaluated at 5 to 7 days for infection, wound dehiscence, or tissue reaction, and at 90 days using the modified Hollander wound evaluation scale. At 1 year, photographs of the wounds were evaluated by two facial plastic surgeons that graded the cosmetic outcome using a previously validated visual analog scale. There were no instances of wound dehiscence, hematoma, or infection in either group. Results of wound evaluation at 90 days determined by the modified Hollander scal revealed equivalent cosmetic results in both groups. Results of the visual analog scale ratings showed scores of 21.7 +/- 16.3 for the 49 patients treated with octyl-2-cyanoacrylate and 29.2 +/- 17.7 for the 51 control patients treated with sutures. The lower visual analog scale score represented a superior cosmetic outcome at 1 year with the octyl-2-cyanoacrylate as compared with sutures. This difference is statistically significant at p = 0.03. Additionally, patient satisfaction was very high in the group treated with octyl-2-cyanoacrylate.\nStudy5: Efficacy of octyl-2-cyanoacrylate tissue glue in blepharoplasty. A prospective controlled study of wound-healing characteristics. To compare the surgical efficacy and wound-healing characteristics of the tissue adhesive octyl-2-cyanoacrylate (approved by the Food and Drug Administration) with traditional suture closure in upper blepharoplasty. Prospective, randomized, blinded study comparing cosmetic and functional outcome and time efficiency. Twenty subjects underwent upper eyelid blepharoplasty. Each patient had a control side and an experimental side determined randomly. One eyelid incision was closed with octyl-2-cyanoacrylate (Dermabond; Ethicon Inc, Somerville, NJ) tissue glue, and the other with 6.0 suture (polypropylene or fast-absorbing gut). Comparisons were performed for the time for closure by each method, wound healing, and patient satisfaction. Macrophotographs of the wounds at 1, 2, and 4 weeks after surgery were graded by 5 observers blinded to the closure method, using a 10-point scale and a modified Hollander wound evaluation scale. No statistically significant difference was found between the quality of octyl-2-cyanoacrylate closure and suture closure at 1 month. There were no differences in wound complications, duration of healing, inflammation, or final incision appearance. By 2 weeks, the sides were indistinguishable in 15 (75%) of the patients. Time for closure averaged 7 minutes with suture and 8 minutes with glue. Octyl-2-cyanoacrylate glue is an excellent alternative to suture closure, producing equivalent quality of closure at all time points and no difference in appearance. This adhesive was sufficient to withstand the forces of closure in upper eyelid blepharoplasty without dehiscence in the absence of sutures.\nStudy6: A randomized controlled trial of high-viscosity 2-octyl cyanoacrylate tissue adhesive versus sutures in repairing facial wounds following Mohs micrographic surgery. High-viscosity 2-octyl cyanoacrylate (HVOCA) is a rapidly polymerizing liquid topical adhesive indicated for epidermal approximation of superficial lacerations and surgical wounds. Use of HVOCA in repair of facial wounds after Mohs micrographic surgery (MMS) has not been reported. To compare aesthetic outcome of HVOCA versus sutured epidermal closure of linearly repaired facial wounds following MMS. Patients undergoing MMS for facial tumors with postoperative wounds >3 cm appropriate for linear closure were recruited. After placement of dermal sutures, half the wound was randomly selected for closure with HVOCA and the other half was closed with 5-0 polypropylene suture. Fourteen patients (13 men and 1 woman; mean age, 72+/-8.8 years; range, 52-81 years) with basal cell or squamous cell carcinoma of the face (n=12) or neck (n=2) were enrolled. The mean wound length was 4.9+/-1.9 cm (range, 3.1-10 cm). No postoperative complications, including bleeding, infection, or dehiscence, occurred. Using photographs obtained 3 months postoperatively, five dermatologists (including two Mohs surgeons) blinded to the intervention rated cosmesis using a visual analog scale from 1 (worst) to 10 (best). The mean ratings for HVOCA half (6.64+/-1.55) versus sutured half (6.77+/-1.88) were not significantly different (p=.35). Paired comparisons of rater preferences similarly showed no cosmetic differences. All 14 patients preferred OCA for ease of postoperative care. HVOCA tissue adhesive is cosmetically equivalent to epidermal sutures in the linear repair of facial wounds following MMS. This technique represents an additional option for Mohs surgeons.\n", + "output": "Conclusions: Sutures were significantly better than tissue adhesives for minimising dehiscence and were found to be significantly faster to use. Although surgeons may consider the use of tissue adhesives as an alternative to other methods of surgical site closure in the operating theatre they must be aware that adhesives may take more time to apply and that if higher tension is needed upon an incision, sutures may minimise dehiscence. There is a need for more well designed randomised controlled trials comparing tissue adhesives and alternative methods of closure. These trials should include people whose health may interfere with wound healing and surgical sites of high tension." + }, + { + "input": "Study1: A blinded, randomized, placebo-controlled trial to compare theophylline and doxapram for the treatment of apnea of prematurity. A blinded, randomized, placebo-controlled trial was conducted to evaluate the effectiveness of theophylline and doxapram therapy in 31 infants with significant apnea of prematurity. Of 10 infants, two had a short-term response to placebo, 8 of 10 infants to theophylline, and 7 of 11 infants to doxapram (placebo vs treatment with theophylline or doxapram: p = 0.01). The two infants who initially responded to placebo remained responsive for the duration of the study. Of the eight infants in whom treatment with placebo failed, five were randomly assigned to receive theophylline, for a total of 15 infants treated with theophylline, and two of the eight were randomly assigned to receive doxapram, for a total of 13 infants treated with doxapram; the remaining infant required tracheal intubation. Of the 15 infants randomly assigned to receive theophylline, seven responded for the duration of the study; of the eight infants who did not respond to treatment with theophylline, five responded to doxapram, one responded to a combination of theophylline and doxapram, and two remained resistant to treatment. Of the 13 infants randomly assigned to receive doxapram four responded for the duration of the study; of the nine who did not respond to doxapram, seven responded to theophylline, one responded to a combination of theophylline and doxapram, and one remained resistant to treatment. This study demonstrates that although therapy with theophylline or doxapram is associated with a significant short-term reduction in the incidence of apnea compared with that in placebo-treated infants, the long-term response to treatment is frequently incomplete and is not sustained more than 1 week.\nStudy2: Theophylline in treatment of apnoea of prematurity. nan\nStudy3: The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants. This prospective controlled study was aimed at evaluating the efficacy of caffeine in treating recurrent idiopathic apnea in the premature infant. Eighteen preterm infants (29 to 35 weeks' gestation) were studied. Recordings during the first 24 hours and on the fifth day of caffeine treatment showed a significant decrease of severe apnea (P less than 0.01) and of mild apnea (P less than 0.001) in the treated group (group 1) as compared with the control group (group II). No treatment of apnea other than caffeine was required in group I, whereas six neonates in group II had such severe and frequent apneic episodes for more than 48 hours that withholding additional treatment was believed to be unethical. No undesirable side effects of caffeine treatment were observed.\n", + "output": "Conclusions: Methylxanthine is effective in reducing the number of apnoeic attacks and the use of mechanical ventilation in the two to seven days after starting treatment. Caffeine is also associated with better longer term outcomes. In view of its lower toxicity, caffeine would be the preferred drug for the treatment of apnoea." + }, + { + "input": "Study1: Effects of low-dose EPA-E on glycemic control, lipid profile, lipoprotein(a), platelet aggregation, viscosity, and platelet and vessel wall interaction in NIDDM. To assess the effects of low-dose eicosapentaenoic acid-ethyl-ester on diabetes regulation, lipid metabolism, blood rheology, and platelet reactivity. In a double-blind, randomized, placebo-controlled study, 24 NIDDM subjects received 1800 mg of EPA-E, 900 mg of EPA-E, or a placebo (1656 mg olive oil) daily for 8 wk. The EPA:arachidonic acid plasma ratio increased over an 8-wk period, then declined after a 4-wk wash-out period in the fish-oil groups in a dose-dependent way. Platelet-activating factor-induced platelet aggregation decreased from 75 +/- 7% at wk 0 to 35 +/- 21% at wk 8 in the 900-mg group (P = 0.016) and from 72 +/- 11 to 40 +/- 30% in the 1800-mg group (P = 0.039), but did not change in the placebo group. No effects on ADP- or collagen-induced aggregation could be attributed to EPA-E. In the 1800-mg group low-density-lipoprotein cholesterol increased significantly, without concomitant rise in apolipoprotein B. Triglycerides, glycemic control, lipoprotein (a), blood and plasma viscosity, erythrocyte deformability, and platelet adhesion to and aggregate formation on extracellular endothelial cell matrix were not significantly influenced. Purified EPA-E in doses of 900 and 1800 mg reduces Platelet-activating factor-induced platelet aggregation without negatively affecting glycemic control. Low-density-lipoprotein cholesterol was elevated in the 1800-mg group.\nStudy2: Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study. To study the effects of a low dose of omega-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellitus (NIDDM). We performed a randomized, prospective, double-blind, controlled study of a low dose of omega-3 fatty acids (2.5 g/day) in 20 ambulatory subjects with NIDDM. Subjects ingested five 1-g fish oil capsules each containing 0.5 g omega-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period. Nine subjects completed the study in each group. Both groups exhibited moderate control of glucose levels; modest elevations in baseline total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels; and normal blood pressure values. In the fish oil group, plasma omega-3 fatty acid levels increased significantly. Fish oil significantly reduced the slope of the dose-response curves for collagen-induced platelet aggregation to one-third the value observed with safflower oil. No difference was observed in collagen-induced production of thromboxane A2 (TXA2, measured as the stable derivative TXB2), or in adenosine-5'-diphosphate- (ADP) induced platelet aggregation or TXA2 generation. Patients with high initial collagen-induced platelet TXA2 production showed a significantly larger drop after fish oil than safflower oil. Fish oil significantly reduced TG levels by 44 mg/dl and decreased upright systolic blood pressure (sBP) by 8 mmHg compared with safflower oil. Fish oil caused a significant but small increase in HbA1c (0.56%) and total cholesterol (20 mg/dl) but had no effect on fasting glucose, high-density lipoprotein cholesterol, or LDL-cholesterol levels. Small doses of fish oil inhibit platelet aggregation and TXA2 production, reduce upright sBP and TG levels, and have only a small effect on glucose and cholesterol levels in patients with moderately controlled NIDDM. Small quantities of omega-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients.\nStudy3: Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. The effects on lipoprotein and glucose metabolism of addition of n-3 fatty acids were studied in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. After MaxEPA treatment, there was a marked increase in long-chain polyunsaturated fatty acids of the n-3 series in the plasma lipid esters and in the platelet phospholipids, while the n-6 fatty acid content decreased. The very low density lipoprotein (VLDL) triglyceride concentrations decreased significantly (by 22%) on MaxEPA treatment. However, these changes were not significantly different from those observed during the placebo period. The blood glucose concentration tended to increase during MaxEPA treatment, and to decrease during the placebo period, the changes under the two regimes being significantly different (P less than 0.01). In addition, the rate constant for glucose disappearance (k value) for the intravenous insulin-tolerance test, which reflected the peripheral insulin sensitivity, tended to decrease during MaxEPA treatment and increase during administration of the placebo, there being a significant difference (P less than 0.03) between the changes during the two treatments. The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear.\nStudy4: Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue. A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design. For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue. A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities.\nStudy5: Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients. The increased risk of coronary heart disease associated with type 2 diabetes may be partially explained by dyslipidemia characterized by high plasma triacylglycerol (TAG), low HDL cholesterol, and a predominance of atherogenic small dense LDLs. Fish oil reduces plasma TAG and has previously been shown to improve the distribution of LDL subclasses in healthy subjects and might, therefore, be a good nonpharmacological treatment for type 2 diabetic patients. In the present study, we investigate the effect of fish oil supplementation on the fasting lipid profile, including LDL and HDL subclasses. A total of 42 type 2 diabetic patients were randomized to supplementation (capsules) with 4 g daily of either fish oil (n = 20) or corn oil (n = 22) for 8 weeks preceded by a 4-week run-in period of corn oil supplementation. Blood was drawn before and after the 8-week intervention period. Plasma lipoproteins, including LDL and HDL subclasses, were separated by ultracentrifugation. Fish oil lowered TAG (group difference: P = 0.025) and raised HDL-2b cholesterol (P = 0.012) and HDL-2a cholesterol (P = 0.007) concentrations as compared with corn oil. We observed no significant effects of fish oil on LDL cholesterol, HDL cholesterol, or the concentration of small dense LDL particles. Fish oil supplementation may partially correct the dyslipidemia of type 2 diabetic patients. However, the putative very important aspect of diabetic dyslipidemia-the predominance of small dense LDL particles-was unaffected by fish oil.\nStudy6: A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. Supplementation of type II diabetic diets with n-3 fatty acids (FAs) from fish oil (FO) has been associated with lowered triglyceride and VLDL levels, although reports of impaired glycemic control have limited their use. Effects of n-3FAs from nonmarine sources are less well documented. Therefore, an investigation comparing the effects of linseed oil (LO) with FO supplementation was undertaken in subjects with type II diabetes. Eleven subjects with type II diabetes were given supplements with LO and FO for 3 months each in a randomized double-blind crossover fashion after 3 months of olive oil placebo. Oils were given as 35 mg FA.kg body wt-1.day-1. After each 3-month period, fasting glucose and insulin levels, HbA1c, lipid profiles, insulin sensitivity (SI), glucose effectiveness (SG), and acute insulin response to glucose (AIRG) were evaluated. HbA1c and lipid values were within the normal range at randomization. Repeated measures analysis of variance testing found no significant differences in weight; fasting glucose and insulin levels; HbA1c; total, LDL, and HDL cholesterol levels; SI; SG; or AIRG with either active oil. FO was associated with significant reductions in triglycerides and a trend toward decreased SI. In a population with well-controlled type II diabetes, 3 months of FO but not LO resulted in lowered triglyceride levels. Neither LO nor FO significantly affected glycemic control, cholesterol values, SG, or insulin secretion, while a nonsignificant trend toward decreased insulin sensitivity was found with FO.\nStudy7: Effects of n-3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation. Effects of fish oil supplements on metabolic variables are insufficiently clarified in type 2 diabetes. We aimed to investigate short-term (1 wk) and longer-term (9 wk) effects of n-3 fatty acids. Twenty-six subjects with type 2 diabetes without hypertriacylglycerolemia participated in a double-blind controlled study. Median intake in the intervention group was 17.6 mL fish oil/d (1.8 g 20:5n-3, 3.0 g 22:6n-3, and 5.9 g total n-3 fatty acids). The control group received 17.8 mL corn oil/d (8.5 g 18:2n-6). Plasma phospholipid 20:5n-3 and 22:6n-3 increased, whereas 18:2n-6 decreased, in the fish oil group compared with the corn oil group after 1 wk. The two n-3 fatty acids also increased in adipose tissue biopsy samples taken after 9 wk in the fish oil group. Glucose concentrations (home-monitored) were approximately 1 mmol/L higher in the fish oil group than in the corn oil group at the end of the intervention (P = 0.035). Glucose utilization measured by using an isoglycemic clamp was lowered in the fish oil group compared with that in the corn oil group at the end of the intervention (P = 0.049), whereas glucagon-stimulated C-peptide tended to increase (P = 0.078). The fish oil group utilized less fat for oxidation after 1 wk, with a change to more fat and less carbohydrate oxidation after 9 wk (P = 0.040), than did the corn oil group. A high intake of fish oil moderately increases blood glucose and decreases insulin sensitivity in persons with type 2 diabetes without hypertriacylglycerolemia and alters carbohydrate and fat utilization in a time-dependent manner.\nStudy8: Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus. The effects of dietary supplementation with n-3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. The serum triglyceride (TG) concentrations decreased by 27% (P < 0.01) after addition of MaxEPA with a reduction of VLDL TG by 36% (P < 0.05) while LDL cholesterol increased by 6% (P = 0.05). The fasting blood sugar and HbA1c concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period. The highest glucose concentrations at fasting and after an i.v. glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged. The peripheral insulin sensitivity, as measured by a euglycaemic, hyperinsulinaemic clamp technique, did not change during the study. The mean plasminogen inhibitor-1 (PAI-1) activity of the patients was elevated compared with healthy controls. In spite of the reduction of the triglyceride concentrations and unchanged insulin levels, there was a significant increase of the activity of PAI-1 (+21%, P < 0.01) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity. In many situations there seems to be a reduction of PAI-1 when the triglycerides are lowered. In the diabetic patients given n-3 fatty acids this was not the case.\nStudy9: The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet. Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change. The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients.\n", + "output": "Conclusions: Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL cholesterol, but may raise LDL cholesterol (although results were non-significant in subgroups) and has no statistically significant effect on glycemic control or fasting insulin. Trials with vascular events or mortality defined endpoints are needed." + }, + { + "input": "Study1: Buccal versus intravaginal misoprostol administration for cervical ripening. The purpose of this study was to compare the efficacy of misoprostol that is administered in the buccal pouch with the intravaginal route of administration. One hundred fifty-seven pregnant women with a singleton live gestation, Bishop score of <7, estimated fetal weight of <4500 g, and gestational age of >24 weeks were randomized to receive misoprostol that would be placed either in the buccal pouch or vagina every 6 hours. In the buccal group, after the first 2 doses of 200 microg, the dose was increased to 300 microg for the duration of the study (up to a total of 1600 microg). In the vaginal group, after the first 2 doses of 50 microg, the dose was increased to 100 microg for the duration of the study (up to a total of 500 microg). The primary outcome variable was the interval from the first dose to vaginal delivery. Power calculations indicated the need to enroll 71 patients in each arm of the study, which would allow for the detection of a 4-hour reduction in vaginal birth interval for buccal misoprostol. The hours from drug administration to vaginal delivery were similar between the buccal and vaginal groups (23.5 +/- 20.8 hours versus 21.3 +/- 13.4 hours), respectively. Thirty-five women (63%) versus 34 women (67%) delivered vaginally within 24 hours (P = not significant). The incidence of tachysystole was higher in the buccal group, 28 occurrences (38%) versus 15 occurrences (19%; P =.01). Buccal misoprostol is effective for cervical ripening but results in a higher incidence of tachysystole than does intravaginal administration.\nStudy2: Sublingual compared with oral misoprostol in term labour induction: a randomised controlled trial. To compare the efficacy and patient acceptability of 50 microg of sublingual misoprostol with 100 microg of oral misoprostol in the induction of labour at term. Non-blinded randomised comparative trial. Tertiary level UK Hospital. Two hundred and fifty women at term with indications for labour induction. Fifty micrograms of sublingual misoprostol or 100 microg of oral misoprostol was administered every four hours after random allocation, to a maximum of five doses. Number of patients delivering vaginally within 24 hours of the induction, mode of delivery, neonatal outcomes and patient acceptability. There was no significant difference in the number of women delivering vaginally within 24 hours of the induction in the sublingual group as compared with the oral group (62.8% vs 59%, RR 1.1, 95% CI 0.6-2.1), or in the mean induction to delivery time (21.8 vs 24.1 h, mean difference 2.3 h 95% CI -2.2 to +6.7). There was no difference in the uterine hyperstimulation rates (1.6% in both groups), operative delivery rates or neonatal outcomes. In the sublingual group, 92.6% found the induction acceptable with 15.8% finding the tablets with an unpleasant taste, while in the oral group it was 96.9% and 4%, respectively. More patients in the oral group thought that they would consider the same method of induction again as compared with the sublingual group (58.6% vs 40%, RR 1.4, 95% CI 1.04-1.9). Fifty micrograms of sublingual misoprostol every four hours has the same efficacy and safety profile as compared with 100 microg orally, but the oral route might be preferred by women.\n", + "output": "Conclusions: Based on only three small trials, sublingual misoprostol appears to be at least as effective as when the same dose is administered orally. There are inadequate data to comment on the relative complications and side-effects. Sublingual or buccal misoprostol should not enter clinical use until its safety and optimal dosage have been established by larger trials.\n[Note: The 17 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]" + }, + { + "input": "Study: Vaginismus treatment. Hypnotherapy versus behavior therapy. To investigate the effectiveness of hypnotherapy in the treatment of vaginismus compared to behavior therapy. A consecutive sample of 36 women with vaginismus (DSM-IV criteria) referred to the out-patient psychiatry clinic at King Abdul-Aziz University Hospital in Riyadh between 1999-2003 were divided into 2 groups for either treatment on a random basis. A female psychologist independently and carefully assessed patients before and after treatment. Patients were treated until they achieved satisfactory sexual intercourse. Although both behavior therapy and hypnotherapy were successful in treating vaginismus, hypnotherapy performed better than behavior therapy in reducing the level of the wife`s sex-related anxiety and in improving the husband`s sexual satisfaction score. Success tended to occur faster in women treated with hypnotherapy as they received fewer treatment sessions. Women with vaginismus can be successfully treated by hypnotherapy without simultaneous treatment of their husbands. Hypnotherapy can provide an acceptable time and cost effective therapeutic tool that helps resolve vaginismus and improves sexual satisfaction in both spouses.\n", + "output": "Conclusions: A clinically relevant effect of systematic desensitisation when compared with any of the control interventions cannot be ruled out. None of the included trials compared other behaviour therapies (e.g. cognitive behaviour therapy, sex therapy) to pharmacological interventions. The findings are limited by the evidence available and as such conclusions about the efficacy of interventions\u00a0for the treatment of vaginismus should be drawn cautiously." + }, + { + "input": "Study1: Intraarticular morphine versus dexamethasone in chronic arthritis. Intraarticular morphine inhibits pain after knee surgery without overt toxicity. This study examined intraarticular morphine in chronic arthritis. We undertook a randomized double-blind comparison between intraarticular morphine (3 mg), dexamethasone (4 mg) and saline (3 ml) in 44 patients with chronic inflammatory arthritis or osteoarthritis of the knee. Pain (the primary outcome measure) was assessed at rest and during activity for 6 days using a visual analog scale (VAS) and the McGill pain questionnaire. Before drug injections and on day 6 synovial leukocyte counts (the secondary outcome measure) were taken. During the first 6 h after injection both morphine and dexamethasone significantly reduced VAS and pain rating indices (PRI) in comparison to saline. Both substances also produced a significant reduction of PRI compared to saline during the subsequent 5 days. No patient displayed untoward side effects. Synovial leukocyte counts were lower after morphine than after saline. In conclusion, intraarticular morphine produces analgesia of similar magnitude to dexamethasone and it may have antiinflammatory actions in chronic arthritis.\nStudy2: Intra-articular therapy in rheumatoid arthritis: comparison of hydrocortisone tertiary butyl acetate and hydrocortisone acetate. nan\nStudy3: The effects of joint washout and steroid injection compared with either joint washout or steroid injection alone in rheumatoid knee effusion. Patients with rheumatoid arthritis attending rheumatology out-patients who had a symptomatic knee effusion were randomly allocated to receive one of three treatments: group I, a steroid injection without washout; group II, a joint washout with normal saline; group III, a joint washout with normal saline and steroid injection. Sixty knees in all were studied. Laboratory parameters for disease activity (erythrocyte sedimentation rate, C-reactive protein) were monitored in all patients prior to the study and at 3 months. Clinical assessment of disease activity (pain, morning stiffness involving the knee, circumference of the knee, walking distance and range of movement) were recorded prior to the study, at 1 month and at 3 months. All three treatments, resulted in a reduction of pain and increased movement. However, patients who had a joint washout alone showed significantly less improvement as compared with the other two groups. Symptomatic improvement was marginally greater in patients following joint washout and injection than in those who had had joint injection alone. The results of the study indicate that the simple procedure of joint aspiration and steroid injection, which can be carried out in the out-patient clinic, provides satisfactory relief of symptoms in rheumatoid patients with knee effusions. Joint washout alone was less beneficial.\nStudy4: Intra-articular rimexolone in the rheumatoid knee: a placebo-controlled, double-blind, multicentre trial of three doses. One-hundred and thirty-seven patients with classical or definite rheumatoid arthritis, involving at least one knee joint, were randomly allocated to a single intra-articular injection of 10, 20 or 40 mg of rimexolone (Org 6216) or placebo. The follow-up period was 84 days, during which clinical and laboratory assessments were done. Clinical improvement of the treated knee joint was measured by the following variables: pain, tenderness, morning stiffness, swelling, range of movement and walking ability. Placebo response was considerable. However, clinical improvement with rimexolone at 20 mg and 40 mg was significantly superior to placebo for most of the variables, whilst with the 10 mg dose only reduction of tenderness was significantly superior. The duration of improvement was longest with 40 mg of rimexolone. One single, intra-articular injection of this dose into the affected knee joint provided significant reduction in pain, tenderness and stiffness and improved the range of movement and walking ability for a period of 8 to 12 weeks.\nStudy5: A randomized controlled study of post-injection rest following intra-articular steroid therapy for knee synovitis. In order to assess the effect of 24 h observed bed rest following intra-articular steroid injection of the knee joint in patients with an inflammatory arthritis such as RA, AS or colitic arthropathy, 91 patients with inflammatory arthritis of one knee joint were randomized to receive 24 h bed rest in hospital following intra-articular steroid injection or were injected in outpatients. The clinical and laboratory assessments such as pain and stiffness on a 10-cm visual analogue scale, knee circumference (cm), 50 ft walking time (s), CRP and ESR were measured before receiving the steroid injection and at 3, 6, 12 and 24 weeks. Both groups of patients improved clinically and serologically at 3 weeks. By 12 weeks the degree of improvement in the pain score, stiffness score, knee circumference, 50 ft walking time and CRP was better in the rest group and these differences persisted to 24 weeks. For each outcome variable the summary measure of response was significantly better in the rest group compared to the no rest group. Intra-articular steroid injection of the knee joint followed by strict i inpatient bed rest for 24 h results in a greater degree of clinical and serological improvement, compared to routine outpatient injections for up to 6 months. It is therefore possible that 24-h post-injection rest will result in a prolonged duration of clinical response and reduce the need for frequent steroid injections and the risk of complications.\n", + "output": "Conclusions: There is some evidence to support the use of IA steroid injections and resting a knee following injections but that wrists should not be rested following injections. The included studies involved adult participants so any conclusions can only cautiously applied to children. Further research is required to examine the use and type of rest and the differential responses of different joints following injections." + }, + { + "input": "Study1: A randomized, controlled trial of the impact of early and rapid diagnosis of viral infections in children brought to an emergency department with febrile respiratory tract illnesses. Acute respiratory tract infections represent a significant burden on pediatric emergency departments (ED) and families. We hypothesized that early and rapid diagnosis of a viral infection alleviates the need for ancillary testing and antibiotic treatment. We conducted a randomized, controlled trial of children 3 to 36 months of age with febrile acute respiratory tract infections at a pediatric ED. Two hundred four subjects were randomly assigned to receive rapid respiratory viral testing on admission or a routine ED admission protocol. Outcome measures were: mean length of visits, rate of ancillary tests, and antibiotic prescription in the ED. A follow-up call was made to all study subjects to inquire about further healthcare visits, ancillary testing, and antibiotic prescription after ED discharge. We did not find a statistically significant difference in ED length of visits, rate of ancillary testing, or antibiotic prescription rate in the ED between the study groups. There was, however, a significant reduction in antibiotic prescription after ED discharge (in the group who had rapid viral testing RR = 0.36; 95% CI = 0.14, 0.95). Rapid multi-viral testing in the ED did not significantly affect ED patient treatment but may reduce antibiotic prescription in the community after discharge from the ED, suggesting a novel strategy to alter community physician antibiotic prescription patterns.\nStudy2: Accuracy and impact of a point-of-care rapid influenza test in young children with respiratory illnesses. To determine whether a point-of-care rapid influenza test impacts the diagnostic evaluation and treatment of children with acute respiratory illnesses. Randomized controlled trial. Pediatric emergency department and acute care clinic of a children's hospital. Children aged younger than 5 years with fever or acute respiratory symptoms during 2 influenza seasons (2002 through 2004). Surveillance days were randomized to performance or no performance of a point-of-care rapid influenza test. All children had a nasal and throat swab obtained for laboratory tests. The rapid test group had another nasal swab obtained for the QuickVue Influenza Test (Quidel Corp, San Diego, Calif), which was performed by nurses; results were shared immediately with treating physicians. Rapid test results were compared with results of the viral culture or 2 polymerase chain reaction assays for influenza. Diagnostic test ordering and antibiotic prescribing were compared for the groups. Of 468 enrolled children, 306 were from the emergency department and 162 from the clinic. Overall, 88 children (19%) had influenza infection. Of 205 children in the rapid test group, 51 (25%) had influenza infection. The rapid influenza test was 82% sensitive and 99% specific. In the emergency department, fewer children in the rapid test group had diagnostic tests ordered than in the no rapid test group (39% vs 51%, P = .03). There was no difference in test ordering in the clinic or in antibiotic prescribing in either setting. The use of antivirals was low. Point-of-care rapid influenza tests were sensitive and specific and were associated with less diagnostic testing in the emergency department.\nStudy3: Effect of point-of-care influenza testing on management of febrile children. To determine the effect of point-of-care testing (POCT) for influenza on the physician management of febrile children who are at risk for serious bacterial illness (SBI) on the basis of age and temperature and who are presenting to a pediatric emergency department (ED) during an influenza outbreak. Patients 2-3 months of age with temperature of > or = 38 degrees C and patients 3-24 months of age with temperature of > or = 39 degrees C who were presenting to a pediatric ED during an influenza outbreak were enrolled into a prospective, quasi-randomized, controlled trial. Influenza testing was performed on enrolled patients by either the POCT or the standard-testing (ST) methods. The two groups were compared in terms of laboratory testing, chest radiography, antibiotic use, visit-associated costs, pediatric ED lengths of stay, inpatient admission, and return visits to the pediatric ED. Similar analyses also were performed on the resulting subgroups of patients on the basis of method of testing (POCT or ST) and test result (positive or negative). Of 767 eligible patients, 700 (91%) completed the study. No significant differences were demonstrated between the POCT and ST groups with respect to laboratory tests ordered, chest radiographs obtained, antibiotic administration, inpatient admission, return visits to the pediatric ED, lengths of stay, or visit-associated costs. In the subgroup analysis, the adjusted odds ratios (ORs) for blood culture in influenza test-positive to -negative patients were 0.59 and 0.71 in the POCT and ST groups, respectively (p = 0.088). The adjusted ORs for urine culture in influenza test-positive to -negative patients were 0.46 and 0.67 in the POCT and ST groups, respectively (p = 0.005). When using a strategy of performing influenza testing on all patients at risk for SBI who presented to a pediatric ED during an influenza outbreak, the method of testing (POCT or ST) did not appear to significantly alter physician management, cost, or length of stay in the pediatric ED. However, if the interaction of the method of testing and the test result (positive or negative) were considered, a positive POCT for influenza was associated with a significant reduction in orders for urinalyses and urine cultures.\nStudy4: Impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial. To determine the impact of the rapid diagnosis of influenza on physician decision-making and patient management, including laboratory tests and radiographs ordered, patient charges associated with these tests, antibiotics/antivirals prescribed, and length of time to patient discharge from the emergency department. Patients aged 2 months to 21 years presenting to an urban children's teaching hospital emergency department were screened for fever and cough, coryza, myalgias, headache, and/or malaise. After obtaining informed consent, patients were randomized to 1 of 2 groups: 1) physician receives (physician aware of) the rapid influenza test result; or 2) physician does not receive (physician unaware of) the result. For patients in the physician aware group, nasopharyngeal swabs were obtained, immediately tested with the FluOIA test for influenza A and B, and the result was placed on the chart before patient evaluation by the attending physician. For the physician unaware group, nasopharyngeal swabs were obtained, stored according to manufacturer's directions, and tested within 24 hours. Results for the physician unaware group were not disclosed to the treating physicians at any time. The 2 resultant influenza-positive groups (aware and unaware) were compared for laboratory and radiograph studies and their associated patient charges, antibiotic/antiviral prescriptions, and length of stay in the emergency department. A total of 418 patients were enrolled, and 391 completed the study. Of these, 202 tested positive for influenza. Comparison of the 96 influenza-positive patients whose physician was aware of the result with the 106 influenza-positive patients whose physician was unaware of the result revealed significant reductions among the former group in: 1) numbers of complete blood counts, blood cultures, urinalyses, urine cultures, and chest radiographs performed; 2) charges associated with these tests; 3) antibiotics prescribed; and 4) length of stay in the emergency department. The number of influenza-positive patients who received prescriptions for antiviral drugs was significantly higher among those whose physician was aware of the result. Physician awareness of a rapid diagnosis of influenza in the pediatric emergency department significantly reduced the number of laboratory tests and radiographs ordered and their associated charges, decreased antibiotic use, increased antiviral use, and decreased length of time to discharge.\n", + "output": "Conclusions: Current evidence is insufficient to support routine rapid viral testing as a means to reduce antibiotic use in pediatric EDs. Results suggest that rapid viral testing may be beneficial in terms of reducing rates of antibiotic usage, urine investigations and blood investigations, but are not statistically significant due to lack of power. Rapid viral testing does reduce the rate of chest X-rays in the ED. A large trial addressing the effect on antibiotic usage is needed." + }, + { + "input": "Study: Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomised trial. Oral anticoagulants and aspirin are antithrombotic drugs that are commonly used in patients with vascular disease. We investigated whether either of these treatments prevented more effectively than the other bypass complications after infrainguinal bypass surgery. We did a multicentre, randomised, open trial. 2690 patients who had undergone infrainguinal grafting were randomly assigned oral anticoagulants (target international normalised ratio 3.0-4.5, n=1339) or aspirin (80 mg daily, n=1351). We followed up patients for a mean of 21 months. The primary outcome was graft occlusion. 308 graft occlusions occurred in the oral-anticoagulants group compared with 322 in the aspirin group (hazard ratio 0.95 [95% CI 0.82-1.11]), which suggested no overall advantage for either treatment. Oral anticoagulants were beneficial in patients with vein grafts (0.69 [0.54-0.88]), whereas aspirin had better results for nonvenous grafts (1.26 [1.03-1.55]). The composite outcome of vascular death, myocardial infarction, stroke, or amputation occurred 248 times in the oral-anticoagulants group and 275 times in the aspirin group (0.89 [0.75-1.06]). Patients treated with oral anticoagulants had more major bleeding episodes than those treated with aspirin (108 vs 56; 1.96 [1.42-2.71]). Oral anticoagulation was better for the prevention of infrainguinal-vein-graft occlusion and for lowering the rate of ischaemic events. Aspirin was better for the prevention of non-venous graft occlusion, and was associated with fewer bleeding episodes.\n", + "output": "Conclusions: Antiplatelet therapy with aspirin had a slight beneficial effect on the patency of peripheral bypass grafts but seemed to have an inferior effect on venous graft patency compared with artificial grafts. The effect of aspirin on cardiovascular outcomes and survival was small and not statistically significant. This might be due to the fact that the majority of patients receiving a peripheral graft have an advanced stage of PAD with critical ischaemia. They are usually seriously ill as a result of cardiovascular disease and have high mortality rates, of 20% per year. Additionally, the number of patients included in this analysis might be too small to reach a statistically significant effect for mortality and cardiovascular morbidity." + }, + { + "input": "Study: Umbilical artery catheterization in newborns. I. Thrombosis in relation to catheter type and position. 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.\n", + "output": "Conclusions: Side hole catheters should be avoided for umbilical arterial catheterisation in the newborn." + }, + { + "input": "Study1: The use of 5,6 benzo-[alpha]-pyrone (coumarin) and heating by microwaves in the treatment of chronic lymphedema of the legs. Sixty patients with leg lymphedema from a variety of etiologies were divided into randomized two groups, matched by Grade, duration, age, sex, and cause of lymphedema. Using a double-blind format, one group received 5,6 benzo-[alpha]-pyrone (coumarin 1,2 benzopyrone, 400 mg/day) for six months; the other received a placebo. For the next six months, both groups received a standardized regimen of heat (using microwaves) coupled with compression garments. Benzopyrone produced approximately 20% reduction in the volume (p = 10(-4)) and improvement in circumferences and tonometry (p = 10(-5) and 10(-7)). Symptoms (feelings of swelling, pain, heaviness and loss of mobility) were also significantly improved (p = 0.03 to 10(-7)). During the second six months, when microwave heat therapy was added to drug therapy, the patients who had previously received the placebo showed significant improvement (p = 0.03 to 10(-9)) in signs and symptoms of lymphedema. Some, but not all, of the group that was receiving benzopyrones were also significantly improved by heat therapy (p = 0.8 to 0.002). Taking benzopyrones for 12 months plus heat treatment for six months was significantly better, for some criteria, than the placebo plus heat therapy (p = 0.7 to 0.04). On the other hand, heat plus either placebo or benzopyrone was often significantly better than either the active or inactive drug without heat (p = 0.8 to 10(-9)).\nStudy2: A double-blind, cross-over trial of O-(beta-hydroxyethyl)-rutosides (benzo-pyrones) in the treatment of lymphoedema of the arms and legs. A randomised, double-blind, cross-over trial was performed on 26 patients with postmastectomy lymphoedema of the arm, and 14 with lymphoedema of the leg. For 6 months, patients took 0-(beta-hydroxyethyl)-rutosides (oxerutin; \"Paroven\", \"Venoruton\", Zyma) in doses of 3 g/day, or the placebos; then they took the reverse. Measurements (volume, circumferences, tonometry and skin temperature) were made monthly. The active drug reduced the volumes of the limbs (p less than 0.05 to 0.01) and their circumferences (p less than 0.05 to 0.001). It increased the softness of the limbs, as shown by the increases in the tonometry values (p less than 0.01 to 0.001). There was a lowering of the elevated skin temperatures (p less than 0.05 to 0.001). Patients reported increased comfort and freedom of movement, a lessening of their bursting pains, heaviness and tension (p less than 0.05 to 0.01), and an increased mobility of their limbs (p less than 0.0001). Most patients (70%) preferred the active drug (p less than 0.0001). An increase in general well-being was reported by 97% of patients when taking the active drug compared with 4% for placebo (p less than 0.0001).\n", + "output": "Conclusions: It is not possible to draw conclusions about the effectiveness of Benzopyrones in the management of lymphoedema from the current available trials." + }, + { + "input": "Study1: The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. II. Chlorthalidone 50 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 50 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reaction.\nStudy2: Comparison of low doses of hydrochlorothiazide plus amiloride and hydrochlorothiazide alone in hypertension in elderly patients. A randomised, double-blind study comparing 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride with 25 mg of hydrochlorothiazide alone was conducted in 40 elderly patients with mild to moderate hypertension. After 8 weeks of treatment, the target blood pressure, supine diastolic blood pressure less than 90 mm Hg, was obtained in 73% of the hydrochlorothiazide plus amiloride treated patients (n = 17) and in 41% of the hydrochlorothiazide treated patients (n = 19; p less than 0.05). However, there was no statistically significant difference in blood pressure reduction between the 2 groups. Four patients dropped out, 3 of them due to side-effects. Serum potassium and magnesium concentrations were reduced in the hydrochlorothiazide group and serum sodium concentration in the hydrochlorothiazide plus amiloride group. Our results suggest that in elderly hypertensive subjects, a higher proportion of patients could be managed with the low dose hydrochlorothiazide plus amiloride regimen than with the low dose hydrochlorothiazide regimen.\nStudy3: The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. I. Chlorthalidone 25 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 25 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reactions.\n", + "output": "Conclusions: ENaC blockers do not have a statistically or clinically significant BP lowering effect at low doses but trials at higher doses are not available. The review did not provide a good estimate of the incidence of harms associated with ENaC blockers." + }, + { + "input": "Study1: Aminophylline therapy for acute bronchospastic disease in the emergency room. To assess the role of aminophylline in the treatment of acute exacerbations of bronchospastic disease when used in addition to inhaled beta-agonists and intravenous corticosteroids. Randomized, double-blind, placebo-controlled intervention study. One hundred thirty-three adult patients with either asthma or chronic obstructive pulmonary disease who presented to the emergency department with asthma or wheezing. All patients received therapy with both aerosolized metaproterenol and intravenous methyl-prednisolone. Patients were randomly assigned to receive either a loading dose of aminophylline followed by a routine infusion (n = 65) or an equal volume of placebo as a loading dose and infusion (n = 68). At discharge from the emergency department, the median serum theophylline concentration for the aminophylline group was 54 mumol/L (9.7 mg/L). The two groups showed no differences (P greater than 0.2) in measurements of forced expiratory volume at 1 second (FEV1), forced vital capacity (FVC), or peak expiratory flow rate (PEFR) at baseline or at 60 or 120 minutes after aminophylline administration. Neither patient satisfaction nor physician assessment of response to therapy differed between the two groups. There was no difference (P greater than 0.2) in the frequency of side effects, except for a trend toward a higher frequency of nausea (P = 0.13) in the aminophylline group. There was, however, a threefold decrease in the hospital admission rate for patients treated with aminophylline (6%) compared with placebo recipients (21%) (P = 0.016). Aminophylline, in doses producing levels just below the commonly accepted therapeutic range, appears to decrease hospital admissions in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. This finding, if confirmed in larger studies, may represent a substantial cost savings.\nStudy2: Intravenous aminophylline in the treatment of acute bronchospastic exacerbations of chronic obstructive pulmonary disease. Often chronic obstructive pulmonary disease (COPD) patients treated for acute exacerbations receive intravenous (IV) aminophylline in addition to inhaled bronchodilators that may raise serum levels of theophylline into the toxic range. A double-blind, randomized study of 52 men with COPD who came to the emergency department for treatment of exacerbations was initiated to establish the efficacy and safety of this common practice. After history and physical examination, patients were treated with 28% oxygen by Venturi mask and 0.3 cc metaproterenol sulfate in 2.5 cc saline by nebulizer; an IV line was started and patients received either aminophylline or D5W. Measurements included baseline and two-hour serum theophylline levels, pulmonary function tests, and symptom questionnaires. Mean values from the entire group showed decreases in respiratory rate, cardiac rate, and pulsus paradoxus, and increases in forced expiratory volume in one second (FEV1) and vital capacity (VC) over a two-hour treatment period (P less than .01). Despite the increase in serum theophylline in the treatment group, the demographic, clinical, pulmonary function, and outcome data were found to have no statistically significant differences when compared to control patients. The data were then analyzed according to serum theophylline levels. Theophylline level greater than 20 micrograms/mL occurred in 15 patients with no untoward effects; premature ventricular contractions (PVCs) were no more frequent in this group than in those with lower serum theophylline levels. A theophylline level greater than 10 micrograms/mL after two hours of treatment resulted in the following differences, which were not statistically significant: mean FEV1 response less than or equal to 10 micrograms/mL vs greater than 10 micrograms/mL, 20% vs 28%; mean VC change, 17% vs 30%; or mean emergency department returns in one week, 0.1 vs 0.26. In our experience, oxygen and inhaled metaproterenol are effective treatment for exacerbations of COPD.\n", + "output": "Conclusions: Given current evidence, methylxanthines should not be used for COPD exacerbations. Possible beneficial effects in lung function and clinical endpoints were modest and inconsistent, whereas adverse effects were significantly increased. More selective agents, tested in larger randomised trials, are necessary if methylxanthines are to have any role in the treatment of COPD exacerbations." + }, + { + "input": "Study: A randomized controlled trial of artemotil (beta-arteether) in Zambian children with cerebral malaria. The efficacy and safety of intramuscular artemotil (ARTECEF) was compared to intravenous quinine in African children with cerebral malaria. This prospective block randomized open-label study was conducted at two centers in Zambia. Subjects were children aged 0 to 10 years of age with cerebral malaria and a Blantyre Coma Score of 2 or less. Ninety two children were studied; 48 received artemotil and 44 quinine. No significant differences in survival, coma resolution time, neurologic sequelae, parasite clearance time, and fever resolution time were seen between the two regimens. Rates for negative malaria smears one month after therapy were similar in both groups. Artemotil was a well-tolerated drug in the 48 patients in this study. It appears to be at least therapeutically equivalent to quinine for the treatment of pediatric cerebral malaria. It has the advantage of being able to be given intramuscularly once daily for only five days.\n", + "output": "Conclusions: More trials with a larger number of participants are needed before a firm conclusion about the efficacy and safety of arteether can be reached." + }, + { + "input": "Study1: Effects of a music therapy intervention on quality of life and distress in women with metastatic breast cancer. This study examined the effects of music therapy (MT), immediate and over time, on patients' psychological functioning, quality of life, and physiologic stress arousal. This intervention, whereby patients use music strategies to cope with cancer-related stressors, is based on a transactional stress-coping framework. Using a longitudinal, randomized controlled design, 70 women with metastatic breast cancer received either MT or usual care. The MT consisted of three individual sessions led by a music therapist. Psychological symptoms were measured with the Hospital Anxiety and Depression Scale and quality of life with the Functional Assessment of Cancer Therapy-General plus a a Spirituality subscale at baseline approximately 6 weeks and 3 months later. Visual analog scales, heart rate, and blood pressure were assessed in the MT group immediately before and after individual session. Significant immediate effects of MT were observed: relaxation, p = < .00001; comfort, p = < . 00001; happiness, p = < .00001; heart rate, p = .0003; although no significant differences between conditions were found over time. A high attrition rate underscored the complexities inherent in conducting intervention research with advanced cancer patients.\nStudy2: Exploring the feasibility of a therapeutic music video intervention in adolescents and young adults during stem-cell transplantation. The purpose of this study was to explore the feasibility and preliminary efficacy of a therapeutic music video (TMV) intervention for adolescents and young adults (AYAs) undergoing stem-cell transplantation (SCT). Twelve AYAs (aged 11-24 years) were randomized to the TMV or an audio-book protocol. The TMV was designed to diminish symptom distress and improve coping, derived meaning, resilience, and quality of life by supporting AYAs in exploring thoughts and feelings. Six sessions with a board-certified music therapist were held twice a week for 3 weeks. The Adolescent Resilience Model guided the selection of a large, comprehensive battery of outcome measures. Major data collections occurred before admission, after intervention, and at 100 days after transplantation. Participants completed a brief set of measures at presession/postsessions 2, 4, and 6. Rates of consent, session completion, and questionnaire completion supported feasibility. Immediate follow-up measures suggest positive trends in the TMV group for hope, spirituality, confidence/mastery, and self-transcendence. Positive trends at 100 days include MOS, symptoms distress, defensive coping, spirituality, and self-transcendence. Therapeutic music video participants also demonstrated gains in quality of life. The TMV intervention may buffer the immediate after-effects of the stem-cell transplantation experience, and a larger study is warranted.\nStudy3: A non-randomized [corrected] controlled trial of the active music engagement (AME) intervention on children with cancer. Coping theorists argue that environmental factors affect how children perceive and respond to stressful events such as cancer. However, few studies have investigated how particular interventions can change coping behaviors. The active music engagement (AME) intervention was designed to counter stressful qualities of the in-patient hospital environment by introducing three forms of environmental support. The purpose of this multi-site randomized controlled trial was to determine the efficacy of the AME intervention on three coping-related behaviors (i.e. positive facial affect, active engagement, and initiation). Eighty-three participants, ages 4-7, were randomly assigned to one of three conditions: AME (n = 27), music listening (ML; n = 28), or audio storybooks (ASB; n = 28). Conditions were videotaped to facilitate behavioral data collection using time-sampling procedures. After adjusting for baseline differences, repeated measure analyses indicated that AME participants had a significantly higher frequency of coping-related behaviors compared with ML or ASB. Positive facial affect and active engagement were significantly higher during AME compared with ML and ASB (p<0.0001). Initiation was significantly higher during AME than ASB (p<0.05). This study supports the use of the AME intervention to encourage coping-related behaviors in hospitalized children aged 4-7 receiving cancer treatment. (c) 2007 John Wiley & Sons, Ltd.\nStudy4: [Role of interactive music in oncological pediatric patients undergoing painful procedures]. The present study has examined whether interactive music may be considered an effective treatment for the attenuation of anxiety in oncological paediatric patients undergoing painful procedures (lumbar injection, bone marrow aspiration, osteomedullary biopsy and arterial catheter). Thirty-nine tumour patients aged between 2 and 12 were randomised into 2 groups: Music (M) (N. 20) and Controls (N. 19) and were treated by M: conscious sedation and intervention of interactive music and C: sedation. The following factors were assessed: temperament on the Emotivity, Activity, Sociability scale, anxiety on the Yale preoperative anxiety scale (mYPAS), the induction compliance checklist (ICC), parent anxiety by cataloguing the trait-state anxiety inventory, and the degree of satisfaction of children, parents and staff using the Barrera questionnaires. Data significance was accepted with values of P<0.05. There was a fall in mYPAS values in M compared to C in the four phases of the process: Phase 1 (P<0.05); Phase 2, 3 and 4 (P<0.01). For the ICC children with a score of 1 were ''non collaborators''; in the music group the trend was for an increase in the number of collaborating children (P<0.07). The M group presents a significant effect of attenuation of anticipatory anxiety and a tendency to great induction compliance compared to group C. The parents do not show any significant anxiety attenuation effect. The degree of satisfaction of children, parents and staff point to a positive role and a beneficial effect of interactive music on the occasion of painful procedures.\nStudy5: Music versus distraction for procedural pain and anxiety in patients with cancer. To test the hypotheses that the effects of a music intervention are greater than those of simple distraction and that either intervention is better at controlling procedural pain and anxiety than treatment as usual. Randomized, controlled experiment. A midwestern comprehensive cancer center. 60 people with cancer having noxious medical procedures such as tissue biopsy or port placement or removal; 58 provided usable data. Participants completed measures of pain and anxiety before and after their medical procedures and provided a rating of perceived control over pain and anxiety after the procedure. Procedural pain, state anxiety, and perceived control over pain and anxiety. Contrary to hypotheses, outcomes achieved with music did not differ from those achieved with simple distraction. Moreover, outcomes achieved under treatment as usual were not significantly different from those obtained with music or distraction interventions. Some patients found that the interventions were bothersome and reported that they wanted to attend to the activities of the surgeon and the medical procedure itself. The effects of music, distraction, and treatment as usual are equivocal. In addition, patients have individual preferences for use of distraction during painful or anxiety-provoking procedures. Patients having noxious medical procedures should be asked about their desire to be distracted before and during the procedure and offered a strategy that is consistent with their preferences.\nStudy6: The effect of the bonny method of guided imagery and music on the mood and life quality of cancer patients. Cancer patients continue to experience elevated levels of emotional distress, even after cancer treatment. Elevated emotional distress negatively impacts immune and endocrine functions and decreases life quality. This study explored the effectiveness of GIM in alleviating mood disturbance and improving quality of life in cancer patients. Eight volunteers with a cancer history were randomly assigned to either an experimental or a wait-list control group. Experimental subjects individually participated in 10 weekly GIM sessions. All subjects completed the Profile of Mood States (POMS) and Quality of Life-Cancer (QOL-CA) questionnaires pretest, posttest, and at a 6-week follow-up. Individuals who participated in GIM sessions scored better on both mood scores and quality of life scores at posttest than those participating in the control group. Additionally, mood and quality of life scores continued to improve in the experimental group, even after sessions were complete. Results indicate that GIM was effective in improving mood and quality of life in these cancer patients.\nStudy7: Use of preferred music to reduce emotional distress and symptom activity during radiation therapy. Music therapy has decreased anxiety levels in many medical settings. This randomized clinical trial examined the effectiveness of a music listening intervention, delivered by a board-certified music therapist, in patients undergoing curative radiation therapy (RT). Emotional distress (anxiety, depression, and treatment-related distress) and symptoms (fatigue and pain) were measured at baseline, mid-treatment, and end of treatment in 63 patients undergoing RT. Although patients who listened to self-selected music reported lower anxiety and treatment-related distress, there was a decline in these outcomes for patients in both groups over the course of RT. Depression, fatigue, and pain were not appreciably affected by music therapy. Within the music group, there was a significant correlation between number of times music was used/week and the change in treatment-related distress, suggesting that higher doses of music produced greater declines in distress. While these findings provided some support for the use of music in reducing distress during RT, further research demonstrating clear differences between intervention and control conditions is needed. Physical symptoms were not affected by the use of music over the course of RT.\nStudy8: Music therapy to reduce pain and anxiety in children with cancer undergoing lumbar puncture: a randomized clinical trial. A nonpharmacological method can be an alternative or complement to analgesics.The aim of this study was to evaluate if music medicine influences pain and anxiety in children undergoing lumbar punctures. A randomized clinical trial was used in 40 children (aged 7-12 years) with leukemia, followed by interviews in 20 of these participants. The participants were randomly assigned to a music group (n = 20) or control group (n = 20). The primary outcome was pain scores and the secondary was heart rate, blood pressure, respiratory rate, and oxygen saturation measured before, during, and after the procedure. Anxiety scores were measured before and after the procedure. Interviews with open-ended questions were conducted in conjunction with the completed procedures. The results showed lower pain scores and heart and respiratory rates in the music group during and after the lumbar puncture. The anxiety scores were lower in the music group both before and after the procedure. The findings from the interviews confirmed the quantity results through descriptions of a positive experience by the children, including less pain and fear.\nStudy9: Effectiveness of music therapy for anxiety reduction in women with breast cancer in chemotherapy treatment. In the last decade, the public use of complementary and alternative therapies for the solution of various health problems has increased dramatically. Listening to music can be considered a support to the traditional medical practice for the reduction of anxiety and stress related to chemotherapy.\nStudy10: Music imagery for adults with acute leukemia in protective environments: a feasibility study. Patients receiving intensive chemotherapy can experience increased distressed related to both the cancer diagnosis and treatment isolation. If not addressed, distress can lead to anxiety, depression, and post-traumatic stress disorder. The purpose of this study was to determine the feasibility and possible benefits of a music imagery intervention for patients hospitalized in a protective environment for the treatment of acute leukemia or high-grade non-Hodgkin's lymphoma. Adults receiving intensive myelosuppressive chemotherapy in a protective environment were randomized to standard care or standard care plus music imagery. The music imagery sessions occurred twice weekly for up to eight sessions. Patients were encouraged to use the music imagery daily. The principal criteria of feasibility were rate of consent, rate of completion of scheduled sessions, and rate of questionnaire completion. Forty-nine out of 78 patients consented, a 63% consent rate. Seventy-two percent of all scheduled music imagery sessions were completed. The rate of questionnaire completion was 60% with missing data because of illness severity and early discharge. The principal outcomes of benefit (e.g., efficacy) were positive and negative affects, fatigue, and anxiety. Both groups improved over time on all outcomes (all p < 0.001). However, a subgroup of individuals with low baseline negative affect who received the intervention reported significantly less anxiety at discharge than individuals with low baseline negative affect who did not receive the intervention. Music imagery is feasible for adults with acute leukemia in protected environments. Patients with lower initial distress may benefit from a music imagery program in terms of reduced anxiety at discharge.\n", + "output": "Conclusions: This systematic review indicates that music interventions may have beneficial effects on anxiety, pain, mood, and QoL in people with cancer. Furthermore, music may have a small effect on heart rate, respiratory rate, and blood pressure. Most trials were at high risk of bias and, therefore, these results need to be interpreted with caution." + }, + { + "input": "Study1: Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient.\nStudy2: A comparative study of danazol, a regimen of decreasing doses of danazol, and norethindrone in the treatment of objectively proven unexplained menorrhagia. Our purpose was to compare the efficacy of the recommended dose of danazol, a reduced-dose danazol regimen, and norethindrone in the treatment of objectively proven menorrhagia. Recurrence after discontinuing treatment was also assessed. The study was a single-blind, randomized, parallel, comparative study. After a placebo run-in period over two menstrual cycles, 57 patients with a baseline mean menstrual blood loss of at least 80 ml per cycle were randomly assigned to receive one of three therapies: danazol, 200 mg/day (n = 19) for three menstrual cycles; danazol, 200 mg/day for one cycle, 100 mg/day for one cycle, and 50 mg/day for one cycle (n = 19); and norethindrone, 5 mg three times daily on days 19 through 26 of the cycle for three consecutive cycles (n = 19). Patients in whom treatment was successful (those experiencing blood loss < 80 ml) were entered in the follow-up phase of the study, receiving placebo for a maximum of four menstrual cycles. The final menstrual blood loss on treatment was significantly less for those patients who received both danazol regimens compared with those who received norethindrone (p = 0.017 for reducing dose danazol vs norethindrone and p = 0.043 for 200 mg of danazol vs norethindrone). Both danazol treatment regimens were significantly more successful in reducing menstrual blood loss to within the normal range than was norethindrone. The reducing-dose danazol regimen was successful in eight of 17 patients (p = 0.027), and 200 mg of danazol was successful in nine of 19 patients (p = 0.029), compared with the two successes of 18 patients treated with norethindrone. Significantly more recipients of 200 mg of danazol than of norethindrone subjectively rated their treatment to be moderately or highly effective (p = 0.033). Both danazol treatment regimens were associated with a higher incidence of adverse events than was norethindrone therapy, although the number of withdrawals were similar and infrequent in the three groups. Both danazol regimens were significantly more effective than norethindrone in reducing the excessive menstrual blood loss of women with unexplained menorrhagia. A subjective assessment by patients found that only the 200 mg of danazol was judged to be significantly more effective than norethindrone in controlling the heaviness of menstrual bleeding. The reduced-dose danazol regimen did not appear to markedly diminish the incidence of adverse events compared with the 200 mg of danazol regimen.\n", + "output": "Conclusions: Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments. The use of Danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. The small number of trials, and the small sample sizes of the included trials limit the recommendations for clinical care. Further studies are unlikely in the future and this review will not be updated unless further studies are identified." + }, + { + "input": "Study1: The efficacy of etodolac for patients with pain following oral surgery. The analgesic efficacy of etodolac for 161 patients reporting moderate to severe pain after oral surgery was evaluated. The patients were given single oral doses of one of the following test drugs--aspirin, 650 mg; etodolac, 50 mg; or etodolac, 200 mg--or placebo. There were at least 39 patients in each drug group. After medication, patients recorded pain intensity and pain relief at half-hour intervals for the first hour and then hourly for up to eight hours. Pain intensity differences, total pain relief, onset of analgesia, and each patient's overall opinion of the drug were analyzed. Time--effect curves were derived from the pain relief and pain intensity difference scores. Analgesic effects produced by both doses of etodolac were comparable with those of 650 mg of aspirin. All active drugs were significantly more effective than placebo, and the 200-mg dose of etodolac provided an earlier onset and longer duration of analgesia than the other test drugs.\nStudy2: Etodolac in postsurgical pain: a double-blind dose-ranging efficacy study with aspirin and placebo. A study was conducted to compare the analgesic activity of single oral doses of etodolac (25, 50, 100, 200, and 400 mg) with 650 mg aspirin and placebo. A total of 146 patients with moderate or severe pain from orthopedic or urologic interventions received one of the test medications 13-25 h after the beginning of surgery and according to a randomized allocation balanced as to initial pain intensity. Data for pain intensity and pain relief were collected at 1/2 h and then hourly for 8 h. Vital signs and adverse reactions were also recorded. One hundred and forty-two patients completed the study: four were excluded because of protocol deviations. The average response to 100, 200, and 400 mg of etodolac was superior to that of placebo. On the basis of SPID, TOTPAR, and duration of analgesia, 400 mg etodolac was also significantly more effective than 650 mg aspirin. Mild side effects probably or possibly related to etodolac were reported by three patients. This study provides evidence that etodolac in doses of 100 mg and higher is an effective and well-tolerated analgesic.\nStudy3: Comparison of etodolac, aspirin and placebo for pain after oral surgery. Single oral doses of etodolac 50, 100 and 200 mg were compared with aspirin 650 mg and placebo in a double-blind, parallel group study of 189 outpatients reporting moderate or severe pain after oral surgery. Overall efficacy of test drugs was evaluated by sum of pain intensity difference (SPID) scores and total pain relief (TOTPAR) scores over 0.5-3, 0.5-6, 0.5-8 and 0.5-12 hours. Etodolac 200 mg provided significantly greater analgesia than aspirin by these measurements over all SPID and all but one TOTPAR interval, and was significantly more effective than placebo over all intervals. Etodolac 100 mg was superior to aspirin for SPID 0.5-8 and 0.5-12 hours, and superior to placebo for both SPID and TOTPAR over all time intervals. Onset of analgesia for etodolac 100 mg, 200 mg and aspirin was 1 hour or less for the majority of patients in each group; 42% receiving etodolac 200 mg reported onset of analgesia within 0.5 hour. Duration of analgesia for etodolac 200 mg appeared twice that of aspirin. A significant positive dose-response relationship was obtained for the three doses of etodolac. A low frequency of side effects was observed in all treatment groups.\nStudy4: The effectiveness of 100 and 200 mg etodolac (Ultradol), aspirin, and placebo in patients with pain following oral surgery. The analgesic efficacy of etodolac (Ultradol) was evaluated in 168 patients experiencing moderate to severe pain following oral surgery. The patients were given either etodolac 100 mg, etodolac 200 mg, aspirin 650 mg, or placebo. There was a minimum of forty patients in each drug group. Patients recorded pain intensity and pain relief at 1/2 hour and then hourly for up to 12 hours after medication. The efficacy variables analyzed were the sum of pain-intensity differences, total pain relief, onset of analgesia, and the patient's opinion of the study drug. Time-effect curves were made from the pain-relief and pain-intensity difference scores. The analgesic potency of both 100 and 200 mg of etodolac was comparable to 650 mg of aspirin and superior to placebo. Like aspirin, both doses of etodolac showed significant analgesia within one hour and a significantly longer duration of action than placebo.\n", + "output": "Conclusions: Etodolac 200 mg may be a useful analgesic in postoperative pain, with efficacy similar to paracetamol 1000 mg and celecoxib 200 mg. Higher doses may provide analgesia equivalent to more commonly used drugs, such as ibuprofen 400 mg, naproxen 500 mg and diclofenac 50 mg." + }, + { + "input": "Study: Trial of nurse-run asthma clinics based in general practice versus usual medical care. The aim of this study was to assess the ability of nurse-run asthma clinics based in general practice compared with usual medical care to produce at least a moderate improvement in the quality of life of adults with asthma. A randomized controlled trial involving 80 asthma clinic and 90 usual medical care asthma participants, aged 18 years and older was conducted in 11 general practices in Adelaide. The main outcome measure was the St George's respiratory questionnaire (SGRQ), from which quality-of-life scores were used to assess therapeutic benefit. Lung function measurements and health services utilization data were also collected. One hundred and fifty-three participants (90%) were reviewed at follow up after 6-9 months. There was little difference between groups in baseline measures or for the 6-month follow-up outcomes, including the mean difference in total SGRQ scores (-0.5, 95% confidence interval (CI) -4.0, 2.9) and the mean difference in percentage predicted FEV(1) (2.3%, 95% CI -0.7, 5.3 pre-bronchodilator; 0.4%, 95% CI -5.1, 5.9 post-bronchodilator). Trends in health services utilization were noted. Nurse-run asthma clinics based in general practice and usual medical care were similar in their effects on quality of life and lung function in adults. These findings cannot be generalized to hospital outpatients and other clinics that manage more severe asthmatic patients.\n", + "output": "Conclusions: We found no significant difference between nurse-led care for patients with asthma compared to physician-led care for the outcomes assessed. Based on the relatively small number of studies in this review, nurse-led care may be appropriate in patients with well-controlled asthma. More studies in varied settings and among people with varying levels of asthma control are needed with data on adverse events and health-care costs." + }, + { + "input": "Study1: Comparison of posttonsillectomy pain using the ultrasonic scalpel, coblator, and electrocautery. To compare postoperative tonsillectomy pain between 3 commonly used surgical devices: the Harmonic Ultrasonic Scalpel (Ethicon Endo-Surgery, Cincinnati, OH), the Coblator (ArthroCare Corp, Sunnyvale, CA), and electrocautery. A prospective, randomized trial. One hundred thirty-four patients were randomly assigned to receive a tonsillectomy with 1 of 3 surgical devices. All patients were asked to fill out a postoperative diary. Statistically significant differences in pain scores were revealed between the Coblator and electrocautery (P = 0.02) and between the Coblator and the Ultrasonic Scalpel (P = 0.003), with the Coblator having lower pain scores. Electrocautery and the Ultrasonic Scalpel did not differ significantly from each other. The Coblation method showed a strong trend toward quicker return to normal diet. Patients undergoing tonsillectomy with the Coblator device reported less pain over a 10-day period than patients undergoing tonsillectomy with electrocautery or the Ultrasonic Scalpel. Pain after tonsillectomy remains a major issue for our patients. The choice of surgical instrument appears to be one way to reduce this pain. EBM rating: A-1b.\nStudy2: A double-blinded randomized controlled trial of coblation versus conventional dissection tonsillectomy on post-operative symptoms. The aim of this study was to compare postoperative symptoms following coblation tonsillectomy with those experienced following a traditional cold dissection. A prospective randomized controlled trial. Secondary otorhinolaryngology care. Ninety-two adult patients with recurrent tonsillitis meriting tonsillectomy were recruited and randomly allocated into either coblation or cold dissection tonsillectomy groups. Primary outcomes were post-operative pain, otalgia, swallowing and analgesia use at 6-8 hours, 1, 3, 7 and 14 days post-operative. Secondary outcomes were post-operative day returned to eating and returned to normal activities/work. No significant differences between the two groups (P >or= 0.1) were found in any of the above primary outcomes, apart from swallowing at 6-8 hrs post-operatively where the cold dissection group had less pain. This group also returned earlier to normal eating (P = 0.03). The power of the study was sufficient to show a difference in the visual analogue scores of 2 between groups. The use of coblation to perform tonsillectomy does not confer any symptomatic benefits to the patient over conventional cold dissection tonsillectomy.\nStudy3: Tonsillectomy by means of plasma-mediated ablation: prospective, randomized, blinded comparison with monopolar electrosurgery. To compare plasma-mediated ablation (PMA) with monopolar electrosurgery (MES) for pediatric tonsillectomy. Prospective, randomized, blinded study. Academic children's hospital. Thirty-four children, aged 4 to 7 years. Tonsillectomy by means of PMA (n = 17) or MES (n = 17). We measured surgical efficacy, estimated blood loss, and surgical time during tonsillectomy and morphine use, immediate postoperative pain, and recovery scores after tonsillectomy. Parents recorded recovery of normal diet and activity and their own return to work for 10 days after surgery. Histopathologic evaluation of excised tonsils was performed. We reviewed medical records and attempted follow-up telephone contact. With no significant difference in blood loss compared with MES, PMA was effective for tonsillectomy. Performance of PMA took longer (24 vs 16 minutes; P =.002). Results of histopathologic evaluation showed less thermal injury with PMA than with MES (P =.03). Morphine consumption, pain, and recovery scores were equivalent between groups. We found no significant difference in recovery of normal diet and activity or parental return to work. Patients undergoing PMA had a greater number of perioperative complications than those undergoing MES, including 2 patients in the PMA group (compared with none in the MES group) who required unplanned admission for postoperative airway obstruction. Plasma-mediated ablation for pediatric tonsillectomy resulted in less histopathologic thermal injury than MES, but did not show a statistically faster recovery to normal activity and diet or parental return to work. In addition, PMA took longer to perform, and had more complications. Therefore, PMA should not replace MES for pediatric tonsillectomy. The reduced thermal injury with PMA supports investigation into other means of using plasma ablation to treat tonsillar hypertrophy.\n", + "output": "Conclusions: In terms of postoperative pain and speed and safety of recovery, there is inadequate evidence to determine whether coblation tonsillectomy is better or worse than other methods of tonsillectomy. Evidence from a large prospective audit suggests that it has been associated with a higher level of morbidity, in terms of postoperative bleeding. Large, well-designed randomised controlled trials supplemented by data from large prospective audits are needed to produce information on effectiveness and morbidity respectively." + }, + { + "input": "Study1: Caregiver bereavement outcome: relationship with hospice at home, satisfaction with care, and home death. This study used a randomized controlled trial design to investigate the impact of hospice at home (HAH) on caregiver bereavement outcome. Secondary analyses considered the association between bereavement, place of death, and carers' assessment of support. Ninety-six informal carers of patients referred to HAH were surveyed six weeks post-bereavement about the quality of terminal care. Carers next completed measures of their own bereavement response and general health six months post-bereavement. There was no evidence that HAH had an impact on bereavement outcome. In contrast, perceptions of inadequate terminal support and high symptom severity were associated with worse carer bereavement response. However, it remains unclear whether carers' retrospective ratings constitute an accurate account of symptoms and care. Home deaths were associated with both better bereavement response and better physical health post-bereavement than were inpatient deaths. Further research is needed to investigate the implications of death at home for the carer.\nStudy2: A randomized trial of the cost effectiveness of VA hospital-based home care for the terminally ill. All admissions to a 1,100-bed Department of Veterans Affairs (VA) hospital were screened to identify 171 terminally ill patients with informal caregivers who were then randomly assigned to VA hospital-based team home care (HBHC, N = 85) or customary care (N = 86). Patient functioning, and patient and caregiver morale and satisfaction with care were measured at baseline, one month, and six months. Health services utilization was monitored over the six-month study period and converted to cost. Findings included no differences in patient survival, activities of daily living (ADL), cognitive functioning, or morale, but a significant increase in patient (p = .02) and caregiver (p = .005) satisfaction with care at one month. A substitution effect of HBHC was seen. Those in the experimental group used 5.9 fewer VA hospital days (p = .03), resulting in a $1,639 or 47 percent per capita saving in VA hospital costs (p = .02). As a result, total per capita health care costs, including HBHC, were $769 or 18 percent (n.s.) lower in the HBHC sample, indicating that expansion of VA HBHC to serve terminally ill veterans would increase satisfaction with care at no additional cost.\nStudy3: A palliative-care intervention and death at home: a cluster randomised trial. The Palliative Medicine Unit at University Hospital of Trondheim, Norway, started an intervention programme that aims to enable patients to spend more time at home and die there if they prefer. Close cooperation was needed with the community health-care professionals, who acted as the principal formal caregivers, and a multidisciplinary consultant team coordinated the care. We did a cluster randomised trial to assess the intervention's effectiveness compared with conventional care Community health-care districts in and around Trondheim, Norway, were defined as the clusters to be randomised. We enrolled 434 patients (235 assigned intervention and 199 conventional care [controls]) in these districts who had incurable malignant disease and an expected survival of 2-9 months. Main outcomes were place of death and time spent in institutions in the last month of life. 395 patients died. Of these, more intervention patients than controls died at home (54 [25%] vs 26 [15%], p<0.05). The time spent at home was not significantly increased, although intervention patients spent a smaller proportion of time in nursing homes in the last month of life than did controls (7.2 vs 14.6%, p<0.05). Hospital use was similar in the two groups. The palliative-care intervention enabled more patients to die at home. More resources for care in the home (palliative care training and staff) and an increased focus on use of nursing homes would be necessary, however, to increase time at home and reduce hospital admissions.\nStudy4: Increased satisfaction with care and lower costs: results of a randomized trial of in-home palliative care. To determine whether an in-home palliative care intervention for terminally ill patients can improve patient satisfaction, reduce medical care costs, and increase the proportion of patients dying at home. A randomized, controlled trial. Two health maintenance organizations in two states. Homebound, terminally ill patients (N=298) with a prognosis of approximately 1 year or less to live plus one or more hospital or emergency department visits in the previous 12 months. Usual versus in-home palliative care plus usual care delivered by an interdisciplinary team providing pain and symptom relief, patient and family education and training, and an array of medical and social support services. Measured outcomes were satisfaction with care, use of medical services, site of death, and costs of care. Patients randomized to in-home palliative care reported greater improvement in satisfaction with care at 30 and 90 days after enrollment (P<.05) and were more likely to die at home than those receiving usual care (P<.001). In addition, in-home palliative care subjects were less likely to visit the emergency department (P=.01) or be admitted to the hospital than those receiving usual care (P<.001), resulting in significantly lower costs of care for intervention patients (P=.03). In-home palliative care significantly increased patient satisfaction while reducing use of medical services and costs of medical care at the end of life. This study, although modest in scope, presents strong evidence for reforming end-of-life care.\n", + "output": "Conclusions: The evidence included in this review supports the use of end of life home-care programmes for increasing the number of patients who will die at home, although the numbers of patients being admitted to hospital while receiving end of life care should be monitored. Future research should also systematically assess the impact of end of life home care on care givers." + }, + { + "input": "Study1: The use of modeling and role playing to increase social interaction among asocial psychiatric patients. nan\nStudy2: Social dramatics: social skills development for the chronically mentally ill. The purpose of this study was to investigate the use of social dramatics as a clinical tool for teaching social skills to the chronically mentally ill on adult inpatient units of a state hospital. The research tested the hypothesis that patients exposed to social dramatics with videotape feedback would demonstrate greater ability to perform social skills as measured by the Nurses' Observation Scale for Inpatient Evaluation (NOSIE-30). Fifteen schizophrenic adults of both sexes meeting specific criteria were randomly assigned to experimental and control groups. Subjects were exposed over an 8-week period to randomly introduced social dramatic scenarios. The Wilcoxin test for two independent samples was used for testing differences between experimental and control groups. The research findings supported the hypothesis for one positive factor, social competence. The findings did not support any treatment effect on either social interest and personal neatness or irritability, manifest psychosis, and psychotic depression. There were no significant differences on the total score NOSIE-30. Recommendations for psychiatric nursing are made. Limitations of research methodologies and sample size were addressed.\nStudy3: Movement and drama therapy with long-stay schizophrenics. nan\n", + "output": "Conclusions: Randomised studies are possible in this field. The use of drama therapy for schizophrenia and schizophrenia-like illnesses should continue to be under evaluation as its benefits, or harms, are unclear." + }, + { + "input": "Study: Nutritional factors and rest reduce pregnancy-induced hypertension and pre-eclampsia in positive roll-over test primigravidas. The possibility of reducing pregnancy-induced hypertension and preeclampsia in primigravidas with low doses of nutritional factors and relative rest in the left lateral position was investigated in a randomized controlled, double-blind trial. Seventy-four normotensive women at 28-29 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because they presented with a mean blood pressure of 80 mmHg or higher and a positive roll-over test, were studied. The treatment protocol was received by 37 women and the other 37 women received standard antenatal control until delivery. Twenty-nine (78.3%) women in the control group developed PIH and/or pre-eclampsia, as opposed to only 4 (10.8%) cases in the treatment group (P < 0.001). There were no adverse effects of treatment in mothers or in infants. This protocol reduces PIH and pre-eclampsia in primigravidas judged to be at risk of hypertension. Further studies are required to evaluate prostacyclin and prostaglandin E2 changes.\n", + "output": "Conclusions: Daily rest, with or without nutrient supplementation, may reduce the risk of pre-eclampsia for women with normal blood pressure, although the reported effect may reflect bias and/or random error rather than a true effect. There is no information about outcomes such as perinatal mortality and morbidity, maternal morbidity, women's views, adverse effects, and costs. Current evidence is insufficient to support recommending rest or reduced activity to women for preventing pre-eclampsia and its complications. Whether women rest during pregnancy should therefore be a matter of personal choice." + }, + { + "input": "Study1: A double-blind placebo controlled trial of simvastatin for the treatment of dyslipidaemia in renal allograft recipients. With current techniques, renal failure patients are now able to regain near-normal health following renal transplantation. However, the development of premature cardiovascular disease is a major problem. Dyslipidaemia may be an important contributor to this. The use of lipid lowering agents in renal allograft recipients has been limited by potential interaction of these agents with the now widely used immunosuppressive agent, cyclosporine. This study was designed to investigate efficacy and safety of simvastatin in subjects taking either cyclosporine or azothioprine post renal transplantation. Fifty-one subjects (32 females, 19 males -- mean age 51 +/- 12.5 yr) who were at least 1 yr post transplant, had creatinine < or = 2.5 mmol/L and a total cholesterol > or = 6 mmol/L were enrolled in a prospective, double-blind, placebo-controlled study. After an initial 10-wk dietary period, the last 4 wk on placebo, subjects were randomised to receive either 5 mg simvastatin/d for 6 wk followed by 10 mg simvastatin/d for 6 wk, or matching placebo. After this 12-wk double-blind phase, there was an open-label phase when all subjects were treated with 10 mg simvastatin/d for a period of 36 wk. Compared to placebo, 5 mg simvastatin/d significantly decreased total cholesterol by 20% (p < 0.01), low-density lipoprotein cholesterol (LDL cholesterol) by 29% (p < 0.01), and Apolipoprotein B (ApoB) by 26% (p < 0.01). Increasing simvastatin to 10 mg/d did not lead to further significant changes. But high-density lipoprotein cholesterol (HDL cholesterol) increased by 9% (p < 0.01) and Apolipoprotein A1 (ApoA1) by 7% (p < 0.01) only on 10 mg simvastatin/d. During the open-label phase, subjects previously randomised to placebo achieved similar significant changes to their lipoprotein profile. The benefits achieved from simvastatin were maintained to the end of the study. There were three withdrawals from the study, all from the simvastatin/ cyclosporine group. Two subjects had musculoskeletal pain and 1 had abdominal pain. Minor adverse events were similar in both the simvastatin- and placebo-treated groups. Low-dose simvastatin is an effective and well-tolerated agent in the treatment of dyslipidaemia in renal allograft recipients.\nStudy2: Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population. We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat. After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups. Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.\nStudy3: Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient. In patients after renal transplantation functional arterial vessel wall properties are impaired. Whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have a sustained effect on endothelial function and arterial distensibility in patients after renal transplantation is not clear. The authors studied the effects of a long-term therapy with fluvastatin on large artery distensibility and flow-mediated vasodilation (FMD) in hypercholesterolemic patients after renal transplantation in a prospective, blinded, and randomized trial. Twenty-six patients who had undergone renal transplantation were assigned randomly to either fluvastatin, 40 mg/d (n = 13) or placebo (n = 13) and underwent follow-up for 3 years. At baseline and after 6, 12, and 36 months of treatment, carotid and brachial artery distensibility, endothelium-dependent FMD, and nitroglycerine-induced vasodilation (NMD) of the brachial artery were measured by a echo-tracking device. A significant decrease in total and low-density cholesterol was observed after 6, 12, and 36 months in patients treated with fluvastatin but not in the placebo group. FMD increased with fluvastatin from 4.6 +/- 2% to 12.4 +/- 2% after 12 months; this improvement was sustained with 13.4 +/- 3% after 36 months (P < 0.05). However, placebo did not alter FMD (P < 0.001 for trend difference between groups by analysis of covariance). Endothelium-independent NMD was similar in both groups at baseline and during therapy. Neither carotid nor brachial artery distensibility coefficients were altered by either treatment. HMG-CoA reductase inhibitor therapy over 3 years results in a significant and sustained improvement of endothelial function in hypercholesterolemic patients after renal transplantation. However, this is not accompanied by a beneficial effect on impaired large artery distensibility even after long-term therapy with fluvastatin.\nStudy4: Safety and efficacy of simvastatin for hyperlipidemia in renal transplant recipients: a double-blind, randomized, placebo-controlled study. nan\nStudy5: Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection. 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitors are established anti-lipidemic agents. They also exert immunomodulatory effects. Two recent reports suggest that pravastatin may be useful in decreasing the incidence and severity of acute rejections (ARs) in heart and kidney transplant recipients. We undertook this prospective, randomized, placebo-controlled, double blind trial to investigate the effect of lovastatin on acute renal allograft rejection. Sixty-five consecutive, one-haplotype-matched, living related first renal transplant recipients were randomized to receive either lovastatin 20 mg/d or placebo for 3 months, in addition to cyclosporine, azathioprine, and steroids. Lipid levels, AR episodes, and liver and muscle enzymes were followed for 3 months post-transplant. At the end of the study period, lovastatin had successfully controlled lipid levels. However, there was no effect on AR episodes (15.15% in the treatment group vs. 18.75% in the placebo group).\nStudy6: Efficacy and drug interactions of the new HMG-CoA reductase inhibitors cerivastatin and atorvastatin in CsA-treated renal transplant recipients. Hyperlipidaemia is an important risk factor for cardiovascular disease in renal transplant recipients. The aim of this study was to test the efficacy and possible drug-drug interactions of the new HMG-CoA reductase inhibitors (statins) atorvastatin and cerivastatin in cyclosporin A (CsA)-treated renal transplant patients. Subjects and methods. Thirty patients with stable graft function and LDL cholesterol of 130 mg/dl were randomly assigned to active treatment groups (10 mg atorvastatin or 0.2 mg cerivastatin), or a control group. CsA blood trough levels were controlled on a weekly basis and adapted if they changed more than 25% from baseline values (100-150 ng/ml). Lipid levels and routine laboratory parameters before and after a treatment period of 3 months were compared. In the group treated with cerivastatin no significant changes in CsA blood trough levels occurred (CsA 116+/-21 ng/ml vs 110+/-20 ng/ml). In contrast, in the group treated with atorvastatin, four of 10 patients had a rise in CsA blood trough levels of more than 25% within 7-14 days of starting therapy. In the remaining patients no significant changes in CsA drug levels occurred. After therapy with atorvastatin or cerivastatin, total cholesterol, LDL cholesterol, and triglycerides were significantly lower compared with baseline conditions. No changes of CsA or lipoprotein levels were present in the control group. In our study population both statins were very effective in lowering elevated LDL cholesterol levels. Cerivastatin did not influence CsA blood trough levels, whereas atorvastatin increased CsA levels in four of 10 patients. Further research in a larger study is necessary in order to confirm these results and to investigate the possible reasons for this drug interaction.\nStudy7: Low-dose simvastatin is a well-tolerated and efficacious cholesterol-lowering agent in ciclosporin-treated kidney transplant recipients: double-blind, randomized, placebo-controlled study in 40 patients. The high prevalence of hypercholesterolemia in kidney transplant recipients probably contributes to the high cardiovascular mortality in these patients. Except for diet, there is no generally recommended cholesterol-lowering treatment. We conducted a double-blind, randomized, placebo-controlled study with low-dose simvastatin in 40 ciclosporin (CS)-treated kidney transplant recipients during 16 weeks, focusing on side effects and dose finding. In the simvastatin group, the mean serum total and LDL cholesterol concentrations decreased by 23 and 33%, respectively, and the mean serum HDL cholesterol concentration increased by 12%, after 4 weeks of treatment with simvastatin 10 mg daily. Increasing the dose to 20 mg daily in a few patients only resulted in marginal further reductions of the serum cholesterol concentrations at the expense of doubling the plasma simvastatin 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity concentrations. The differences between the changes in the serum cholesterol concentrations in the simvastatin group and the negligible changes in the placebo group were statistically significant. There was no case of proximal myopathy and the serum creatine kinase concentrations did not differ between treatment groups. In conclusion, low-dose simvastatin appears to be a well tolerated and efficacious cholesterol-lowering treatment in CS-treated kidney transplant recipients. Simvastatin 10 mg daily seems to be the most suitable dose for the majority of these patients.\nStudy8: Effect of fluvastatin on acute renal allograft rejection: a randomized multicenter trial. Statin therapy has been reported to reduce the acute rejection rate following renal transplantation in a pilot study. The present study is the first randomized, double-blind and adequately powered study to examine the effect of statins on acute rejection of renal allografts. A total of 364 patients were randomly assigned to receive either fluvastatin 40 mg or placebo in combination with conventional cyclosporine-based immunosuppressive therapy. The primary end point was treated first acute rejection. Secondary end points included biopsy-proven rejection, histological severity of rejection, occurrence of steroid-resistant rejection, and serum creatinine at three months following transplantation. Fluvastatin was well tolerated; no patients developed myositis or rhabdomyolysis. There was no difference in the acute rejection rate [86 (47.3%) fluvastatin vs. 87 (47.8%) placebo] and no significant difference in the severity of rejection, steroid resistant rejection or mean serum creatinine at three months (160 micromol/L vs. 160 micromol/L). Total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglyceride levels increased following renal transplantation. With the exception of the increase in HDL-C, which was augmented, the increases in lipid parameters were significantly reduced by fluvastatin (total cholesterol +17.5% vs. 35.7%; LDL-C +6.3% vs. 46.7%; HDL-C +43.3% vs. 38.1%; triglyceride +52.2% vs 77.6%). Contrary to the reported effects of statins, fluvastatin had no effect on the incidence or severity of acute rejection following renal transplantation. There were no increases in adverse events. A significant and potentially beneficial alteration in the lipid profile was observed in the early post transplant period. We conclude that fluvastatin may be used safely to correct dyslipidemia in patients with end-stage renal failure through the peri-transplant period.\nStudy9: Pravastatin improves low-density lipoprotein oxidation in renal transplantation. nan\nStudy10: The effects of lipid-lowering agents on acute renal allograft rejection. Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown. Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52). Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study. Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.\n", + "output": "Conclusions: Statins significantly reduced hyperlipidaemia and tended to reduce cardiovascular events in kidney transplant recipients, but no effect has yet been demonstrated for mortality outcomes. Most of the data was derived from one large long-term study. Considering the significant impact of statins on all-cause and cardiovascular mortality in the general and predialysis populations, more studies are needed in kidney transplant patients." + }, + { + "input": "Study1: Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease. Tumour necrosis factor-alpha (TNF alpha) is thought to have a central role in the pathogenesis of Crohn's disease. We tested the hypothesis that CDP571, a genetically engineered human antibody to TNF alpha, is effective in modifying disease activity in patients with moderately active Crohn's disease. In this double-blind, placebo-controlled study, 31 patients were randomly assigned to CDP571 (n = 21) or placebo (n = 10). The primary endpoint was change in Crohn's disease activity index 2 weeks after a single infusion of CDP571 (5 mg/kg), or human albumin as placebo. One patient who attended no follow-up assessments was excluded from the analyses (CDP571 group). The median Crohn's disease activity index fell from 263 (IQR 186.5-323.5) at baseline to 167 (137.5-294.0) at 2 weeks in the CDP571-treated patients (p = 0.0003); the change in the placebo group (253 [240-334] to 247 [183-256]) was not significant. In the treated group, there were also significant differences between baseline and 2 weeks in Harvey-Bradshaw score (p = 0.0005), key symptom score (p = 0.049), alpha 1-glycoprotein concentration (p = 0.012), and erythrocyte sedimentation rate (p = 0.01); concentrations of C-reactive protein fell, but not significantly (p = 0.067). Six patients achieved remission (Crohn's disease activity index < or = 150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group. A single 5 mg/kg infusion of CDP571 reduced disease activity in Crohn's disease at 2 weeks. These data suggest that antibody neutralisation of TNF alpha is a potentially effective strategy in the management of Crohn's disease. The use of CDP571 in Crohn's disease requires further study.\nStudy2: An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial. We evaluated CDP571, a humanized antibody to tumor necrosis factor, for the treatment of active Crohn's disease. One hundred sixty-nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week placebo-controlled trial. Patients were initially randomized to a single dose of 10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess subsequent dosing intervals. The primary endpoint was clinical response at week 2, defined as a decrease in the Crohn's Disease Activity Index score > or = 70 points. At week 2, clinical response occurred in 45% of CDP571-treated patients compared with 27% of patients in the placebo group (P = 0.023). Patients appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of the results for secondary endpoints were statistically significant. The frequency of severe or serious adverse events was similar among all groups. CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment of patients with moderate-to-severe Crohn's disease. Preliminary evidence suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks may also be beneficial, but additional studies are needed.\nStudy3: Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. We evaluated etanercept, a human soluble tumor necrosis factor receptor: Fc fusion protein, for the treatment of active Crohn's disease. Forty-three patients with moderate to severe Crohn's disease were enrolled in an 8-week placebo-controlled trial. Patients were randomized to subcutaneous etanercept 25 mg or placebo twice weekly. The primary outcome measure was clinical response at week 4, defined as a decrease in the baseline Crohn's Disease Activity Index score > or =70 points or a Crohn's Disease Activity Index score <150 points. At week 4, 39% of etanercept-treated patients had clinical response as compared with 45% of placebo-treated patients (P = 0.763). The frequency of common adverse events including headache, new injection site reaction, asthenia, abdominal pain, Crohn's disease-related anemia, and skin disorders was similar in both groups. Likewise, the frequency of severe or serious adverse events was similar in both groups. Subcutaneous etanercept at a dose of 25 mg twice weekly is safe, but not effective, for the treatment of patients with moderate to severe Crohn's disease. The dose of etanercept administered in this study is that approved for rheumatoid arthritis. Higher doses or more frequent dosing may be required to attain a response in patients with active Crohn's disease.\n", + "output": "Conclusions: Evidence from one randomized controlled trial suggests that a single infusion of infliximab may be effective for induction of remission in Crohn's disease. Based on this study, we can recommend a dose of 5 mg/kg. There is also some evidence that CDP571 may be effective in inducing remission in Crohn's disease. We did not find any evidence that supports the use of etanercept in Crohn's disease. The period of follow up for the patients in these studies was probably too short to allow adequate assessment of recently reported serious adverse effects such as tuberculosis and lymphoma." + }, + { + "input": "Study1: The effect of oral magnesium substitution on pregnancy-induced leg cramps. Our purpose was to determine whether women with pregnancy-related leg cramps would benefit from oral magnesium supplementation. Seventy-three women with pregnancy-related leg cramps were interviewed about their symptoms in a prospective, double-blind, randomized trial. Initial serum magnesium levels and diurnal magnesium excretion was determined in 50% of the patients. Oral magnesium or placebo was given for 3 weeks, after which new interviews and laboratory analyses were performed. Serum magnesium levels in these patients were at or below the lower reference limit, as is also often the case in healthy pregnant patients. Oral magnesium substitution decreased leg cramp distress (p < 0.05 compared with the placebo group, p < 0.001 compared with initial complaints), but did not significantly increase serum magnesium levels, excess magnesium being excreted as measured by an increase in urinary magnesium levels (p < 0.002). Oral magnesium supplementation seems to be a valuable therapeutic tool in the treatment of pregnancy-related leg cramps.\nStudy2: Effects of a multivitamin mineral supplement on zinc and copper status during pregnancy. The effect of a multivitamin-mineral supplement was investigated during pregnancy according to a double-blind protocol by determining zinc and copper in maternal plasma, mononuclear and polynuclear zinc and copper at the third, sixth, eighth, and ninth months of gestation. The subjects were supplemented from the first trimester until delivery. A significant decrease was observed in plasma zinc that varied from 11.5 mumol/L to 10.8 mumol/L in the supplemented group (n = 29) and from 11 mumol/L to 10 mumol/L in the placebo group (n = 33) at 3 and 9 mo of gestation, respectively. In contrast, plasma copper levels increased in a way depending upon the stage of gestation in both groups: from 24.7 to 28.2 mumol/L in the treated group and from 24.9 to 30.9 mumol/L in the placebo group at 3 and 9 mo of gestation, respectively, but the difference was only significant in the placebo group. No difference between groups was observed in mononuclear and polynuclear zinc or copper levels. These trace elements were also determined in cord blood at delivery. There were no statistically significant differences in zinc and copper concentration found in placebo group and supplemented group. Finally, the beneficial effect of supplementation on muscular cramps and appearance of vergetures was noted.\nStudy3: Calcium and magnesium status in pregnant women. A comparison between treatment with calcium and vitamin C in pregnant women with leg cramps. 60 pregnant women underwent a double blind trial with calcium or ascorbic acid (1 g twice daily) as treatment for leg cramps. There was no significant difference between the two treatment groups with respect to clinical improvement. In 14 out of 60 patients the symptoms were totally abolished and in another 27 patients the symptoms were significantly decreased by the treatment (irrespective of drug used). In 17 patients the symptoms were unaffected while only two patients experienced an increase in frequency of their leg cramps during therapy. Serum total and ionized calcium concentrations, serum total magnesium and albumin concentrations were determined and were not significantly changed throughout therapy in any of the groups. No biochemical differences were found between the different treatment regimens or between those patients relieved or not relieved of their symptoms. Serum magnesium concentrations were at or just below the lower normal limit (for non pregnant women) in treated women and pregnant controls.\nStudy4: Calcium treatment of leg cramps in pregnancy. Effect on clinical symptoms and total serum and ionized serum calcium concentrations. Up to 30 per cent of pregnant women suffer from leg cramps. The cause of these cramps is not known, but changes in calcium concentration have been suggested. Therefore 42 pregnant women with leg cramps were studied. No differences in total serum or ionized serum calcium concentrations were found as compared with a control group of pregnant women without leg cramps. Twenty-one patients were treated with 1 g calcium orally twice daily for 2 weeks and in this group good clinical improvement was achieved (p less than 0.001). The treatment increased the total serum calcium concentration from 2.25 mmol/l to 2.30 mmol/l but did not alter the ionized serum calcium concentration. Twenty-one untreated patients had the same frequency of cramps and showed no change in serum calcium concentrations throughout the investigation.\n", + "output": "Conclusions: The evidence that calcium reduces cramp is weak and seems to depend on placebo effect. The evidence for sodium chloride is stronger but the results of the sodium chloride trial may no longer be relevant because of dietary changes which include an increased sodium intake in the general population. It is not possible to recommend multivitamins with mineral supplementation, as it is not clear which ingredient, if any, is helping. If a woman finds cramp troublesome in pregnancy, the best evidence is for magnesium lactate or citrate taken as 5mmol in the morning and 10mmol in the evening.\n[Note: The five citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]" + }, + { + "input": "Study1: Prevention of neonatal group B streptococcal disease: intrapartum detection and chemoprophylaxis of heavily colonized parturients. Parturients with heavy vaginal colonization of group B streptococci were selected randomly to receive either penicillin or no antibiotic. A simple and fast latex agglutination test, applied in 8977 consecutive parturients, detected 412 women with heavy colonization with group B streptococcus, 199 of whom were eligible for the study. The offspring of penicillin-treated women had a lower incidence of early-onset group B streptococcal disease (1.1%; 95% confidence interval 0-3.4%) than the controls (9.0%; 95% confidence interval 3.6--14.4%) (P less than .01). Among the offspring of streptolatex-negative parturients, the incidence of streptococcal disease was very low (0.07%). Thus, antibiotic prophylaxis of latex agglutination test-positive parturients would reduce the total incidence of group B streptococcal disease in the newborn by 25-80%.\nStudy2: Prevention of early-onset neonatal group B streptococcal disease with selective intrapartum chemoprophylaxis. Most cases of neonatal group B streptococcal disease with early onset have an intrapartum pathogenesis. Attack rates are increased substantially in infants born to mothers with prenatal group B streptococcal colonization and various perinatal risk factors (premature labor, prolonged membrane rupture, or intrapartum fever). In a randomized controlled trial, we studied the effect of selective intrapartum prophylaxis with ampicillin in 160 such high-risk women. In infants born to mothers who received intravenous ampicillin during labor, as compared with controls who received no treatment, neonatal colonization with group B streptococci was present in 8 of 85 (9 percent) versus 40 of 79 (51 percent; P less than 0.001), colonization at multiple (greater than or equal to 3) sites was observed in 3 of 85 (4 percent) versus 24 of 79 (30 percent; P less than 0.001), and bacteremia occurred in none of 85 versus 5 of 79 (6 percent; P = 0.024). The side effects of ampicillin were limited to a single episode of urticaria in a mother who had no history of penicillin allergy. We conclude that intrapartum ampicillin prophylaxis in women with positive prenatal cultures for group B streptococci who have certain perinatal risk factors can prevent early-onset neonatal group B streptococcal disease.\n", + "output": "Conclusions: Intrapartum antibiotic prophylaxis appeared to reduce EOGBSD, but this result may well be a result of bias as we found a high risk of bias for one or more key domains in the study methodology and execution. There is lack of evidence from well designed and conducted trials to recommend IAP to reduce neonatal EOGBSD.\nIdeally the effectiveness of IAP to reduce neonatal GBS infections should be studied in adequately sized double-blind controlled trials. The opportunity to conduct such trials has likely been lost, as practice guidelines (albeit without good evidence) have been introduced in many jurisdictions." + }, + { + "input": "Study1: Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda-Case Western Reserve University Research Collaboration. Adjunctive immunotherapy with heat-killed Mycobacterium vaccae was studied in a randomized, placebo-controlled trial of 120 non-human immunodeficiency virus-infected adults with newly diagnosed pulmonary tuberculosis. Patients were randomized to a single dose of M. vaccae or placebo 1 week after beginning chemotherapy and were followed up for 1 year. M. vaccae was safe and well tolerated. The rate of sputum culture conversion after 1 month of tuberculosis treatment was 35% in the M. vaccae group and only 14% in the placebo group (P=.01) but was comparable at 2 months and thereafter. Patients receiving M. vaccae had greater improvement on chest radiography at 6 months (91% vs. 77% for placebo recipients; P=.04) and 12 months (94% vs. 80%; P=.04) after initiation of tuberculosis treatment. These data provide evidence of an early increase in sputum culture conversion and greater radiographic improvement among patients who received M. vaccae. Further studies are warranted.\nStudy2: Mycobacterium vaccae: a study of safety and outcome measures. nan\nStudy3: Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial. Durban Immunotherapy Trial Group. Mycobacterium vaccae, an environmental saprophyte, has immunogenic properties that enhance the host immune response. Immunotherapy with M. vaccae has been suggested to shorten short-course antituberculosis chemotherapy. We tested the hypothesis that the addition of M. vaccae to standard short-course antituberculosis chemotherapy would decrease the time to achieve a negative sputum culture. Patients with newly diagnosed tuberculosis were randomly assigned an injection of saline (placebo) or M. vaccae on day 8. All patients received antituberculosis chemotherapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. Sputum samples were checked by microscopy and culture every week for the first 8 weeks and monthly until the end of chemotherapy at 6 months. The primary outcome was the time to a negative sputum culture in the first 8 weeks. Intention-to-treat analysis was used and time to sputum clearance was assessed by log-rank test and Cox's proportional-hazards regression. 172 patients received M. vaccae and 175 patients received placebo. At 8 weeks, 70 patients in the M. vaccae group and 65 patients in the placebo group had a negative culture; there was no difference between groups in the time to a negative culture (p=0.83). There was no interaction between HIV status and treatment. M. vaccae immunotherapy has no benefit when added to standard antituberculosis chemotherapy.\nStudy4: Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 2. Chronic or relapsed disease. In this study of 102 patients with culture-positive chronic treatment failure or repeatedly relapsed pulmonary tuberculosis receiving chemotherapy, 56 received an injection of killed Mycobacterium vaccae as immunotherapy after 1 month of treatment. At the start of treatment, there was little difference between those receiving immunotherapy and the 46 patients in the control group receiving chemotherapy alone. Thereafter, the two groups diverged so that 1 yr later, 43 of 56 (77%) patients receiving M. vaccae had a successful outcome, in comparison with 24 of 46 (52%) patients receiving chemotherapy alone (P < 0.02). Successful results were obtained from patients infected with drug-resistant bacilli, 20 of 32 (63%) patients compared with 11 of 25 (44%) patients, respectively, as well as from fully drug-sensitive cases (23 of 24 compared with 12 of 21 patients; P = 0.004). At the final follow-up after 22 months, 13 of 56 patients receiving immunotherapy had an unfavourable outcome compared with 26 of 46 members of the control group (P = 0.0006). During the study, 16 patients died of tuberculosis (six after immunotherapy), and 12 were lost to follow-up. Not only was bacteriological success improved by immunotherapy, chest X-ray showed markedly better resolution of cavities and other radiological lesions, recovery of body weight was improved, and the mean erythrocyte sedimentation rate returned almost to normal (P < 0.001) in comparison with those receiving chemotherapy alone. These changes were seen even in those failing bacteriological cure, suggesting that the immunotherapy had been effective, but that bacilli were replicating in an extracellular situation, protecting them from its effects.\nStudy5: Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis in Romania. 1. Newly-diagnosed pulmonary disease. In this study, 206 previously untreated patients with sputum culture positive pulmonary tuberculosis were randomized to receive an injection of killed Mycobacterium vaccae as immunotherapy, or of saline as placebo, after 1 month of a 6-month chemotherapeutic regime. Not surprisingly in a disease for which there is good chemotherapy, the difference in numbers which were culture negative at the end of treatment was small, and the final outcome at the latest post-treatment follow-up did not reach statistical significance between the two arms of the study. Nonetheless, those receiving immunotherapy showed better progression in every parameter measured, suggesting faster and more complete cure. Whereas seven of 97 patients receiving immunotherapy required a course of re-treatment and five still had active disease after a mean follow-up of 2 yr, 13 of 109 placebo recipients required re-treatment and nine still had active disease at the end of the study. Only one patient receiving M. vaccae plus chemotherapy died of tuberculosis, compared with four of those receiving chemotherapy alone. A degree of drug resistance was shown by the bacilli cultured from 25 of 175 (14%) patients, and seven of them (4.0%) were multi-drug resistant. Fourteen patients received immunotherapy of whom 13 were cured, including all three of those showing multi-drug resistance. Of the 11 patients with drug resistance in the control group, eight were cured, and one patient with multi-drug-resistant disease died of tuberculosis during re-treatment.\nStudy6: An investigation of patients with pulmonary tuberculosis in Kuwait in preparation for studies of immunotherapy with Mycobacterium vaccae. Sixty-five patients, many of them immigrant to Kuwait, with bacteriologically proven, adult type, pulmonary tuberculosis were studied by many parameters over the 4 months following diagnosis. Twelve were infected with tubercle bacilli resistant to at least one anti-tuberculosis drug. Preliminary evidence suggested that this was frequently primary resistance in patients infected in their countries of origin. The Kuwaiti environment results in very high skin test and lymphocyte proliferative responses (LTT) to shared and species specific antigens of mycobacteria in healthy persons. In comparison, patients with tuberculosis lacked cellular responses to group i and group ii antigens, but had increased IgG and IgA binding to mycobacterial antigens in general. LTT responses to added interleukin 2, and production of alpha interferon, were normal in our patients, but induction of gamma interferon in response to phytohaemagglutinin was reduced initially, rising towards normal during treatment. Biochemical and haematological abnormalities present at the time of diagnosis rapidly corrected. The disease differed from that reported in most previous studies in that fever was uncommon, the disease was never fatal, and most tuberculin tests were not necrotising. This implied that a detrimental immunopathological component is less pronounced in those exposed to the Kuwaiti environment, and a hypothesis is put forward to explain this.\nStudy7: Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial. Mortality rates of HIV-infected patients treated for tuberculosis remain high. This study aimed to assess the effect on mortality of immunotherapy with single-dose SRL172 added to standard antituberculosis chemotherapy in such patients. The double-blind trial enrolled 1229 patients aged 18-60 years, who had never received antiretroviral treatment and who presented with newly diagnosed, sputum-smear-positive pulmonary tuberculosis to referral centres in Lusaka, Zambia, and Karonga, Malawi. Both HIV-positive and HIV-negative patients were enrolled, to avoid stigmatisation. Participants were randomly assigned a single injection of SRL172 or matching placebo within 2 weeks of starting 8 months of antituberculosis chemotherapy and followed up for at least 12 months. The primary endpoint was time to death in the HIV-infected population. Analyses were based on 760 HIV-positive patients after exclusion of 84 patients with errors in storage of the injection, no bacteriological confirmation, or no HIV result. Of 760 HIV-infected patients, 374 received SRL172 and 386 received placebo. SRL172 did not cause any serious adverse events. The follow-up rate was 88% at 12 months in both groups. Of the HIV-positive patients, 109 (19.5 per 100 person-years) of 372 assigned SRL172 and 107 (19.3 per 100 person-years) of 386 assigned placebo died. In the Cox's regression analysis, stratified by centre, the hazard ratio of deaths (SRL172/placebo) was 1.03 (95% CI 0.79-1.35). There was no evidence of benefit to the group assigned SRL172. Immunotherapy with single-dose SRL172 as an adjunct to standard antituberculosis treatment in HIV-positive adults with pulmonary tuberculosis had no significant effect on survival or bacteriological outcome, though the treatment was safe and well tolerated.\n", + "output": "Conclusions: M. vaccae immunotherapy does not benefit people with tuberculosis. No further trials are warranted and, as a result, the authors do not intend to update this review." + }, + { + "input": "Study1: Rehabilitation of oral function in head and neck cancer patients after radiotherapy with implant-retained dentures: effects of hyperbaric oxygen therapy. Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy often result in an anatomic and physiological oral condition unfavorable for prosthodontic rehabilitation. The objective of this prospective study was to assess the effect of hyperbaric oxygen therapy on treatment outcome (condition of peri-implant tissues, implant survival, oral functioning and quality of life) of prosthodontic rehabilitation with implant-retained lower dentures in radiated head and neck cancer patients 6 weeks and 1 year after placing the new dentures. The treatment outcome was assessed in a group of 26 head neck cancer patients who were subjected to radiotherapy after tumour surgery. Standardized questionnaires were completed and clinical and radiographic assessments were performed. After randomization, endosseous Br\u00e5nemark implants were placed in the anterior part of the mandible either under antibiotic prophylaxis (13 patients) or under antibiotic prophylaxis combined with pre and postsurgery hyperbaric oxygen (HBO) treatment (13 patients). In the HBO and non-HBO group eight implants (implant survival 85.2%) and three implants (implant survival 93.9%) were lost, respectively. Peri-implant tissues had a healthy appearance in both groups. Osteoradionecrosis developed in one patient in the HBO group. All patients functioned well with their implant-retained lower denture. The quality of life related to oral functioning and denture satisfaction were improved to a comparable extent in the HBO and non-HBO group. Implant-retained lower dentures can improve the quality of life related to oral functioning and denture satisfaction in head and neck cancer patients. Adjuvant hyperbaric oxygen therapy could not be shown to enhance implant survival in radiated mandibular jaw bone.\nStudy2: Does hyperbaric oxygen administration decrease side effect and improve quality of life after pelvic radiation? to evaluate the influence of HBOT to the side effect and quality of life after pelvic radiation. this is an open randomized, parallel, prospective study conducted in Department of Obstetrics and Gynecology, Oncology Division and Department of Radiotherapy. Endoscopy procedure was performed in Department of Internal Medicine and tissue biopsy in Department of Pathology Anatomy. The hyperbaric oxygen therapy (HBOT) was done in Dr. Mintohardjo, Navy Seal Hospital Jakarta. The side effect was measured using LENT SOMA scale ratio, the quality of life used the Karnofsky score. The difference of two mean was analyzed using student t test. of 32 patients undergoing HBOT and 33 patients as control, the ratio of ASE of control group was 44.1+/-28.2%, HBOT group was 0.7+/-30.1%; p<0.001; the LSE of control group was 33.6+/-57.6%, HBOT group was -19.6+/-69.4%; p=0.008. Quality of life of control group after intervention was 4.5+/-10.7%; HBOT group was 19.7+/-9.6%; p <0.001. After 6 months of intervention the quality of life was 2.5+/-16.1% in the control group, and HBOT group was 15.2+/-14.7%; p =0.007. the study showed that HBOT decreased acute and late side effect, also improved the quality of life of patients with proctitis radiation.\nStudy3: Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. A prospective randomized trial comparing hyperbaric oxygen and systemic antibiotics in the prevention of osteoradionecrosis was presented. The results indicated, in a high-risk population who required tooth removal in irradiated mandibles, that up-front hyperbaric oxygen produced an incidence of osteoradionecrosis of 5.4% as compared with the antibiotic group of 29.9% (P = .005). Hyperbaric oxygen should be considered a prophylactic measure when post-irradiation dental care involving trauma to tissue is necessary.\nStudy4: Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer. A non-randomised phase II study suggested a therapeutic effect of hyperbaric oxygen (HBO) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer, justifying further investigation in a randomised trial. Fifty-eight patients with \u2265 15% increase in arm volume after supraclavicular \u00b1 axillary radiotherapy (axillary surgery in 52/58 patients) were randomised in a 2:1 ratio to HBO (n=38) or to best standard care (n=20). The HBO group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks. Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume. Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire. Of 53/58 (91.4%) patients with baseline assessments, 46 had 12-month assessments (86.8%). Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2% (IQR 122.7-151.5%) in the control group and 133.5% (IQR 122.3-144.9%) in the treatment group. Results for the secondary endpoints were similar between randomised groups. No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer. Copyright \u00a9 2010 Elsevier Ireland Ltd. All rights reserved.\nStudy5: Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis. This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety. At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms. Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation.\nStudy6: Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy. Radiation-induced brachial plexopathy (RIBP) is an untreatable complication of curative radiotherapy for early breast cancer, characterized by chronic neuropathic pain and limb paralysis. Hyperbaric oxygen (HBO2) therapy is known to promote healing of tissue rendered ischaemic by radiotherapy, but is untested in RIBP. Thirty four eligible research volunteers suffering from RIBP were randomized to HBO2 or control group. The HBO2 group breathed 100% oxygen for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The control group accompanied the HBO2 group and breathed a gas mixture equivalent to breathing 100% oxygen at surface pressure. All volunteers and investigators, except the operators of the hyperbaric chamber and the trial statistician, were blind to treatment assignments. The warm sensory threshold, which measures the function of small sensory fibres, was selected as the primary endpoint. Pre-treatment neurophysiological tests were grossly abnormal in the affected hand compared to the unaffected hand in both HBO2 and control groups, as expected, but no statistically significant differences were noted in either group at any time up to 12 months post-treatment. However, normalization of the warm sensory threshold in two of the HBO2 group was reliably recorded. Two cases with marked chronic arm lymphoedema reported major and persistent improvements in arm volume for at least 12 months after treatment with HBO2. IINTERPRETATION: There is no reliable evidence to support the hypothesis that HBO2 therapy slows or reverses RIBP in a substantial proportion of affected individuals, although improvements in warm sensory threshold offer some suggestion of therapeutic effect. Improvement in long-standing arm lymphoedema was not anticipated, and justifies further investigation.\nStudy7: Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain. Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain. Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neuropsychological test at 3 months without treatment in that period and started HBO thereafter. All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance. HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement.\n", + "output": "Conclusions: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected patients and tissues may be justified. Further research is required to establish the optimum patient selection and timing of any therapy. An economic evaluation should be undertaken." + }, + { + "input": "Study1: Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d). To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions. One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, postvoid residual volume, prostate-specific antigen level, participants' global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms. Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -0.36) with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P = .91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified. Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. clinicaltrials.gov Identifier: NCT00603304.\nStudy2: Serenoa repens extract for benign prostate hyperplasia: a randomized controlled trial. To compare the effect of a Serenoa repens extract with placebo for symptoms of benign prostatic hyperplasia (BPH). In a double-blind placebo-controlled randomized trial between January 1999 and March 2000, 100 men with symptoms of BPH, aged < 80 years, with a maximum urinary flow rate of 5-15 mL/s for a voiding volume of 150 mL, were randomly and equally allocated to 320 mg S. repens extract or placebo (paraffin oil). The main outcome measures were the International Prostate Symptom Score (IPSS), peak urinary flow rate, and the Rosen International Index of Erectile Function (IIEF) questionnaire. There was no significant difference between the treatments over the 12 weeks of the study in the IPSS, peak urinary flow rate or for the IIEF questionnaire. During the trial all participants had some improvement in their symptoms of BPH but there was no significant beneficial effect of this S. repens extract over placebo in this 12-week trial.\nStudy3: Effect of saw palmetto soft gel capsule on lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized trial in Shanghai, China. We determined the effect of Prostataplex in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. A total of 92 Chinese men between 49 and 75 years old with lower urinary tract symptoms were randomly assigned in this double-blind, placebo controlled trial. The 46 patients in the intervention group were given 2 Prostataplex soft gels daily for 12 weeks, while the 46 in the control group were given 2 placebo soft gels for the same time. The treated and control groups appeared to have more than a 95% compliance rate, as judged by counting the remaining pills in the bottle collected at the end of trial months 1 to 3. After 12 weeks of intervention the mean +/- SD maximum urinary flow rate was significantly higher in the treatment group than in the control group (14.07 +/- 2.56 vs 11.74 +/- 1.23 ml per second, p <0.001), while relative urinary resistance was significantly lower in the treatment group than in the control group (2.35 +/- 0.83 vs 3.02 +/- 1.18, p = 0.002). While there was no significant difference in mean prostate volume or International Prostate Symptom Score between the 2 groups, 18 of 46 patients (39.1%) in the treatment group showed an International Prostate Symptom Score improvement (decrease of 3 or greater) after intervention, whereas only 1 of 46 (2.2%) in the control group showed an International Prostate Symptom Score improvement (chi-square test p <0.001). Prostataplex may have short-term effects in improving symptoms and objective measures in Chinese men with lower urinary tract symptoms associated with benign prostatic hyperplasia.\nStudy4: Treatment of benign prostatic hyperplasia with phytosterols. In a randomised, double-blind study, the preparation Curbicin, obtained from pumpkin seeds and dwarf palm plants (Cucurbita pepo L. and Sabal serrulata), was compared with a placebo in the treatment of symptoms caused by prostatic hyperplasia; 53 patients took part in the study, which was carried out over a 3-month period. Urinary flow, micturition time, residual urine, frequency of micturition and a subjective assessment of the effect of treatment were all significantly improved in the treatment group. No untoward side effects were noted.\nStudy5: A double-blind trial of an extract of the plant Serenoa repens in benign prostatic hyperplasia. nan\nStudy6: Randomized trial of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH). Because benign prostatic hyperplasia (BPH) is relatively common, it is important to discover safe and effective means to treat this often debilitating perturbation. Accordingly, we examined the effectiveness of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) in treating symptoms of BPH. We undertook a randomized, placebo-controlled, double-blind study. Patients were enrolled from 3 urological practices in the USA. 144 subjects were randomized for study. 17 subjects eventually withdrew, leaving 70 patients in the test group and 57 in the placebo group to complete the study. Inclusion criteria consisted of a diagnosis of BPH, no evidence of cancer, and a maximal urinary flow rate between 5 and 15 ml/second. Patients received either placebo or the combined natural products for 3 months. Evaluations were performed via the American Urological Association (AUA) Symptom Index score, urinary flow rate, PSA measurement, and residual bladder volume. Nocturia showed a markedly significant decrease in severity in patients receiving the combined natural products compared to those taking placebo (p < 0.001). Daytime frequency was also lessened significantly (p < 0.04). When the average individual total AUA Symptom Index score in the test group was compared to that in the placebo group at the end of the study, the difference proved highly significant (p < 0.014). PSA measurements, maximal and average urinary flow rates, and residual volumes showed no statistically significant differences. When taken for 3 months, a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) compared to placebo can significantly lessen nocturia and frequency and diminish overall symptomatology of BPH as indicated by an improvement in the total AUA Symptom Index score. The combination of natural products caused no significant adverse side effects.\nStudy7: Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. A randomized, double-blind study versus tamsulosin. The aim of this prospective, randomized, double-blind, double-dummy, multicenter clinical trial was to investigate the efficacy and safety of PRO 160/120 (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly out-patients suffering from LUTS caused by BPH, with an initial score > or = 13 points in the International Prostate Symptom Score (I-PSS), received 2 x 1 capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure for efficacy was the change in I-PSS total score, the percentage of patients with an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well. During 60 weeks of randomized treatment the I-PSS total score was reduced by a median of 9 points in both groups. In total, 32.4 % of the patients in the PRO 160/120 group and 27.9% in the tamsulosin group were responders (test for non-inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs were well tolerated, with one adverse event in 1514 treatment days for PRO 160/120 and one event in 1164 days for tamsulosin. The study supports non-inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS caused by BPH.\nStudy8: [Treatment of obstructive symptomatology caused by prostatic adenoma with an extract of Serenoa repens. Double-blind clinical study vs. placebo]. nan\nStudy9: Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients. Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH). This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point. Both Permixon and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); Permixon improved symptoms with little effect on volume (-6%) and no change in PSA levels. Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence. Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH.\nStudy10: Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study. While the lipido-sterolic extract of Serenoa repens (LSESr)-Permixon((R))-has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with alpha-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin. Eight hundred and eleven men with symptomatic BPH (I-PSS> or =10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4mg/day (N=354) or Permixon 320mg/day (N=350). I-PSS, QoL and Q(max) were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol population of 542 patients (tamsulosin: N=273; Permixon: N=269). At 12 months, I-PSS decreased by 4.4in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Q(max) was similar in both treatment groups (1.8ml/s Permixon, 1.9ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group. This study demonstrates that Permixon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.\n", + "output": "Conclusions: Serenoa repens, at double and triple doses, did not improve urinary flow measures or prostate size in men with lower urinary tract symptoms consistent with BPH." + }, + { + "input": "Study1: Operative or conservative treatment for trochanteric fractures of the femur. A randomised epidemiological trial in elderly patients. All elderly patients with extracapsular hip fractures seen in hospitals in Newcastle upon Tyne over a 12-month period were studied and followed up for six months. At one of the hospitals, patients were randomised to treatment by AO dynamic hip-screw or by traction. Complications specific to the two treatments were low, and general complications, six-month mortality and prevalence of pain, leg swelling and unhealed sores, showed no difference between the two modes of treatment. Operative treatment gave better anatomical results and a shorter hospital stay, but significantly more of the patients treated by traction showed loss of independence six months after injury.\nStudy2: The treatment of unstable intertrochanteric fractures of the hip: a prospective trial of 150 cases. We report a prospective clinical trial of 150 cases for the treatment of unstable intertrochanteric fracture of the neck of the femur. Three methods were tested in our series--skeletal traction with a tibial pin, medial displacement osteotomy and valgus osteotomy--with 50 patients in each group. Our results showed no significant difference between those treated with the Dimon and Hughston osteotomy and those treated by the Sarmiento osteotomy. Conservative treatment of skeletal traction for unstable fracture was found to be well tolerated by the Chinese patient. A low mortality and morbidity rate was found in this series with an overall infection rate of 4 per cent.\n", + "output": "Conclusions: Although there is a lack of available evidence to inform practice for undisplaced intracapsular fractures, variation in practice has reduced and most fractures are treated surgically. The limited available evidence from randomised trials does not suggest major differences in outcome between conservative and operative management programmes for extracapsular femoral fractures, but operative treatment is associated with a reduced length of hospital stay and improved rehabilitation. Conservative treatment will be acceptable where modern surgical facilities are unavailable, and will result in a reduction in complications associated with surgery, but rehabilitation is likely to be slower and limb deformity more common. Currently, it is difficult to conceive circumstances in which future trials would be practical or viable." + }, + { + "input": "Study1: Effects of antibiotic prophylaxis on women undergoing nonelective cesarean section in a community hospital. A randomized, double-blind, placebo-controlled study was done of a short course of cefamandole administered intravenously after cord clamping as prophylaxis in women undergoing primary nonelective cesarean section in a community hospital. Duration of labor equal to or more than 14 hours was the only significant risk factor between patients who had postoperative infectious morbidity and those who had none. Four of 43 patients (9.3%) who received cefamandole, as opposed to 13 of 47 (27.7%) who received the placebo, developed infections (p less than 0.05). This difference was reflected totally in the difference in endomyometritis development between the groups. The use of intraoperative culturing predicted infection in 4 of 13 patients in the placebo group who developed infections postoperatively. No adverse side effects were noted, and there were no cases of delayed serious infection.\nStudy2: Perioperative use of cefoxitin in primary cesarean section. We performed a randomized, double-blind trial on a relatively low-risk population comparing the use of three doses of cefoxitin vs. placebo in the prevention of infection following primary cesarean section. Major site-related morbidity (endometritis, wound infection and septicemia) was significantly reduced in the cefoxitin group (8.9% vs. 27.8%; p = 0.017). Febrile morbidity alone tended to occur in the cefoxitin group (15.6% vs. 3.7%; p = 0.091), and all five urinary tract infections occurred in the cefoxitin group as well. Total morbidity was therefore not significantly different (cefoxitin, 35.6%; placebo, 31.5% [not significant]). Duration of hospitalization (mean, 6.0 days) and need for further postoperative antibiotic therapy were similar in the two groups. Our study demonstrated a modest benefit from the perioperative use of antibiotics in relatively low-risk patients undergoing primary cesarean section. Issues that need further study include definition of the optimal prophylactic regimen and of high-risk populations for whom prophylaxis would be most helpful.\nStudy3: [Prophylactic use of antibiotics in cesarean section]. The objective of this investigation was to determine the effectiveness of ampicillin administration as a prophylactic regime in patients undergoing cesarean section. A double blind randomized study compared a long course of ampicillin (7 days) to a short course of ampicillin (three doses) to placebo. Thirty one patients were included in the placebo group and sixty patients in the drug groups. Only one patient in the placebo group and one in the drug group developed infectious morbidity. There was no significant difference (p less than 0.001) between the placebo and ampicillin groups.\nStudy4: Prevention of postoperative infection in cesarean section after rupture of the membranes. Patients having a cesarean section more than 6 h after rupture of the membranes constitute a high risk group for postoperative infections. Two such groups were studied. Patients were given either cefuroxime 1.5 g every 8th hour for 24 h followed by cefadroxil 0.5 g twice daily for 6 days or received no medication. The infection rate was significantly reduced in the treatment group as compared to the control group (15% vs. 48%). Non-infected patients had a significantly shorter stay in hospital (8 days vs. 12 days). Combined use of these drugs for prevention of post-cesarean infection has not previously been reported. No side effects of the antibiotic prophylaxis were reported.\nStudy5: Antibiotic prophylaxis in low-risk cesarean section. This prospective study was undertaken in an effort to evaluate the role of systemic antibiotic prophylaxis in elective abdominal delivery. Eighty-two patients undergoing elective cesarean section who were not in labor and who did not have ruptured membranes were assigned on a randomized, double-blind basis to receive a three-dose perioperative course of either placebo or ampicillin. Postoperatively, patients were evaluated for the development of infection-related complications. Patients in the antibiotic group experienced less febrile morbidity, had lower fever indices and developed fewer operative-site infections than did patients in the control group. No patient in either group, however, developed a potentially life-threatening infection, and all infected patients responded promptly to parenteral antibiotic therapy. Because of the limited morbidity associated with elective cesarean section in this patient population, it is concluded that the theoretical risks of antibiotic prophylaxis outweigh the expected benefits.\nStudy6: Single-dose ampicillin for cesarean section prophylaxis. A single 2-g dose of ampicillin or a placebo identical in appearance was administered intravenously in a randomized, prospective, double-blind manner to 71 patients undergoing cesarean section. The solutions were given either on call to the operating room or during the intraoperative period. Postoperative morbidity from infection occurred in 59.4% of patients receiving placebo and in 14.7% of those receiving ampicillin (P less than .0001). In those individuals undergoing primary cesarean section the incidence of infection with placebo was 65% and with ampicillin 6.3% (P less than .0004). In patients undergoing repeat cesarean section the incidence was 53% in the placebo group and 22% in the treatment group (P greater than .05). There were no differences in the effectiveness of the drug whether given preoperatively or intraoperatively. Serious infections and wound infections were not encountered in patients receiving ampicillin.\nStudy7: Comparison of four different antibiotics as prophylaxis in caesarean section. nan\nStudy8: Single-dose antibiotic prophylaxis in high-risk patients undergoing cesarean section. A prospective, double-blind, placebo-controlled study was performed to determine the effectiveness of single-dose antibiotic prophylaxis in decreasing infectious complications after primary cesarean section. One hundred women at high risk for postoperative infectious morbidity were randomly assigned to receive either placebo or one 2-g dose of ceftizoxime at cord clamping. The incidence of endometritis in the antibiotic group was 6.0 versus 24.5% in the placebo group (P less than .05). The incidence of febrile morbidity in the group receiving one dose of ceftizoxime was 14.0 versus 32.7% in the placebo group (P less than .05). Single-dose ceftizoxime prophylaxis significantly reduced the incidence of endometritis and febrile morbidity in high-risk patients undergoing cesarean section.\nStudy9: Single-dose mezlocillin prophylaxis in emergency cesarean section. A single 5-gm dose of mezlocillin or a placebo was administered intravenously 30 minutes before surgery to patients undergoing emergency cesarean section. The assignment of drug or placebo was randomized. Postoperative morbidity occurred in 62.5% of patients receiving placebo and in 18.4% of those receiving mezlocillin (P less than 0.001). The incidences of febrile morbidity, endometritis, and urinary tract infection were significantly lower in the group given mezlocillin. Other benefits of antibiotic prophylaxis included a shorter hospital stay and no serious infections in the group given mezlocillin.\nStudy10: Role of preventive antibiotics in patients undergoing cesarean section. Eighty patients in labor and requiring cesarean section were selected randomly for a double-blind study using prophylactic cephalosporin and placebo. There were 26 treated patients who had no morbidity versus 13 in the control group. The reduction in endometritis was significant (P = less than .05). The most prevalent organism was Streptococcus viridans, followed by Escherichia coli. Bacterioides organisms were recovered 17 time in 11 patients. Tabulation of the fever index showed significant difference. No major complication occurred in the treatment group. Gastric aspirates from infants showed a good correlation with maternal morbidity and are suggested as a screening procedure.\n", + "output": "Conclusions: Endometritis was reduced by two thirds to three quarters and a decrease in wound infection was also identified. However, there was incomplete information collected about potential adverse effects, including the effect of antibiotics on the baby, making the assessment of overall benefits and harms complicated. Prophylactic antibiotics given to all women undergoing elective or non-elective cesarean section is clearly beneficial for women but there is uncertainty about the consequences for the baby." + }, + { + "input": "Study1: Nafarelin in the management of endometriosis: quality of life assessment. Quality of life is important when comparing the relative advantages of nafarelin versus danazol for the treatment of endometriosis. Recent studies have investigated the potential differences between the safety profiles of nafarelin and danazol and the impact of these profiles on the patient's quality of life. Results show that although these drugs have similar efficacy, they are associated with very different safety profiles. Most notable are the androgenic effects such as weight gain associated with danazol. With nafarelin, hypoestrogenic side effects, such as hot flashes, are more common. More important, these differences in safety profiles may prove to be relevant to patient satisfaction and compliance with therapy.\nStudy2: Reversible pituitary ovarian suppression induced by an LHRH agonist in the treatment of endometriosis--comparison of two dose regimens. Buserelin [D-Ser(TBU)6-des Gly NH2(10) LHRH ethylamide], an LHRH agonist, was administered intranasally at two dose levels, 200 micrograms t.d.s or 300 micrograms t.d.s., to 20 women with proven endometriosis, many with recurrent disease. Both dose schedules achieved significant suppression of circulating 17 beta-oestradiol levels often to within the postmenopausal range, the larger dose inducing significantly greater suppression (P less than 0.05). Serum FSH values were suppressed below baseline but serum LH remained at pretreatment levels or above, whilst on treatment. Complete resolution of endometriotic deposits was achieved in 68% of cases following 6 months treatment with dramatic and long-standing relief of symptoms with no apparent dose difference. In all other subjects there was significant reduction in the extent of endometriotic deposits and improvement in American Fertility Society classification of disease stage. The most commonly occurring side effect was hot flushes; their intensity and frequency related to the degree of suppression of serum oestradiol and the dose of Buserelin administered.\nStudy3: A comparative treatment trial of endometriosis using the gonadotrophin-releasing hormone agonist, nafarelin, and the synthetic steroid, danazol. A randomized and double-blind trial was carried out comparing intranasal nafarelin acetate (400 micrograms daily) and oral danazol (600 mg daily), given over 6 months, in the treatment of 49 patients with laparoscopically proven endometriosis. Both drugs produced a highly significant and similar reduction (of 60 to 70%) in objective American Fertility Society scoring, even in severe disease. No effect was seen on adhesions. Both drugs suppressed oestradiol levels to a similar extent, although nafarelin caused a substantial rise in the first 2 weeks after the initiation of therapy. Nafarelin suppressed LH substantially and FSH, testosterone and prolactin to a small degree, whereas FSH and LH increased slightly during danazol. Pregnancies occurred in 12 of 22 infertile women in the 12 months following nafarelin, and in 6 of 14 in the danazol group. Side-effects were reported at a similar rate with both drugs, but the pattern was different. Hot flushes were the predominant side effect with nafarelin, although oestradiol levels were not suppressed to the extent expected. Small amounts of spotting or light bleeding were experienced with both drugs, but these tended to decrease with time with nafarelin and increase with danazol.\nStudy4: Nafarelin vs. leuprolide acetate depot for endometriosis. Changes in bone mineral density and vasomotor symptoms. Nafarelin Study Group. To compare intranasal nafarelin and intramuscular leuprolide acetate (LA) depot in the management of endometriosis. A multicenter, prospective, randomized, double-placebo, double-blind study was conducted on subjects who had symptoms and signs of endometriosis and bone mineral density (BMD) within the age-appropriate normal range. For 6 months, 99 subjects received nafarelin, 200 micrograms twice daily, and placebo injections once monthly; 93 subjects received LA depot injections, 3.75 mg once monthly, and placebo nasal spray, twice daily. Subjects were followed throughout treatment and for six months after treatment. The main outcome measures were changes in endometriosis symptoms and signs, BMD measurements, subject-reported and objectively measured hot flushes and circulating estradiol concentrations. Nafarelin was as effective as LA depot in alleviating symptoms and signs of endometriosis. LA depot recipients lost significantly more BMD, had more days with subjective hot flushes and more objectively measured hot flushes than did nafarelin recipients. In the nafarelin group, estradiol levels were consistently higher than in the leuprolide depot group, with significant differences by month 3 of dosing. Nafarelin and LA depot were equally effective despite higher estradiol levels in nafarelin recipients. Nafarelin-treated subjects lost less BMD, had fewer days with hot flushes and had fewer objectively measured hot flushes.\nStudy5: Buserelin versus danazol in the treatment of endometriosis-associated infertility. A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 micrograms/day and the other (30 patients) received intranasal buserelin 1200 micrograms/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe.\n", + "output": "Conclusions: GnRHas appear to be more effective at relieving pain associated with endometriosis than no treatment/placebo. There was no evidence of a difference in pain relief between GnRHas and danazol although more adverse events reported in the GnRHa groups. There was no evidence of a difference in pain relief between GnRHas and levonorgestrel and no studies compared GnRHas with analgesics." + }, + { + "input": "Study: Cidofovir efficacy in recurrent respiratory papillomatosis: a randomized, double-blind, placebo-controlled study. We performed a prospective, double-blind, placebo-controlled, longitudinal adjuvant therapy trial to determine the efficacy of cidofovir in the treatment of severe recurrent respiratory papillomatosis (RRP). Although results of case series suggest that cidofovir may decrease the frequency and rapidity of papilloma regrowth, no blinded placebo-controlled studies have demonstrated efficacy. Adults and children (n = 19) with aggressive RRP received either active drug (cidofovir) or placebo. When surgical intervention was needed, drug or placebo was injected into affected areas after surgical removal of disease. The following measures were made at baseline and at 2-month intervals for the course of 12 months: Derkay papilloma severity grading scale, Voice Handicap Index, Health-Related Quality of Life, and total number of procedures performed over 12 months. At 2- and 12-month follow-ups, there was a significant (p < .05) improvement in the Derkay Severity Score within the cidofovir and placebo groups, but no difference between groups, and no difference between groups in the number of procedures performed. Significant improvement was found in Voice Handicap Index scores in the cidofovir group at the 12-month follow-up. No differences were seen in Health-Related Quality of Life. A randomized, blinded, placebo-controlled trial is necessary in the study of RRP, because the natural history of the disease can include remissions and reactivations. We found a significant improvement in the Derkay Severity Score 12 months after the baseline assessment in patients treated with cidofovir. This effect, however, was also seen in the placebo group. Accordingly, we were unable to provide proof of efficacy of cidofovir in the treatment of RRP.\n", + "output": "Conclusions: There is insufficient evidence to support the efficacy of antiviral agents as adjuvant therapy in the management of recurrent respiratory papillomatosis in children or adults. The included randomised controlled trial showed no advantage of intralesional cidofovir over placebo at 12 months. The study was limited by a small sample size and a change in the cidofovir concentration midway through the trial, from 0.3 mg/ml in children and 0.75 mg/ml in adults, to 5 mg/ml in both adults and children. An adequately powered randomised controlled trial of intra-lesional cidofovir, consistently using higher concentrations of cidofovir in comparison with injected placebo, would be required to determine effectiveness convincingly. Future studies must include health-related quality of life and symptom-based outcome measures." + }, + { + "input": "Study1: Prospective randomized clinical trial comparing nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic surgery. Recent publications demonstrating the safety and advantages of N2O for pneumoperitoneum (PP) prompted us to reconsider N2O as an agent for PP in general surgical laparoscopy. The purpose of this prospective, double-blind, randomized clinical trial was to determine whether N2O PP has any benefits over CO2 PP. One hundred three patients received N2O (group I, n = 52) or CO2 (group II, n = 51) PP for elective laparoscopic surgery. Heart rate, mean arterial blood pressure, end-tidal CO2, minute ventilation, and O2 saturation were recorded before PP, during PP, and in the recovery room. Postoperative pain medication use was recorded. Pain was assessed by means of visual analog scale (VAS) at postoperative hours 2 and 4, and on day 1. There were no differences between groups I and II in patient age, gender, weight, anesthesia risk (American Society of Anesthesiologists Score > 2), operative time, duration of PP, or length of hospital stay. Mean end-tidal CO2 increase under anesthesia was greater in group II than group I (3.0 versus 0.5 mmHg, p < 0.001) despite a greater mean intraoperative increase in minute ventilation in group II than group I (0.7 versus -0.2 L/min p < 0.001). The patients who had N2O PP had less pain 2 hours postoperatively (VAS: 4.9 versus 5.7, p <0.05), 4 hours postoperatively (VAS: 3.3 versus 5.1, p < 0.01), and 1 day postoperatively (VAS: 1.7 versus 3.5, p < 0.01) than patients who had CO2 PP. Postoperative narcotic or ketorolac use was not statistically different between groups. There were no adverse events related to either N2O or CO2 pneumoperitoneum. These results suggest that the use of N2O PP has sufficient advantages over CO2 that it should be considered as the standard agent for therapeutic PP.\nStudy2: Comparison of N2O and CO2 pneumoperitoneums during laparoscopic cholecystectomy with special reference to postoperative pain. To study the possible benefits of N2O pneumoperitoneum, 40 patients scheduled for laparoscopic cholecystectomy for symptomatic cholelithiasis were randomized into either CO2-induced (n = 20) or N2O-induced (n = 20) pneumoperitoneum groups. The intensity of postoperative pain was assessed by the patients themselves using an visual analogue pain score scale. CO2 insufflation caused respiratory acidosis. The total amount of anesthetic enflurane needed was lower in the N2O than in the CO2 group (p < 0.041). The N2O group experienced less pain 1 hour (p < 0.040) and 6 hours (p < 0.017) postoperatively and the next morning. Serum cortisol and plasma adrenaline concentrations in the N2O group did not differ from those in the CO2 group. Patients with N2O pneumoperitoneum seem to have less pain without the side effects caused by CO2. The N2O pneumoperitoneum is a good alternative to the CO2 pneumoperitoneum, especially for prolonged laparoscopic operations in patients with chronic cardiopulmonary diseases.\n", + "output": "Conclusions: 1. Nitrous oxide pneumoperitoneum during laparoscopic abdominal surgery appears to decrease post-operative pain in patients with low anaesthetic risk.\n2. Helium pneumoperitoneum decreases the cardiopulmonary changes associated with laparoscopic abdominal surgery. However, this did not translate into any clinical benefit over carbon dioxide pneumoperitoneum in patients with low anaesthetic risk. \n3. The safety of nitrous oxide and helium pneumoperitoneum has yet to be established. More randomized controlled trials on this topic are needed. Future trials should include more patients with high anaesthetic risk. Furthermore, such trials need to use adequate methods to reduce the risk of bias." + }, + { + "input": "Study: A randomized multicenter trial of adjuvant therapy in superficial bladder cancer: transurethral resection only versus transurethral resection plus mitomycin C versus transurethral resection plus bacillus Calmette-Guerin. Participating Clinics. A randomized multicenter trial was done to compare transurethral resection only to transurethral resection plus adjuvant mitomycin C and bacillus Calmette Guerin (BCG) instillation for treatment of superficial bladder cancer (stage pTa/1 grades 1 to 3 except primary stage pTa grade 1). Included in the study were 337 patients with superficial stage pTa/1 grades 1 to 3 bladder cancer except primary stage pTa grade 1 tumors. One group underwent transurethral resection alone. Mitomycin C (20 mg./50 ml. sodium chloride) was given every 2 weeks during year 1 and once a month during year 2. BCG (120 mg/50 ml. sodium chloride was instilled once a week for 6 weeks and once a month for 4 months. At a median followup of 20.2 months, a decrease in recurrence rate was noted for both drug instillations compared to transurethral resection only. The relative risk of recurrence was 0.508 after mitomycin C and 0.618 after BCG instillation compared to transurethral resection alone. There was no significant difference between the mitomycin C and BCG instillations. The progression rate was comparable in all 3 therapy groups, with an estimated common progression rate of 4.22% per year. Side effects occurred most frequently during or after BCG instillation, most often consisting of cystitis. One patient required cystectomy because of ulcerating cystitis and a prostatic abscess subsequent to unsuccessful tuberculostatic therapy. There were no systemic complications. Our study showed a positive effect of adjuvant chemotherapy and immunotherapy on decreasing tumor recurrence rate. No influence was observed concerning progression rate, which was low overall.\n", + "output": "Conclusions: In patients with medium/high risk Ta or T1 bladder cancer, immunotherapy with intravesical BCG following TUR appears to provide a significant advantage over TUR alone in delaying tumour recurrence." + }, + { + "input": "Study1: Randomized, controlled trial of biofeedback with anal manometry, transanal ultrasound, or pelvic floor retraining with digital guidance alone in the treatment of mild to moderate fecal incontinence. A prospective, three-armed, randomized, controlled trial was performed to assess whether pelvic floor exercises with biofeedback using anal manometry or transanal ultrasound are superior to pelvic floor exercises with feedback from digital examination alone in terms of continence, quality of life, physiologic sphincter strength, and compliance. Its secondary objectives were to assess whether there are any differences in these outcomes between biofeedback with transanal ultrasound vs. anal manometry and to correlate the physiologic measures with clinical outcome. One hundred twenty patients with mild to moderate fecal incontinence were randomized into one of three treatment groups: biofeedback with anal manometry, biofeedback with transanal ultrasound, or pelvic floor exercises with feedback from digital examination alone. Commencing one week after an initial 45-minute assessment session, patients attended monthly treatments for a total of five sessions. Each session lasted 30 minutes and involved sphincter exercises with biofeedback that involved instrumentation or digital examination alone, and patients were encouraged to perform identical exercises twice per day between outpatient visits. One hundred two patients (85 percent) completed the four-month treatment program. Across all treatment allocations, patients experienced modest but highly significant improvements in all nine outcome measures during treatment, with 70 percent of all patients perceiving improvement in symptom severity and 69 percent of patients reporting improved quality of life. With the possible exception of isotonic fatigue time, there were no significant differences between the three treatment groups in compliance, physiologic sphincter strength, and clinical or quality-of-life measures. Correlations between physiologic measures and clinical outcomes were much stronger with ultrasound-based measures than with manometry. Although patients in this study who completed pelvic floor exercises with feedback from digital examination achieved no additional benefit from biofeedback and measurement with transanal ultrasound or manometry, it may be that the guidance received through digital examination alone offered patients in the pelvic floor exercise group an effective biofeedback mechanism. Contrary to our hypothesis, the use of transanal ultrasound offered no benefit over manometry, but the use of ultrasound for isotonic fatigue time and isometric fatigue contractions provided potentially important physiologic measures that require further study. This study has confirmed, through a large sample of patients, that pelvic floor retraining programs are an effective treatment for improving physiologic, clinical, and quality-of-life parameters in the short term.\nStudy2: Randomized clinical trial of intra-anal electromyographic biofeedback physiotherapy with intra-anal electromyographic biofeedback augmented with electrical stimulation of the anal sphincter in the early treatment of postpartum fecal incontinence. The purpose of this study was to compare intra-anal electromyographic biofeedback alone with intra-anal biofeedback that was augmented with electrical stimulation of the anal sphincter in the treatment of postpartum fecal incontinence. A secondary aim was to examine the impact of the treatment on continence-related quality of life. Sixty symptomatic women were assigned randomly to receive intra-anal electromyographic biofeedback or electrical stimulation of the anal sphincter once weekly for 12 weeks and to perform daily pelvic floor exercises between treatments. Therapeutic response was evaluated with a symptom questionnaire to determine continence score, anal manometry, and endoanal ultrasound scanning. Quality of life was assessed before and after treatment with a validated questionnaire. Fifty-four women completed the treatment; 52 women (96%) had ultrasonic evidence of an external anal sphincter defect. After the treatment, both groups demonstrated significant improvement in continence score (P < .001) and in squeeze anal pressures (P < .04). Resting anal pressures did not alter significantly. Quality of life improved after the completion of physiotherapy, but there were no differences in outcome between intra-anal electromyographic biofeedback and electrical stimulation of the anal sphincter. Intra-anal electromyographic biofeedback therapy was associated with improved continence and quality of life in women with altered fecal continence after delivery. The addition of electrical stimulation of the anal sphincter did not enhance symptomatic outcome.\nStudy3: Triple-target treatment versus low-frequency electrostimulation for anal incontinence: a randomized, controlled trial. In the nonsurgical treatment of anal incontinence, the combination of amplitude-modulated medium-frequency stimulation and electromyographic biofeedback (EMG-BF), known as triple-target treatment (3T), is superior to EMG-BF alone. The aim of this trial is to compare 3T with the standard treatment, low-frequency stimulation (LFS). 80 patients with anal incontinence of Grade I or higher who presented to physicians or centers specialized in coloproctology were enrolled in this multicenter randomized trial with blinded observer. The trial had an open parallel-group design. Randomization was performed centrally by telephone. The primary endpoint was the Cleveland Clinic Score (CCS) after self-training at home with either 3T or LFS in two 20-minute sessions per day for 6 months. The secondary endpoints included the proportion of patients regaining continence, and the patients' quality of life (QoL). On completion of the trial as planned, the results were evaluated with an intention-to-treat analysis. Study registration: DRKS00000138 (http://register.germanctr.de). 39 patients were randomized to 3T, and 41 to LFS. After 6 months of treatment, the CCS (mean \u00b1 standard deviation) was 3.1 \u00b1 4.2 in the 3T group and 9.6 \u00b1 3.9 in the LFS group. The median improvement in the CCS at 6 months compared to baseline was 7 points greater in the 3T group than in the LFS group (95% CI: 5-9, p<0.001). Anal continence was regained by 54% of the 3T patients, but none of the LFS patients (95% CI for the difference: 37.18% - 69.91%, p<0.001). QoL scores were higher in all dimensions in the 3T group than in the LFS group. No major adverse effects occurred in either group. 3T is superior to LFS in the treatment of anal incontinence. The available evidence suggests that the success of 3T is based on the combined effect of biofeedback and medium-frequency stimulation. LFS of the type applied in this trial has no effect. 3T should be used in routine clinical practice instead of LFS.\nStudy4: Adjuvant biofeedback following anal sphincter repair: a randomized study. To evaluate the impact of adjuvant biofeedback following sphincter surgery. Thirty-eight patients were randomized into sphincter repair or sphincter repair plus biofeedback groups. Outcome measures included a symptom questionnaire, patient's rating of satisfaction with continence function and improvement, change in continence score, quality of life and anorectal physiology. Endoanal ultrasonography was also performed pre- and post-operatively. Immediately following surgery, there was no statistically significant difference in any of the functional or physiological variables between the groups. Continence and patient satisfaction scores improved with a mean difference of -0.48 (95% CI: -3.30-2.33, P = 0.73) and 1.03 (95% CI: -1.40-3.46, P = 0.39), respectively. Only the difference in embarrassment scores reached statistical significance (mean) 0.56 (95% CI: 0.12-0.99, P = 0.014). Resting and squeeze pressures also improved. Thirteen of 14 in the biofeedback and 11 of 17 (control) reported symptomatic improvement. In the biofeedback group, although not statistically significant continence and satisfaction scores improved and were sustained over time. In the control group, continence and satisfaction scores changed little between 3 and 12 months (P = NS). Quality of life measures improved within the biofeedback group but there was no statistical difference between the groups. Following surgery continence function improves in all patients but adjuvant biofeedback therapy improves quality of life and maintains symptomatic improvement over time. Copyright 2004 Blackwell Publishing Ltd\nStudy5: Randomized controlled trial of biofeedback for fecal incontinence. Behavioral treatment (biofeedback) has been reported to improve fecal incontinence but has not been compared with standard care. A total of 171 patients with fecal incontinence were randomized to 1 of 4 groups: (1) standard care (advice); (2) advice plus instruction on sphincter exercises; (3) hospital-based computer-assisted sphincter pressure biofeedback; and (4) hospital biofeedback plus the use of a home electromyelogram biofeedback device. Outcome measures included diary, symptom questionnaire, continence score, patient's rating of change, quality of life (short-form 36 and disease specific), psychologic status (Hospital Anxiety and Depression scale), and anal manometry. Biofeedback yielded no greater benefit than standard care with advice (53% improved in group 3 vs. 54% in group 1). There was no difference between the groups on any of the following measures: episodes of incontinence decreased from a median of 2 to 0 per week (P < 0.001). Continence score (worst = 20) decreased from a median of 11 to 8 (P < 0.001). Disease-specific quality of life, short-form 36 (vitality, social functioning, and mental health), and Hospital Anxiety and Depression scale all significantly improved. Patients improved resting, squeeze, and sustained squeeze pressures (all P < 0.002). These improvements were largely maintained 1 year after finishing treatment. Conservative therapy for fecal incontinence improves continence, quality of life, psychologic well-being, and anal sphincter function. Benefit is maintained in the medium term. Neither pelvic floor exercises nor biofeedback was superior to standard care supplemented by advice and education.\nStudy6: Biofeedback vs. electrostimulation in the treatment of postdelivery anal incontinence: a randomized, clinical trial. This study was designed to evaluate the effect of biofeedback and electrostimulation in a randomized, clinical trial for the treatment of patients with postdelivery anal incontinence. Forty-nine females who sustained third-degree or fourth-degree perineal rupture with a mean age of 36 (range, 22-44) years were included in the study. The females were randomized to biofeedback or electrostimulation treatment. Forty females completed the study: 19 in the biofeedback and 21 in the electrostimulation group. Biofeedback or electrostimulation sessions were performed two times daily for eight weeks in each group. Wexner incontinence score, fecal incontinence quality of life scores, and reduced quality of life on visual analog scale were registered before and after treatment. Patients' self-rating of treatment effect also was registered in both groups. The primary outcome measure was the Wexner incontinence score. There were no differences in treatment effect between groups. Comparing pretreatment status to posttreatment in each group showed no improvement in Wexner score, reduced quality of life, or any of the fecal incontinence quality of life scores. Patients' self-rating of the treatment effect, however, showed a subjective improvement of symptoms both in the biofeedback and in the electrostimulation group (median, 7 vs. 5.) This study shows that there was no difference in effect between biofeedback and electrostimulation. Neither biofeedback nor electrostimulation treatments improved Wexner incontinence score, reduced quality of life, or fecal incontinence quality of life scores. Both treatments resulted in improvement of patients' subjective perception of incontinence control.\nStudy7: The effects of low-frequency endo-anal electrical stimulation on faecal incontinence: a prospective study. Faecal incontinence is a distressing problem that is often not amenable to surgical correction. Chronic low-frequency electrical stimulation of damaged axons is thought to reduce synaptic resistance, increase the size of motor units by axonal sprouting and increase the rate of conduction of the pudendal nerve. The aim of this study was to prospectively evaluate the effect of chronic low-frequency endo-anal electrical stimulation on faecal incontinence using a home-based unit and hospital-supervised therapy. Forty-eight patients with faecal incontinence completed a prospective randomised trial. Patients were allocated randomly to one of two groups; group 1 was exposed to endo-anal pudendal nerve stimulation daily at home with a portable home unit, group 2 attended the physiotherapy department for endo-anal electrical stimulation under supervision. Continence scores improved significantly after treatment in both groups (p<0.001). Both groups showed improved manometric scores, although only group 1 showed significant improvement in both resting and squeeze pressures (mean total resting pressure 184-224 mmHg, p<0.001; mean total squeeze pressure 253-337 mmHg, p<0.001). This was also reflected by an improvement in quality of life in both groups. Low-frequency endo-anal electrical stimulation significantly improves continence scores and quality of life in patients with faecal incontinence not amenable to surgical correction. It leads to improved manometric values when carried out on a daily basis with a portable home unit.\nStudy8: Triple target treatment (3T) is more effective than biofeedback alone for anal incontinence: the 3T-AI study. The efficacy of EMG-biofeedback and low-frequency electrical stimulation for the treatment of anal incontinence has not been proven. Our purpose was to evaluate a novel therapeutic concept, termed triple target treatment, which combines amplitude-modulated medium-frequency stimulation and EMG-biofeedback. Patients with anal incontinence were randomly assigned to the triple target regimen or EMG-biofeedback alone for a 9-month treatment period in a multicenter randomized clinical trial with blinded observers (ClincialTrials.gov registration number NCT00525291). Primary end points were changes in the Cleveland Clinic score and the adapted St. Mark's (Vaizey) score at 9 months compared with baseline. Secondary end points included therapy acceptance and proportion of patients achieving continence or improvement in grade or frequency of incontinence. We enrolled 158 patients with anal incontinence. The median decrease in the Cleveland Clinic score from baseline to 9 months was 3 points greater for the triple target regimen than for EMG-biofeedback (95% CI, 1-4; P = .0024). The improvement was 8 points for the triple target regimen (95% CI, 7-9) and 5 points for EMG-biofeedback (95% CI, 4-7). Results were similar for the Vaizey score. Of patients treated for at least 3 months, continence was achieved by 50% of patients with the triple target regimen and 25.8% of those with EMG-biofeedback. The combination of amplitude-modulated medium-frequency electrostimulation with EMG-biofeedback in the triple target regimen is superior to EMG-biofeedback alone in the treatment of anal incontinence. Therapy programs for fecal incontinence are most effective if patients participate for longer than 2 to 3 months.\nStudy9: Randomized controlled trial shows biofeedback to be superior to pelvic floor exercises for fecal incontinence. This study aimed to compare manometric biofeedback with pelvic floor exercises for the treatment of fecal incontinence in a randomized controlled trial controlling for nonspecific treatment effects. After excluding patients who were adequately treated with medication, education, and behavioral strategies (21%), 108 patients (83 females; average age, 59.6 years) underwent either pelvic floor exercises alone (n = 63) or manometric biofeedback plus pelvic floor exercises (n = 45). Patients in both groups were taught behavioral strategies to avoid incontinence. At three-month follow-up, biofeedback patients had significantly greater reductions on the Fecal Incontinence Severity Index (P = 0.01) and fewer days with fecal incontinence (P = 0.083). Biofeedback training increased anal canal squeeze pressure more than pelvic floor exercises did (P = 0.014) and with less abdominal tension during squeeze (P = 0.001). Three months after training 76% of patients treated with biofeedback vs. 41% patients treated with pelvic floor exercises (chi-squared = 12.5, P < 0.001) reported adequate relief. Before treatment, the groups did not differ on demographic, physiologic, or psychologic variables, symptom severity, duration of illness, quality-of-life impact, or expectation of benefit. At 12-month follow-up, biofeedback patients continued to show significantly greater reduction in Fecal Incontinence Severity Index scores (F = 4.83, P = 0.03), and more patients continued to report adequate relief (chi-squared = 3.64, P = 0.056). This investigation provides definitive support for the efficacy of biofeedback. Biofeedback training resulted in greater reductions in fecal incontinence severity and days with fecal incontinence. Biofeedback was also more effective than pelvic floor exercises alone in producing adequate relief of fecal incontinence symptoms in patients for whom conservative medical management had failed.\n", + "output": "Conclusions: The limited number of identified trials together with methodological weaknesses of many do not allow a definitive assessment of the role of anal sphincter exercises and biofeedback therapy in the management of people with faecal incontinence. We found some evidence that biofeedback and electrical stimulation may enhance the outcome of treatment compared to electrical stimulation alone or exercises alone. Exercises appear to be less effective than an implanted sacral nerve stimulator. While there is a suggestion that some elements of biofeedback therapy and sphincter exercises may have a therapeutic effect, this is not certain. Larger well-designed trials are needed to enable safe conclusions." + }, + { + "input": "Study1: Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. Oral selenium (200 \u03bcg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-\u03b1-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. Prostate cancer incidence. This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. Clinicaltrials.gov Identifier: NCT00006392.\nStudy2: Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Findings from animal models suggest that selenium supplementation improves glucose metabolism. To examine the effect of long-term selenium supplementation on the incidence of type 2 diabetes. Secondary analysis of a randomized, double-blind, placebo-controlled trial. Areas of low selenium consumption of the eastern United States. 1202 persons seen in dermatology clinics who did not have type 2 diabetes at baseline. Oral administration of selenium, 200 microg/d, or placebo. Incidence of type 2 diabetes. During an average follow-up of 7.7 years (SD, 2.7), type 2 diabetes developed in 58 selenium recipients and 39 placebo recipients (incidence, 12.6 cases per 1000 person-years vs. 8.4 cases per 1000 person-years, respectively; hazard ratio, 1.55 [95% CI, 1.03 to 2.33]). The lack of benefit of selenium supplementation on the incidence of type 2 diabetes persisted in analyses stratified by age, sex, body mass index, and smoking status. An exposure-response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level (hazard ratio, 2.70 [CI, 1.30 to 5.61]). Diabetes was a secondary outcome in the parent trial. Diagnoses of diabetes were self-reported but were validated in most participants. The sample was mostly older and white. Selenium supplementation does not seem to prevent type 2 diabetes, and it may increase risk for the disease. Click here for related information on selenium.\nStudy3: Frequent consumption of selenium-enriched chicken meat by adults causes weight loss and maintains their antioxidant status. To assess the effects of a moderately high-protein intake on the body composition, biochemical, and antioxidant status parameters in young adults depending on either selenium- (Se) or non-enriched chicken consumption. The volunteers (n = 24) that completed the 10-week nutritional intervention were distributed in two parallel groups and randomly assigned to follow an isocaloric diet with moderately high content in protein (30% energy), either with the consumption of four 200 g portions/week of Se- or non-enriched chicken breasts. Blood samples were taken at the beginning and at the end of the study and body composition was monitored during the trial. There was a significant reduction in weight, accompanying a decrease on fat mass in both groups, while fat-free mass remained unchanged during the 10 weeks of intervention, without differences between both dietary groups. Selenium blood levels and plasma glutathione peroxidase activity, as well as lipid, glucose, and selected inflammation biomarkers remained stable during the intervention period in both dietary groups. Frequent chicken consumption, within a controlled diet with a moderately high content in protein, produced a slight but statistically significant weight reduction mainly due to the loss of fat mass. An extra Se supplementation (22 \u03bcg/day) in the Se-enriched chicken breast did not affect tachyphylactic antioxidant status of the participants neither inflammatory-related markers after weight loss.\nStudy4: No effect of selenium supplementation on serum glucose levels in men with prostate cancer. Literature indicates a relationship between selenium supplementation and risk of diabetes. However, because these data are inconclusive, we investigated the effect of selenium supplementation on serum glucose levels in men with prostate cancer enrolled in a clinical trial testing of the effect of selenium on prostate cancer progression. Subjects were randomized to receive placebo (n=46), selenium 200 microg/day (n=47), and selenium 800 microg/day (n=47). Serum glucose levels were obtained every 6 months for up to 5 years. Longitudinal analysis was carried out to assess whether rate of change of serum glucose levels was significantly different in the selenium-supplemented groups as compared with placebo. Sensitivity analyses were performed to assess the robustness of findings. Changes in serum glucose levels during the course of the trial were not statistically significantly different as compared with placebo for the selenium 200 microg/day (P=.56) or selenium 800 microg/day (P=.91) treatment groups. These results do not support a relationship between selenium supplementation and changes in serum glucose levels. Recommendations about selenium supplementation and risk of diabetes will require more definitive studies. Copyright 2010 Elsevier Inc. All rights reserved.\nStudy5: A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin. Evidence that selenium affects the risk of type-2 diabetes is conflicting, with observational studies and a few randomized trials showing both lower and higher risk linked to the level of selenium intake and status. We investigated the effect of selenium supplementation on the risk of type-2 diabetes in a population of relatively low selenium status as part of the UK PRECISE (PREvention of Cancer by Intervention with SElenium) pilot study. Plasma adiponectin concentration, a recognised independent predictor of type-2 diabetes risk and known to be correlated with circulating selenoprotein P, was the biomarker chosen. In a randomized, double-blind, placebo-controlled trial, five hundred and one elderly volunteers were randomly assigned to a six-month intervention with 100, 200 or 300 \u00b5g selenium/d as high-selenium or placebo yeast. Adiponectin concentration was measured by ELISA at baseline and after six months of treatment in 473 participants with one or both plasma samples available. Mean (SD) plasma selenium concentration was 88.5 ng/g (19.1) at baseline and increased significantly in the selenium-treatment groups. In baseline cross-sectional analyses, the fully adjusted geometric mean of plasma adiponectin was 14% lower (95% CI, 0-27%) in the highest than in the lowest quartile of plasma selenium (P for linear trend = 0.04). In analyses across randomized groups, however, selenium supplementation had no effect on adiponectin levels after six months of treatment (P = 0.96). These findings are reassuring as they did not show a diabetogenic effect of a six-month supplementation with selenium in this sample of elderly individuals of relatively low selenium status.\nStudy6: Does dietary arsenic and mercury affect cutaneous bleeding time and blood lipids in humans? Fish species may contain considerable amounts of trace elements, such as selenium (Se), arsenic (As), and mercury (Hg). The present study investigated the relationships between dietary intake of these elements and cutaneous bleeding time and blood lipids in 32 healthy volunteers. For 6 wk, one group (n = 11) consumed approx 250 g Se-rich fish daily, providing them with an average Se intake of 115 +/- 31 micrograms Se/d, Hg intake of 18 +/- 8 micrograms/d, and As intake of 806 +/- 405 micrograms/d, all values analyzed in 4-d duplicate food collections. To study the effect of Se alone, one group (n = 11) included Se-rich bread in their normal diet, giving them a Se intake (135 +/- 25 micrograms/d) that was comparable to the fish group. A control group (n = 10) ate their normal diet, providing 77 +/- 25 micrograms Se/d, 3.1 +/- 2.5 micrograms Hg/d, and 101 +/- 33 micrograms As/d. The dietary As load strongly correlated both with bleeding times and changes in bleeding times (r = 0.48, p < 0.01 and r = 0.54, p < 0.002, respectively). Dietary Hg showed a positive correlation with LDL-cholesterol (r = 0.55, p < 0.01), whereas dietary Hg in the fish group showed a strong negative relationship with HDL-cholesterol (r = -0.76, p < 0.01). Selenium seemed to have only a modest effect on bleeding time. Our results suggest that mercury and arsenic from fish may be factors contributing to or modifying some of the known effects of fish ingestion.\nStudy7: Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial. High selenium status has been linked to elevated blood cholesterol levels in cross-sectional studies. To investigate the effect of selenium supplementation on plasma lipids. Randomized, placebo-controlled, parallel-group study stratified by age and sex. Participants, research nurses, and persons assessing outcomes were blinded to treatment assignment. (International Standard Randomised Controlled Trial Number Register registration number: ISRCTN25193534) 4 general practices in the United Kingdom. 501 volunteers aged 60 to 74 years. Participants received selenium, 100 mcg/d (n = 127), 200 mcg/d (n = 127), or 300 mcg/d (n = 126), as high-selenium yeast or a yeast-based placebo (n = 121) for 6 months. Total and high-density lipoprotein (HDL) cholesterol concentrations were measured in nonfasting plasma samples stored from participants in the UK PRECISE (United Kingdom PREvention of Cancer by Intervention with SElenium) Pilot Study at baseline (n = 454) and at 6 months (n = 394). Non-HDL cholesterol levels were calculated. Mean plasma selenium concentration was 88.8 ng/g (SD, 19.2) at baseline and increased statistically significantly in the treatment groups. The adjusted difference in change in total cholesterol levels for selenium compared with placebo was -0.22 mmol/L (-8.5 mg/dL) (95% CI, -0.42 to -0.03 mmol/L [-16.2 to -1.2 mg/dL]; P = 0.02) for 100 mcg of selenium per day, -0.25 mmol/L (-9.7 mg/dL) (CI, -0.44 to -0.07 mmol/L [-17.0 to -2.7 mg/dL]; P = 0.008) for 200 mcg of selenium per day, and -0.07 mmol/L (-2.7 mg/dL) (CI, -0.26 to 0.12 mmol/L [-10.1 to 4.6 mg/dL]; P = 0.46) for 300 mcg of selenium per day. Similar reductions were observed for non-HDL cholesterol levels. There was no apparent difference in change in HDL cholesterol levels with 100 and 200 mcg of selenium per day, but the difference was an adjusted 0.06 mmol/L (2.3 mg/dL) (CI, 0.00 to 0.11 mmol/L [0.0 to 4.3 mg/dL]; P = 0.045) with 300 mcg of selenium per day. The total-HDL cholesterol ratio decreased progressively with increasing selenium dose (overall P = 0.01). The duration of supplementation was limited, as was the age range of the participants. Selenium supplementation seemed to have modestly beneficial effects on plasma lipid levels in this sample of persons with relatively low selenium status. The clinical significance of the findings is unclear and should not be used to justify the use of selenium supplementation as additional or alternative therapy for dyslipidemia. This is particularly true for persons with higher selenium status, given the limitations of the trial and the potential additional risk in other metabolic dimensions. The Cancer Research Campaign (now Cancer Research UK) and the University of Surrey.\nStudy8: Intervention trial with selenium for the prevention of lung cancer among tin miners in Yunnan, China. A pilot study. This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium (Se) in Yunnan Tin Corporation, the People's Republic of China, where the incidence rates of lung cancer are extraordinarily high among the miners. Forty healthy miners were randomized to either 300 micrograms of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year. Subjects consumed their usual daily diet. The low Se concentrations in plasma (0.05 +/- 0.008 microgram/mL) and hair (0.442 +/- 0.085 microgram/g) reflected their low dietary Se intake in the control subjects. In Se-supplemented group, the Se status was increased by 178% for serum and 194.8% for hair. The serum GSHpx activity was increased by 155.7%, whereas the lipid peroxide level was reduced by 74.5% compared to the placebo. The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation. Se-supplementation did not affect the liver function test (SGPT), as well as the concentrations of hemoglobin, albumin, and cholesterol. Thus, daily intake of 300 micrograms Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status.\nStudy9: Increased consumption of wheat biofortified with selenium does not modify biomarkers of cancer risk, oxidative stress, or immune function in healthy Australian males. Increased intake of selenium (Se) may reduce the risk of degenerative diseases including cancer but excessive intake may be toxic. Wheat is a major source of dietary Se in humans. However, the effect of Se from wheat that is agronomically biofortified with Se on biomarkers of human health status is unknown. This study aimed to investigate whether improving Se status, by increased dietary intake of Se-biofortified wheat, affects biomarkers of cancer risk, cardiovascular disease risk, oxidative stress, and immune function in healthy South Australian men. A 24-week placebo-controlled double-blind intervention was performed in healthy older men (n = 62), with increased dose of Se intake every 8 weeks. Wheat was provided as 1, 2, and 3 puffed wheat biscuits, during weeks 1-8, 9-16, and 17-24, respectively. Blood was collected to measure a wide range of disease risk biomarkers. Consumption of Se-biofortified wheat was found to increase plasma Se concentration from a baseline level of 122 to 192 microg/L following intake of three biscuits/day, which provided 267 microg Se. Platelet glutathione peroxidase, chromosome aberrations, and DNA damage in lymphocytes measured using the cytokinesis-block micronucleus cytome assay and with the Comet assay, plasma F2-isoprostanes, protein carbonyls, plasma C-reactive protein, and leukocyte number were unaffected by the improved Se status. Improvement of Se status by consumption of Se-biofortified wheat did not substantially modify the selected biomarkers of degenerative disease risk and health status in this apparently selenium-replete cohort of healthy older men in South Australia. Copyright 2009 Wiley-Liss, Inc.\nStudy10: Selenium supplementation does not improve vascular responsiveness in healthy North American men. Selenium is an essential trace nutrient required for the synthesis of selenoproteins such as glutathione peroxidase and thioredoxin reductase, the major forms of selenium in the endothelium that have important functions relevant to inflammation and cardiovascular disease. Selenium deficiency is associated with cardiomyopathy and sudden cardiac death in animals, and a low selenium status is associated with cardiovascular disease in humans. Endothelial dysfunction, measured as the impaired flow-mediated vasorelaxation of the brachial artery, is a reliable indicator of future cardiovascular disease risk in healthy individuals. To test whether selenium supplementation affects endothelial function, we conducted a randomized, placebo-controlled trial in healthy men who were administered 300 microg of selenium a day as high-selenium yeast for 48 wk. Brachial artery responsiveness to transient occlusion was assessed at baseline and after 24 and 48 wk of supplementation. The supplementation increased the selenium concentration by more than half in blood plasma and erythrocytes. However, there was no effect of selenium on arterial diameter or blood flow rate before or after transient occlusion or on the maximum dilated diameter after the administration of nitroglycerin. This study indicates that selenium supplementation is not likely to improve endothelial function or peripheral arterial responsiveness in healthy North American men receiving adequate selenium from their diets.\n", + "output": "Conclusions: The limited trial evidence that is available to date does not support the use of selenium supplements in the primary prevention of CVD." + }, + { + "input": "Study1: Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's disease. To evaluate the efficacy and safety of rapidly titrated rivastigmine administered twice (BID) or three times (TID) daily in patients with mild to moderate Alzheimer's disease (AD). This was a 26 week international, randomised, double blind, placebo controlled study in which 678 patients with probable AD received placebo or rivastigmine 2-12 mg/day BID or TID. Primary outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog) and categorical analysis of the Clinician Interview Based Impression of Change incorporating caregiver information (CIBIC-Plus). Secondary outcomes were the CIBIC-Plus change from baseline, Progressive Deterioration Scale, ADAS-cogA, Mini-Mental State Examination and Global Deterioration Scale. At week 26, mean rivastigmine dose was 9.6 (2.76) mg/day in the TID group and 8.9 (2.93) mg/day in the BID group. Mean ADAS-cog changes from baseline in the TID and BID rivastigmine treated groups were -0.2 (SD 7.3) and 1.2 (SD 7.2) versus 2.8 (SD 7.2) for the placebo group (p<0.05). Differences between rivastigmine TID and placebo on the CIBIC-Plus categorical responder analysis were significant (31% vs 19%; p<0.05, intention to treat). No significant differences were seen between BID and placebo for this outcome measure. Adverse events were predominantly gastrointestinal, occurring mainly during dose titration. Withdrawal because of adverse events accounted for 17% of BID, 11% of TID and 9% of placebo patients. Rivastigmine administered as a BID or TID regimen significantly benefited cognitive, function and global performances in AD patients. The TID regimen showed a tendency for superior tolerability and permitted titration to higher doses, an outcome that is significant as the efficacy of rivastigmine is dose related.\nStudy2: Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease. Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease. To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia. We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation. This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD. Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment. Copyright 2004 John Wiley & Sons, Ltd.\n", + "output": "Conclusions: Rivastigmine appears to be beneficial for people with mild to moderate Alzheimer's disease. In comparisons with placebo, improvements were seen in the rate of decline of cognitive function, activities of daily living, and severity of dementia with daily doses of 6 to 12 mg. Adverse events were consistent with the cholinergic actions of the drug. A transdermal patch has been tested in one trial, and there is evidence that the lower dose smaller patch is associated with fewer side effects than the capsules or the higher dose larger patch and has comparable efficacy to both. This review has not examined economic data." + }, + { + "input": "Study1: An interactive technology approach to educate older adults about drug interactions arising from over-the-counter self-medication practices. An interactive computer program (Personal Education Program [PEP]) designed for the learning styles and psychomotor skills of older adults was used to teach older adults about potential drug interactions that can result from self-medication with over-the-counter (OTC) agents and alcohol. Subjects used the PEP on notebook computers equipped with infrared sensitive touchscreens. Subjects were recruited from senior centers. Those who met age, vision, literacy, independence, and medication use criteria were randomly assigned to one of three groups: (1) PEP plus information booklet; (2) information booklet only; or (3) control. A repeated measures (three time periods 2 weeks apart), three-group design was used. Users of PEP had significantly greater knowledge and self-efficacy scores than both the conventional and control groups at all three time points. The PEP group reported fewer adverse self-medication behaviors over time. Reported self-medication behaviors did not change over time for either the conventional or control groups. Subjects indicated a high degree of satisfaction with the PEP and reported their intent to make specific changes in self-medication behaviors.\nStudy2: Preventing prescription drug misuse: field test of the SmartRx Web program. Purpose of the project was to test a Web-based program designed to prevent prescription drug misuse. Study sample consisted of 346 working women randomized into either an experimental or wait-list control condition. Analysis of covariance and logistic regression were used to compare responses. Women receiving the intervention had greater knowledge of drug facts and greater self-efficacy in medication adherence and ability to manage problems with medications compared with controls. Women receiving the intervention also had reduced symptoms reported on the CAGE for prescription medications. Findings suggest that multimedia Web-based programs can be a beneficial addition to substance misuse prevention services. The study's limitations are noted.\nStudy3: Evaluation of the addition of video-based education for patients receiving standard pre-chemotherapy education. Preparing cancer patients and their families for chemotherapy treatment is difficult. The challenge lies in finding ways to promote self-care and improve their ability to recall instructions. The aim of this study was to evaluate the usefulness of an educational video with regard to patients' ability to recall and report side effects of treatment. Patients referred for adjuvant chemotherapy for breast and colorectal cancer were randomized to receive standard pre-chemotherapy education or standard education plus addition of a video. Patients completed a base line questionnaire assessing existing knowledge and another questionnaire prior to the second chemotherapy cycle evaluating recall of information. Patients who watched the video were asked to assess the video after six cycles of chemotherapy. Telephone calls to the department reporting symptoms were monitored for both groups. The video group demonstrated trends towards higher recall in information concerning fever, mouth problems, low red cell count and prevention of constipation. They more commonly telephoned reporting medical problems of nausea, vomiting and signs of infection compared with the standard group. In summary, our study demonstrated inclusion of video to standard chemotherapy education improves retention of information regarding management of predictable chemotherapy side effects and reporting of treatment-related symptoms.\nStudy4: Preoperative PCA teaching program to manage postoperative pain. Patient-controlled analgesia (PCA) therapy was designed to provide patients with greater control in managing their pain. However, many patients continue to suffer from moderate to severe pain due to lack of knowledge about how to use PCA therapy. The results of this quasi-experimental study demonstrated that patients who received structured preoperative teaching had statistically significant higher knowledge regarding the use of PCA therapy and more positive attitudes toward using pain medicine. Patients who received the video teaching reported better pain control and satisfaction with pain management 4 and 8 hours following their surgical procedures.\nStudy5: Improving informed consent to chemotherapy: a randomized controlled trial of written information versus an interactive multimedia CD-ROM. This randomized controlled trial aimed to determine whether an interactive CD-ROM improved cancer patients' recall of chemotherapy treatment information over standard written information, and whether demographic, cognitive, and psychological factors better predicted recall than this format of delivery. One-hundred-and-one new patients about to commence chemotherapy were randomized to receive written information or a CD-ROM containing treatment information before giving informed consent. Patients' recall, concentration, short-term memory, reading comprehension, anxiety, depression, and coping styles were assessed with standardized measures pre-treatment. Seventy-seven patients completed tests for recall of treatment information before their second chemotherapy session. Intention-to-treat analyses indicated no significant differences between the written information and CD-ROM groups across recall questions about number of drugs received (p=.43), treatment length (p=.23), and treatment goal (p=.69). Binary logistic regressions indicated that for groups combined different variables predicted each of the recall questions. An interactive CD-ROM did not improve cancer patients' recall of treatment information enough to warrant changes in consent procedures. Different variables predicted recall of different treatment aspects highlighting the complex nature of attempting to improve patient recall. Attending to the effect of depression on patient knowledge and understanding appears paramount.\nStudy6: A video game improves behavioral outcomes in adolescents and young adults with cancer: a randomized trial. Suboptimal adherence to self-administered medications is a common problem. The purpose of this study was to determine the effectiveness of a video-game intervention for improving adherence and other behavioral outcomes for adolescents and young adults with malignancies including acute leukemia, lymphoma, and soft-tissue sarcoma. A randomized trial with baseline and 1- and 3-month assessments was conducted from 2004 to 2005 at 34 medical centers in the United States, Canada, and Australia. A total of 375 male and female patients who were 13 to 29 years old, had an initial or relapse diagnosis of a malignancy, and currently undergoing treatment and expected to continue treatment for at least 4 months from baseline assessment were randomly assigned to the intervention or control group. The intervention was a video game that addressed issues of cancer treatment and care for teenagers and young adults. Outcome measures included adherence, self-efficacy, knowledge, control, stress, and quality of life. For patients who were prescribed prophylactic antibiotics, adherence to trimethoprim-sulfamethoxazole was tracked by electronic pill-monitoring devices (n = 200). Adherence to 6-mercaptopurine was assessed through serum metabolite assays (n = 54). Adherence to trimethoprim-sulfamethoxazole and 6-mercaptopurine was greater in the intervention group. Self-efficacy and knowledge also increased in the intervention group compared with the control group. The intervention did not affect self-report measures of adherence, stress, control, or quality of life. The video-game intervention significantly improved treatment adherence and indicators of cancer-related self-efficacy and knowledge in adolescents and young adults who were undergoing cancer therapy. The findings support current efforts to develop effective video-game interventions for education and training in health care.\nStudy7: [Randomized evaluation of two teaching methods using aerosol dosers]. The administration of antiasthmatic drugs by pressurised aerosols is limited by the difficulties of the inhalation technique. The development of teaching aids may help their use. The aim of this study was to assess and to compare 2 educational methods of inhalation: a standardised inhalation card and a video film. Forty five asthmatic patients who were poor coordinators were separated randomly into 3 groups: education by card, education by video film and a third group served as a positive control and had been educated by video film and also an additional education in a room set aside for teaching inhalation techniques. The FEV1 (VEMS) had been read before the education session and 15 days after, and on each occasion before and after inhalation of a beta-2-mimetic. An inhalation score was measured on the same date. The 2 educational methods enabled an improvement in the score to be shown which was more marked in the video group than in the card group. The VEMS (mean + or - one standard deviation) before inhalation of beta-2-mimetics was significantly superior to J15 in relation to J1 in the video group (2.38 +/- 0.84 and 1.89 +/- 0.61 respectively) and in the control group (2.05 +/- 0.81 and 1.71 +/- 0.66 respectively) whilst the values did not differ in the card group (2.09 +/- 0.63 and 2.01 +/- 0.7 respectively). This study suggests the value of education of these patients and the superiority of video education in relation to reading a standardised card in the optimisation of treatment administered by the inhaled route.\nStudy8: Tricyclic antidepressant education program and its evaluation. The objectives of this study were (1) to develop an individualized tricyclic audiovisual education program and (2) to compare the program's effectiveness with that of traditional education. The program is designed to increase short-term and long-term knowledge about tricyclic antidepressants and depression. The patient's dose was stabilized, and then a pretest was given. If the patient was in the study group, he received the seven-minute slide-tape program and a posttest within 72 hours. The control group received the posttest within five days of the pretest. Both groups were given knowledge tests at approximately four weeks. Statistical analysis of the data from this small study group revealed significance at the 95% confidence level for the following statement: the study group showed a greater increase in factual short-term and long-term knowledge about its tricyclic therapy as shown by differences in pretest, posttest, and scores of tests at four weeks. This study demonstrates an effective standardized alternative to traditional education which can be used to educate the majority of patients about tricyclic antidepressants and depression with a minimum time investment.\nStudy9: Inhaler technique in Turkish people with poor English: a case of information discrimination? (a) To compare metered dose inhaler (MDI) technique in users with poor English and fluent English, (b) to evaluate two interventions: a translated patient information leaflet (PIL) plus support from an translator (PIL + verbal) and a multimedia touch screen system (MTS) using video clips and own-language instruction. (a) Inhaler technique was videotaped and key steps rated blind for 105 fluent English-speakers (FE) and 69 Turkish-speakers with poor English (EP). (b) The EP group was randomised to receive information by MTS (n = 34) or PIL + verbal (n = 35). Inhaler technique was videotaped before and after information. (a) Global inhaler technique; (b) breathing-in time; (c) co-ordination of inspiration and inhaler actuation. Global technique, co-ordination and breath-holding were all significantly worse in MDI users with poor English. Only 17% of that group had adequate technique compared to over half (62%) of FE. The EP group were significantly less likely than the FE group to report ever seeing the practice nurse about their asthma. After information, global technique was rated as improved in 50% of the MTS group compared to 28% of those given a translated PIL. A further six people (17%) in the PIL group improved after subsequent verbal advice in their own language. Both information methods significantly increased inhaler shaking and mouthpiece checking, but co-ordination only improved in a small number of people. The study suggests that Turkish-speaking MDI users with poor English may be disadvantaged in terms of access to medicines information in the UK. The acceptability of pharmacy-based support services for this, and other specific language groups should be explored. Multimedia offers an alternative to a translator for brief explanations, particularly for first-time users, but improving poor co-ordination requires individualised \"hands on\" teaching from health professionals.\nStudy10: Results of a randomized controlled trial of a brief behavioral intervention for pelvic inflammatory disease in adolescents. The objective of this research was to examine the effectiveness of a brief behavioral intervention, provided at the time of diagnosis of pelvic inflammatory disease, on subsequent behaviors by patients who were urban adolescents in a community in which sexually transmitted infection was prevalent. 121 adolescents aged 15 to 21 years with mild to moderate pelvic inflammatory disease were enrolled in a randomized trial. All participants received standardized care, completed baseline audio computerized self-interviews, received full courses of medication at discharge, and were interviewed after the 2-week treatment course. The intervention group also watched a 6-minute intervention video. Medication completion, temporary sexual abstinence during the 14-day treatment period, partner notification, partner treatment, and return for 72-hour follow-up were studied. Data were evaluated using multivariate regression analysis. Of the participants, 61% were located and could participate in the 2-week interview by the disease intervention specialist. The intervention participants had higher rates of 72-hour follow-up (32% vs. 16%) and partner treatment (71% vs. 53%) in bivariate analyses at a P = 0.1 level. There were no differences in medication completion (66% vs. 66%), sexual abstinence (78% vs. 89%), or partner notification (88% vs. 92%). Only the partner-treatment finding persisted in multivariate models (AOR = 3.10; 95% CI, 1.03-9.39, P = .045). Adolescent girls randomized to a community-specific video intervention at diagnosis of pelvic inflammatory disease were three times more likely to have their partners treated than those in the control group. Given the value of partner treatment in secondary prevention of sexually transmitted diseases, this video may be an essential component of discharge programming in urgent care settings. Additional structural supports may be necessary to facilitate improved adherence to other key adherence behaviors. Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.\n", + "output": "Conclusions: This review provides evidence that multimedia education about medications is more effective than usual care (non-standardised education provided by health professionals as part of usual clinical care) or no education, in improving both knowledge and skill acquisition. It also suggests that multimedia education is at least equivalent to other forms of education, including written education and education provided by a health professional. However, this finding is based on often low quality evidence from a small number of trials. Multimedia education about medications could therefore be considered as an adjunct to usual care but there is inadequate evidence to recommend it as a replacement for written education or education by a health professional. Multimedia education may be considered as an alternative to education provided by a health professional, particularly in settings where provision of detailed education by a health professional is not feasible. More studies evaluating multimedia educational interventions are required in order to increase confidence in the estimate of effect of the intervention.\nregarding the effect of multimedia education were limited by the lack of information provided by study authors about the educational interventions, and variability in their content and quality. Studies testing educational interventions should provide detailed information about the interventions and comparators. Research is required to establish a framework that is specific for the evaluation of the quality of multimedia educational programs. were also limited by the heterogeneity in the outcomes reported and the instruments used to measure them. Research is required to identify a core set of outcomes which should be measured when evaluating patient educational interventions. Future research should use consistent, reliable and validated outcome measures so that comparisons can be made between studies." + }, + { + "input": "Study1: Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial. The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer. Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates. A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity. This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.\nStudy2: [Intensive chemotherapy and autograft of hematopoietic stem cells in the treatment of metastatic cancer: results of the national protocol Pegase 04]. We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients. Inclusion criteria were: age < or = 60 year, PS < 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m2, Cyclophosphamide: 120 mg/kg, Melphalan: 140 mg/m2), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled: 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response. The median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12). The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival.\n", + "output": "Conclusions: Although there is evidence that high dose chemotherapy and autograft significantly improves event-free survival compared to conventional chemotherapy in women with metastatic breast cancer there is no significant evidence of benefit in overall survival. High dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials." + }, + { + "input": "Study: Aquatic fitness training for children with juvenile idiopathic arthritis. To evaluate the effects of an aquatic training programme for JIA patients. Fifty-four patients with JIA (age range 5 to 13 yr) participated in this study and were randomized into an experimental (n = 27) and a control (n = 27) group. The children in the experimental group received a training programme consisting of a 1 h per week supervised training programme in a local pool of approximately 20 sessions. Effects were analysed on the following domains: functional ability, health-related quality of life, joint status and physical fitness. Although all measures improved more in the experimental group than the control group, none of the differences was statistically significant. The current research found no significant effect of an aquatic fitness training programme in children with JIA. Since there were no signs of worsening in health status, one can conclude that this was a safe exercise programme.\n", + "output": "Conclusions: Overall, based on 'silver-level' evidence (www.cochranemsk.org) there was no clinically important or statistically significant evidence that exercise therapy can improve functional ability, quality of life, aerobic capacity or pain. The low number of available RCTs limits the generalisability. The included and excluded studies were all consistent about the adverse effects of exercise therapy; no short-term detrimental effects of exercise therapy were found in any study. Both included and excluded studies showed that exercise does not exacerbate arthritis. The large heterogeneity in outcome measures, as seen in this review, emphasises the need for a standardised assessment or a core set of functional and physical outcome measurements suited for health research to generate evidence about the possible benefits of exercise therapy for patients with JIA. Although the short-term effects look promising, the long-term effect of exercise therapy remains unclear." + }, + { + "input": "Study1: Effectiveness of a social relations intervention program for aggressive and nonaggressive, rejected children. A sample of 52 Black aggressive, rejected and nonaggressive, rejected children were randomly assigned to receive a social relations intervention or to be in a nonintervention control group. The school-based intervention for fourth-grade children focused on positive social skill training and cognitive-behavioral strategies to promote deliberate, nonimpulsive problem solving. At both the post-treatment and the 1-year follow-up assessments, the social relations intervention was found to be effective only with the aggressive, rejected children. Implications for the importance of assessing subtypes of rejected children are discussed.\nStudy2: Cognitive self-instructional training approach for reducing disruptive behavior of young children. nan\nStudy3: School-based secondary prevention for children with disruptive behavior: initial outcomes. First through fourth graders from 22 suburban elementary schools were screened for cross-setting disruptive behavior as eligibility criteria for participation in a longitudinal secondary prevention study aimed at reducing the risk for serious externalizing behavioral disorders. Three hundred nine subjects participated in either a multicomponent competence enhancement intervention (MCEI) or an information/attention control (IAC) condition over a 2-year period. Following baseline requirements, initial intervention effects were assessed at the end of intervention Year 1, at the beginning of intervention Year 2 (fall of the next school year), and at the end of intervention Year 2. Multisource assessments were not supportive of the efficacy of the MCEI over the IAC condition. Children in both groups rated themselves as improved over time in terms of increased adaptive skills and decreased school problems and internalizing symptoms. Teacher and parent ratings of externalizing behavior did not yield evidence of positive change, but teachers noted improved problem solving and observers noted a decrease in behavioral interference in both groups over time, possibly as a result of maturation.\nStudy4: Improving the social behavior and peer acceptance of rejected boys: effects of social skill training with instructions and prohibitions. nan\nStudy5: Behavioral and cognitive effects of a moral reasoning development intervention for high-risk behavior-disordered adolescents. nan\nStudy6: Modification of anger in children by affective imagery training. From a school population of normal children (third through fifth grades), thirty children initially identified as \"angry\" were randomly assigned to either an affective imagery training group, an attention group, or a control group. The treatment group received three sessions of affective imagery in which they focused on physiological changes and on their thoughts associated with prior emotional experiences. Teachers recorded pre-, post-, and short term follow-up aggressive behaviors for all thirty children. Cognitive perceptions and attributions were recorded at the same three occasions on the Affect Questionnaire. Results suggested that, as a result of affective imagery training, angry children's perceptions and cognitions shifted from \"angry\" towards \"sad,\" and there was a concomitant decrease in observed aggressive classroom behavior.\nStudy7: A cognitive-ecological approach to preventing aggression in urban settings: initial outcomes for high-risk children. A multiyear, multicontext aggression prevention intervention was provided during the early or late elementary school years in an inner-city and an urban poor community. Sixteen schools were randomly assigned to 1 of 4 conditions: (a) no-treatment control, (b) general enhancement classroom program, (c) general enhancement plus small-group peer-skills training, or (d) general enhancement plus small-group peer-skills training plus family intervention. This article reports on results for the high-risk subsample of 1,500 children. Results from hierarchical linear modeling indicate that comprehensive interventions, if provided in early grades, can be effective for children in schools in settings with resources adequate to support learning and development, but some unintended effects can occur in schools in the most distressed communities when delivered too late in development.\nStudy8: \"Think aloud\": a program for developing self-control in young aggressive boys. \"Think Aloud\" was designed as a training program to improve self-control in 6- to 8-year-old boys. It involved modeling and verbalization of cognitive activity to foster use of verbal mediation skills in dealing with both cognitive and interpersonal problems. It was hypothesized that this training would lead to improvement in test performance and teacher ratings of classroom behavior in hyperaggressive boys. Twelve aggressive second grade boys participated in daily, 30-minute, individual sessions for 6 weeks. Normal and aggressive control subjects received no intervention. Teachers rated both trained and untrained aggressive boys as improving in aggressive behaviors but they rated the experimental group as showing improvement on a significantly larger number of prosocial behaviors. The pattern of performance on cognitive tests also changed significantly in the experimental group. On pretest, their pattern differed from normals and resembled the aggressive control group, while on posttest their pattern resembled normals and differed from agressive controls. Suggestions were made concerning additional refinements needed in the program, but overall results indicated potential value in the present approach for providing assistance to aggressive boys in the early grades.\n", + "output": "Conclusions: School-based secondary prevention programmes to reduce aggressive behaviour appear to produce improvements in behaviour greater than would have been expected by chance. Benefits can be achieved in both primary and secondary school age groups and in both mixed sex groups and boys-only groups. Further research is required to establish whether such programmes reduce the incidence of violent injuries or if the benefits identified can be maintained beyond 12 months." + }, + { + "input": "Study1: A randomized study to assess two different techniques of aspiration while performing transabdominal chorionic villus sampling. The technique used to perform transabdominal chorionic villus sampling (CVS) is not standardized, but aspiration of villi is generally obtained by discontinuous vacuum created in a syringe, manually or by a hand-grip device. We evaluated the feasibility of a new method of performing CVS which employs a 4-mL Vacutainer connected to the needle, producing a continuous negative pressure. Two hundred pregnant women, whose gestational age ranged from 10 + 2 to 16 + 2 (mean, 12 + 1) weeks, entered the randomized study, which was powered to detect with 90% probability the absence of any difference in the size of chorionic samples obtained by using a 20-mL syringe with the vacuum obtained by a hand-grip device (Group 1) or by a vacutainer (Group 2). Four operators with different levels of experience performed all the procedures, which were done transabdominally using a freehand technique with a 20-gauge needle under ultrasound guidance. Maternal age, body mass index, gestational age and the way the needle was inserted within the chorion were similar in the two groups. The median amount of villi sampled was 20 mg, with no differences between the two groups. The rate of fetal loss was 1.7%. All losses occurred in women of Group 1 who had only one needle insertion. A second needle insertion was required more frequently while using the vacutainer. This new technique for performing transabdominal CVS uses a readily available device and is as effective as traditional sampling systems to aspirate villi. It has the advantage of being a one-operator procedure.\nStudy2: The role of hexoprenaline in suprapubic amniocentesis during late pregnancy. A pilot study. Suprapubic amniocentesis is often complicated by the fetal head being fixed in the pelvis, oligohydramnios or a hyperirritable myometrium. These factors limit the success rate associated with the procedure. If the myometrium is relaxed with a beta 2-stimulant, a higher success rate may be achieved. This was investigated in a randomized, prospective, double-blind pilot study using hexoprenaline. When four- or five-fifths of the fetal head was palpable above the pelvis, hexoprenaline (17 amniocenteses) showed no advantage over a placebo (16 amniocenteses). However, when three-fifths or less of the fetal head was palpable above the brim, 4 dry taps were obtained in the control group using a placebo (17 amniocenteses), while none occurred in the study group (19 amniocenteses) (P less than 0,05). Elevation of the fetal head was less difficult in the study group, but this difference was not statistically significant. These results suggest that hexoprenaline is not indicated for routine use during amniocentesis. When a dry tap is obtained or when marked difficulty is encountered in lifting the fetal head from the pelvis, 10 micrograms hexoprenaline administered intravenously 5 minutes before amniocentesis appears to facilitate successful completion of the procedure. However, a larger series is necessary to confirm this observation.\nStudy3: A randomised trial of progesterone prophylaxis after midtrimester amniocentesis. Midtrimester amniocentesis to investigate fetal karyotype carries a small risk of fetal loss. To test the hypothesis that progesterone prophylaxis may reduce this. A randomised controlled trial comparing a short prophylactic treatment with progesterone after amniocentesis with untreated controls. There were no differences in frequency of miscarriage, preterm delivery or neonatal outcome. Prophylactic progesterone treatment after amniocentesis does not improve obstetric outcome.\n", + "output": "Conclusions: Overall, the quality of evidence summarised in this review is not of sufficient quality to change current clinical practice. In the absence of clear evidence, the operators should continue to use methods and technique modifications with which they are most familiar with.\nAny randomised trials of technique modifications that are performed to high standard with adequate safety outcomes and power to detect important clinical differences would be clearly welcome." + }, + { + "input": "Study: Specific exercises reduce brace prescription in adolescent idiopathic scoliosis: a prospective controlled cohort study with worst-case analysis. To compare the effect of Scientific Exercises Approach to Scoliosis (SEAS) exercises with \"usual care\" rehabilitation programmes in terms of the avoidance of brace prescription and prevention of curve progression in adolescent idiopathic scoliosis. Prospective controlled cohort observational study. Seventy-four consecutive outpatients with adolescent idiopathic scoliosis, mean 15 degrees (standard deviation 6) Cobb angle, 12.4 (standard deviation 2.2) years old, at risk of bracing who had not been treated previously. Thirty-five patients were included in the SEAS exercises group and 39 in the usual physiotherapy group. The primary outcome included the number of braced patients, Cobb angle and the angle of trunk rotation. There were 6.1% braced patients in the SEAS exercises group vs 25.0% in the usual physiotherapy group. Failures of treatment in the worst-case analysis were 11.5% and 30.8%, respectively. In both cases the differences were statistically significant. Cobb angle improved in the SEAS exercises group, but worsened in the usual physiotherapy group. In the SEAS exercises group, 23.5% of patients improved and 11.8% worsened, while in the usual physiotherapy group 11.1% improved and 13.9% worsened. These data confirm the effectiveness of exercises in patients with scoliosis who are at high risk of progression. Compared with non-adapted exercises, a specific and personalized treatment (SEAS) appears to be more effective.\n", + "output": "Conclusions: There is a lack of high quality evidence to recommend the use of SSE for AIS. One very low quality study suggested that these exercises may be more effective than electrostimulation, traction and postural training to avoid scoliosis progression, but better quality research needs to be conducted before the use of SSE can be recommended in clinical practice." + }, + { + "input": "Study1: Daily versus weekly azithromycin in cystic fibrosis patients. Four randomised, placebo-controlled trials have previously documented the clinical benefits of azithromycin (AZM) in cystic fibrosis (CF) patients. The present study examined whether the beneficial effect of AZM is equivalent when administered daily or weekly. A double-blind, randomised study was carried out in 208 CF patients aged 6-58 yrs who were assigned to AZM either 250 mg daily (n = 103) or 1,200 mg weekly (n = 105) for 6 months, with assessments at baseline and at 1, 3, 6 and 7 months. Patients were taken from five adult and children CF centres in South-east Queensland, Australia. Equivalence was demonstrated between the two groups (daily versus weekly) with respect to improvements in lung function (forced expiratory volume in one second and forced vital capacity), C-reactive protein, days spent in hospital, admission rates and nutrition (body mass index, z-scores) using 95% confidence intervals with a tolerance interval of +/-10%. In patients aged <18 yrs the daily group had significantly better improvements in z-scores for height and weight after 6 months. In children, a nutritional advantage for daily administration was found. Gastro-intestinal adverse effects were more common with weekly therapy. Apart from these findings, daily and weekly administered azithromycin demonstrated similar outcomes for cystic fibrosis patients.\nStudy2: Long term effects of azithromycin in patients with cystic fibrosis: A double blind, placebo controlled trial. Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis. A multicentre, randomised, double blind, placebo controlled trial was conducted from October 2001 to June 2003. The criteria for enrollment were age older than 6 years and forced expiratory volume in 1 second (FEV1) of 40% or more. The active group received either 250 mg or 500 mg (body weight < or > or =40 kg) of oral azithromycin three times a week for 12 months. The primary end point was change in FEV1. Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV1 85 (22)% predicted were randomised: 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa. The relative change in FEV1 at month 12 did not differ significantly between the two groups. The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p < 0.005), the time elapsed before the first pulmonary exacerbation (hazard ratio 0.37 (95% CI 0.22 to 0.63), p < 0.0001), and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status (count ratio 0.55 (95% CI 0.36 to 0.85), p < 0.01). No severe adverse events were reported. Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa.\nStudy3: Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial. The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial. 41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat. Median relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects. A 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.\n", + "output": "Conclusions: This review provides evidence of improved respiratory function after six months of azithromycin. Data beyond six months were less clear, although reduction in pulmonary exacerbation was sustained.\u00a0Treatment appeared safe over a six-month period; however, emergence of macrolide resistance was a concern. A multi-centre trial examining long-term effects of this antibiotic treatment is needed, especially for infants recognised through newborn screening." + }, + { + "input": "Study: Live and inactivated adenovirus vaccines. Clinical evaluation of efficacy in prevention of acute respiratory disease. nan\n", + "output": "Conclusions: This Cochrane review has found a lack of evidence on the effects of vaccines for the common cold in healthy people. Only one RCT was found and this did not show differences between comparison groups; it also had a high risk of bias. There are no conclusive data to support the use of vaccines for preventing the common cold in healthy people. We identified the need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Unless RCTs provide evidence of a treatment effect and the trade-off between potential benefits and harms is established, policy-makers, clinicians and academics should not recommend the use of vaccines for preventing the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety and mortality related to the vaccine." + }, + { + "input": "Study1: Iron deficiency anemia and iron therapy effects on infant developmental test performance. The behavioral effects of iron deficiency and its treatment were evaluated in a double-blind randomized controlled community-based study of 191 Costa Rican infants, 12 to 23 months of age, with various degrees of iron deficiency. The Bayley Scales of Infant Development were administered before and both 1 week and 3 months after IM or oral administration of iron. Appropriate placebo-treated control infants were also tested. Infants with iron deficiency anemia showed significantly lower mental and motor test scores, even after considering factors relating to birth, nutrition, family background, parental IQ, and the home environment. After 1 week, neither IM nor oral iron treatments differed from placebo treatment in effects on scores. After 3 months, lower mental and motor test scores were no longer observed among iron-deficient anemic infants whose anemia and iron deficiency were both corrected (36%). However, significantly lower mental and motor test scores persisted among the majority of initially anemic infants (64%) who had more severe or chronic iron deficiency. Although no longer anemic, they still showed biochemical evidence of iron deficiency after 3 months of treatment. These persistent lower scores suggest either that iron therapy adequate for correcting anemia is insufficient to reverse behavioral and developmental disturbances in many infants or that certain ill effects are long-lasting, depending on the timing, severity, or chronicity of iron deficiency anemia in infancy.\nStudy2: Reversal of developmental delays in iron-deficient anaemic infants treated with iron. Iron-deficient anaemic infants perform worse in tests of mental and motor development than do iron-sufficient infants of a comparable age. A randomised, double-blind trial was done to monitor the effects of iron supplementation on performance in the Bayley scales of mental and motor development among 12-18-month-old infants in Indonesia. Iron-deficient anaemic infants (n = 50) were assigned randomly to receive dietary ferrous sulphate or placebo for 4 month. Similar treatment randomisation was done among nonanaemic iron-deficient (n = 29) and iron-sufficient (n = 47) infants. Before intervention, the mean mental and motor scores of the iron-deficient anaemic infants were significantly (p < 0.01) lower than those of the nonanaemic iron-deficient and iron-sufficient classes. After intervention, developmental delays were reversed among iron-deficient anaemic infants who had received iron but they remained the same among placebo-treated iron-deficient anaemic infants. Neither ferrous sulphate nor placebo had significant effects on the scores of the other two iron-status classes. The poor performance of 12-18-month-old iron-deficient anaemic infants in the Bayley scales of mental and motor development can be improved to the level of performance of iron-sufficient infants by treatment with ferrous sulphate.\nStudy3: Infancy: mental and motor development. In a prospective cohort study of 196 infants from birth to age 15 mo, the relationship of iron status to psychomotor development, the effect of a short-term trial of oral iron or placebo, and the effect of longer-term oral iron therapy was assessed. Development was assessed with the Bayley Scale of Infant Development in anemic, nonanemic, iron-deficient, and control children. Anemic infants had significantly lower indices than did control or nonanemic, iron-deficient infants. Control infants and nonanemic, iron-deficient infants performed comparably. No difference between the effect of oral administration of iron or placebo was noted after 10 d or 3 mo of iron therapy. A hemoglobin concentration of less than 105 g/L and anemia duration greater than 3 mo were correlated with significantly lower motor and mental scores, suggesting that when iron deficiency progresses to anemia, adverse influences in the performance of developmental tests appear and persist, despite iron therapy.\nStudy4: Treatment with iron increases weight gain and psychomotor development. Previous work at this hospital and elsewhere has shown that anaemia in toddlers is common and is associated with psychomotor delay. It seemed unclear, however, whether this association was cause and effect or merely due to the same underprivileged environment. A double blind randomised intervention study was, therefore, performed. After an initial assessment 97 children with anaemia (haemoglobin 8-11 g/dl) aged 17-19 months received either iron and vitamin C or vitamin C only (control group) for two months and were then reassessed. The children who received the iron had an increased rate of weight gain and more of them achieved the expected rate of development. While iron deficiency anaemia is unlikely to be the only factor in the slower development of children living in underprivileged circumstances, it can at least be easily identified and treated. Routine child health surveillance in such areas should include a haemoglobin determination.\nStudy5: The effects of short-term oral iron therapy on developmental deficits in iron-deficient anemic infants. To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia, 68 Guatemalan babies 6 to 24 months of age, with and without mild iron deficiency anemia, were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment. The two major findings of the study were developmental deficits in the anemic group prior to treatment, and lack of rapid improvement with short-term oral iron therapy. The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants. The anemic group's pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group. In a double-blind randomized study, six to eight days of oral iron therapy did not reverse these deficits. Consequently, the deficits of the anemic group cannot be unequivocably attributed to iron lack. However, no significant differences were found between anemic and nonanemic groups in birth histories, socioeconomic level, or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies.\n", + "output": "Conclusions: There is no convincing evidence that iron treatment of young children with IDA has an effect on psychomotor development or cognitive function within 30 days after commencement of therapy. The effect of longer-term treatment remains unclear. There is an urgent need for further large randomised controlled trials with long-term follow-up." + }, + { + "input": "Study1: A comparison of labial and crestal incisions for the 1-stage placement of IMZ implants: a pilot study. The aim of this study was to compare the crestal incision with the labial flap design when inserting a 2-stage implant system in a nonsubmerged manner. Ten consecutive edentulous patients with a severely resorbed mandible (Cawood Class V to VI) that resulted in reduced stability and insufficient retention of the lower denture were included. In all patients, 2 IMZ implants were inserted in a 1-stage procedure in the mandibular canine regions as part of an implant overdenture treatment. In 5 patients, the labial flap approach was used, and a crestal incision approach was used in the other 5 patients. Standardized evaluations were performed at 2, 6, and 12 weeks after implant placement and 12 months after placement of the new prosthesis. In the first postoperative weeks, more hyperplasia occurred around the implants inserted by the crestal incision than the labial flap. However, after 1 year of function, no striking differences between the 2 groups were present with regard to the clinical and radiographic parameters. From this pilot study, it was concluded that both the crestal incision and the labial flap approach are reliable procedures for insertion of IMZ implants in a 1-stage procedure. However, because of the smaller risk of soft tissue overgrowth, there is a preference for the labial flap approach.\nStudy2: Flapless versus open flap implant surgery in partially edentulous patients subjected to immediate loading: 1-year results from a split-mouth randomised controlled trial. To evaluate the efficacy of flapless versus open flap implant placement in partially edentulous patients. Forty patients with two separate edentulous areas characterised by residual bone at least 5 mm thick and 10 mm in height had these sites randomised following a split-mouth design to receive at least one implant to each side after flap elevation or not. Implants were first placed in one site, and after 2 weeks in the other site freehand. Implants inserted with a torque >48 Ncm were immediately loaded with full occluding acrylic temporary restorations. Definitive single cemented crowns or screw-retained metal ceramic fixed dental prostheses were delivered after 2 months. Outcome measures were prosthesis and implant failures, complications, postoperative swelling and pain, consumption of analgesics, patient preference, surgical time, marginal bone level changes, and implant stability quotient (ISQ) values. Seventy-six implants were placed flapless and 67 after flap elevation. In the flapless group, four flaps had to be raised to control the direction of the bur, whereas one haemorrhage and one fracture of the buccal bone occurred in two patients of the flap elevation group. Four implants did not reach the planned stability (three belonging to the flapless group) and they were all immediately replaced by larger diameter ones. After 1 year, no drop-outs occurred. Two definitive bridges could not be placed when planned (one in each group) and two crowns had to be remade (one in each group). Two implants failed in each group, all in different patients. There were no statistically significant differences for prosthetic and implant failures, complications, ISQ values and marginal bone levels between groups. However, flapless implant placement required significantly less operation time (17 minutes less, saving almost two-thirds of the time for implant placement), induced less postoperative pain, swelling, analgesic consumption and was preferred by patients. Mean ISQ values of both groups significantly decreased over time. Implants can be successfully placed flapless and loaded immediately, reducing treatment time and patient discomfort.\nStudy3: Connective tissue grafts for thickening peri-implant tissues at implant placement. One-year results from an explanatory split-mouth randomised controlled clinical trial. Nothing to declare. To evaluate whether connective tissue grafts performed at implant placement could be effective in augmenting peri-implant soft tissues. Ten partially edentulous patients requiring at least one single implant in the premolar or molar areas of both sides of the mandible were randomised to have one side augmented at implant placement with a connective soft tissue graft harvested from the palate or no augmentation. After 3 months of submerged healing, abutments were placed and within 1 month definitive crowns were permanently cemented. Outcome measures were implant success, any complications, peri-implant marginal bone level changes, patient satisfaction and preference, thickness of the soft tissues and aesthetics (pink aesthetic score) evaluated by an independent and blinded assessor 1 year after loading. One year after loading, no patients dropped out, no implants failed and no complications occurred. Both groups lost statistically significant amounts of peri-implant bone 1 year after loading (0.8 mm in the grafted group and 0.6 mm in the non-grafted group), but there was no statistically significant difference between groups. Soft tissues at augmented sites were 1.3 mm thicker (P < 0.001) and had a significantly better pink aesthetic score (P < 0.001). Patients were highly satisfied (no statistically significant differences between treatments) though they preferred the aesthetics of the augmented sites (P = 0.031). However, five patients would not undergo the grafting procedure again and two were uncertain. Connective tissue grafts are effective in increasing soft tissue thickness, thus improving aesthetics. Longer follow-ups are needed to evaluate the stability of peri-implant tissues over time.\nStudy4: Erbium:YAG laser application in the second phase of implant surgery: a pilot study in 20 patients. Conventional implant dentistry implies 2 surgical stages. In this context, pain is often present in the second stage, despite the fact that it is comparatively less aggressive for the patient. The present pilot study proposes application of Erbium:YAG (Er:YAG) laser for second-stage implant surgery. Twenty patients were studied with a total of 50 implants in which osseointegration was complete. The subjects were divided into 2 groups: a control group (10 patients with 25 implants), subjected to conventional second-stage surgery; and a group of 10 subjects (also with 25 implants) treated with the Er:YAG laser at second-stage implant surgery. The use of Er:YAG laser obviated the need for local anesthesia and minimized postoperative pain and time needed before starting the second stage. With regard to surgical duration, quality of hemostasis, and success in implant treatment, no differences were reported. In the second stage of implant surgery, different types of laser have been used, taking advantage of their bacteridal effect; disadvantages arise from inducing damage to the implant surface and adverse thermal effects. The advantages afforded by laser treatment include technical simplicity, the possibility of obviating local anesthesia, absence of postoperative pain and edema, and complete tissue healing by day 5, thus facilitating rapid prosthetic rehabilitation. The technique described can be used in all cases except situations where esthetic considerations prevail in anterior areas, or in the event of a lack of keratinized gingiva surrounding the implant.\n", + "output": "Conclusions: There is limited weak evidence suggesting that flapless implant placement is feasible and has been shown to reduce patient postoperative discomfort in adequately selected patients, that augmentation at implant sites with soft tissue grafts is effective in increasing soft tissue thickness improving aesthetics and that one technique to increase the height of keratinised mucosa using autografts or an animal-derived collagen matrix was able to achieve its goal but at the price of a worsened aesthetic outcome (0.5 mm of recession). There is insufficient reliable evidence to provide recommendations on which is the ideal flap design, the best soft tissue augmentation technique, whether techniques to increase the width of keratinised/attached mucosa are beneficial to patients or not, and which are the best incision/suture techniques/materials. Properly designed and conducted RCTs, with at least 6 months of follow-up, are needed to provide reliable answers to these questions." + }, + { + "input": "Study: Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107 patients. The objective of this study was to evaluate the efficacy of Daflon 500 mg (Dios)* in venous ulcers. A multicenter, double-blind, randomized, controlled versus placebo (Plac) trial was conducted, with stratification according to the size of ulcer (< or = 10 cm and > 10 cm). The protocol called for a two-month treatment with Dios (one tablet = 450 mg micronized purified Diosmin) or a placebo, two tablets/day, in addition to compression therapy. Evaluations were performed every fifteen days, from D0 to D60. The primary endpoint, in accordance with Alexander House group requirements were: percentage of patients with complete ulcer healing, ie, comparison between Dios and Plac group at D60, and comparison of survival curves in each group between D0 and D60 (log rank test). Secondary endpoints included ulcer surface area assessed by computerized planimetric measurements, qualitative evaluation of ulcers, and symptoms. The patients were 105 men and women ranging in age from eighteen to eighty-five years, with standard compression stocking, who were undergoing standardized local care of ulcer and had no significant arterial disease (ankle/arm systolic pressure index > 0.8). Fifty-three patients received Dios, and 52 received Plac. The 2 groups were well matched for age (m +/- 1 SD = seventy-one +/- eleven years), gender, ulcer size, and associated disorders. Among patients with ulcer size < or = 10 cm (Dios = 44, Plac = 47) a significantly larger number of patients had a complete ulcer healing at two months in the Dios group (n = 14) in comparison with the Plac group (n = 6) (32% vs 13%, P = 0.028) with a significantly shorter time duration of healing (P = 0.037). No difference was shown for the secondary criteria, except for sensation of heavy legs (P = 0.039) and a less atonic aspect of ulcer (P = 0.030) in favor of Dios. Among the 14 patients with ulcer size > 10 cm (Dios = 9, Plac = 5), subjected to a descriptive analysis only, no ulcer healed. This study showed that a two-month course of Daflon 500 mg at a daily dose of two tablets, in addition to conventional treatment, is of benefit in patients with venous ulcer < or = 10 cm by accelerating complete healing.\n", + "output": "Conclusions: Although the overall estimate of the number of healed ulcers appeared to show a significant effect in favour of flavonoids (both MPFF and HR), this result needs to be interpreted cautiously, as most of these trials were poorly reported, and so had an unclear risk of bias for randomisation, allocation concealment, blinding and methods for addressing incomplete outcome data. There was also a possibility of publication bias." + }, + { + "input": "Study1: Naftidrofuryl in chronic arterial disease. Results of a six month controlled multicenter study using Naftidrofuryl tablets 200 mg. The study was carried out on patients with intermittent claudication (Fontaine's stage II). The arterial and atheromatous origin of the disease was confirmed and localized by angiography or Doppler velocimetry examination. One hundred eighty-six patients were selected initially. Their pain-free walking distance on a treadmill (at a speed of 3 km/hour and an inclination of 10%) had to be 150-300 m. During the first month all patients received 3 placebo tablets daily. At the end of this run-in period (D-30; D 0) and after checking walking distance stability (allowed variation: +/- 20% between the two measurements) the patients were included in the study. One hundred fifty-four patients were selected and 118 remained during the whole study. The study was designed as a double-blind, using two parallel randomly selected groups. Sixty-four patients received for six months Naftidrofuryl (3 X 200 mg tablets daily with meals); 54 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (D 90 and D 180). After checking the initial homogeneity of the Naftidrofuryl and placebo-groups, the comparison between groups indicates a significant improvement in Naftidrofuryl group after 3 and 6 months of treatment. At the end of the study the observed differences in walking distance with Naftidrofuryl are approximately twice the difference in the reference group (D 90: p less than 0.05; D 180: p less than 0.02). The results of this study indicate that Naftidrofuryl is an efficient pharmacological tool for treatment of patients with chronic arterial disease (Fontaine's stage II).\nStudy2: [Naftidrofuryl in arterial occlusive disease. Controlled multicenter double-blind study with oral administration]. The efficacy of naftidrofuryl ( Dusodril ) for treatment of stage II arterial occlusive disease was evaluated in a controlled multi-centre study in a total of 104 out-patients with angiographically documented localization of occlusion. The therapeutic effect was assessed over three months by measurements of walking distance using standardized treadmill conditions. Further parameters were venoocclusive plethysmography and Doppler ultrasonography measurement of pressures. The complaint-free walking distance increased significantly during daily application of 600 mg naftidrofuryl orally (n = 54) during the 12-week assessment period when compared to the placebo group (n = 50). Taking the intraindividual variability of 17.2 m in assessment of walking distance into account, the increase of painless walking of 93 m after treatment for 12 weeks in the active-drug group is considered the result of treatment-induced increased performance.\nStudy3: [Effect of naftidrofuryl on physiological walking distance in patients with intermittent claudication]. To evaluate the physiological walking distance measured with the Peripheral Arterial Disease Holter Control device (PADHOC) after 12 months of treatment with naftidrofuryl in a double blind placebo controlled, parallel group study, in patients presenting with intermittent claudication. The outpatients selected were of both sexes, aged 40 to 80, with a chronic, stable intermittent claudication and an ankle brachial index between 0.60 and 0.90. They received naftidrofuryl 200 mg tid or placebo for 12 months. Outcome measures included physiological painfree and maximal walking distances using the PADHOC device. The principle of this device is the measurement of the intermalleolar distances using ultrasound telemetry. The PADHOC measures the walking distance and the speed profile in an ambulatory subject. 182 patients were randomised and 168 entered the intention to treat analysis. The two groups were well matched for demographic variables, risk factors and history of vascular disease. After 12-month treatment, patients who received naftidrofuryl had a 107% improvement of geometric physiological pain-free walking distance versus 12% in the placebo group (P < 0.001) and 74% improvement of geometric maximal physiological walking distance versus 1% in the placebo group (P < 0.001). This study demonstrates the efficacy of naftidrofuryl versus placebo in patients with intermittent claudication using a new device measuring the walking distances of the patients in a more physiological way than the treadmill test.\nStudy4: An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl. A randomized placebo-controlled study was undertaken in 188 patients with severe intermittent claudication attending two vascular clinics in Manchester and Liverpool. After a 4-week run-in period, patients received active or placebo treatment for 24 weeks. Patients were assessed on a treadmill prior to the 4-week run-in period, at randomization, and at 8, 16, and 24 weeks. Outcome was measured in terms of change in pain-free walking distance, maximum walking distance, and pressure indices. In this severe claudication population, in which the patients presented with a mean pain-free walking distance of 60 m, an intention-to-treat analysis demonstrated that the outcome in the naftidrofuryl-treated group was significantly better than in the group receiving placebo (p = 0.045). Additionally, 7% of patients in the naftidrofuryl group deteriorated compared with 22% in the placebo group (p = 0.005). Of the various risk factors that were recorded during the study--smoking habits, the presence of hypertension, diabetes, obesity, and duration of illness--only duration of illness had a significant influence on outcome. Maximum walking distances alone were not significantly influenced by treatment, but the use of a combined index of pain-free walking distance, maximum walking distance, and pressure indices to record success or failure confirmed a significant treatment effect (p = 0.047). A higher incidence of minor gastrointestinal symptoms was recorded in the naftidrofuryl-treated group. Treatment with naftidrofuryl was shown to prevent or slow the deterioration observed in a group of patients with severe claudication over a 24-week period.\nStudy5: Treatment of stage II chronic arterial disease of the lower limbs with the serotonergic antagonist naftidrofuryl: results after 6 months of a controlled, multicenter study. A study was carried out in patients with intermittent claudication (Fontaine's stage II). The atheromatous origin of the disease was confirmed and localized by angiography or Doppler. One hundred eight-three patients were selected initially (day -30) with a pain-free walking distance on a treadmill (at a speed of 3 km/h and a slope of 10%) ranging from 150 to 300 m. During the first month (washout period) all patients received two placebo tablets daily. At the end of this run-in period (day -30; day 0) and after checking walking distance stability (allowed variation: 20% between the two measurements), patients were included in the study. According to this criterion, 112 patients were selected and 94 remained during the whole study. The study was designed in double-blind, using two parallel, randomly selected groups. Fifty-two patients received naftidrofuryl (2 x 316.5 mg tablets daily with meals) for 6 months; 42 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (day 90 and day 180). After checking the initial homogeneity of the naftidrofuryl and placebo groups, the comparison between the two groups indicates a significant improvement in the naftidrofuryl group after 3 months and 6 months of treatment, for the pain-free walking distance. For the maximal walking distance, a significant improvement was found at day 180. Nonparametric analysis (chi 2 test) also indicated a significant improvement for the naftidrofuryl group. These results confirm that naftidrofuryl is beneficial in the treatment of patients with chronic arterial disease.\n", + "output": "Conclusions: Oral naftidrofuryl has a statistically significant and clinically meaningful, although moderate, effect of improving walking distance in the six months after initiation of therapy for people with intermittent claudication. Access by researchers to data from RCTs that are suitable for IPD analysis should be possible through repositories of data from pharmacological trials. Regular formal appraisal of the balance of risk and benefit is needed for older pharmaceutical products." + }, + { + "input": "Study1: Intensive vascular training in stage IIb of peripheral arterial occlusive disease. The additive effects of intravenous prostaglandin E1 or intravenous pentoxifylline during training. In a randomized open study, the combination of either prostaglandin E1 (PGE1) or pentoxifylline with controlled vascular training was compared with vascular training alone in patients with peripheral arterial occlusive disease in stage IIb. Forty-four patients were randomly assigned to treatment either of intensive vascular training alone (n = 15) or in combination with either i.v. pentoxifylline (200 mg over 2 hours BID, n = 15) or PGE1 (40 micrograms over 2 hours BID, n = 14). The basic therapy was a well-defined routine for vascular training, which was identical for all groups. The duration of therapy was 4 weeks. In all three test groups, there was a significant increase in the walking distance. There was a 119% increase in symptom-free walking distance in the exercise-only group. In comparison with exercise alone, the additional administration of pentoxifylline produced no greater effect; the increase was 105%. In contrast, administration of PGE1 combined with exercise achieved a remarkable improvement of 604%. Between-group comparison revealed the significant superiority of treatment with PGE1 (P < .05). During the 1-year follow-up, there was a reduction in the walking performance in all groups, albeit of variable extent. In the exercise-only and the pentoxifylline groups, the maintained increase in walking distance was only 30% compared with baseline values before the beginning of therapy. In the PGE1 group, on the other hand, the maintained improvement was 149%. Nine of 14 patients were still in stage IIa of peripheral arterial occlusive disease 1 year after PGE1 therapy.\nStudy2: Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication. Intermittent claudication due to peripheral arterial occlusive disease (PAOD) is a common cause of pain and disability in the middle-aged. Clinical trials of the potent vasodilator prostaglandin E1 have been disappointing. This is the first report of a controlled clinical trial of AS-0:3, a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has been developed to improve delivery of the active compound to blood vessel walls. Eighty patients with stenosis or occlusion, symptoms of intermittent claudication, and maximum walking distance of > or = 30 and < or = 300 m on a standard treadmill test were randomized to placebo or one of three dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4, and 8. A statistically significant increase in maximum walking distance was observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20; for active treatment: median, 28.0 m; IQR, 81; P < .01, Mann-Whitney test). A similar response was seen at 8 weeks (for placebo; median, -11.2 m; IQR, 35; for active treatment: median, 35 m; IQR, 68; P < .01, Mann-Whitney test). Dose-related improvements in pain-free walking distance and quality of life were observed. No serious safety issues were noted. These promising clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could provide an effective and acceptable treatment for patients with intermittent claudication. Studies to investigate the optimal dosing regimen, duration of clinical benefit, and effects in more severe forms of peripheral arterial disease are warranted.\n", + "output": "Conclusions: Whilst results from some individual studies suggested a beneficial effect of PGE1, the quality of these studies and of the overall evidence available is insufficient to determine whether or not patients with intermittent claudication derive clinically meaningful benefit from the administration of prostanoids. Further well-conducted randomised, double blinded trials with a sufficient number of participants to provide statistical power are required to answer this question." + }, + { + "input": "Study1: A single blind comparison of amisulpride, fluoxetine and clomipramine in the treatment of restricting anorectics. 1. The study evaluated the efficacy of amisulpride, fluoxetine and clomipramine at the beginning of the re-feeding phase of the treatment of restricting anorexia nervosa according to DSM-IV criteria. 2. 13 patients, mean weight 37.61 kg +/- 9.80 SD, were treated with clomipramine at a mean dosage of 57.69 mg +/- 25.79 SD; 10 patients, mean weight 40.90 kg +/- 6.98 SD, were treated with fluoxetine at a mean dosage of 28.00 mg +/- 10.32 SD; 12 patients, mean weight 38.41 kg +/- 8.33 SD, were treated with amisulpride at a mean dosage of 50.00 mg +/- 0.00 SD. 3. Clinical evaluation was carried out under single-blind condition at basal time and after three months by a structured clinical interview, the Eating Disorder Interview based on Long Interval Follow-up Evaluation (LIFE II BEI). 4. Patients treated with amisulpride showed a more significant increase (p=0.016) of mean weight. Concerning weight phobia, body image disturbance and amenorrhoea, no significant difference resulted.\nStudy2: Combined cognitive-behavioral, psychopharmacological and nutritional therapy in eating disorders. 1. Anorexia nervosa--restricted type. Twenty-two female patients with anorexia nervosa, restricted type, 14-35 years old, were treated with a 4-month course of combined cognitive-behavioral therapy, nutritional counselling and antidepressant drugs (nortriptyline for 7, fluoxetine for 15). Patients were monitored for body mass index (BMI), for eating disorder symptoms by the Eating Disorder Inventory (EDI) and the Bulimic Investigation Test (BITE) and for depression and anxiety by the Hamilton Rating Scales for Depression and for Anxiety (HRS-D and -A). The scores were determined before and after 1, 2 and 4 months of therapy. BMI, depression, anxiety and EDI scores improved significantly and equally in both groups during the 4 months of therapy, while BITE scores did not change.\nStudy3: Combined cognitive-behavioral, psychopharmacological and nutritional therapy in eating disorders. 2. Anorexia nervosa--binge-eating/purging type. Thirteen women with anorexia nervosa, binge-eating/purging type (AN-BP), 17-43 years old, were treated with a 4-month course of combined cognitive-behavioral, nutritional and antidepressant therapy (7 with amineptine and 6 with fluoxetine). Patients were monitored before and after 1, 2 and 4 months of treatment for body mass index (BMI), for eating disorder symptoms by the Eating Disorder Inventory (EDI) and the Bulimic Investigation Test (BITE) and for depression and anxiety by the Hamilton Rating Scales for Depression and for Anxiety. BMI, EDI scores, depression and anxiety improved significantly and equally in the two groups during the 4 months of therapy, while BITE scores did not change.\nStudy4: Amitriptyline in the treatment of anorexia nervosa: a double-blind, placebo-controlled study. The tricyclic antidepressant drug amitriptyline was evaluated as a short-term treatment of anorexia nervosa patients. In a 5-week double-blind, placebo-controlled study 11 patients were given amitriptyline and 14 received placebo. In addition, 18 patients who refused to participate in the drug trial and received only psychosocial treatment were used as an additional comparison group. Overall, patients in the three groups showed little improvement. No statistically significant differences favoring amitriptyline were found in any of the outcome variables. Plasma levels varied widely among patients receiving similar doses. No association was found between plasma levels and improvement in either psychiatric symptomatology or weight. Amitriptyline patients did not manifest any tendency for a reduction of depressive symptomatology. In addition, amitriptyline treatment was associated with substantial discomfort and adverse affects.\nStudy5: Hunger, food intake and weight: the impact of clomipramine on a refeeding anorexia nervosa population. This double-blind controlled study examines the impact of clomipramine when taken by an anorexia nervosa population, refeeding in hospital, over and above that generated by the established treatment programme. Of the 16 patients studied, all reached their target weights including three who asked to leave the study. Clomipramine was significantly associated with increased hunger, appetite and energy intake. It tended, though, to be associated with a reduced rate of weight gain, possibly because activity was increased. Patients receiving clomipramine were more stable in their eating habits and maintained body weight better than those on placebo after leaving the trial. These findings indicate the sensitivity of the hypothalamus to changes in body weight. Clomipramine, which is known to act at a hypothalamic level, seems to influence hunger, appetite and dietary intake according to the body weight of the patient. The threshold weights which have been shown to trigger hypothalamic sexual responses, may also influence hunger, appetite, motility and voluntary energy intake.\n", + "output": "Conclusions: A lack of quality information precludes us from drawing definite conclusions or recommendations on the use of antidepressants in acute AN. Future studies testing safer and more tolerable antidepressants in larger, well designed trials are needed to provide guidance for clinical practice." + }, + { + "input": "Study1: Oral dexamethasone pulse therapy versus daily prednisolone in sub-acute onset myositis, a randomised clinical trial. To determine if high-dose pulsed dexamethasone is more effective and safer than daily high-dose prednisolone in treatment-naive adult patients with inflammatory myopathies (sporadic inclusion body myositis excluded) we performed a multicenter, double-blind randomised controlled clinical trial with 18 months follow-up. Sixty-two patients were randomised into 28-day cycles of oral high-dose dexamethasone or daily high-dose prednisolone. Primary outcome measures included (1) seven point composite score of six clinically relevant outcomes and (2) (time-to) remission and (time-to) relapse. No difference between both treatment groups on the composite score was found. Side-effects occurred significantly less frequently in the dexamethasone group. Median time to relapse was 60 (2.9) weeks in the prednisolone and 44 (4.7) weeks in the dexamethasone group (log-rank test p=0.03). In conclusion, pulsed high-dose oral dexamethasone is not superior to daily prednisolone as first-line treatment of idiopathic inflammatory myopathies, but is a good alternative by causing substantially fewer side-effects.\nStudy2: Azathioprine with prednisone for polymyositis. A controlled, clinical trial. A controlled, prospective, double-blind, therapeutic trial of azathioprine was conducted in the initial therapy of polymyositis. Sixteen patients received 60 mg prednisone per day plus either azathioprine (2 mg/kg of body weight per day) or placebo for a period of 3 months. Creatine phosphokinase (CPK) levels fell to normal slightly sooner in the placebo group, but not significantly so. The azathioprine group did not become significantly stronger (P = 0.58) and did not manifest significantly greater improvement of histopathologic features of muscle (P = 0.80) than the placebo group. Initial CPK elevations were significantly related to the degree of muscle inflammation (P = 0.037), but this was not the case at 3 months (P greater than 0.05). Normalization of the CPK could not be equated with disease control. Type II fiber atrophy, attributed to steroid therapy, was more marked in women than in men (P less than 0.03).\nStudy3: Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens. To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (I.V. MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with I.V. therapy (P = 0.09). Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis.\nStudy4: Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis. To determine the effectiveness and tolerance of treatment with cyclosporine A (CyA) or methotrexate (MTX) added to corticosteroids in patients with severe, active polymyositis (PM) and dermatomyositis (DM). Thirty-six patients (20 with DM, 16 with PM) were enrolled into the study and randomized in MTX (n = 17) and CyA (n = 19) groups. Muscle endurance and functional test (MEFT), clinical assessment (CA), global patient's assessment (GPA), muscle MRI, serum CK, myoglobin, IL-1Ra, and autoantibody status were used to assess the response to therapy after 1, 3, and 6 months. Significant improvement in MEFT, CA, GPA, and muscle MRI was found in both groups. Patients treated with MTX showed insignificantly better response than patients with CyA. CK levels in the MTX group decreased significantly after 1, 3, and 6 months, whereas a significant reduction in the CyA group was first observed after 6 months. IL-1Ra serum levels significantly dropped in the CyA group after two weeks, whereas in the MTX group the significant decrease was first seen after 3 months of treatment. Good correlation was found between each of the clinical parameters (MEFT, CA, and GPA), none of them showed any correlation with CK or IL-1Ra levels. Administration of MTX or CyA added to corticosteroids was associated with clinical and laboratory improvement. Changes in CK and IL-1Ra levels were not associated with parameters of clinical disease severity measured in this study.\n", + "output": "Conclusions: This systematic review highlights the lack of high quality RCTs that assess the efficacy and toxicity of immunosuppressants in inflammatory myositis." + }, + { + "input": "Study: Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease. To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV+IV group (n=87) or an IV group (n=80). The number of patients with CLD experiencing infectious acute exacerbation (P=0.022), but not pneumonia (P=0.284), was significantly lower in the PV+IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P=0.037). In patients with CLD, the Kaplan-Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P=0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P=0.019), but not during the second year (P=0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.\n", + "output": "Conclusions: Current but limited evidence support the use of 23-valent pneumococcal vaccine as routine management in adults with bronchiectasis. Circumstantial evidence also support the use of routine 23-valent pneumococcal vaccination in children with bronchiectasis. Further randomised controlled trials examining the efficacy of this intervention using various vaccine types in different age groups are needed. There is no data on the efficacy of pneumococcal vaccine on pulmonary decline. With the lack of evidence in how often the vaccine should be given, it is recommended that health providers adhere to national guidelines." + }, + { + "input": "Study1: Endoscopic balloon dilatation is a safe method in the management of common bile duct stones. Endoscopic sphincterotomy is a widely accepted treatment for patients with common bile duct stones. Despite improvement in this technique, endoscopic sphincterotomy is still associated with some biliary complications. Endoscopic balloon dilatation is a less traumatic and sphincter preserving method for removal of common bile duct stones. However, the results of controlled studies in comparison with these two methods are contradictory. The aim of this study is to compare the safety and efficacy of endoscopic balloon dilatation and endoscopic sphincterotomy in Chinese patients. A total of 104 patients with common bile duct stones on endoscopic retrograde cholangiopancreatography were enrolled. They were randomly assigned to endoscopic balloon dilatation or endoscopic sphincterotomy. Endoscopic balloon dilatation was performed by using a balloon dilator to dilate the sphincter for 5 min. The common bile duct stones were then removed by a Dormia basket after endoscopic balloon dilatation or endoscopic sphincterotomy. Mechanical lithotripsy was performed if the stones were difficult to remove by Dormia basket. After discharge, patients were regularly followed up for biliary complications. The successful bile duct stone clearance rate was 94.1% in endoscopic balloon dilatation group and 100% in endoscopic sphincterotomy group. Post-procedural significant haemorrhage was higher in endoscopic sphincterotomy group than in endoscopic balloon dilatation group (14/53 versus 1/48, P < 0.001). The bleeding patient from endoscopic balloon dilatation group was a case of uremia and bleeding occurred 48 h after endoscopic balloon dilatation. All the patients with post-procedural haemorrhage were controlled endoscopically. The post-procedural serum amylase level showed no significant difference in both groups and none of them developed clinical pancreatitis. After a mean 16 months follow-up, three patients (6.3%) in endoscopic balloon dilatation group and four patients (7.5%) in endoscopic sphincterotomy group developed recurrent common bile duct stones. The recurrent common bile duct stones were multiple and muddy in consistency. They were successfully removed endoscopically. Both endoscopic balloon dilatation and endoscopic sphincterotomy are safe and effective techniques for the treatment of common bile duct stones. Endoscopic balloon dilatation can be safely applied in patients with coagulopathy and does not increase the incidence of pancreatitis or bleeding.\nStudy2: Endoscopic sphincterotomy and endoscopic papillary balloon dilatation for bile duct stones: A prospective randomized controlled multicenter trial. Endoscopic papillary balloon dilatation may be an alternative to endoscopic sphincterotomy in the treatment of bile duct stones. However, there is a controversy as to the effectiveness and safety of endoscopic papillary balloon dilatation. Two hundred eighty-two patients with bile duct stones were enrolled and randomized to an endoscopic sphincterotomy or endoscopic papillary balloon dilatation group. The success rate for duct clearance as well as the frequency and types of complications were evaluated prospectively. Endoscopic sphincterotomy was performed in a standard manner. Endoscopic papillary balloon dilatation was carried out with gradual inflation of a 4-, 6-, or 8-mm diameter balloon. Complete duct clearance was achieved in 100% in the endoscopic sphincterotomy group and 99.3% in the endoscopic papillary balloon dilatation group (not significant). Complications occurred in 11.8% of patients in the endoscopic sphincterotomy group and 14.5% of those in the endoscopic papillary balloon dilatation group (not significant). No complication was severe; there was no mortality. The frequency of acute pancreatitis was higher in the endoscopic papillary balloon dilatation group than the endoscopic sphincterotomy group (respectively, 10.9% vs. 2.8%; p < 0.045). Hemorrhage occurred only in the endoscopic sphincterotomy group. Endoscopic sphincterotomy and endoscopic papillary balloon dilatation were approximately equal in terms of successful clearance of bile duct stones. They were also similar with respect to overall complications. Endoscopic papillary balloon dilatation is an alternative to endoscopic sphincterotomy as a treatment of bile duct stones.\nStudy3: Endoscopic papillary balloon dilation and endoscopic sphincterotomy for bile duct stones: long-term outcomes in a prospective randomized controlled trial. Little is known about the long-term outcome of endoscopic papillary balloon dilation for removal of bile duct stones. A randomized trial that compared long-term outcomes after endoscopic papillary balloon dilation and endoscopic sphincterotomy was conducted. Thirty-two patients with bile duct stones were randomized to endoscopic papillary balloon dilation or endoscopic sphincterotomy, with 16 patients in each group. Endoscopic papillary balloon dilation was performed by using an 8-mm-diameter balloon; endoscopic sphincterotomy was performed in the standard manner. The success rates for stone removal, as well as the frequency and types of early (<15 days), mid-term (<1 year), and long-term (1-6 years) post-procedure complications were evaluated. The success rates for stone removal and early complication rates were similar for both groups. The frequency of stone recurrence was approximately 4-fold higher in the endoscopic papillary balloon dilation group (25%) vs. the endoscopic sphincterotomy group (6.3%) at mid-term evaluation. However, over the long term, Kaplan-Meier estimated probability of stone recurrence tended to be higher in the endoscopic sphincterotomy group vs. the endoscopic papillary balloon dilation group; recurrent stones were found in, respectively, 26.7% vs. 6.3%. Complications occurred in 7 patients in each group. Long-term outcome of endoscopic papillary balloon dilation for bile duct stone removal is satisfactory, provided that consideration is given to recurrence of stones by early follow-up evaluation.\nStudy4: Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones. A randomized trial with manometric function. To circumvent the long-term effects of papillary ablation for extracting common bile duct stones (< 12 mm in diameter) in endoscopic sphincterotomy (EST), endoscopic papillary dilation (EPD) was attempted in 20 patients. To evaluate papillary function before and after the procedures, manometry of the sphincter of Oddi was carried out in 13 with EPD and 10 of 20 patients with EST. Extraction of all stones was successful (100%) in both groups at an equal rate. Repeated numbers of procedures were common in both groups. However, the mean duration of the procedure was high in EPD compared to EST (63 min vs 42 min, P < NS). Adjunctive therapies like mechanical lithotripsy (ML), nasobiliary drainage, and choledochoscopy were included in EPD, while EST required a basket catheter and ML. There was no significant difference on manometry before and after the procedures (P = NS), although papillary function was found to have decreased after the EPD. In contrast, all patients in the EST group lost papillary function after the procedure. Thirty-day morbidity and mortality rate were absent in both groups. Immediate and 2.5-year follow up complications were uncommon in both groups. As a simple method, EPD may be an effective and safe alternative to EST in the management of patients with bile duct stones who require maintenance of papillary function.\nStudy5: Endoscopic balloon dilatation versus endoscopic sphincterotomy for the removal of bile duct stones: a prospective randomised trial. Endoscopic balloon dilatation (EBD) of the sphincter of Oddi has been proposed as an alternative therapy with possible advantages, as compared with endoscopic sphincterotomy (ES), for removal of bile duct stones. In a randomised study, we compared the efficacy and complication rate of the two techniques in 202 patients with common bile duct stones. Patients were followed up for 12 months. A total of 103 patients were randomised to the EBD group and 99 to the ES group. Overall duct clearance was 87.1% and did not differ between the two groups (EBD 87.4%; ES 86.9%). The complication rate at 24 hours was 6.8% in the EBD group and 3.0% in the ES group (NS). Complications during follow up were 11.7% and 15.2% respectively (NS). A multivariate logistic regression analysis showed only the size of the largest stone to be predictive of success for either technique. Endoscopic balloon dilatation offers no significant advantage over the well established technique of endoscopic sphincterotomy for the removal of bile duct stones.\n", + "output": "Conclusions: Endoscopic balloon dilation is slightly less successful than endoscopic sphincterotomy in stone extraction and more risky regarding pancreatitis. However, endoscopic balloon dilation seems to have a clinical role in patients who have coagulopathy, who are at risk for infection, and possibly in those who are older." + }, + { + "input": "Study: The effects of procaine/haematoporphyrin on age-related decline: a double-blind trial. A randomized, double-blind study of procaine/haematoporphyrin (KH3) has been carried out over two years in a selected population of healthy elderly subjects. The period of study exceeds 500 patient years. The trial population was weighted to contain a larger proportion of subjects aged over 75 years than a standard population; those receiving active KH3 had similar characteristics on entry to those receiving placebo. Over the course of two years, KH3 was shown to be an active substance in that: (a) decrement in the consolidation of new learning was prevented in the treatment group (less than 1.0%, as against 38% in the placebo group); (b) the prevalence of incontinence increased significantly in the placebo group, but not in the active group (P less than 0.05); (c) there was a significant increase in grip strength in the active treatment group (+22%, P less than 0.01 v. placebo); (d) more adverse reactions were observed on treatment with KH3 (P less than 0.005).\n", + "output": "Conclusions: This review suggests that the evidence for detrimental effects of procaine and its preparations is stronger than the evidence for benefit in preventing and/or treating dementia or cognitive impairment.\nThere is some evidence from older studies that procaine preparations might improve memory in persons without cognitive impairment. However, the clear evidence of side effects suggests that the risks might outweigh the benefits.\u00a0In the light of this, the strong marketing claims for procaine preparations should be withdrawn until trials of adequate size, duration and quality have been conducted." + }, + { + "input": "Study: Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine. A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals. differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups. Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain.\n", + "output": "Conclusions: The updated review contains new information supporting the previous conclusions that methadone has similar analgesic efficacy to morphine. The additional study examined neuropathic and non-neuropathic pain, finding no superiority for methadone in the former group. The new study also addresses a clinically relevant concern about short term/single dose studies. Use beyond a few days may result in methadone accumulation leading to delayed onset of adverse effects. In an assessment over 28 days there was a higher rate of withdrawal due to side effects in the methadone group. This observation reinforces the advice that experienced clinicians should take responsibility for initiation and careful dose adjustment and monitoring of methadone." + }, + { + "input": "Study1: Ileocolonic anastomosis after right hemicolectomy for carcinoma: stapled or hand-sewn? A prospective, multicenter, randomized trial. 440 patients were prospectively enrolled in a randomized, multicenter trial to compare 4 types of manual (84 interrupted end-to-end, 77 continuous end-to-end, 82 interrupted end-to-side, and 91 continuous end-to-side) (polyglycolic derived suture) and 1 type of stapled (106 side-to-side with GIA+TA devices) ileocolonic anastomosis after right hemicolectomy for carcinoma. The trial was designed according to Schwartz' pragmatic formulation. All 5 groups were well-matched, except for a lower rate of intraoperative sepsis in the stapled group (P < 0.02). The main end point was anastomotic leakage detected clinically or by routine sodium diatrizoate enema on the 8-10th postoperative day. Results showed that stapled ileocolonic anastomosis was associated with less anastomotic leakages (2.8%) than all the other techniques combined (8.3%). In spite of the fact that staples are approximately ten times more expensive, our results suggest performing side-to-side (GIA+TA) mechanical anastomosis after right resection for carcinoma.\nStudy2: Comparison of manually constructed and stapled anastomoses in colorectal surgery. West of Scotland and Highland Anastomosis Study Group. The authors compared both the initial and the long-term outcomes of patients undergoing stapled and sutured colorectal anastomoses. Sutured and stapled large bowel anastomoses are perceived to be equally safe, but concern has been raised about increased rates of tumor recurrence with the use of stapling instruments. The outcome of patients with sutured and stapled colorectal anastomoses were compared in a prospective, multicenter, randomized study. Factors affecting long-term outcomes were assessed by both univariate and multivariate analysis. Seven hundred thirty-two patients were recruited. There was a significant increase in radiologic leakage in the sutured group (14.4% vs. 5.2%, p < 0.05), but there was no difference in clinical anastomotic leak rates, morbidity, or postoperative mortality. Tumor recurrence and cancer-specific mortality were higher in the sutured patients (7.5% and 6.7%, respectively) and in patients with anastomotic leaks. This study shows that suturing or stapling are equally safe in large bowel surgery. However, it also shows a long-term benefit of stapling in colorectal cancer patients.\nStudy3: A prospective randomized study of sutured versus stapled bowel anastomoses in patients with cancer. Eighty-eight cancer patients with the presence of one or more adverse factors for healing (carcinomatosis, adhesions, prior chemotherapy and radiation therapy, bowel obstruction, anemia, and low leukocyte count or albumin value) were prospectively randomized to undergo conventional two-layer hand suturing (45 patients) or mechanical stapling with a GIA/TA instrument (U.S. Surgical Corp., Norwalk, CT) (43 patients) of the large or small bowel anastomosis. Age, sex, complete blood count findings, and all biochemical plasma values were comparable in both groups. The anastomosis took an average of 19 minutes for the sutured and 9 minutes for the stapled technique (P = 0.0001), but the average length of operation, postoperative return of bowel function, and hospital stay were comparable in both groups. Bowel fistula was seen in one case of stapled anastomosis (P = not significant). The pulmonary and wound complication rates were the same in both groups. Of the four deaths (4.5%) due to causes unrelated to bowel anastomosis, three occurred in the stapled and one in the sutured group. It was concluded that a stapled anastomosis is as safe as a sutured one in patients with advanced-stage cancer. It saves time in anastomosis, but does not save time in postoperative return of the bowel function and hospital stay.\n", + "output": "Conclusions: Stapled functional end to end ileocolic anastomosis is associated with fewer leaks than handsewn anastomosis." + }, + { + "input": "Study: Long-term intraocular pressure control of eyes that developed encapsulated blebs following trabeculectomy. To evaluate the long-term intraocular pressure (IOP) control of eyes that developed an encapsulated bleb (EB) following trabeculectomy. Between 1994 and 1995, 25 eyes developed EBs and were randomized to medical treatment or needling without adjunct antimetabolites. Among the 25 patients who developed an EB, 21 were followed for at least 6 months. A control group of 21 consecutive eyes, which underwent trabeculectomy during the same period and that did not develop EBs was retrospectively selected. Success was defined as IOP <21 mmHg with or without medications. Kaplan-Meier survival analysis was performed to compare the groups. Among the 21 eyes that developed EBs, 12 (57%) had undergone transconjunctival needling and nine (43%) had received medical treatment. Mean follow-ups were 30.0 +/- 14.0 months, 33.3 +/- 18.5 months, and 37.4 +/- 2.6 months for the needling, medical treatment, and control groups, respectively (P = 0.19). Kaplan-Meier survival curves demonstrated that the control group showed a significantly lower chance of failure than both the needling and the medical treatment groups (P < 0.0001). Encapsulated blebs may be associated with an increased risk for surgical failure.\n", + "output": "Conclusions: Evidence from one small trial suggests that needling of encapsulated trabeculectomy blebs is not better than medical treatment in reducing intraocular pressure." + }, + { + "input": "Study1: A prospective, randomized trial limiting perioperative red blood cell transfusions in vascular patients. Patients undergoing major arterial reconstruction have traditionally been transfused with red blood cells to keep hemoglobin concentrations above 10 g/dL in order to prevent anemia-induced myocardial ischemia. There are no data to support this practice. The hypothesis that vascular patients will tolerate a hemoglobin concentration of 9 g/dL was examined. Ninety-nine patients undergoing elective aortic and infrainguinal arterial reconstructions were prospectively randomized preoperatively to receive transfusions to maintain a hemoglobin level of either 10 g/dL or 9 g/dL. Despite significantly different postoperative hemoglobin levels of 11.0 +/- 1.2 versus 9.8 +/- 1.3 g/dL (P <0.0001), there were no differences in mortality or cardiac morbidity rates or length of hospital stay. There were no differences in hemodynamic parameters. Oxygen delivery was lower in the group with lower hemoglobin levels, but there was no difference in O2 consumption between the groups. A lower hemoglobin concentration was tolerated without adverse clinical outcome. Patients did not compensate for anemia by increased myocardial work, but by increasing O2 extraction in the peripheral tissues.\nStudy2: Silent myocardial ischaemia and haemoglobin concentration: a randomized controlled trial of transfusion strategy in lower limb arthroplasty. Red cell transfusion is commonly used in orthopaedic surgery. Evidence suggests that a restrictive transfusion strategy may be safe for most patients. However, concern has been raised over the risks of anaemia in those with ischaemic cardiac disease. Perioperative silent myocardial ischaemia (SMI) has a relatively high incidence in the elderly population undergoing elective surgery. This study used Holter monitoring to compare the effect of a restrictive and a liberal red cell transfusion strategy on the incidence of SMI in patients without signs or symptoms of ischaemic heart disease who were undergoing lower limb arthroplasty. We performed a multicentre, controlled trial in which 260 patients undergoing elective hip and knee replacement surgery were enrolled and randomized to transfusion triggers that were either restrictive (8 g/dl) or liberal (10 g/dl). Participants were monitored with continuous ambulatory electrocardiogram (ECG) (Holter monitoring), preoperatively for 12 h and postoperatively for 72 h. The tapes were analysed for new ischaemia by technicians blinded to treatment. The total ischaemia time in minutes was divided by the recording time in hours and an ischaemic load in min/h was calculated. Haemoglobin levels were measured preoperatively, postoperatively in the recovery room, and on days one, three and five after surgery. The mean postoperative haemoglobin concentration was 9.87 g/dl in the restrictive group and 11.09 g/dl in the liberal group. In the restrictive group, 34% were transfused a total of 89 red cell units, and in the liberal group 43% were given a total of 119 red cell units. A postoperative episode of silent ischaemia was experienced by 21/109 (19%) patients in the restrictive group and by 26/109 (24%) patients in the liberal group [mean difference -4.6%; 95% confidence interval (CI): -15.5% to 6%, P = 0.41). There was no significant difference (P = 0.53) between the overall ischaemic load in the restrictive group (median 0 min/h, range 0-4.18) and the liberal group (median 0 min/h, range 0-19.48). In those patients who did experience postoperative SMI, the mean ischaemic load was 0.48 min/h in the restrictive group and 1.51 min/h in the liberal group (ratio 0.32, 95% CI: 0.14-0.76, P = 0.011). The median postoperative length of hospital stay in the restrictive group was 7.3 days [range 5-11; interquartile range (IQR) 6-8] compared with 7.5 days (range 5-13; IQR 7-8) in the liberal group. The numbers were not large enough to conclude equivalence. In patients without preoperative evidence of myocardial ischaemia undergoing elective hip and knee replacement surgery, a restrictive transfusion strategy seems unlikely to be associated with an increased incidence of SMI. A proportion of these patients experience moderate SMI, regardless of the transfusion trigger. Use of a restrictive transfusion strategy did not increase length of hospital stay, and use of this strategy would lead to a significant reduction in red cell transfusion in orthopaedic surgery. Our data did not indicate any potential for harm in employing such a strategy in patients with no prior evidence of cardiac ischaemia who were undergoing elective orthopaedic surgery.\nStudy3: The illness of trauma. nan\nStudy4: A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation. Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia. A multicenter, single-blinded pilot randomized controlled trial (RCT) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin (Hb) concentration on bleeding risk. Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups: standard transfusion strategy (transfusion of 2 units of red blood cells [RBCs] when their Hb level was less than 80 g/L) or an augmented transfusion strategy (transfusion of 2 units of RBCs when their Hb level was less than 120 g/L). Sixty patients were enrolled: 29 in the control group and 31 in the experimental group. The proportions of patients experiencing clinically significant bleeding and the time to first bleed were not significantly different between the control and experimental groups. The experimental group received more RBC transfusions (transfusions/patient-day) than the control group (0.233 vs. 0.151; relative risk, 1.56; 95% confidence interval, 1.16-2.10; p = 0.003). The proportion of patient-days with platelet (PLT) transfusions was not different between the experimental and control groups. The mean number of donor exposures (PLT and RBC transfusions) was not different between experimental and control groups. Bleeding symptoms were systematically documented. This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients.\nStudy5: Predonated autologous blood transfusions after total knee arthroplasty: immediate versus delayed administration. Efforts to avoid complications associated with transfusion of allogeneic blood have increased the use of preoperatively donated autologous blood (PAB). A major controversy has arisen: Should the same criteria be used for transfusion of autologous as allogeneic red cells? This study prospectively and randomly compared giving PAB immediately after total knee arthroplasty (TKA), beginning in the recovery room or delaying a transfusion until the patient's hemoglobin had fallen to less than a 9.0 g/dL transfusion trigger point. The results show that patients who received immediate transfusion had fewer nonsurgical complications (P < .002). Because TKAs are associated with an average blood loss of 1,400 mL, we recommend that PAB be used in the immediate postoperative period, especially in the elderly, in whom the risk for cardiac or nonsurgical complications is inherently increased.\nStudy6: The effects of liberal versus restrictive transfusion thresholds on ambulation after hip fracture surgery. Perioperative anemia leads to increased morbidity and mortality and potentially inhibits rehabilitation after hip fracture surgery. As such, the optimum transfusion threshold after hip fracture surgery is unknown. A total of 120 elderly, cognitively intact hip fracture patients admitted from their own home were randomly assigned to receive transfusion at a hemoglobin threshold of 10.0 g per dL (liberal) versus 8.0 g per dL (restrictive) in the entire perioperative period. Patients were treated according to a well-defined multimodal rehabilitation program. Primary outcome was postoperative functional mobility measured with the cumulated ambulation score (CAS). Patients in the liberal group received transfusions more frequently than those in the restrictive group (44 patients vs. 22 patients; p < 0.01) and received more transfusions during hospitalization (median, 2 units [interquartile range, 1-2] vs. 1 [1-2]; p < 0.0001). There were no significant differences in postoperative rehabilitation scores (CAS: median, 9 [9-15] vs. 9 [9-13.5]; p = 0.46) or in length of stay (median, 18 days vs. 16 days, respectively; p = 0.46). There were fewer patients in the liberal transfusion group with cardiovascular complications (2% vs. 10%; p = 0.05) and a lower mortality (0% vs. 8%; p = 0.02). Although a liberal transfusion trigger did not result in increased ambulation scores, restrictive transfusion thresholds should be treated with caution in elderly high-risk hip fracture patients, until their safety has been proved in larger randomized studies.\nStudy7: A randomized comparison of transfusion triggers in elective orthopaedic surgery using leucocyte-depleted red blood cells. In elective orthopaedic hip- and knee replacement surgery patients, we studied the effect of implementation of a uniform transfusion policy on RBC usage. A randomized, controlled study. A new uniform, restrictive transfusion policy was compared with standard care, which varied among the three participating hospitals. Only prestorage leucocyte-depleted RBC(s) were used. Primary end-point was RBC usage, related to length of hospital stay. Secondary end-points were Hb levels, mobilization delay and postoperative complications. Six hundred and three patients were evaluated. Adherence to the protocol was over 95%. Overall mean RBC usage was 0.78 U/patient in the new policy group and 0.86 U/patient in the standard care policy group (mean difference 0.08;95% CI [-0.3; 0.2]; P = 0.53). In two hospitals, the new transfusion policy resulted in a RBC reduction of 30% (0.58U RBC/patient) (P = 0.17) and 41% (0.29 U RBC/patient) (P = 0.05) respectively. In the third hospital, however, RBC usage increased by 39% (0.31 U RBC/patient) (P = 0.02) with the new policy, due to a more restrictive standard care policy in that hospital. Length of hospital stay was not influenced by either policy. Implementation of a uniform transfusion protocol for elective lower joint arthroplasty patients is feasible, but does not always lead to a RBC reduction. Length of hospital stay was not affected.\nStudy8: Transfusion requirements in critical care. A pilot study. Canadian Critical Care Trials Group. To evaluate the effects of a restrictive and a liberal red blood cell (RBC) transfusion strategy on mortality and morbidity in critically ill patients. Multicenter, prospective, randomized clinical trial. Sixty-nine normovolemic critically ill patients admitted to one of five tertiary level intensive care units with hemoglobin values less than 90 g/L within 72 hours of admission. Patients were randomly allocated to one of two RBC transfusion strategies. Hemoglobin values were maintained between 100 and 120 g/L in the liberal transfusion group and between 70 and 90 g/L in the restrictive group. Primary diagnosis and mean +/- SD age (58.6 +/- 15 vs 59.0 +/- 21 years and Acute Physiology and Chronic Health Evaluation II score (20 +/- 6.2 vs 21 +/- 7.2) were similar in the restrictive and liberal groups, respectively. Daily hemoglobin values averaged 90 g/L in the restrictive group vs 109 g/L in the liberal group (P < .001). The restrictive group received 2.5 U per patient compared with 4.8 U per patient in the liberal group. This represents a 48% relative decrease (P < .001) in RBC units transfused per patient. The 30-day mortality rate was 24% in the restrictive group compared with 25% in the liberal group; the 95% confidence interval around the absolute difference was -19% to 21%. Similar observations were noted for intensive care unit mortality (P = .76) and 120-day mortality (P > .99). In addition, survival analysis comparing time until death in both groups did not reveal any significant difference (P = .93) between groups. Organ dysfunction scores were also similar (P = .44). In this small randomized trial, neither mortality nor the development of organ dysfunction was affected by the transfusion strategy, which suggests that a more restrictive approach to the transfusion of RBCs may be safe in critically ill patients. However, the study lacked power to detect small but clinically significant differences. Therefore, further investigations of RBC transfusion strategies are warranted.\nStudy9: The effect of red blood cell transfusion on cerebral oxygenation and metabolism after severe traumatic brain injury. There is evidence to suggest that anemia after severe traumatic brain injury (sTBI) is detrimental. However, there is a paucity of evidence supporting the use of transfusion of packed red blood cells in patients with sTBI. To understand the acute effect of packed red blood cell transfusion on cerebral oxygenation and metabolism in patients with sTBI. Prospective clinical study. Addenbrooke's Neurosciences Critical Care Unit, a 21-bed tertiary academic unit. Thirty patients with sTBI. Patients were randomized by computer random number generator to one of three transfusion thresholds: 8, 9, or 10 g/dL. When the patients' hemoglobin concentration fell below their assigned threshold, two units of packed red blood cells were transfused over 2 hours. A 1-hour period of stabilization was observed before final data collection. The primary outcome was change in brain tissue oxygen (Pbto2). Secondary outcomes included dependence of baseline hemoglobin concentration and baseline Pbto2 on the relationship of transfusion and Pbto2, and the effect of transfusion on lactate pyruvate ratio (LPR) and brain pH as markers of cerebral metabolic state. Fifty-seven percent of patients experienced an increase in Pbto2 during the course of the study, whereas in 43% of patients, Pbto2 either did not change or decreased. Multivariable generalized estimating equation analysis revealed change in hemoglobin concentration to significantly and positively associated with change in Pbto2 [0.10 kPa/(g/dL) 95% confidence interval 0.03-0.17, p = 0.003]. Improvement in Pbto2 was not associated with baseline hemoglobin concentration or low Pbto2 (<1 kPa). Fifty-six percent of patients experienced an increase in LPR. No significant relationship between change in LPR or transfusion on pHbt and change in hemoglobin could be demonstrated. Transfusion of packed red blood cells acutely results in improved brain tissue oxygen without appreciable effect on cerebral metabolism. ISRCTN89085577.\nStudy10: Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome. There is controversy regarding the application of transfusion triggers in cardiac surgery. The goal of this study was to determine if lowering the hemoglobin threshold for red cell (RBC) transfusion to 8 g per dL after coronary artery bypass graft surgery would reduce blood use without adversely affecting patient outcome. Consecutive patients (n = 428) undergoing elective primary coronary artery bypass graft surgery were randomly assigned to two groups: study patients (n = 212) received RBC transfusions in the postoperative period if the Hb level was < 8 g per dL or if predetermined clinical conditions required RBC support, and control patients (n = 216) were treated according to individual physician's orders (hemoglobin levels < 9 g/dL as the institutional guideline). Multiple demographic, procedure-related, transfusion, laboratory, and outcome data were analyzed. Questionnaires were administered for patient self-assessment of fatigue and anemia. Preoperative and operative clinical characteristics, as well as the intraoperative transfusion rate, were similar for both groups. There was a significant difference between the postoperative RBC transfusion rates in study (0.9 +/- 1.5 RBC units) and control (1.4 +/- 1.8 RBC units) groups (p = 0.005). There was no difference in clinical outcome, including morbidity and mortality rates, in the two groups; group scores for self-assessment of fatigue and anemia were also similar. A lower Hb threshold of 8 g per dL does not adversely affect patient outcome. Moreover, RBC resources can be saved without increased risk to the patient.\n", + "output": "Conclusions: The existing evidence supports the use of restrictive transfusion triggers in most patients, including those with pre-existing cardiovascular disease. As there are no trials, the effects of restrictive transfusion triggers in high-risk groups, such as acute coronary syndrome, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood, the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells." + }, + { + "input": "Study1: Lithium versus fluphenazine for prophylaxis in mainly schizophrenic schizo-affectives. nan\nStudy2: A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. Lithium combined with major tranquilizers was administered to 22 hospitalized chronic schizophrenic patients with minimal neurotoxicity or other side effects. Moreover, 10 of the patients benefited significantly with lithium as compared to placebo in terms of blind psychiatric and nursing ratings and nonblind clinical judgments of outcome. These results contrast with previous negative reports in the literature and the generally poor prognosis in chronic schizophrenic patients. The authors suggest that a trial combining lithium with psychotropic drugs is warranted in schizophrenic patients who do not respond satisfactorily to conventional treatment\n", + "output": "Conclusions: There is no randomised trial-based evidence that lithium on its own is an effective treatment for people with schizophrenia. The evidence available on augmentation of antipsychotics with lithium is inconclusive, but does justify further, large, simple and well-designed trials. These should concentrate on two target groups: 1) people with no affective symptoms, so that trialists can determine whether lithium has an effect on the core symptoms of schizophrenia, 2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use." + }, + { + "input": "Study: [Initial experience with using phosphocreatine in patients in the early (up to 6 hours) period of myocardial infarction]. A randomized study of 60 patients with myocardial infarction (MI) admitted to hospital in the first 6 hours of the disease was performed in order to study the effect of phosphocreatine (PC) on the course of MI. 30 patients were treated with PC; control group consisted also of 30 patients. PC infusion in the early period of MI resulted in the decreased frequency of ventricular arrhythmias (including paroxysms of ventricular tachycardia) and lowered likelihood of cardiac failure development. No reliable influence of PC on the central hemodynamics, heart rate, heart conduction and myocardial necrosis size was determined.\n", + "output": "Conclusions: This review found inconclusive evidence to decide on the use of creatine analogues in clinical practice. In particular, it is not clear whether there is an effect on mortality, progression of myocardial infarction and ejection fraction, while there is some evidence that dysrhythmia and dyspnoea might improve. However, it is not clear which analogue, dose, route of administration, and duration of therapy is most effective. Moreover, given the small sample size of the discussed trials and the heterogeneity of the population included in these reports, larger clinical studies are needed to confirm these observations." + }, + { + "input": "Study1: Ceftriaxone alone compared to ampicillin and chloramphenicol in the treatment of bacterial meningitis. One hundred patients (71 males and 29 females) with bacterial meningitis were randomly assigned into two therapeutic regimens. Patients in group I were intravenously given ceftriaxone (CRO: Rocephin) to adults and intramuscularly to children once daily in a dose of 100 mg/kg/day. Patients in group II received ampicillin 160 mg/kg/day and chloramphenicol (AMCL) 100 mg/kg/day (i.v. to adults and i.m. to children) every 6 h. No significant difference was observed between the two therapeutic regimens with regard to mortality, time taken to become afebrile, fully alert and sequelae. Seven patients in the CRO group died compared to 10 in the AMCL group. The mean number of days taken to become afebrile were 3.4 and 3.5, and to become fully alert 3.9 and 3.5 for groups I and II, respectively. CRO administered in a single daily dose appears to be as effective as a combination of ampicillin and chloramphenicol given every 6 h in the treatment of acute bacterial meningitis. However, the once daily dose is more appropriate for use especially in areas where nursing care is limited.\nStudy2: Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study. In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis. In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses. Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported. Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.\nStudy3: Ceftriaxone versus ampicillin and chloramphenicol for treatment of bacterial meningitis in children. 78 patients with bacterial meningitis were evaluated in a prospective, randomised study comparing twice-daily ceftriaxone as single-drug therapy with ampicillin and chloramphenicol given every 6 h. The groups were comparable in age, sex, days of illness before admission, and bacterial colony counts in cerebrospinal fluid (CSF). The pathogens were Haemophilus influenzae type b (54 cases), streptococci (9 cases), meningococci (9 cases), and unknown (6 cases). In 40 CSF specimens obtained 4-12 h after initiation of therapy, cultures were negative in 57% of the ceftriaxone patients and in 42% of the others. The mean falls in the CSF bacterial colony counts were 4.7 and 5.0 log10 colony-forming units/ml, respectively. Mean bactericidal activity in CSF was significantly greater in the ceftriaxone than in the conventional treatment group at the beginning and end of therapy. There were no significant differences in clinical responses or in frequency of complications, except for mild diarrhoea, which occurred in 16 ceftriaxone patients and in 8 in the other group (p less than 0.05).\nStudy4: Cefotaxime versus penicillin-chloramphenicol in purulent meningitis: a controlled single-blind clinical trial. In a prospective, controlled, randomized single-blind clinical trial, treatment with cefotaxime (CTX) was compared with that with standard therapy (ST), which consisted of a penicillin-chloramphenicol combination with or without sulphadiazine, in 31 patients (excluding neonates) with proven bacterial meningitis. The two groups of patients were comparable in age, sex, clinical presentation and causative pathogens. The case fatality rate was 12.5% for the CTX group and 20% for the ST group, but this difference was not significant. The times taken for the cerebrospinal fluid (CSF) to become sterile and the temperature to normalize, the mean duration of treatment, complications and adverse effects were similar for the two regimens. Neurological or developmental abnormalities on follow-up were not significantly different for the two groups. It is concluded that CTX is a suitable alternative for treatment of bacterial meningitis in infants and children.\nStudy5: Comparison of the efficacy and safety of ceftriaxone to ampicillin/chloramphenicol in the treatment of childhood meningitis. Ceftriaxone is a new cephalosporin with a broad spectrum of antibacterial activity and unique serum and CSF pharmacokinetics. The drug was compared in a randomized fashion with ampicillin and chloramphenicol in the treatment of 19 children with Haemophilus influenzae type b meningitis. Ceftriaxone was also administered non-randomly to six other patients including three children with Gram-negative meningitis. Among the children with H. influenzae meningitis, no deaths were noted and the outcomes of the study and the control groups were similar. Ninety per cent of the isolates of H. influenzae were inhibited by 0.0625, 1 and 1 mg/l of ceftriaxone, ampicillin and chloramphenicol respectively. One child with pneumococcal meningitis and two children with meningococcal meningitis recovered rapidly and without incident during ceftriaxone therapy. Three children with Gram-negative meningitis caused by multiply-drug resistant organisms were bacteriologically cured within five days of the onset of therapy. Persistent pleocytosis and neurological disabilities were noted in two at the conclusion of therapy. Ceftriaxone, as a single agent, was comparable in efficacy with traditional antimicrobial therapy usually employed in childhood meningitis.\nStudy6: Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis. Ceftriaxone, a new third-generation cephalosporin, appears to be promising for the therapy of acute bacterial meningitis. The 90% MBCs of ceftriaxone against 54 recent cerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were less than or equal to 0.06 to 0.25 micrograms/ml. We examined the efficacy and safety of ceftriaxone therapy of meningitis in Bahia, Brazil. The study was conducted in two phases; in phase A, ceftriaxone was coadministered with ampicillin. The mean cerebrospinal fluid concentrations of ceftriaxone 24 h after an intravenous dose of 80 mg/kg were 4.2 and 2.3 micrograms/ml on days 4 to 6 and 10 to 12 of therapy, respectively. These concentrations were 8- to more than 100-fold greater than the 90% MBCs against the relevant pathogens. In phase B, ceftriaxone (administered once daily at a dose of 80 mg/kg after an initial dose of 100 mg/kg) was compared with conventional dosages of ampicillin and chloramphenicol in a prospective randomized trial of 36 children and adults with meningitis. The groups were comparable based on clinical, laboratory, and etiological parameters. Ceftriaxone given once daily produced results equivalent to those obtained with ampicillin plus chloramphenicol, as judged by cure rate, case fatality ratio, resolution with sequelae, type and severity of sequelae, time to sterility of cerebrospinal fluid, and potentially drug-related adverse effects. The cerebrospinal fluid bactericidal titers obtained 16 to 24 h after ceftriaxone dosing were usually 1:512 to greater than 1:2,048 even late in the treatment course, compared with values of 1:8 to 1:32 in patients receiving ampicillin plus chloramphenicol. Ceftriaxone clearly deserves further evaluation for the therapy of meningitis; the optimal dose, dosing frequency (every 12 h or every 24 h), and duration of therapy remain to be determined.\nStudy7: Cefotaxime vs. conventional therapy for the treatment of bacterial meningitis of infants and children. Eighty-five infants and children were prospectively randomized to receive cefotaxime or ampicillin and chloramphenicol for therapy of bacterial meningitis. The two therapy groups of patients were comparable as to sex, age, clinical status on admission, prior administration of antibiotics and etiology. Three infants (7%) died in each therapy group. Mean number of days of positive cerebrospinal fluid cultures, time to defervescence and duration of treatment and of hospital stay and complications developing during treatment were similar for the two treatment regimens. Median cerebrospinal fluid bactericidal titers against the patients' pathogens in cefotaxime-treated patients (1:64) were larger than those in patients who received conventional therapy (1:8). Mild to moderate motor sequelae were more frequent in those given conventional therapy at the time of discharge only, and not at 4 months or longer of follow-up. We conclude that cefotaxime has similar efficacy when compared with conventional therapy for the management of bacterial meningitis in pediatric patients.\nStudy8: Comparison of ceftriaxone with standard therapy for bacterial meningitis. nan\nStudy9: Ceftriaxone versus penicillin G in the short-term treatment of meningococcal meningitis in adults. Short-term treatment with ceftriaxone 2 g once daily for two days (group 1) was compared to treatment with a standard regimen of penicillin G (group 2) for six days in adults with meningococcal meningitis. Thirty-six patients were allocated in a randomized fashion to a treatment group: 16 to group 1 and 20 to group 2. The clinical and microbiological results were comparable in the two treatment groups. In both groups cultures of cerebrospinal fluid were sterile after 24 hours. One patient in each group died. In group 1 one case of fulminant meningococcemia and one case of brain abscess required further antibiotic treatment. It is concluded that short-term treatment with ceftriaxone is feasible but patients with severe forms of meningitis would not be eligible for treatment with this regimen, and careful follow-up of the patients receiving ceftriaxone is necessary.\nStudy10: Intravenous chloramphenicol plus penicillin versus intramuscular ceftriaxone for the treatment of pyogenic meningitis in Nepalese children. nan\n", + "output": "Conclusions: The review shows no clinically important difference between third generation cephalosporins (ceftriaxone or cefotaxime) and conventional antibiotics (ampicillin-chloramphenicol combination, or chloramphenicol alone). Therefore the choice of antibiotic will depend on cost and availability. The antimicrobial resistance pattern against various antibiotics needs to be closely monitored in low- to middle-income countries as well as high-income countries." + }, + { + "input": "Study1: Trial of cyclosporin in corticosteroid-dependent chronic severe asthma. The treatment of chronic severe asthma is unsatisfactory for many patients. In a randomised, double-blind, placebo-controlled, crossover trial we have tested whether cyclosporin, which is thought to act primarily by inhibition of T lymphocyte activation, improves lung function in corticosteroid-dependent asthmatics. After a 4-week run-in period, 33 patients with longstanding asthma (mean duration 27 years), and who had required continuous oral corticosteroids for a mean of 9.3 years, were randomised to receive either cyclosporin (initial dose 5 mg/kg per day) or placebo for 12 weeks, crossing over after a 2-week washout period. Mean baseline forced expiratory volume in 1 s (FEV1) was 60.1% of the predicted value. 2 patients failed to complete the protocol and 1 withdrew because of hypertrichosis. Cyclosporin therapy resulted in a mean increase above placebo of 12.0% in morning peak expiratory flow rate (PEFR; p less than 0.004) and 17.6% in FEV1 (p less than 0.001). The frequency of disease exacerbations requiring an increased prednisolone dose was reduced by 48% in patients on cyclosporin compared with placebo (p less than 0.02). Diurnal variation in PEFR decreased by a mean of 27.6% (p = 0.04). Cyclosporin for 12 weeks was well tolerated by this group of chronic asthmatics, in whom the mean whole-blood trough concentration was 152 micrograms/l. These findings provide further evidence of a role for activated T lymphocytes in the pathogenesis of asthma. Specific pharmacological targeting of this cell could form the basis of a novel approach to the treatment of asthma.\nStudy2: Treatment of steroid-dependent bronchial asthma with cyclosporin. The treatment of chronic severe asthma is unsatisfactory for many patients. The aim of the study was to determine the effects of treatment of steroid-dependent asthma with cyclosporin. We performed a double-blind, placebo-controlled, randomized, parallel group trial on the effect of cyclosporin on pulmonary function, asthma severity and tapering of prednisone in 34 steroid-dependent asthmatics (mean oral prednisone dose: 16 mg.day-1). The study consisted of: 1) baseline period (12 weeks); 2) experimental period divided into two parts: Part I (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or placebo treatment and oral prednisone reduction; and 3) follow-up observation (8 weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MEF50), biochemical profile and blood cyclosporin levels were monitored throughout the study. Following cyclosporin administration, a slight beneficial effect on some subjective parameters of asthma severity was observed. At the same time, no beneficial effect on pulmonary function was noted. The time trends analysis of mean daily prednisone doses between the treatment groups revealed a statistically significant difference indicating that, during prednisone reduction, cyclosporin seemed to be slightly more efficient than placebo in reducing the requirement for systemic corticosteroid, even though the steroid reduction was accompanied by slight impairment of some pulmonary function. However, there was no significant difference in the final dose reduction between the treatment groups. These data and the known toxicity of the drug suggest a limited place for cyclosporin treatment in steroid-dependent bronchial asthma.\n", + "output": "Conclusions: The changes with cyclosporin are small and of questionable clinical significance. Given the side effects of cyclosporin, the evidence available does not recommend routine use of this drug in the treatment of oral corticosteroid dependent asthma." + }, + { + "input": "Study: Laparoscopic compared with robotic sacrocolpopexy for vaginal prolapse: a randomized controlled trial. To compare conventional laparoscopic and robotic-assisted laparoscopic sacrocolpopexy for vaginal apex prolapse. This single-center, blinded randomized trial included participants with stage 2-4 posthysterectomy vaginal prolapse. Participants were randomized to laparoscopic or robotic sacrocolpopexy. The primary outcome was total operative time from incision to closure. Secondary outcomes were postoperative pain, functional activity, bowel and bladder symptoms, quality of life, anatomic vaginal support, and cost from a health care system perspective. A total of 78 patients enrolled and were randomized (laparoscopic n=38; robotic n=40). Total operative time was significantly longer in the robotic group compared with the laparoscopic group (+67-minute difference; 95% confidence interval [CI] 43-89; P<.001). Anesthesia time, total time in the operating room, total sacrocolpopexy time, and total suturing time were all significantly longer in the robotic group. Participants in the robotic group also had significantly higher pain at rest and with activity during weeks 3 through 5 after surgery and required longer use of nonsteroidal anti-inflammatory drugs (median, 20 compared with 11 days, P<.005). The robotic group incurred greater cost than the laparoscopic group (mean difference +$1,936; 95% CI $417-$3,454; P=.008). Both groups demonstrated significant improvement in vaginal support and functional outcomes 1 year after surgery with no differences between groups. Robotic-assisted sacrocolpopexy results in longer operating time and increased pain and cost compared with the conventional laparoscopic approach.\n", + "output": "Conclusions: Currently, the limited evidence showed that robotic surgery did not benefit women with benign gynaecological disease in effectiveness or in safety. Further well-designed RCTs with complete reported data are required to confirm or refute this conclusion." + }, + { + "input": "Study1: Oestriol in the treatment of postmenopausal urgency: a multicentre study. Oestrogen deficiency in postmenopausal women is thought to be important in the genesis of lower urinary tract symptoms, in particular the 'urge syndrome'. Evidence to support the use of oestrogen therapy in symptomatic postmenopausal women is, however, limited. Oestriol is a weak, naturally occurring oestrogen that may be beneficial to the urogenital tissues without stimulating the endometrium. We have investigated the use of oestriol in the treatment of postmenopausal sensory and motor urge incontinence. Materials and methods: A double-blind, placebo-controlled, randomised, multicentre study of 3 mg oral oestriol/day for 3 months in the treatment of women with urge incontinence was undertaken. Results and conclusions: Sixty-four women were recruited into the study. Although oestriol produced both subjective and objective improvement in lower urinary tract function, it was not significantly better than placebo. Some of the difficulties of running a multicentre study were encountered.\nStudy2: Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women. To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence, urogenital atrophy, and recurrent urinary tract infections in postmenopausal women. Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospective, randomized, placebo-controlled study. Participants were randomly divided into two groups, with each group consisting of 44 women. Women in the treatment group received intravaginal estriol ovules: 1 ovule (1 mg) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy. Women in the control group received inert placebo vaginal suppositories in a similar regimen. We evaluated urogenital symptomatology, urine cultures, colposcopic findings, urethral cytologic findings, urethral pressure profiles, and urethrocystometry before as well as after 6 months of treatment. After therapy, the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group. Thirty (68%) of the treated participants, and only seven (16%) of the control participants registered a subjective improvement of their incontinence. In the treated participants, we observed significant improvements of colposcopic findings, and there were statistically significant increases in mean maximum urethral pressure, in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra. Urethrocystometry showed positive but not statistically significant modifications. Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo standard hormone therapy.\nStudy3: Urethral sphincteric insufficiency in postmenopausal females: treatment with phenylpropanolamine and estriol separately and in combination. A urodynamic and clinical evaluation. A randomized open comparative cross-over trial was carried out in 20 postmenopausal women, mean age 69 years, suffering from urinary incontinence due to urethral sphincteric insufficiency. They were treated with phenylpropanolamine (PPA) 50 mg p.o. twice daily or estriol vaginal suppositories 1 mg daily separately and in combination for periods of 4 weeks. Urodynamic investigations were carried out before and after each period of treatment. Both PPA and estriol increased the maximal urethral closure pressure and the continence area significantly compared to the initial values, but combined treatment was substantially more effective. The functional urethral length increased significantly while on estriol. No significant change was registered in the bladder pressure or in the pressure transmission ratio. PPA was clinically more effective than estriol, but not sufficient to obtain complete continence. With combined treatment 8 patients became completely continent, 9 were considerably improved and only 1 patient remained unchanged. 2 patients dropped out of the study because of side effects. Combined treatment with PPA and estriol represents a recommendable treatment to postmenopausal women with urinary incontinence due to urethral sphincteric insufficiency.\nStudy4: Efficacy of estrogen supplementation in the treatment of urinary incontinence. The Continence Program for Women Research Group. To assess the efficacy of cyclic postmenopausal hormone replacement in treating urinary incontinence in hypoestrogenic women. Eighty-three hypoestrogenic women complaining of urinary incontinence were included. All patients were community-dwelling, age 45 years or older, with involuntary loss of urine occurring at least once a week and urodynamic evidence of genuine stress incontinence and/or detrusor instability. Evaluation consisted of a comprehensive clinical and urodynamic research protocol. The hypoestrogenic entry criterion was a plasma estradiol level of 30 pg/mL or less. Parabasal cells on vaginal smears were also monitored. The primary outcome was the number of incontinent episodes per week, as documented on a standardized urinary diary. Secondary outcomes were the quantity of fluid loss, voluntary diurnal and nocturnal micturition frequency, generic and condition-specific health-related quality of life measurements, and patient satisfaction. A randomized, placebo-controlled, double-blind design was used. Subjects in the treatment group were given conjugated equine estrogens (0.625 mg) and medroxyprogesterone (10 mg) cyclically for 3 months. Controls received placebo tablets. (All results are presented as mean +/- standard deviation.) Subjects were 67 +/- 9 years old. The menopause duration was 18 +/- 11 years. The duration of incontinence was 9 +/- 9 years. Estradiol level at baseline was 9 +/- 9 pg/mL, and the parabasal cell count was 42 +/- 44%. The number of incontinent episodes at baseline was 13 +/- 10 for the treatment group and 16 +/- 4 for controls. No significant changes occurred in the number of incontinent episodes after treatment: 10 +/- 10 for the treatment group, and 13 +/- 14 for the controls (P = .7). Also, fluid loss was not changed: 176 +/- 106 g for the treatment group and 64 +/- 88 g for the control group at baseline, and 101 +/- 150 and 51 +/- 69 g after treatment, respectively (P = .7). There were no significant differences for either diurnal or nocturnal voluntary micturition, quality of life measures, or patient's perception of improvement. Three-month cyclic hormone replacement therapy did not affect either clinical or quality of life variables of incontinent, hypoestrogenic women. Long-term effects are unlikely to be substantially different. The use of estrogen supplementation as preventive or adjuvant therapy was not evaluated in this study.\nStudy5: Effects of oral estrogen and progestin on the lower urinary tract among female nursing home residents. To examine the effects of oral estrogen/progestin on incontinence and related lower urinary tract conditions among female nursing home (NH) residents. Randomized placebo-controlled trial. Five NHs. Thirty-two incontinent female residents of average age 88. Subjects were randomized to receive either oral estrogen (0.625 mg) combined with progesterone (2.5 mg) or placebo, daily for 6 months. Measures of incontinence severity, the clinical appearance of the vagina, vaginal and urethral cytology, and urine and vaginal cultures were made at baseline, 3 months, and 6 months. In addition to active drug or placebo, all subjects received regular toileting assistance (prompted voiding) by trained research aides during 3-day data-collection periods to compensate for mobility and cognitive impairments. At 3 and 6 months there were no significant differences between the groups in the severity of incontinence, the prevalence of bacteriuria, or the results of vaginal cultures. Several clinical findings associated with atrophic vaginitis improved more in the active than the placebo group and vaginal pH and vaginal and urethral cytology exhibited a partial estrogenic effect. Our results must be interpreted with caution because of the size and the select nature of our subject sample. Up to 6 months of oral estrogen had only a partial estrogenic effect on vaginal and urethral epithelium and no clinical effects in this patient population. We believe that future studies of estrogen for urinary incontinence in frail NH residents should utilize a topical preparation and consider targeting urinary tract infection as an additional outcome measure.\nStudy6: Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. The use of oestrogens in the treatment of genuine stress incontinence was assessed by a double-blind prospective trial in 36 postmenopausal women with genuine stress incontinence who received 3 months of cyclical treatment with either piperazine oestrone sulphate or a matching placebo. Patients were assessed subjectively and objectively before and after treatment by 7-day bladder charts, urethral pressure profiles (UPP), the Urilos nappy test, vaginal cytology and hormone assays (plasma oestrogens and gonadotrophins). There was no statistical difference in the subjective response to treatment between the two groups. After 6 weeks of treatment there was a greater reduction in the number of pad changes/24 h in the oestrogen-treated patients that approached statistical significance but, because of a marked response in the placebo group, this difference was not significant after 3 months of treatment. There were also no significant differences between the two groups with respect to the UPP or Urilos measurements but the vaginal cytology and hormone profiles were significantly affected by oestrogens. In view of the possible risks of oestrogen therapy its use in genuine stress incontinence is limited.\nStudy7: [Intravesical administration of estriol in sensory urge incontinence--a prospective study]. Local intravaginal application of oestriol is part of the therapeutical programme of sensory urge-incontinence. The effectiveness of a new method--intravesical administration of 1 mg oestriol versus a placebo--has been proved in a prospective randomised study. 21 patients each were treated over a period of three weeks with oestriol or with the placebo-substance intravesically. The effectiveness of the administered therapy was checked with clinical and urodynamic parameters. The intravesical administration of 1 mg oestriol proved to be efficient and free of side effects in respect of the parameters such as imperative micturition, bladder capacity, of the maximum urethral closure pressure as well as the number of micturitions per diem. The intravesical administration of oestriol may be considered as additional method of therapy for treatment of sensory urge-incontinence.\nStudy8: Occurrence, nature and treatment of urinary incontinence in a 70-year-old female population. An intervention trial using oral oestriol to treat urinary incontinence was performed in a number of patients taken from a representative sample of 562 women aged 75 yr. The clinical series consisted of 34 patients who took part in a double-blind crossover study of the possible effects of oestriol, given in a single daily dose of 3 mg, and of a placebo over a period of 3 mth. The clinical examinations included bacteriological cultures and an assessment of the degree of atrophy of the surface membranes in the vagina. In most patients, oestriol was effective in reversing the atrophy. The clinical effect was excellent in urgency and mixed incontinence, but not in stress incontinence.\nStudy9: The use of oestradiol therapy in postmenopausal women after TVT-O anti-incontinence surgery. To investigate whether patients who were treated with TVT-O procedure for urodynamic stress incontinence had a significant improvement in their urodynamic findings and their post-operative symptoms (frequency, urgency, nocturia) if they were treated post-operatively with vaginal oestradiol for 6 months compared to the non-treated group. Prospective randomised study. 190 patients were asked to participate in our study. Finally, a total of 92 patients in group 1 and 91 patients in group 2 completed the study. In group 1, which was the treatment group, patients having the TVT-O procedure for urodynamic stress incontinence were instructed to use post-operatively oestradiol tablets, 25 micrograms (Vagifem, Novo Nordisk) vaginally, once daily, nocte, for 2 weeks and then twice weekly for 6 months. The patients in group 2 (control group) had the TVT-O procedure only. All patients were reviewed in 2 months and again in 6 months time. There was no statistically significant difference between the two groups concerning pre-operative and post-operative haemoglobin, operative time, hospital stay or return to work. The within group analysis did not show significant differences between pre-operative and post-operative urodynamic data in both groups. Patients treated with vaginal estradiol post-operatively showed a statistically significant reduction in relation to the symptoms of urgency and frequency but not in relation to nocturia and urge incontinence compared to the non-treated group. There is no difference in relation to the efficacy of TVT-O procedure between the groups at 6 months follow-up. It appears that vaginal oestradiol treatment could be offered to postmenopausal patients after a TVT-O procedure having the symptoms of frequency and urgency provided they are aware of the lack of evidence regarding long term benefit. Copyright 2010. Published by Elsevier Ireland Ltd.\nStudy10: [The effectiveness of intravaginal estriol tablet administration in women with urge incontinence]. In postmenopausal patients, stress and urge incontinence often occur as a consequence of oestrogen deficiency. We performed a comparative study in a prospectively randomised and placebo controlled group of women with urge incontinence to investigate different dosages of intravaginally applied oestriol. Clinical and urodynamic parameters were also compared. 15 women (Group I) received 1 mg oestriol applied daily intravaginally over 3 weeks; 15 women (Group II) received a daily dosage of 3 mg and 10 women received a placebo. A complete clinical and urodynamic evaluation was carried out twice at a 4-week interval. The women receiving a daily dose of 3 mg oestriol applied intravaginally demonstrated a significant improvement of the parameters strong desire to void, pollakisuria, and nycturia. No improvement was seen in patients with motoric urge incontinence.\n", + "output": "Conclusions: Urinary incontinence may be improved with the use of local oestrogen treatment. However, there was little evidence from the trials on the period after oestrogen treatment had finished and no information about the long-term effects of this therapy was given. Conversely, systemic hormone replacement therapy using conjugated equine oestrogen may worsen incontinence. There were too few data to reliably address other aspects of oestrogen therapy, such as oestrogen type and dose, and no direct evidence comparing routes of administration. The risk of endometrial and breast cancer after long-term use of systemic oestrogen suggests that treatment should be for limited periods, especially in those women with an intact uterus." + }, + { + "input": "Study: Use of a vaginal sponge during aerobic exercises in patients with stress urinary incontinence. A newly marketed vaginal sponge intended to support the urethra was tested during aerobic exercise in a group of 6 women suffering from stress urinary incontinence. The patients performed half an hour of aerobic exercises on 2 consecutive days, with and without the vaginal sponge. A pad was worn during exercise and weighed before and after. Without the vaginal sponge the patients had a mean loss of 7 g (range 2-18 g) during exercise. With the vaginal sponge in situ there was no leakage. The sponge can be recommended for use during sports in patients with mild to moderate incontinence.\n", + "output": "Conclusions: The place of mechanical devices in the management of urinary incontinence remains in question. Currently there is little evidence from controlled trials on which to judge whether their use is better than no treatment and large well-conducted trials are required for clarification. There was also insufficient evidence in favour of one device over another and little evidence to compare mechanical devices with other forms of treatment." + }, + { + "input": "Study1: Potential therapeutic effects of contrast materials in hysterosalpingography: a prospective randomized clinical trial. Kaiser Permanente Infertility Work Group. To evaluate the influence of the contrast material used in hysterosalpingography (HSG) on subsequent reproductive success, independent of other therapeutic interventions. In a prospective, multisite, randomized trial, 666 women who had been infertile for more than 1 year and were scheduled to undergo HSG as part of their evaluation were assigned to one of three groups: those receiving water-soluble contrast material (WSCM) (n = 260), those receiving oil-soluble contrast material (OSCM) (n = 273), and those receiving both OSCM and WSCM (n = 133). Possible causes of infertility and therapeutic interventions were abstracted from the medical records. Data on conception within 1 year and the outcome of conception were ascertained from multiple sources. Of 666 women, 204 (30.6%) had at least one pregnancy, and 136 (20.4%) had live births. The rates of live births were 20.4% (54 of 260) after HSG with WSCM, 19.4% (53 of 273) after HSG with OSCM, and 21.8% (29 of 133) after HSG with both WSCM and OSCM. Differences in reproductive outcome among contrast material groups were not statistically significant ((chi2)8 = 6.08, P = .64). Whatever the cause of infertility, the use of different contrast materials led to no significant differences in the rates of live births. There is no evidence to suggest that the choice of contrast material affects the rate of term pregnancy.\nStudy2: Pregnancy rates after hysterosalpingography with oil- and water-soluble contrast media. Hysterosalpingography can be accomplished with either oil or water-soluble contrast medium. This randomized prospective study compared pregnancy rates in women who had hysterosalpingography with either water- or oil-soluble contrast material and were followed for six months. Fifteen of 60 (25%) patients who received water-soluble dye conceived compared with 14 of 46 (30%) patients in the oil-soluble group, a statistically insignificant difference. Furthermore, no difference in pregnancy rates within each subgroup of fertility diagnosis was detected. Intravasation was more common in patients administered oil-based contrast materials (six of 46 versus one of 60 patients, P = .02), although no serious consequences occurred. No difference in the amount of pain as assessed by pain scoring was experienced by patients in each group. The authors conclude that pregnancy rates are similar after hysterosalpingography with oil- and water-soluble contrast material, during at least the first six months after the procedure.\nStudy3: The therapeutic effects of oil-soluble hysterosalpingography contrast medium following water-soluble hysterosalpingography contrast medium. Previous studies have revealed that patients who underwent hysterosalpingography (HSG) with an iol-soluble contrast medium (OSCM) rather than a water-soluble contrast medium (WSCM) had higher subsequent fertility rates. In this randomized prospective study, the fertility rates among 109 patients following HSG were found to be 31% (19/61) in the WSOM group and 38% (18/48) in the WSOM + OSCM group. No significant difference was noted between these two groups, whether their infertility was associated with endocrine factor, male factor, endometriosis, mechanical factor or some other unexplained factor.\nStudy4: Oil-soluble contrast during hysterosalpingography in women with proven tubal patency. To determine if there are therapeutic advantages to oil-soluble contrast medium compared with water-soluble medium during hysterosalpingography.A randomized, controlled trial including 56 infertile patients undergoing hysterosalpingography was performed. After a hysterosalpingogram with water-soluble contrast demonstrated tubal patency, 30 patients were randomized to receive oil-soluble contrast medium (oil group) and 26 patients received no additional contrast medium (control group). The outcome was pregnancy and timing of pregnancy in relation to hysterosalpingography. There were 18 (64%) pregnancies in the oil group and 14 (56%) pregnancies in the control group. Mean time to achieve pregnancy was shorter in the oil group: 3.8 months in the oil group compared with 6.1 months in the control group (P =.06) There was a clinically meaningful improvement in pregnancy rates between the oil group and the control group at 1 month postprocedure (relative risk [RR] 2.1, 95% confidence interval [CI] 0.6, 7.2). However, at 12 months postprocedure, the advantage was diminished. (RR 1.3, CI 0.8, 2.1)Eighteen months after hysterosalpingography, contrast does not appear to influence cumulative pregnancy rates; however, the addition of oil-soluble contrast medium to water-soluble contrast medium may have the potential to reduce the time to conception.\nStudy5: A randomized study of laparoscopic chromopertubation with lipiodol versus saline in infertile women. Eighty-eight infertile patients undergoing laparoscopy were randomized to undergo chromopertubation with lipiodol or with normal saline. The cumulative probability of conception at 1, 3, and 6 months following laparoscopy was not statistically different between the lipiodol group (21%, 31% , and 43%, respectively) and the saline group (18%, 21%, and 33%, respectively).\n", + "output": "Conclusions: There is evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy and live birth versus no intervention. The limited evidence of an increase in the odds of live birth from tubal flushing with oil-soluble contrast media versus water-soluble contrast media must be interpreted cautiously. Further robust randomised trials, comparing oil-soluble versus water-soluble media and comparing water-soluble media versus no intervention, would be a useful further guide to clinical practice. Trials are also required to ascertain the place of flushing with oil-soluble contrast media compared to established treatments for unexplained infertility, such as intrauterine insemination and in vitro fertilisation and compared to laparoscopic removal of endometriosis. Further research is merited to ascertain the mechanism of the fertility enhancing effect of oil-soluble media, as to whether this is a 'tubal flushing' phenomenon, an effect on the intraperitoneal environment, or an implantation enhancing effect on the endometrium." + }, + { + "input": "Study1: Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group. The novel agent sirolimus (SRL; Rapamune; rapamycin) inhibits the immune response by a mechanism distinct from those of calcineurin antagonists or antimetabolites. This randomized, controlled, multicenter, single blind, phase II trial examined the combination of SRL, steroids, and full versus reduced doses of cyclosporine (CsA) for prophylaxis of acute renal allograft rejection. A total of 149 recipients of mismatched cadaveric- or living-donor primary renal allografts were randomized into six groups. Three groups received placebo or 1 or 3 mg/m2/day SRL, as well as steroids and full-dose CsA (Sandimmune). Three groups received steroids, reduced-dose CsA (target trough level 50% of full-dose range), and 1, 3, or 5 mg/m2/day SRL. The incidence of biopsy-proven acute rejection episodes within the first 6 months after transplant was reduced from 32.0% in the control group to 8.5% in patients receiving SRL (1 or 3 mg/m2/day) and full-dose Sandimmune CsA (P=0.018). Similar low rates of acute rejection episodes were observed among non-African-Americans, but not African-Americans, treated with SRL and reduced-dose Sandimmune CsA. Despite the augmented immunosuppression, 1-year patient and graft survival rates did not differ significantly across groups. Adverse effects attributable to CsA, including hypertension and new-onset diabetes mellitus, were not exacerbated by SRL. Except for an increased incidence of pneumonia among patients receiving full-dose CsA and 3 mg/m2/day SRL, the incidences of opportunistic infections were similar in all treatment groups. Although SRL produced more frequent, but reversible, hematological and lipid abnormalities, it had no apparent nephrotoxic effects to exacerbate CsA-induced renal dysfunction. SRL in combination with CsA and steroids not only lowers the incidence of biopsy-proven acute renal allograft rejection episodes, but also may permit CsA sparing, at least among Caucasian patients, without an increased risk of rejection.\nStudy2: Randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 6 months. This is the first report of a randomized, multicenter, clinical trial comparing the combination of sirolimus or mycophenolate mofetil (MMF) with tacrolimus-based immunosuppression in kidney transplantation. Results at 6 months of follow-up are presented. Before transplantation, patients were randomized to receive tacrolimus plus corticosteroids with sirolimus (n=185) or MMF (n=176). The primary endpoint of the study was the incidence of biopsy-confirmed acute rejection. Patient and graft survival, renal function, and composite endpoints also were evaluated. Safety was assessed by monitoring laboratory parameters and adverse events. By 6 months of follow-up, the incidence of biopsy-confirmed acute rejection was similar in both treatment groups (13.0% tacrolimus+sirolimus vs. 11.4% tacrolimus+MMF; P=0.64 log-rank). Patient survival (97.3% tacrolimus+sirolimus vs. 97.7% tacrolimus+MMF) and graft survival (93.0% tacrolimus+sirolimus vs. 95.5% tacrolimus+MMF) were equivalent (P=0.53, overall survival log-rank). There was a significantly higher incidence of study drug discontinuation in patients receiving sirolimus (21.1% vs. 10.8%; P=0.008). Renal function was significantly better in the MMF-treatment group (serum creatinine 1.44+/-0.45 mg/dL vs. 1.77+/-1.42 mg/dL; P=0.018). Hyperlipidemia was significantly more prevalent in the sirolimus-treatment group. Diastolic blood pressure was significantly higher in sirolimus-treated patients. There were significantly more leukopenia and gastrointestinal adverse events in the MMF-treatment group. The incidence of posttransplant diabetes mellitus was 7.6% in the sirolimus group and 7.7% in the MMF group. Tacrolimus is equally effective in renal transplantation when combined with sirolimus or MMF. The tacrolimus-MMF combination may be superior in terms of improved renal function and improved cardiovascular risk factors including hyperlipidemia and hypertension.\nStudy3: A single-center open label randomized trial of the safety and efficacy of the use of sirolimus versus azathioprine in one-haplotype living related kidney transplant recipients-preliminary results. nan\n", + "output": "Conclusions: TOR-I have been evaluated in four different primary immunosuppressive algorithms; as replacement for CNI and for antimetabolites, in combination with CNI at low and high dose and with variable dose of CNI. Generally, surrogate endpoints for graft survival favour TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust RCTs are still needed." + }, + { + "input": "Study1: The use of cold compression dressings after total knee replacement: a randomized controlled trial. This prospective, controlled study compared cold compressive dressings with wool and crepe in the postoperative management of patients undergoing total knee replacement (TKR). Forty TKR patients were assessed for blood loss, pain, swelling, and range of motion. Patients in the cold compression group had less blood loss through suction drainage (982 mL versus 768 mL). A higher proportion of patients in the treatment group did not require blood transfusion postoperatively. Mean opiate requirements were lower in the cold compression group (0.57 versus 0.71 mg/kg/48 hours). The cold compression device appeared to reduce blood loss and pain following TKR.\nStudy2: Continuous-flow cold therapy after total knee arthroplasty. Cryotherapy is widely used as an emergency treatment of sports trauma and postoperatively especially after anterior cruciate ligament reconstruction. Studies in the literature on the effect of cryotherapy after total knee arthroplasty (TKA) have been limited and controversial. In this prospective study, 60 primary TKAs were done on 30 patients (all staged bilateral TKAs). For every patient, 1 TKA had a continuous-flow cooling device applied over the surgical dressing immediately postoperatively. The other TKA in the same patient (control TKA) was done 6 weeks later and had no cooling device. The study compared the range of motion, the volume of hemovac output and blood loss, visual analog pain score, analgesic consumption, and wound healing in the 2 limbs of the same patient. This study showed that continuous-flow cold therapy is advantageous after TKA because it provides better results in all the areas compared. Copyright 2002, Elsevier Science (USA).\nStudy3: Postoperative cryotherapy after total knee arthroplasty: a prospective study of 86 patients. A study of 86 patients undergoing total knee arthroplasty (TKA) was performed to evaluate the role of cold compression. The patients were treated with cold compression or epidural analgesia for 3 days after TKA. Pain was measured on a visual analog scale, and total consumption of analgesics was recorded. Range of movement (ROM) was recorded before TKA until 3 weeks postoperatively. Weight bearing, blood loss, and time in hospital were recorded. Visual analog scale scores and analgesic consumption were equal in both groups. Range of movement at discharge was 75 degrees in the cold compression group vs 63 degrees in the control group. By 3 weeks' follow-up, ROM was 99 degrees vs 88 degrees. Mean Hb values averaged 120 mmol/L in the cold compression group vs 109 mmol/L in the control group after surgery. Mean time in hospital of patients with cold compression averaged 4.8 days vs 6.2 days in the control group. The study shows that cold compression therapy improves the control of pain and might thus lead to improvement in ROM and shorter hospital stay.\nStudy4: The role of cold compression dressings in the postoperative treatment of total knee arthroplasty. A prospective randomized study was performed to evaluate the role of cold compressive dressings in the postoperative treatment of total knee arthroplasty (TKA). Eighty consecutive unilateral and ten bilateral primary total knee replacements were evaluated in terms of blood loss, pain relief, and range of motion. Patients in the cold compression group demonstrated an average of 548 ml in suction drainage, whereas those in the control group averaged 807 ml. This resulted in an average 3.1 mg hemoglobin drop in the cold compression group and 4.7 mg in the control group. When body habitus and weight were taken into account in the cold compression group, an average total blood loss of 1298 cc was calculated, with 744 ml arising from soft tissue extravasation. The corresponding total blood loss calculated average was 1908 ml in the control group, with 1101 ml attributed to soft tissue extravasation. Total injectable morphine per kilogram per initial 48 hours averaged 0.53 mg in the cold compression patients and 0.69 mg in the control patients. In the cold compression knees, range of motion averaged 86 degrees before operation, 53 degrees on postoperative day (POD) 7, and 77 degrees on POD 14. In the control knees, range of motion averaged 88 degrees before operation, 44 degrees on POD 7, and 65 degrees on POD 14. The use of cold compression in the postoperative period of TKA results in a dramatic decrease in blood loss. In addition, mild improvements are seen in early return of motion and injectable narcotic pain needs in the postoperative period.\nStudy5: Cryotherapy temperature differences after total knee arthroplasty: a prospective randomized trial. In spite of its widespread use after orthopaedic procedures, the literature evaluating the clinical efficacy of cryotherapy is controversial. The purpose of this prospective randomized trial was to compare two different temperatures for administering cryotherapy after total knee arthroplasty with regards to short-term postoperative outcomes. Sixty-four subjects were assigned either the 45 degrees F group or the 75 degrees F group. Subjects in the 45 degrees group were as likely to report a lower pain score at the time of follow-up compared to the 75 degrees group. Our results demonstrate no additional analgesic effect associated with the lower temperature of cryotherapy. Postoperative narcotic consumption, postoperative drainage, self-reported knee function, and range of motion were not affected by the different cryotherapy temperatures. No adverse effects were reported with the cryotherapy treatment.\nStudy6: The effect of cold therapy on the postoperative course of total hip and knee arthroplasty patients. Fifty total hip arthroplasty (THA) patients and 24 total knee arthroplasty (TKA) patients were randomized in a controlled study to examine the effects of cold therapy (via thermal blankets) in the postoperative period. The postoperative hospital stay was significantly shorter for the cold-therapy (50 degrees F) compared with control (70 degrees F) groups (by 1.4 days, P = 0.03) for THA patients. There was a similar but nonsignificant trend observed in the TKA groups (1.5 days shorter, P = 0.19). Total knee arthroplasty patients using cold therapy achieved independent ambulation an average of 1 day sooner than TKA control patients, but this difference did not reach statistical significance (P = 0.08). There were no statistically significant differences between the control groups or the test groups for both THA and TKA patients in narcotic usage, postoperative range-of-motion (ROM), or rate of progression of ROM.\nStudy7: Cold compressive dressing after total knee arthroplasty. The efficacy of a cold compressive dressing after total knee arthroplasty (TKA) was prospectively studied in 105 knees in 76 patients. All components were cemented. All patients were placed in continuous passive motion machines after operation. A cold compressive Cryocuff dressing was applied to 50 knees after operation. An ACE wrap and ice pack were applied to the knees of 55 control patients after operation. Postoperative range of motion was recorded as maximum active flexion at two to four days (interval one), at seven to 14 days (interval two), and four to six weeks (interval three). Swelling was measured at the same time intervals by circumference at the midpatella and circumference at the distal thigh one inch proximal to the superior pole of the patella. Use of postoperative narcotics was calculated for postoperative days zero to three and for postoperative days four to seven. Wound drainage was recorded for all knees. The use of a cold compressive dressing after TKA was not associated with an increase in range of motion at any point after the operation. The Cryocuff dressing did not appreciably reduce swelling around the knee after TKA. No significant difference was found in the amount of postoperative wound drainage between the two groups of patients. In patients undergoing unilateral TKA, no significant difference existed between the narcotic requirements of control patients and patients wearing the cold compressive dressing.\nStudy8: A randomized, controlled trial comparing compression bandaging and cold therapy in postoperative total knee replacement surgery. To examine the difference between compression bandaging and cold therapy after total knee arthroplasty. Eighty-four postoperative, unilateral, total knee replacement, surgical clients. Clients were randomized into two groups: those receiving compression bandaging, and those receiving cryo-pad technology. Subjects were assessed for total length of stay, blood loss, blood transfusion, swelling, flexion, pain, and opiate use. Unlike other studies, the results of these data showed no significant differences between groups on the measured outcomes. A simple cost benefit analysis shows that the compression bandage is cheaper and more labor efficient than the cold therapy as delivered by cryo-pad technology.\nStudy9: Cryotherapy for postoperative pain relief following knee arthroplasty. Ninety consecutive patients undergoing primary knee arthroplasty received local cryotherapy 72 hours after surgery for pain relief. Thermal-pad circulating temperatures were randomly assigned to 50 degrees, 60 degrees, or 70 degrees F (room temperature). Pain relief was monitored using patient-controlled analgesia machines. The amount of morphine received and number of attempts per hour were statistically analyzed with relation to temperature group, age, sex, weight, side, and diagnosis. The amount of morphine injected was positively correlated to the number of attempts per hour and moderately correlated to body weight. There was no correlation between thermal-pad temperature or any other parameter and the amount of morphine injected after surgery.\nStudy10: [Cryotherapy as analgesic technique in direct, postoperative treatment following elective joint replacement]. The application of crushed ice or hydrogenated silicate, a micro-crystalline substitute has been used as a method to treat posttraumatic and postoperative irritations of the locomotor system for a long time. Closed systems using pumps can be viewed as further development as they enable continuous, water-free cooling of operating areas. The analgetic effect of postoperative cold therapy was evaluated in a prospective clinical trial, including 312 patients after total knee or hip arthroplasty. Conventional cold packs, consisting of microcrystalline silicate were compared to a continuous applicable closed system. Continuous cryotherapy resulted in a depression of skin temperature to 12 degrees C, whereas intermittent cooling only caused a mean temperature decrease of 1 degree C. Clinically continuous cold application leads to a more than 50% decrease of analgetic demands in both, systemic and regional application (p < 0.001). This observation was found in a significant correlation with patient's pain sensation as well as primary range of motion. Intermittent cryotherapy was found to be ineffective in postoperative pain relieve in hip- and adequate in knee arthroplasty patients. We could not report an influence on postoperative blood loss, as discussed in previous reports.\n", + "output": "Conclusions: Potential benefits of cryotherapy on blood loss, postoperative pain, and range of motion may be too small to justify its use, and the quality of the evidence was very low or low for all main outcomes. This needs to be balanced against potential inconveniences and expenses of using cryotherapy. Well designed randomised trials are required to improve the quality of the evidence." + }, + { + "input": "Study1: Helicopters and the civilian trauma system: national utilization patterns demonstrate improved outcomes after traumatic injury. The role of helicopter transport (HT) in civilian trauma care remains controversial. The objective of this study was to compare patient outcomes after transport from the scene of injury by HT and ground transport using a national patient sample. Patients transported from the scene of injury by HT or ground transport in 2007 were identified using the National Trauma Databank version 8. Injury severity, utilization of hospital resources, and outcomes were compared. Stepwise logistic regression was used to determine whether transport modality was a predictor of survival or discharge to home after adjusting for covariates. There were 258,387 patients transported by helicopter (16%) or ground (84%). Mean Injury Severity Score was higher in HT patients (15.9 \u00b1 12.3 vs. 10.2 \u00b1 9.5, p < 0.01), as was the percentage of patients with Injury Severity Score >15 (42.6% vs. 20.8%; odds ratio [OR], 2.83; 95% confidence interval [CI], 2.76-2.89). HT patients had higher rates of intensive care unit admission (43.5% vs. 22.9%; OR, 2.58; 95% CI, 2.53-2.64) and mechanical ventilation (20.8% vs. 7.4%; OR, 3.30; 95% CI, 3.21-3.40). HT was a predictor of survival (OR, 1.22; 95% CI, 1.17-1.27) and discharge to home (OR, 1.05; 95% CI, 1.02-1.07) after adjustment for covariates. Trauma patients transported by helicopter were more severely injured, had longer transport times, and required more hospital resources than those transported by ground. Despite this, HT patients were more likely to survive and were more likely to be discharged home after treatment when compared with those transported by ground. Despite concerns regarding helicopter utilization in the civilian setting, this study shows that HT has merit and impacts outcome.\nStudy2: Influence of prehospital treatment on the outcome of patients with severe blunt traumatic brain injury: a single-centre study. AIM, PATIENTS, AND METHODS: To compare retrospectively the outcomes of patients with severe traumatic brain injury (Injury Severity Score, ISS total >or=15; the Abbreviated ISS-head, aISS(head) >or=9) admitted to our Intensive Care Unit by helicopter (helicopter emergency medical service, HEMS group = 89) with those transported by ambulance (GROUND group = 105) from January 2002 to December 2007. The groups were comparable for age, Glasgow Coma Scale, ISS total, and aISS(head). The preadmission time of the HEMS group was significantly longer as compared with the GROUND group, but the interval from admission to definitive care was significantly shorter. In the prehospital phase, HEMS patients were more aggressively treated, as indicated by a significantly greater number of procedures performed (i.e. tracheal intubation and positioning of intravenous lines) and larger volumes of fluids infused. The overall mortality was lower in the HEMS than in the GROUND patients (21 vs. 25% respectively, P<0.05). The survival with or without only minor neurological disabilities was higher in the HEMS than in the GROUND group (54 vs. 44% respectively, P<0.05); among the survivors, the rate of severe neurological disabilities was lower in the HEMS than in the GROUND group (25 vs. 31%, P<0.05). In our experience, aggressive early treatment of patients with severe traumatic brain injury was associated with a better outcome likely because of the prevention of secondary brain injury and a shorter interval elapsing from the trauma to definitive care despite more time spent on the scene by the intervening team.\n", + "output": "Conclusions: Due to the methodological weakness of the available literature, and the considerable heterogeneity of effects and study methodologies, an accurate composite estimate of the benefit of HEMS could not be determined. Although five of the nine multivariate regression studies indicated improved survival associated with HEMS, the remainder did not. All were subject to a low quality of evidence as assessed by the GRADE Working Group criteria due to their non-randomised design. Similarly, TRISS-based studies, which all demonstrated improved survival, cannot be considered strong evidence because of their methodology, which did not randomize the use of HEMS. The question of which elements of HEMS may be beneficial for patients has not been fully answered. The results from this review provide motivation for future work in this area. This includes an ongoing need for diligent reporting of research methods, which is imperative for transparency and to maximise the potential utility of results. Large, multicentre studies are warranted as these will help produce more robust estimates of treatment effects. Future work in this area should also examine the costs and safety of HEMS, since multiple contextual determinants must be considered when evaluating the effects of HEMS for adults with major trauma." + }, + { + "input": "Study1: Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection. Osteopenia and osteoporosis are frequent complications of HIV infection and/or its treatment. Alendronate is the only bisphosphonate approved for the treatment of osteoporosis in men and women. We conducted a 48-week prospective, randomized, open-label study to evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone mineral density (BMD) in patients with HIV infection. Thirty-one HIV-infected subjects with lumbar spine BMD t-scores less than -1.0 on antiretroviral therapy for a minimum of 6 months were randomized to receive (n = 15) or not to receive (n = 16) 70 mg of alendronate weekly for 48 weeks. All subjects received calcium (1000 mg daily as calcium carbonate) and vitamin D supplementation (400 IU daily). The study was powered to detect 3% changes in BMD in the lumbar spine within arms at 48 weeks. Thirty-one patients were enrolled; most were male, with an average length of HIV infection of 8 years. Eighty-four percent had an HIV RNA load below 400 copies/mL, with a current median CD4+ T-cell count of 561 cells/mm3 (median nadir CD4 cell count of 167 cells/mm). At baseline, the median t-score in the lumbar spine was -1.52 and the median t-score in the hip was -1.02. Alendronate in combination with vitamin D and calcium increased lumbar spine BMD by 5.2% (95% confidence interval [CI]: 1.3-6.4) at 48 weeks compared with an increase of 1.3% (95% CI: -2.4 to 4.0) in subjects receiving vitamin D and calcium alone. One subject discontinued treatment in each arm. There were no serious adverse events. Alendronate, vitamin D, and calcium are safe and potentially useful in the treatment of osteopenia/osteoporosis associated with HIV infection.\nStudy2: Reversal of HIV-1-associated osteoporosis with once-weekly alendronate. HIV-1-infected patients with osteoporosis were randomly assigned to alendronate 70 mg once-weekly plus dietary counselling (n = 11) or diet counselling alone (n = 14). At week 96, 27% of patients on alendronate versus 96% of controls presented with osteoporosis. Spine bone mineral density (BMD) increases were detected at week 48, and progressed thereafter. Improvements in trochanter BMD were obtained after 2 years. Once-weekly oral alendronate may be an effective and safe treatment for HIV-1-associated osteoporosis.\nStudy3: Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis. To evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone metabolism and bone mineral density (BMD) in both HIV-infected men and women treated with highly active antiretroviral therapy (HAART). We performed a 52-week prospective, multicenter, randomized, open-label clinical trial. Eligible participants were on stable HAART and had BMD values at the femoral neck or lumbar spine that corresponded to a t score less than -1. Patients were randomized to receive alendronate 70 mg weekly or no alendronate; calcium 1000 mg daily and vitamin D 500 IU daily were provided to all study recipients. Primary endpoint of the study was the change in bone metabolism evaluated by N-telopeptide of type 1 collagen and bone-specific alkaline phosphatase; the secondary endpoint was BMD variation. 18 patients were randomized to the alendronate and 23 to the no-alendronate group (controls). The alendronate-treatment group compared to controls had a significant decrease in serum N-telopeptides, 1914 +/- 1433.4 vs. 3967 +/- 1650.5 pM/L (p = .005) after 1 year. Lumbar spine BMD increased by 4% in the alendronate group (p = .004) vs. 3.7% (p = .062) in controls, compared to baseline values. Femoral neck BMD decreased by 0.5% in the alendronate group (p = .05) and by 3.5% in the control group (p = .04). No between-groups differences for BMD were found (Delta lumbar-BMD 0.0351 +/- 0.0406 in cases and 0.0356 +/- 0.073 in controls [p = .977], Delta femoral-BMD -0.085 +/- 0.160 in cases and -0.100 +/- 0.165 in controls [p = .795]). Alendronate plus vitamin D and calcium was effective in reducing bone resorption. Alendronate improved lumbar BMD and minimized femoral BMD decrease after 52 weeks compared to treatment with vitamin D and calcium alone in patients on HAART with osteopenia/osteoporosis.\nStudy4: Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome. Multiple endocrine and metabolic consequences of human immunodeficiency virus (HIV) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss >10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23, P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.\n", + "output": "Conclusions: The very limited data reviewed showed that bisphosphonate therapy andin those with AIDS wasting syndrome, testosteronemay be safe and possibly effective methods to improve bone mineral density in HIV patients. The available studies are small, of short duration, and not powered to detect changes in WHO categories and fracture rates.\nLarger studies using bisphosphonates are currently underway. The role of colecalciferol, androgen replacement in women, and growth hormone are also under investigation." + }, + { + "input": "Study: Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer. This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure. There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m(2); P =.55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (-8.59 v 1.85 g/cm(2); P =.033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P =.11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P =.0003) and fatigue (10% v 0%; P =.013). Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.\n", + "output": "Conclusions: For the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction, only one RCT is available. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side-effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity.\nFor the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity, only one RCT is available. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatment on echocardiographic function and clinical outcomes.\nWe did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors.\nHigh-quality studies should be performed." + }, + { + "input": "Study1: Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection. The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months. Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor. For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.\nStudy2: Nitrofurantoin versus trimethoprim prophylaxis in recurrent urinary tract infection in children. A randomized, double-blind study. The efficiency of nitrofurantoin and trimethoprim prophylaxis in preventing recurrent urinary tract infections (UTI) was compared by means of actuarial percentage recurrence-free curves in a randomized, double blind study in 130 children (126 girls, 4 boys) aged 1 to 14 years (mean 7.5). The children received the antibiotics for 6 months. Nitrofurantoin proved to be the most efficient prophylactic drug in patients with abnormal urography and/or reflux (n = 60) as evaluated by actuarial percentage recurrence-free analysis (p = 0.0025). However, no differences was found in patients without urinary tract abnormalities. Nitrofurantoin prophylaxis altered neither the pattern of resistance nor the bacteriological constellation, while patients receiving trimethoprim prophylaxis had 76% trimethoprim resistant bacteria during prophylaxis, compared with 8% before (p less than 0.0001) and 17% after (p less than 0.0001) prophylaxis. The percentage of recurrences due to E. coli (70-80%) was unaffected by trimethoprim prophylaxis, but the proportion due to trimethoprim resistant E. coli was significantly higher during prophylaxis (65%) than before (6%, p less than 0.0001) and after (11%, p less than 0.001). The percentage of Staphylococcus epidermidis UTI was significantly higher during trimethoprim prophylaxis (27%) than before (2%, p less than 0.0003). Following prophylaxis there was no difference in the actuarial percentage recurrence-free curves of the two regimens. Side effects occurred more frequently in the nitrofurantoin group (37%) than in the trimethoprim group (21%) (p = 0.05). The majority of side effects in the nitrofurantoin group derived from gastrointestinal symptoms. In conclusion, nitrofurantoin is recommended as the first choice prophylactic treatment of children with recurrent UTI and urinary tract abnormalities.\nStudy3: Antibiotic prophylaxis and recurrent urinary tract infection in children. Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children. We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data. From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions). Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.) 2009 Massachusetts Medical Society\nStudy4: [Prophylaxis of recurrent urinary tract infections in children. Results of an open, controlled and randomized study about the efficacy and tolerance of cefixime compared to nitrofurantoin]. Urinary tract infections are quite frequent in children. Urinary tract obstruction combined with recurrent urinary tract infections increase the risk for renal impairment. Therefore prophylaxis of reinfection is an important nephroprotective procedure. The aim of this open, controlled, randomised pilot study was to compare the efficacy and tolerance of a low dose prophylaxis with Cefixime versus Nitrofurantoin. 60 girls aged 1 to 11 years with at least 2 urinary tract infections within the preceding year were included in the study. The minimum duration of therapy was 6 months and was extended to 12 months for most of the children. The number of recurrent infections was the main criteria for efficacy evaluation, whereas adverse events were analysed to evaluate tolerance. Statistical significant differences between the two treatment groups, regarding recurrence rates could not be demonstrated. Tolerance was comparable in both groups. The influence on gut flora of cefixime given as a low dose regimen over a long period of time corresponds with already published results and was not correlated with a higher number of gastrointestinal side effects. Low-dose Cefixime (2 mg/kg bodyweight) is effective and well tolerated in the prophylaxis of recurrent urinary tract infections. Efficacy and tolerance of cefixime were comparable to the results obtained with nitrofurantoin. Due to the small number of patients this study was only a pilot study. Low-dose cefixime, however, could become an alternative to standard regimens in the prophylaxis of recurrent urinary tract infections. This should be investigated in further studies.\nStudy5: Prevention of recurrent urinary tract infections in girls. Eighteen girls between the ages of 3 and 13 years--with a history of at least three culture-documented episodes of bacteriuria in the previous year, but without radiologic evidence of major urinary tract abnormality--were placed on a double-blind, crossover study comparing the effectiveness of nitrofurantoin macrocrystals against a placebo in preventing the recurrence of bacteriuria. Each child was placed on a daily low dose of nitrofurantoin (1.2 to 2.4 mg/kg/day) or an identical-appearing placebo for six months. Each child was then placed on the opposite capsule for a similar period. There were 35 episodes of bacteriuria (4.2 episodes/patient/yr) in the patients taking the placebo, which compared with a rate of 3.8 episodes/patient/yr during the year prior to the study. Only two episodes (0.2 episodes/patient/yr) occurred in the patients taking the drug. The difference in the rate of recurrent bacteriuria between the girls on placebo and on medication is significant at the 0.01 level using the Wilcoxin matched-pairs test. There were no adverse reactions to the drug. Nitrofurantoin macrocrystals in a single daily low dose appear to be a safe, effective method of preventing recurrent bacteriuria in girls at high risk.\nStudy6: Controlled trial of prophylactic treatment in childhood urinary-tract infection. nan\nStudy7: [Long-term Cefadroxil prophylaxis in children with recurrent urinary tract infections]. The aim of the study was to evaluate the efficacy and safety of low-dose, long-term cefadroxil prophylaxis in preventing recurrent urinary tract infections in children. A prospective, randomized trial in 33 children (32 female, 1 male) aged 2-14 years (mean 8.1+/-2.8) was conducted. Children with recurrent urinary tract infections were commenced to six-month prophylaxis with cefadroxil at the dosage of 12.5-15.0 mg/kg at bedtime administered every night (group I, n=15) or alternate night (group II, n=18). Escherichia coli was the most frequently isolated agent (90.9%), followed by Proteus mirabilis (3.0%) and Klebsiella oxytoca (3.0%) and Staphylococcus epidermidis (3.0%). Cefadroxil prophylaxis was effective in 80% of patients in group I and in 78% patients in group II. Reinfection occurred in 3/15 (20%) patients in-group I and in 4/18 (22.2%) patients in-group II (odds ratio--1.14; 95% confidence interval--0.16-8.3). The difference of reinfection rate between the groups was not significant (p=0.88). The rate of day- and night-time wetting in both groups before prophylaxis of urinary tract infections was high. It decreased significantly at the end of prophylactic treatment with cefadroxil (from 42.4% to 9.1% and from 39.4% to 6.1% respectively). Mild adverse reaction (nausea) was observed in 1/33 patient. In conclusion our study shows that cefadroxil is an effective, well-tolerated and safe agent in the urinary tract infections prophylaxis. Prophylaxis of recurrent urinary tract infections in children with cefadroxil on alternate night regimen might reduce the cost of the treatment.\n", + "output": "Conclusions: Long-term antibiotics appear to reduce the risk of repeat symptomatic UTI in susceptible children but the benefit is small and must be considered together with the increased risk of microbial resistance." + }, + { + "input": "Study1: Being controlled by normative influences: self-determination as a moderator of a normative feedback alcohol intervention. The objectives of this research were to evaluate the efficacy of computer-delivered personalized normative feedback among heavy drinking college students and to evaluate controlled orientation as a moderator of intervention efficacy. Participants (N = 217) included primarily freshman and sophomore, heavy drinking students who were randomly assigned to receive or not to receive personalized normative feedback immediately following baseline assessment. Perceived norms, number of drinks per week, and alcohol-related problems were the main outcome measures. Controlled orientation was specified as a moderator. At 2-month follow-up, students who received normative feedback reported drinking fewer drinks per week than did students who did not receive feedback, and this reduction was mediated by changes in perceived norms. The intervention also reduced alcohol-related negative consequences among students who were higher in controlled orientation. These results provide further support for computer-delivered personalized normative feedback as an empirically supported brief intervention for heavy drinking college students, and they enhance the understanding of why and for whom normative feedback is effective.\nStudy2: Screening and brief intervention for high-risk college student drinkers: results from a 2-year follow-up assessment. This randomized controlled trial evaluated the efficacy of a brief intervention designed to reduce the harmful consequences of heavy drinking among high-risk college students. Students screened for risk while in their senior year of high school (188 women and 160 men) were randomly assigned to receive an individualized motivational brief intervention in their freshman year of college or to a no-treatment control condition. A normative group selected from the entire screening pool provided a natural history comparison. Follow-up assessments over a 2-year period showed significant reductions in both drinking rates and harmful consequences, favoring students receiving the intervention. Although high-risk students continued to experience more alcohol problems than the natural history comparison group over the 2-year period, most showed a decline in problems over time, suggesting a developmental maturational effect.\nStudy3: Two brief alcohol interventions for mandated college students. Encouraging but limited research indicates that brief motivational interventions may be an effective way to reduce heavy episodic drinking in college students. At 2 campuses, students (83% male) mandated to a substance use prevention program were randomly assigned to 1 of 2 individually administered conditions: (a) a brief motivational interview (BMI; n = 34) or (b) an alcohol education session (AE; n = 30). Students in the BMI condition reported fewer alcohol-related problems than the AE students at 3-and 6-month assessments. Trends toward reductions in number of binge drinking episodes and typical blood alcohol levels were seen in both groups. Process measures confirmed the integrity of both interventions. The findings demonstrate that mandated BMIs can reduce alcohol problems in students referred for alcohol violations. ((c) 2005 APA, all rights reserved).\nStudy4: Indicated prevention for incoming freshmen: personalized normative feedback and high-risk drinking. This research evaluated the efficacy of a computerized, freshmen-specific personalized normative feedback (PNF) intervention on reducing alcohol consumption among high-risk drinking freshmen. Students (N=316; 53.8% female) completed measures of perceived drinking norms and drinking behavior. After completing the baseline assessment, students were randomly assigned to receive either freshmen-specific PNF that was gender-specific or gender-neutral, or to assessment only control. Findings demonstrated that students exhibited normative misperceptions for typical freshmen drinking behavior and that perceptions of typical same-sex freshmen drinking were positively associated with riskier drinking behavior. At follow-up, students randomly assigned to receive PNF reduced perceptions of typical freshmen drinking behavior and personal drinking behavior relative to those who did not receive PNF. Findings extend previous evaluations of computer-based PNF and suggest that computer-based PNF for incoming freshmen utilizing freshmen-specific norms that are gender-specific may constitute a promising prevention strategy.\nStudy5: Randomized controlled trial of a web-based primary care intervention for multiple health risk behaviors. Physical inactivity, low fruit and vegetable intake, hazardous drinking, and smoking are leading risk factors for disease and injury. The aim of this study was to obtain estimates of efficacy in reducing the first three of these behaviors. The design was a randomized controlled trial: 218 patients (17-24 years) attending a student health service at a New Zealand university in 2003 were assigned to: (A) web-based assessment and personalized feedback (n = 72); or (B) assessment only (n = 74); or (C) minimal contact (n = 72). Outcome measures were the proportion meeting recommendations for fruit and vegetable consumption, physical activity, and alcohol consumption 6 weeks later. Follow-up assessments were attained for 86% of participants, with no evidence of differential attrition. There were significant differences in the proportion meeting recommendations for fruit and vegetable consumption and physical activity in group A relative to C. Hazardous drinking prevalence did not vary significantly by group. Differences appear attributable to the intervention. The intervention could be routinely provided in primary care, and its efficacy could be assessed in a large randomized controlled trial.\nStudy6: Randomized controlled trial of web-based alcohol screening and brief intervention in primary care. There is compelling evidence supporting screening and brief intervention (SBI) for hazardous drinking, yet it remains underused in primary health care. Electronic (computer or Web-based) SBI (e-SBI) offers the prospects of ease and economy of access. We sought to determine whether e-SBI reduces hazardous drinking. We conducted a randomized controlled trial in a university primary health care service. Participants were 975 students (age range, 17-29 years) screened using the Alcohol Use Disorders Identification Test (AUDIT). Of 599 students who scored in the hazardous or harmful range, 576 (300 of whom were women) consented to the trial and were randomized to receive an information pamphlet (control group), a Web-based motivational intervention (single-dose e-SBI group), or a Web-based motivational intervention with further interventions 1 and 6 months later (multidose e-SBI group). Relative to the control group, the single-dose e-SBI group at 6 months reported a lower frequency of drinking (rate ratio [RR], 0.79; 95% confidence interval [CI], 0.68-0.94), less total consumption (RR, 0.77; 95% CI, 0.63-0.95), and fewer academic problems (RR, 0.76; 95% CI, 0.64-0.91). At 12 months, statistically significant differences in total consumption (RR, 0.77; 95% CI, 0.63-0.95 [equivalent to 3.5 standard drinks per week]) and in academic problems (RR, 0.80; 95% CI, 0.66-0.97) remained, and the AUDIT scores were 2.17 (95% CI, -1.10 to -3.24) points lower. Relative to the control group, the multidose e-SBI group at 6 months reported a lower frequency of drinking (RR, 0.85; 95% CI, 0.73-0.98), less total consumption (RR, 0.79; 95% CI, 0.64-0.97 [equivalent to 3.0 standard drinks per week]), reduced episodic heavy drinking (RR, 0.65; 95% CI, 0.45-0.93), and fewer academic problems (RR, 0.78; 95% CI, 0.65-0.93). At 12 months, statistically significant differences in academic problems remained (RR, 0.75; 95% CI, 0.62-0.90), while the AUDIT scores were 2.02 (95% CI, -0.97 to -3.10) points lower. Single-dose e-SBI reduces hazardous drinking, and the effect lasts 12 months. Additional sessions seem not to enhance the effect. Trial Registration www.anzctr.org.au Identifier:ACTRN012607000103460.\nStudy7: Effects of a brief motivational intervention with college student drinkers. This study consisted of a randomized controlled trial of a 1-session motivational intervention for college student binge drinkers. Sixty students who reported binge drinking 2 or more times in the past 30 days were randomly assigned to either a no-treatment control or a brief intervention group. The intervention provided students with feedback regarding personal consumption, perceived drinking norms, alcohol-related problems, situations associated with heavy drinking, and alcohol expectancies. At 6-week follow-up, the brief intervention group exhibited significant reductions on number of drinks consumed per week, number of times drinking alcohol in the past month, and frequency of binge drinking in the past month. Estimates of typical student drinking mediated these reductions. This study replicates earlier research on the efficacy of brief interventions with college students and extends previous work regarding potential mechanisms of change.\nStudy8: A controlled trial of web-based feedback for heavy drinking college students. Alcohol consumption has been a growing concern at U.S. colleges, particularly among first-year students, who are at increased risk for problems. This study tested the efficacy of the \"electronic Check-Up to Go\" (e-CHUG), a commercially-available internet program, at reducing drinking among a group of at-risk college freshman. The design was a randomized controlled trial: 106 freshmen students who reported heavy episodic drinking were randomly assigned to receive feedback or to assessment only. Assessment measures were completed at baseline, 8 weeks, and 16 weeks. At 8 weeks, the feedback group showed a significant decrease in drinks per week and peak BAC over control. By 16 weeks, the control group also declined to a point where there were no differences between groups. Changes in normative drinking estimates mediated the effect of the intervention. An additional 245 abstainers and light drinkers who were also randomized to condition did not show any intervention effect. This study provides preliminary support for the efficacy of this intervention at reducing short-term drinking among at-risk students.\n", + "output": "Conclusions: WF and IFF are probably effective in reducing alcohol misuse. No direct comparisons of WF against IFF were found, but WF impacted across a broader set of outcomes and is less costly so therefore might be preferred. Significant effects were more apparent for short-term outcomes (up to three months). For mailed and group feedback, and social norms marketing campaigns, the results are on the whole not significant and therefore cannot be recommended." + }, + { + "input": "Study1: [Variation of weigth among users of the contraceptive with depot-medroxyprogesterone acetate according to body mass index in a six-year follow-up]. To determine weight variation in women with different Body Mass Index (BMI) in use of trimestral injections of depot-medroxyprogesterone acetate (DMPA), and compare it to women users of a non-hormonal method. Retrospective study with the chart review of 226 DMPA users and 603 controls, users of DIU TCu380A. Women were distributed in categories, according to their initial BMI, as having normal weight (<25 kg/m(2)), overweight (25 to 29,9 kg/m(2)) and being obese (>or=30 kg/m(2)), and were followed-up for six years, with yearly measurements of weight and BMI. The statistic test ANOVA was used to measure the weight variation among the groups in each BMI category every year. The average age at the onset of the method employed was higher in the study group than in the controls, in all the BMI categories: 31.6+/-SD 7.1 X 27.4+/-SD 5.5 in the normal weight category (p<0.0001); 37.3+/-SD 6.8 X 29.2+/-SD 6.0 in the overweight category (p<0.0001); and 35.3+/-SD 6.4 X 29.7+/-SD 5.8 among obese women (p<0.0001). DMPA users showed weight increase as compared to the controls in the overweight category (p=0.0082); and the weight increase along the observation period was also higher among the DMPA users than among the controls, for the normal weight (p<0.0001) and overweight (p=0.0008) categories. In the obese group, there was no BMI variation between the groups, nor along the period during which they were using the method. There was no change in weight gain among DMPA users from the obese category. Prospective studies should be done with metabolic tests to establish the determining factors of weight gain in normal and overweight women.\nStudy2: A longitudinal comparison of body composition changes in adolescent girls receiving hormonal contraception. The objective of this study was to examine body composition changes in adolescent girls initiating depot medroxyprogesterone acetate (DMPA), oral contraceptives, or no hormonal contraceptive method. At 6 months, DMPA resulted in significant increases in adiposity with concomitant decreases in lean body mass. Supplemental estrogen may lessen these DMPA effects.\nStudy3: The performance of levonorgestrel rod and Norplant contraceptive implants: a 5 year randomized study. A new contraceptive (LNG rod implants, Jadelle, Leiras Oy's registered trademark for rod implants) was prospectively evaluated in randomized 5 year comparison with Norplant (Population Council's registered trademark for contraceptive implants releasing levonorgestrel) capsule implants. The study involved 1198 women at seven centres. No pregnancies occurred in the first 4 years. At 5 years, the cumulative pregnancy rate was 1 per 100 users or less for each regimen. Annual discontinuation rates averaged 11-12 per 100 users (P > 0.05), corresponding to 5 year continuation rates of 55.1 for rods and 53.0 per 100 for capsules. Mean annual discontinuation rates for menstrual disturbances were 3.5 and 4.2 per 100 for rod and capsule implants respectively (P > 0.05), and mean annual removal rates for medical problems were 3.5 and 3.0 per 100 (P > 0.05) respectively. Apart from menstrual problems, headache, weight gain and acne were the principal medical reasons for removal. In proportional hazard analyses, family formation variables, age, parity and desire/non desire for another child, recorded at admission, significantly affected discontinuation rates for major decrement categories and for all reasons combined. Mean rod removal time was half that of Norplant (P < 0.01); complications of rod removal were at a lower rate. With these contraceptives indistinguishable in performance except for ease and speed of removal, LNG rod implants appear to be preferable to Norplant for use through 5 years by virtue of relative ease of removal.\nStudy4: A study of glucose tolerance, serum transaminase and lipids in women using depot-medroxyprogesterone acetate and a combination-type oral contraceptive. nan\nStudy5: Contraceptive efficacy and safety of DMPA-SC. DMPA-SC 104 mg/0.65 mL is a new, low-dose subcutaneous (SC) formulation of Depo-Provera contraceptive injection (150 mg/mL medroxyprogesterone acetate injectable suspension) that provides efficacy, safety and immediacy of onset equivalent to Depo-Provera intramuscular (IM) injection. Two large, open-label, Phase 3 studies assessed the 1-year contraceptive efficacy, safety and patient satisfaction with DMPA-SC administered every 3 months (12-13 weeks). Zero pregnancies were reported in both studies, which included a total of 16,023 woman-cycles of exposure to DMPA-SC and substantial numbers of overweight or obese women. DMPA-SC was well-tolerated and adverse events were similar to those reported previously with Depo-Provera IM. Thus, DMPA-SC offers women a new, highly effective and convenient long-acting contraceptive option. Copyright 2004 Elsevier Inc.\nStudy6: Weight changes in clients on hormonal contraceptives in Zaria, Nigeria. Misconceptions exist in Nigeria about the effects of hormonal contraceptives on weight, which may have negative effects on contraceptive use. Data from case notes of clients attending the reproductive health centre at the Ahmadu Bello University Teaching Hospital, Zaria, between 1993 and 1995, were analysed to determine the effects of hormonal contraceptives on body weight, comparing them to clients using intrauterine contraceptive devices. Weight changes were not significantly different in clients using hormonal contraceptives and those using intrauterine contraceptive devices. This information will be beneficial in contraceptive counselling for clients in this environment and provide a baseline for further research.\nStudy7: A comparative study of one-year weight gain among users of medroxyprogesterone acetate, levonorgestrel implants, and oral contraceptives. With the recent introduction and growing popularity of Depo-Provera Contraceptive Injection, concern about the potential for weight gain during treatment has been raised. The purpose of the present study was to determine whether or not Depo-Provera Contraceptive Injection is associated with greater weight gain, and incidence thereof, than Norplant implants or oral contraceptives. A retrospective chart review of patients seen at a state- and federally-funded clinic was conducted. Fifty women in each treatment group who met the study criteria were identified and included in the study evaluation. Mean one-year weight gain for subjects in each group was as follows: -2.0 pounds in the oral contraceptive group, -1.8 pounds in the Norplant implants group, and +0.1 pounds in the Depo-Provera Contraceptive Injection group. While results among treatment groups differed slightly, no significant weight change occurred in any of the treatment groups.\nStudy8: Efficacy and acceptability of injectable medroxyprogesterone. A comparison of 3-monthly and 6-monthly regimens. Five hundred Black Rhodesian women given injections of 150 mg Depo-Provera every 3 months (group A) and 500 women given an injection of 450 mg Depo-Provera every 6 months (group B) were reviewed after 6 months. Group B had a significantly lower rate of defaulters. There was no significant difference between the groups with regard to weight gain, systolic and diastolic blood pressure increase, overall abnormal bleeding patterns and complaints of side-effects. Among those women who reported abnormal bleeding patterns, significantly more in group B had amenorrhoea. There was no significant increase of prolonged bleeding in group B. Among those women who complained of side-effects, significantly more in group B complained of headaches and a bloated abdomen. No pregnancies occurred in either group. The increased annual cost of the 450 mg injections, which was the main reason for women not accepting this regimen, is outweighed by convenience and reduced travel costs. Depo-Provera 450 mg given by 6-monthly injection is well tolerated and effective, and appears to be even more satisfactory as regards continued acceptance than 150 mg given every 3 months.\nStudy9: Body weight and composition in users of levonorgestrel-releasing intrauterine system. There is little information about body weight and body composition (BC) among users of the levonorgestrel-releasing intrauterine system (LNG-IUS). The aim of this study was to evaluate body weight and BC in LNG-IUS users compared to users of the TCu380A intrauterine device (IUD). A prospective study was done with 76 new users of both contraceptive methods. Women were paired by age (\u00b12 years) and body mass index (BMI, kg/m\u00b2, \u00b12). Body weight and BC (% lean mass and % fat mass) were evaluated by a trained professional at baseline and at 1 year of contraceptive use. The BC measurements were obtained using Lunar DXA equipment. Weight and BC were evaluated in each woman at baseline and at 12 months and analyzed as the mean change within each woman. Then, the changes in weight and BC for each woman were calculated and then compared between LNG-IUS and TCu380A IUD users (paired data for each woman). The central-to-peripheral fat ratio was calculated by dividing trunk fat by the upper and lower limb fat. There were no significant differences at time of IUD insertion between LNG-IUS and TCu380A IUD users regarding age (mean\u00b1SD) (34.4\u00b17.5 vs. 33.9\u00b18.0 years), BMI (25.3\u00b14.1 vs. 25.9\u00b14.1) and number of pregnancies (1.9\u00b10.2 vs. 1.7\u00b10.2), respectively. Mean body weight gain of 2.9 kg was observed among LNG-IUS users at 12 months (p=.0012), whereas the body weight of TCu380A IUD users only increased by 1.4 kg (p=.067). There was no significant difference in body weight change between the two groups of users at 12 months. The variation in the central-to-peripheral fat ratio was the same between the two groups (-1.6% vs. -0.2%; p=.364). LNG-IUS users showed a 2.5% gain in fat mass (p=.0009) and a 1.4% loss of lean mass, whereas TCu380A IUD users showed a loss of 1.3% of fat mass (p=.159) and gain of 1.0% of lean mass (p=.120). TCu380A IUD users gained more lean mass than LNG-IUS users (p=.0270), although there was no significant difference between the two groups after 12 months of use. Although an increase in mean fat mass among LNG-IUS users at 12 months of use was observed, it should be noted that an increase of body weight was also observed in both groups after 1 year of insertion of the device. However, a study with a larger number of women and long-term evaluation is necessary to evaluate these body changes. Copyright \u00a9 2012 Elsevier Inc. All rights reserved.\nStudy10: Adolescent use of the monthly contraceptive injection. To compare weight and continuation among adolescents using monthly medroxyprogesterone acetate (MPA)/ethinyl estradiol cypionate (E2C), tri-monthly depot MPA (DMPA), and daily oral contraceptive pills (OCP). Medical records were reviewed for body mass index, demographics, and sexual history at baseline; and weight and continuation at 3, 6, 9, and 12 months. Bivariate analyses were performed by method, and continuation functions were compared by the log-rank and Wilcoxon tests. The effect of method on use duration was assessed by Cox regression. Hospital adolescent clinic. 12- to 21-year-old patients who initiated MPA/E2C, DMPA, or OCPs in 2001. Weight gain and method continuation. MPA/E2C was initiated by 40 (18%) patients, DMPA by 63 (28%), and OCPs by 119 (54%, P < 0.001). OCP users were younger (P = 0.005) and more likely to be white, privately insured, and in school (P < 0.004) than MPA/E2C or DMPA users. Previous DMPA and OCP use, pregnancy, and sexually transmitted infections (STI) were more common among MPA/E2C than DMPA or OCP users (P < or = 0.001). Baseline BMI was lowest (P = 0.06) among DMPA users, and MPA/E2C users were most likely to be overweight (P = 0.03). There were non-significant differences in weight change. Continuation functions differed by the method only in the first three months of use (P = 0.03). Leading reasons for discontinuation were unavailability of MPA/E2C (20%), bleeding with DMPA (22%), and forgetting OCPs (17%). Duration of use was independently associated with white race (P < 0.005) and STI-never (P < 0.0001) but not with method type. Although MPA/E2C use was associated with overweight status and early discontinuation, it also was associated with previous use of other methods. For all methods, poor continuation at one year supports the ongoing search for effective contraceptive alternatives.\n", + "output": "Conclusions: The overall quality of evidence was moderate to low, given that the studies were evenly divided across the evidence quality groups (high, moderate, low, or very low quality). We found limited evidence of weight gain when using POCs. Mean gain was less than 2 kg for most studies up to 12 months. Weight change for the POC group generally did not differ significantly from that of the comparison group using another contraceptive. Two studies that assessed body composition showed that POC users had greater increases in body fat and decreases in lean body mass compared to users of non-hormonal methods. Appropriate counseling about typical weight gain may help reduce discontinuation of contraceptives due to perceptions of weight gain." + }, + { + "input": "Study1: Rivastigmine for dementia associated with Parkinson's disease. Cholinergic deficits are prominent in patients who have dementia associated with Parkinson's disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients. Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimer's Disease Cooperative Study-Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini-Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test. A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer's disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P<0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group, and clinically meaningful worsening was observed in 13.0 percent and 23.1 percent, respectively (mean score at 24 weeks, 3.8 and 4.3, respectively; P=0.007). Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables. The most frequent adverse events were nausea (affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001), and tremor (10.2 and 3.9 percent, P=0.01). In this placebo-controlled study, rivastigmine was associated with moderate improvements in dementia associated with Parkinson's disease but also with higher rates of nausea, vomiting, and tremor. Copyright 2004 Massachusetts Medical Society.\nStudy2: Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease. To evaluate the efficacy and safety of donepezil, an acetylcholinesterase inhibitor, as a treatment for cognitive impairment and dementia in patients with Parkinson' s disease (PD). Using a randomized, double-blind, placebo-controlled design, nine patients received placebo and seven patients received donepezil (2.5-10 mg/day) for a mean (SD) duration of 15.2 (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory, attention, psychomotor speed, and visuospatial and executive functions. Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings. Primary safety measures were motor signs and assessments of adverse effects. Patients on donepezil showed selective and significant (p<0.05) improvement on the memory subscale of the Dementia Rating Scale. There was also a trend toward improvement on a measure of psychomotor speed and attention. There were no group differences in psychiatric status, motor function, or activities of daily living as measured at baseline or end-point. Adverse effects resulted in premature withdrawal of four patients on donepezil, two for peripheral cholinergic effects and one for increased parkinsonism. Side effects were associated with dosage increases. Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment. However, variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD, especially with dosage increases. Copyright 2004 John Wiley & Sons, Ltd.\n", + "output": "Conclusions: The currently available evidence supports the use of cholinesterase inhibitors in patients with PDD, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales. The effect in DLB remains unclear. There is no current disaggregated evidence to support their use in CIND-PD." + }, + { + "input": "Study1: The effect of brief interventions on alcohol consumption among heavy drinkers in a general hospital setting. (i) To evaluate the effect of receiving one of two brief interventions in reducing alcohol consumption among general hospital patients compared with usual care. (ii) To assess whether a brief intervention of self-efficacy enhancement was superior to a self-help booklet in reducing alcohol consumption. A three-arm cluster randomized controlled trial. Seven general medical, six general surgical, one dermatology and two otolaryngology wards of a large teaching hospital covering a large urban and rural area. A total of 215 of 789 in-patients aged 18-75 years, who screened positive for alcohol consumption in excess of national recommended limits according to a 7-day retrospective drinking diary. Participants were allocated to receive one of three interventions: (i) face-to-face self-efficacy enhancement; (ii) a self-help booklet; or (iii) usual care. The primary outcome measure was change in reported alcohol consumption at 6-month follow-up as measured by a 7-day retrospective drinking diary. Secondary outcomes were change in: number of alcohol drinking days in last week; the maximum units of alcohol consumed on any one day in last week; and Drinking Refusal Self-efficacy Expectancy Questionnaire score. Compared to the usual care group the self-efficacy enhancement group (-10.1 units 95% CI -16.1 to -4.1) and the self-help booklet group (-10.0 units 95% CI -16.0 to -3.9) had greater reductions in self-reported weekly alcohol consumption. There was no evidence that self-efficacy enhancement was superior to the self-help booklet (P = 0.96). Brief interventions delivered in hospital offer simple means of helping heavy drinkers to reduce their alcohol consumption.\nStudy2: Counselling problem drinkers in medical wards: a controlled study. Seven hundred and thirty one men admitted to medical wards were interviewed to identify problem drinkers who had not received previous treatment for alcoholism and who had some social support. One hundred and sixty one met the diagnostic criteria; 156 agreed to a follow up interview and were allocated to one of two groups. One group received a session of counselling about their drinking habits from a nurse while the other received only routine medical care. Both groups reported a reduction in alcohol consumption when interviewed 12 months later, but the counselled group had a significantly better outcome than the control group. It is concluded that systematic screening for alcohol consumption and related problems should become a routine part of medical assessment and that advice on drinking habits is effective if given before irreversible physical or psychosocial problems have developed.\nStudy3: Randomized controlled trial of a brief intervention for unhealthy alcohol use in hospitalized Taiwanese men. To evaluate the effectiveness of a brief intervention in hospitalized Taiwanese men to reduce unhealthy alcohol consumption. Randomized controlled trial. Medical/surgical wards of a medical centre in Taipei, Taiwan. Of 3669 consecutive adult male in-patients, 616 were identified as unhealthy alcohol users (>14 drinks/week) and assigned randomly to either usual care (n = 308) or a brief intervention (n = 308). Primary outcomes were changes in alcohol consumption at 4, 9 and 12 months, including self-reported weekly alcohol consumption, drinking days and heavy drinking episodes assessed by 7-day time-line follow-back. Secondary outcomes were (i) self-reported alcohol problems, (ii) health-care utilization (hospital days and emergency department visits), (iii) self-reported seeking of speciality treatment for alcohol problems and (iv) 3-month Quick Drinking Screen. Based on intention-to-treat analyses, the intervention group consumed significantly less alcohol than the control group among both unhealthy drinkers and the subgroup of alcohol-dependent participants over 12 months, on both 7-day and 3-month assessments. Adjunctive analyses of only those who completed all assessments found that total drinks consumed did not remain significant. Significantly more participants with alcohol use disorders in the intervention than in the control group (8.3%, 19 of 230 versus 2.1%, four of 189) consulted specialists by 12 months (P = 0.01). However, alcohol-related problems and health-care utilization did not differ significantly in the two groups during follow-up. Data from Taiwan confirm that brief in-hospital intervention can result in a reduction in alcohol intake by men who drink heavily or are diagnosed with an alcohol use disorder. \u00a9 2011 The Authors, Addiction \u00a9 2011 Society for the Study of Addiction.\nStudy4: Implementing an effective intervention for problem drinkers on medical wards. Many medical inpatients have alcohol related problems but evidence of the feasibility of instituting a brief intervention is incomplete. An alcohol counsellor trained nurses on five general medical wards to screen patients routinely for alcohol problems. She counselled appropriate patients using one or two counselling sessions. Efficacy of the counselling was assessed at interview six months following the admission. We found that 19.6% of male and 4.8% of female medical patients were drinking more than 50 units (U) or 33 drinks per week (male) or 35 U or 23 drinks per week (female). Counselling, with one or two sessions led to a reduction from a median of 74 U (49 drinks) per week at admission to 26 U (17 drinks) per week at six months follow-up. A second counselling session after discharge showed no advantage over a single one administered while the patient was in the ward. The barriers to developing a successful alcohol screening and counselling service in medical wards can be overcome provided there is also adequate support and training of the ward nursing staff.\nStudy5: Brief intervention for medical inpatients with unhealthy alcohol use: a randomized, controlled trial. The efficacy of brief intervention in reducing alcohol consumption is well established for selected outpatients but not for medical inpatients. To determine whether brief intervention improves alcohol outcomes in medical inpatients who were identified by screening as having unhealthy alcohol use. Randomized, controlled trial. Medical service of an urban hospital. 341 medical inpatients who were drinking risky amounts of alcohol (defined for eligibility as >14 drinks/wk or > or =5 drinks/occasion for men and >11 drinks/wk or > or =4 drinks/occasion for women and persons > or =66 y); 77% had alcohol dependence as determined by the Composite International Diagnostic Interview Alcohol Module. A 30-minute session of motivational counseling given by trained counselors during a patient's hospitalization (n = 172) versus usual care (n = 169). Self-reported primary outcomes were receipt of alcohol assistance (for example, alcohol disorders specialty treatment) by 3 months in dependent drinkers and change in the mean number of drinks per day from enrollment to 12 months in all patients. The intervention was not significantly associated with receipt of alcohol assistance by 3 months among alcohol-dependent patients (adjusted proportions receiving assistance, 49% for the intervention group and 44% for the control group; intervention-control difference, 5% [95% CI, -8% to 19%]) or with drinks per day at 12 months among all patients (adjusted mean decreases, 1.5 for patients who received the intervention and 3.1 for patients who received usual care; adjusted mean group difference, -1.5 [CI, -3.7 to 0.6]). There was no significant interaction between the intervention and alcohol dependence in statistical models predicting drinks per day (P = 0.24). Baseline imbalances existed between randomized groups. Patients who received usual care were assessed and advised that they could discuss their drinking with their physicians. Brief intervention is insufficient for linking medical inpatients with treatment for alcohol dependence and for changing alcohol consumption. Medical inpatients with unhealthy alcohol use require more extensive, tailored alcohol interventions.\nStudy6: Alcohol interventions in a trauma center as a means of reducing the risk of injury recurrence. Alcoholism is the leading risk factor for injury. The authors hypothesized that providing brief alcohol interventions as a routine component of trauma care would significantly reduce alcohol consumption and would decrease the rate of trauma recidivism. This study was a randomized, prospective controlled trial in a level 1 trauma center. Patients were screened using a blood alcohol concentration, gamma glutamyl transpeptidase level, and short Michigan Alcoholism Screening Test (SMAST). Those with positive results were randomized to a brief intervention or control group. Reinjury was detected by a computerized search of emergency department and statewide hospital discharge records, and 6- and 12-month interviews were conducted to assess alcohol use. A total of 2524 patients were screened; 1153 screened positive (46%). Three hundred sixty-six were randomized to the intervention group, and 396 to controls. At 12 months, the intervention group decreased alcohol consumption by 21.8+/-3.7 drinks per week; in the control group, the decrease was 6.7+/-5.8 (p = 0.03). The reduction was most apparent in patients with mild to moderate alcohol problems (SMAST score 3 to 8); they had 21.6+/-4.2 fewer drinks per week, compared to an increase of 2.3+/-8.3 drinks per week in controls (p < 0.01). There was a 47% reduction in injuries requiring either emergency department or trauma center admission (hazard ratio 0.53, 95% confidence interval 0.26 to 1.07, p = 0.07) and a 48% reduction in injuries requiring hospital admission (3 years follow-up). Alcohol interventions are associated with a reduction in alcohol intake and a reduced risk of trauma recidivism. Given the prevalence of alcohol problems in trauma centers, screening, intervention, and counseling for alcohol problems should be routine.\nStudy7: A study of minimal interventions for problem drinkers in acute care settings. This article reports an investigation of three minimal interventions for potential problem drinkers in general hospital wards. The interventions were: (a) brief advice; (b) the provision of health education literature; (c) a combination of both the advice and literature. One year after recruitment the mean levels of alcohol consumption and the number of alcohol-related problems reported by the cohort was significantly reduced. These reductions were supported by reductions in the mean levels of GGT and AST, but not in mean MCV. No statistically significant treatment effects were found. The results are presented and implications for nursing are discussed.\nStudy8: Intervention of heavy drinking--a prospective and controlled study of 438 consecutive injured male patients. We studied 120 injured male patients of working age who were heavy drinkers or alcoholics, obtaining seven points or more in the Michigan Alcoholism Screening Test (MAST). They were randomly allocated either to an intervention group (IG) or to a control group (CG). In addition to the MAST interview, the consumption of alcohol during the previous week prior to hospital admission was calculated and laboratory measures (serum GGT, ASAT and ALAT) were obtained. Counselling of the patients in the IG was carried out by a trained assistant nurse and a physician. Forty-nine patients in IG and 40 patients in CG were re-examined after 6 months. In the IG 45% and in the CG 20% of the patients were improved (Chi square test, P less than 0.05). Improvement criteria were a decrease in alcohol consumption by at least one-third and decrease of S-GGT by at least 20% during the follow-up period. In respect to the laboratory measures the groups were identical at the beginning of the study and after 6 months' follow-up. Our results are encouraging and suggest that the assessment of heavy drinking should be a routine in the treatment of alcohol-related injuries and that education and counselling must be intensive to be effective.\nStudy9: Trauma center brief interventions for alcohol disorders decrease subsequent driving under the influence arrests. A substantial number of trauma center admissions are related to driving under the influence (DUI); however, there has been no prior report of brief intervention (BI) after injury reducing subsequent DUI arrests. The hypothesis of this study was that injured patients receiving BI would have a lower risk of DUI arrest within 3 years of discharge than those receiving standard care (SC). This prospective, randomized clinical trial randomly allocated patients involved in motor vehicle collisions to receive SC or a BI regarding alcohol use. The primary outcome measure was DUI arrest within 3 years of hospital discharge. DUI arrests were documented by matching demographic information to state traffic safety data. After randomization (N = 126), BI and SC groups were similar in age, prior DUI arrests, and alcohol screening score. BI sessions lasted an average of 30 minutes and were performed by either a social worker or a trauma surgeon. Approximately one in six participants (n = 21, 16.7%) had a DUI arrest within 3 years of hospital discharge. Within 3 years of hospital discharge, 14 of 64 patients (21.9%) in the SC group had an arrest for DUI compared with only 7 of 62 patients (11.3%) who received the BI. Multivariate analysis demonstrated that BI was the strongest protective factor against DUI arrest (odds ratio [OR], 0.32; 95% confidence interval < or =CI], 0.11-0.96). Prior number of DUIs (OR, 1.43; 95% CI, 1.03-2.01) and age (OR, 0.94; 95% CI, 0.88-0.99) were also associated with DUI arrest post-hospitalization, but alcohol screening score (OR, 1.06; 95% CI, 0.99-1.13) was not. The absolute risk reduction implies that only nine patients would need to receive a BI to prevent one DUI arrest. Patients who receive BI during a trauma center admission are less likely to be arrested for DUI within 3 years of discharge. BI represents a viable intervention to reduce DUI after trauma center admission.\nStudy10: Effects of brief counselling among male heavy drinkers identified on general hospital wards. Although the prevalence of heavy alcohol consumption among patients of general hospitals is well documented, no study has yet reported an effect of counselling on the ward in reducing the level of consumption among such patients after discharge. This study was designed to evaluate brief counselling to reduce alcohol consumption among male heavy drinkers identified on general hospital wards. Male patients were screened on wards of four teaching hospitals in Sydney, Australia. Identified heavy drinkers (n = 174) showing predominantly low levels of alcohol dependence were allocated to one of two forms of brief counselling (skills-based counselling or brief motivational interviewing) or to a non-intervention control group. Blind follow-up for 123 patients (71%) was carried out approximately 6 months after discharge from hospital and self-reports of alcohol consumption were compared with collateral sources of information. Patients who received counselling showed a significantly greater mean reduction in a quantity-frequency measure of weekly alcohol consumption than controls but there were no significant differences in reduced consumption between the two intervention groups. However, patients who were deemed \"not ready to change\" showed greater reductions if they had received brief motivational interviewing than if they had received skills-based counselling. The implications of these findings for counselling male in-patients to reduce alcohol consumption are discussed.\n", + "output": "Conclusions: The main results of this review indicate that there are benefits to delivering brief interventions to heavy alcohol users admitted to general hospital wards in terms of reduction in alcohol consumption and death rates. However, these findings are based on studies involving mainly male participants. Further research is required determine the optimal content and treatment exposure of brief interventions within general hospital settings and whether they are likely to be more successful in patients with certain characteristics." + }, + { + "input": "Study1: Effects of a stress management program on vital exhaustion and depression in women with coronary heart disease: a randomized controlled intervention study. Psychosocial factors, including depression and vital exhaustion (VE) are associated with adverse outcome in coronary heart disease (CHD). Women with CHD are poor responders to psychosocial treatment and knowledge regarding which treatment modality works in them is limited. This randomized controlled clinical study evaluated the effect of a 1-year stress management program, aimed at reducing symptoms of depression and VE in CHD women. Patients were 247 women, < or =75 years, recruited consecutively after a cardiac event and randomly assigned to either stress management (20 2-h sessions) and medical care by a cardiologist, or to obtaining usual health care as controls. Measurements at; baseline (6-8 weeks after randomization), 10 weeks (after 10 intervention sessions), 1 year (end of intervention) and 1-2 years follow-up. For VE, intention to treat analysis showed effects for time (P < 0.001) and time x treatment interaction (P = 0.005), reflecting that both groups improved over time, and that the decrease of VE was more pronounced in the intervention group. However, the level of VE was higher in the intervention group than amongst controls at baseline, 22.7 vs. 19.4 (P = 0.036) but it did not differ later. The change in depressive symptoms did not differ between the groups. CHD women attending our program experienced a more pronounced decrease in VE than controls. However, as they had higher baseline levels, due to regression towards the mean we cannot attribute the decrease in VE to the intervention. Whether the program has long-term beneficial effects needs to be evaluated.\nStudy2: Behavioral effects of a comprehensive, multifactorial program for lifestyle change after percutaneous transluminal coronary angioplasty: a prospective, randomized controlled study. A group of 93 coronary patients recently treated with percutaneous transluminal coronary angioplasty (PTCA) were randomly assigned to either an intervention or a control group. Subjects in the intervention group participated in a comprehensive behaviorally oriented program aimed at achieving significant long-term changes in risk factor-related lifestyle behavior. Assessments of lifestyle behaviors, psychological factors, biological risk factors, and rehabilitation as well as secondary prevention endpoints were carried out, at inclusion and after 12 months. Results showed that the intervention patients, as compared with controls, improved significantly on measures assessing smoking, exercise, and diet habits. These self-rated changes were confirmed by weight reductions and improved exercise capacity, as well as by between-group differences in subclinical chest pain during an exercise test. However, few effects were found on the different psychological variables, as well as on morbidity or return to work.\nStudy3: Psychosocial nursing therapy following sudden cardiac arrest: impact on two-year survival. Although psychosocial therapy has been shown to reduce mortality after myocardial infarction, it is unknown whether the benefits of psychosocial therapy on mortality reduction extend to out-of-hospital sudden cardiac arrest, a main cause of cardiovascular mortality. Describe efficacy of psychosocial therapy on two-year cardiovascular mortality in sudden cardiac arrest survivors. Survivors of out-of-hospital ventricular fibrillation or asystole (N = 129), documented by electrocardiograms from registries of a citywide Medic One unit and two countywide emergency units, were randomized into a two group, experimental, longitudinal design. The intervention consisted of 11 individual sessions, implementing three components: physiologic relaxation with biofeedback training focused on altering autonomic tone; cognitive behavioral therapy aimed at self-management and coping strategies for depression, anxiety, and anger; and cardiovascular health education. The primary outcome measure was cardiovascular mortality. Risk of cardiovascular death was significantly reduced 86% by psychosocial therapy, p = .03. Six of the seven cardiovascular deaths in the control group were caused by ventricular arrhythmias. The cardiovascular death in the therapy group was due to stroke. Controlling for depression, previous myocardial infarction, low ejection fraction, decreased heart rate variability, and ventricular ectopic beats had little impact on estimated treatment effect. The risk of all-cause mortality was reduced by 62% in the therapy group, p = .13. There were a total of three deaths in the therapy group and eight deaths in the control group. Psychosocial therapy significantly reduced the risk of cardiovascular death in sudden cardiac arrest survivors.\nStudy4: Effect of intervention for psychological distress on rehospitalization rates in cardiac rehabilitation patients. Psychosocial factors affect the development of coronary heart disease and morbidity and mortality of patients with known coronary heart disease. A prior study has shown that psychological distress in patients with known coronary heart disease increased medical and economic costs. This study examined the effects of commonly available psychological interventions offered to patients entering cardiac rehabilitation after hospitalization for angina, myocardial infarction, angioplasty, or coronary artery bypass grafting. A total of 380 patients were screened with the Symptom Checklist-90-Revised (SCL-90-R). Those with T-scores > or = 63 (> or = 91 percentile) on the General Severity Index (GSI) subscale were randomly assigned to usual care or special intervention. Special intervention included a psychiatric evaluation, plus one to seven sessions of behavioral therapy. The percentage of patients rehospitalized for cardiac symptoms within 12 months of psychological evaluation was 43% for special intervention and 40% for usual care (NS). A correction for crossover between the treatment groups resulted in a favorable trend toward intervention, with 35% of the psychologically treated patients rehospitalized vs. 48% of the untreated patients (NS). Although there was a nonsignificant reduction of the SCL-90-R's GSI T-score, the depression score was significantly reduced in the special intervention group.\nStudy5: Psychological rehabilitation after myocardial infarction: multicentre randomised controlled trial. To evaluate rehabilitation after myocardial infarction. Randomised controlled trial of rehabilitation in unselected myocardial infarction patients in six centres, baseline data being collected on admission and by structured interview (of patients and spouses) shortly after discharge and outcome being assessed by structured interview at six months and clinical examination at 12 months. Six district general hospitals. All 2328 eligible patients admitted over two years with confirmed myocardial infarction and discharged home within 28 days. Rehabilitation programmes comprising psychological therapy, counselling, relaxation training, and stress management training over seven weekly group outpatient sessions for patients and spouses. Anxiety, depression, quality of life, morbidity, use of medication, and mortality. At six months there were no significant differences between rehabilitation patients and controls in reported anxiety (prevalence 33%) or depression (19%). Rehabilitation patients reported a lower frequency of angina (median three versus four episodes a week), medication, and physical activity. At 12 months there were no differences in clinical complications, clinical sequelae, or mortality. Rehabilitation programmes based on psychological therapy, counselling, relaxation training, and stress management seem to offer little objective benefit to patients who have experienced myocardial infarction compared with previous reports of smaller trials.\nStudy6: Improving psychologic adjustment to chronic illness in cardiac patients. The role of depression and anxiety. Poor mood adjustment to chronic medical illness is often accompanied by decrements in function. To evaluate the effectiveness of a telephone-based intervention for psychologic distress and functional impairment in cardiac illness. Randomized, controlled trial. We recruited survivors of acute coronary syndromes using the Hospital and Anxiety Depression Scale (HADS) with scores indicative of mood disturbances at 1-month postdischarge. Recruited patients were randomized to experimental or control status. Intervention patients received 6 30-minute telephone counseling sessions to identify and address illness-related fears and concerns. Control patients received usual care. Patients' responses to the HADS and the Workplace Social Adjustment Scale (WSAS) were collected at baseline, 2, 3, and 6 months using interactive voice recognition technology. At baseline, the PRIME-MD was used to establish diagnosis of depression. We used mixed effects regression to study changes in outcomes. We enrolled 100 patients. Mean age was 60; 67% of the patients were male. Findings confirmed that the intervention group had a 27% improvement in depression symptoms (P=.05), 27% in anxiety (P=.02), and a 38% improvement in home limitations (P=.04) compared with controls. Symptom improvement tracked those for WSAS measures of home function (P=.04) but not workplace function. The intervention had a moderate effect on patient's emotional and functional outcomes that were observed during a critical period in patients' lives. Patient convenience, ease of delivery, and the effectiveness of the intervention suggest that the counseling can help patients adjust to chronic illness.\nStudy7: Feasibility of altering type A behavior pattern after myocardial infarction. Recurrent Coronary Prevention Project Study: methods, baseline results and preliminary findings. We studied 1035 consecutive postinfarction patients to determine the feasibility of altering type A behavior and the effect such alteration might have on subsequent rates of infarction and cardiovascular death. Approximately 300 subjects were enrolled in small groups and primarily received cardiologic counseling on the usually accepted coronary risk factors. Six hundred subjects received, in addition to cardiologic counseling, advice and instructions designed to diminish the intensity of their type A behavior. The remaining subjects, serving as controls, received no counseling, but were examined and interviewed annually, as were those who dropped out of counseling groups. More than 98% of the 1035 subjects exhibited moderate-to-severe type A behavior during a videotaped structured interview. After the first year of this 5-year study, the rates of infarction and cardiovascular death were lower (p less than 0.01 and p less than 0.05, respectively) among subjects who received both cardiologic and behavioral counseling than among the control subjects. The rate of nonfatal infarction was lower (p less than 0.05) among subjects who received behavioral counseling than among those who received only cardiologic counseling or those who dropped out of either counseling group. The circumstances that most often preceded recurrent infarction or cardiovascular death were emotional crisis, excess physical activity, ingestion of a single fatty meal or a combination of these phenomena.\nStudy8: The group counseling v exercise therapy study. A controlled intervention with subjects following myocardial infarction. One hundred six postmyocardial infarction subjects who either achieved a mean work load of less than seven mets on treadmill testing, who were rated as anxious and/or depressed, or who met both criteria, participated in a controlled study comparing the rehabilitation effectiveness of exercise therapy and group counseling. Each intervention lasted 12 weeks. Follow-up evaluations were scheduled at three months, six months and one year. Exercise substantially increased mean work capacity, decreased fatigue, lessened anxiety and depression, and promoted independence and sociability. Counseling substantially reduced depression and promoted a sense of friendliness, and decreased interpersonal friction as well as greater independence and sociability. The control group reported no substantial change on any measured factor. Neither counseling nor exercise had an effect on mortality though subjects in the exercise group reported fewer major cardiovascular sequelae.\nStudy9: Brief group therapy in myocardial infarction rehabilitation: three- to four-year follow-up of a controlled trial. A trial of brief group therapy as part of a rehabilitation program for postmyocardial infarction (MI) patients was carried out. Forty-four patients surviving their first MI were randomly allocated to either group therapy or control group status and were followed over 4 years. An additional group of 17 patients were referred for post-MI group therapy sessions after the termination of the controlled experiment and were followed for 3 years. Patients who received group therapy had significantly less follow-up coronary morbidity and mortality, and returned to work at significant higher percentages than control patients. Although neither group therapy nor control group patients meaningfully altered conventional coronary risk factors, group therapy patients (in the controlled trial) successfully altered selected coronary-prone behaviors. Educational information regarding the physiological and psychological aspects of coronary heart disease, presented in the group therapy sessions, was forgotten over follow-up. It is concluded that the supportive aspects of the group therapy experience played the most important role in determining the rehabilitation advantages seen for treatment patients.\nStudy10: Effects of a health education programme with telephone follow-up during cardiac rehabilitation. A health education and counselling programme was offered to myocardial infarction patients during and after hospitalization. A randomized pre-test-post-test control group design was used to evaluate the effects of the experimental intervention. During hospitalization the intervention consisted of two individual counselling sessions and two group health education sessions focusing on medication, healthy habits, anxiety and depression. On completion of these sessions, weekly telephone calls were made to patients for a period of six weeks after discharge from hospital. The intervention was offered to 30 myocardial infarction patients and their partners (the experimental group) in addition to standard medical care. Thirty control patients received standard medical care only. Two months after myocardial infarction, patients in the experimental condition reported a significantly greater increase in physical activity, and a significantly greater decrease in unhealthy eating habits. No effects were found regarding smoking cessation, anxiety and depression. Twelve months after discharge from hospital patients in the experimental condition reported a significantly greater decrease in unhealthy eating habits. No effects were found regarding smoking cessation, physical activity, anxiety and depression. In addition, two months after myocardial infarction, it was found that patients whose partners participated in the health education sessions showed a significantly greater decrease in smoking and unhealthy eating habits and a significantly greater increase in physical activity than patients with no partner participating. Twelve months after discharge the only significant result favouring the patients whose partner participated in the health education sessions concerned smoking cessation.\n", + "output": "Conclusions: Psychological treatments appear effective in treating psychological symptoms of CHD patients. Uncertainly remains regarding the subgroups of patients who would benefit most from treatment and the characteristics of successful interventions." + }, + { + "input": "Study1: Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in french haemodialysis units: II, Haemodialysis patients. A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in 138 haemodialysis patients in a placebo-controlled randomised double-blind trial. In an interim analysis, hepatitis B infections were observed in 21% of the vaccine group and 45% of the placebo group (p less than 0.02). 2 of the infections in the vaccine group and 12 of the infections in the placebo group occurred after the third injection. 60% of the vaccine recipients had an immune response. 4 months after the first injection the mean titre of anti-HBs was 120 mlU/ml.\nStudy2: [Recombinant vaccine and extracting vaccine against hepatitis B in patients with kidney insufficiency: comparative immunogenicity]. Patients with chronic renal failure respond rather poorly to hepatitis B vaccines. A better response could be expected from recombinant vaccines including both the S and the pre-S2 antigens. We therefore prospectively compared the immunogenicity of plasma-derived Hevac B vaccine (H) with that of recombinant GenHevac B vaccine (G). Vaccinations were performed in 120 non-dialyzed patients with chronic renal failure. The patients were randomly divided into two groups. Group G included 60 patients (24 males, mean age 58 +/- 16 years, mean creatinine clearance 25.3 +/- 12.6 ml/min) who were given the Hevac B vaccine at the dose of 5 micrograms. Group H included 60 patients (31 males, mean age 60 +/- 15 years, mean creatinine clearance 24.4 +/- 11.1 ml/min) who were given GenHevac B vaccine at the dose of 20 micrograms. All vaccinations were repeated at 0, 1, 2, 4 and 12 months. Following the fourth injection, seroconversion (anti-Hbs > or = 2 mlU/ml) was observed in 50/59 (85%) of the patients in group G versus 38/58 (67%) in group H (p < 0.02). Seroprotection (> or = 10 mlU/ml) was obtained in 42/59 (71%) vs 34/58 (59%), (NS) in the two groups respectively with a geometric mean titer of 112 versus 229 mlU/ml (NS) in responders. Following the booster injection at the 12th month, seroconversion was achieved in 48/51 (94%) vs 40/53 (76%) (p < 0.01) and seroprotection in 84% vs 70% (p = 0.053) respectively. The mean geometric titers were 879 and 1001 mlU/ml. Recombinant GenHevac B vaccine elicits seroconversion and seroprotection in a higher proportion of patients with chronic renal failure than the plasma-derived Hevac B vaccine, with comparably high antibody titers in responders. Therefore, GenHevac B vaccine should be recommended for vaccinating patients with chronic renal failure against hepatitis B.\nStudy3: Immunogenicity of recombinant hepatitis B vaccine in dialysis patients. Eighty-eight dialysis patients were vaccinated with recombinant hepatitis B vaccine prepared in yeast. Fourty-nine patients were immunized 3 times (months 0, 1, 6) intragluteally with 40 micrograms hepatitis B surface antigen (HBsAg) per dose. Only 32 of them (65.3%) showed anti-HBs concentrations above 10 IU/l with a geometric mean titer (GMT) of 180.7 IU/l after 3 vaccinations, whereas all of the 16 healthy controls, vaccinated 3 times with a 10-micrograms dose of the same vaccine batch, had specific antibodies higher than 10 IU/l (GMT 897.4 IU/l). Responses of patients were slightly higher than those of dialysis patients vaccinated in an earlier study with plasma-derived vaccine according to the same schedule. Results in 20 patients immunized 6 times intragluteally with 40 micrograms HBsAg/dose in monthly intervals were not better (at month 7, 65% showed anti-HBs concentrations greater than 10 IU/l; GMT = 126.6 IU/l), and 19 patients receiving 6 times 20 micrograms HBsAg monthly showed significantly lower responses (anti-HBs greater than 10 IU/l in 42% of vaccinees, GMT = 89.5 IU/l). The vaccine was tolerated well; side-effects were slight, and no serious adverse reactions were observed. In conclusion, recombinant hepatitis B vaccine is comparable to plasma-derived vaccine also in the case of dialysis patients; a 6-dose schedule does not seem to have much advantage compared to the conventional 3-dose regimen.\nStudy4: Hepatitis B vaccines in patients with chronic renal failure before dialysis. Hepatitis B remains a significant risk to patients receiving chronic hemodialysis, but no certain method of prevention has been identified. We tested two vaccines, plasma-derived vaccine (40-micrograms dose) and recombinant-derived vaccine (40-micrograms and 20-micrograms doses), in 61 patients with chronic renal failure who were not yet dependent on dialysis. Patients were followed up clinically and with laboratory tests of kidney function and hepatitis B virus serology for one year. Significantly more recipients of plasma-derived vaccine responded to vaccination; they also achieved a higher titer of antibody to hepatitis B virus than did recipients of recombinant-derived vaccine when evaluated at 6, 7, 9, and 12 mo after vaccination. No serious side effects were observed with any vaccine preparation, nor were excessive adverse effects observed in any group. Compared with the dialysis patients previously studied, patients with renal failure who were not yet dependent on dialysis responded more favorably to the hepatitis B virus vaccine.\nStudy5: Hepatitis B vaccine in patients receiving hemodialysis. Immunogenicity and efficacy. We evaluated the immunogenicity and efficacy of hepatitis B vaccine (Heptavax-B) in a randomized, double-blind, placebo-controlled trial involving 1311 patients receiving hemodialysis in the United States. After three doses of vaccine (40 micrograms each) had been administered, 63 per cent of the patients were antibody-positive. After correction for possible passive transfer of antibodies by blood transfusion, only 50 per cent of vaccine recipients were considered vaccine responders. The incidence of hepatitis B viral infection during the 25 months of the trial was much lower than had been anticipated and was virtually the same in the vaccine and placebo recipients (6.4 and 5.4 per cent, respectively). Four cases of hepatitis B occurred in patients who had an apparent antibody response to the vaccine, but in each case either antibody had reached low or undetectable levels before hepatitis B surface antigen was detected or the patient had been receiving immunosuppressive therapy. This study did not demonstrate the efficacy of the vaccine in a population of patients receiving dialysis in whom both the rate of antibody response to hepatitis B vaccine and the viral attack rate were low. Other measures to control transmission of hepatitis B virus in dialysis units, including surveillance for hepatitis B surface antigen and isolation of patients who are positive for the antigen, must be continued.\nStudy6: Efficacy of heat-inactivated hepatitis B vaccine in haemodialysis patients and staff. Double-blind placebo-controlled trial. The efficacy of a heat-inactivated hepatitis B vaccine, 3 micrograms of surface antigen (HBsAg), given at 0, 1, 2, and 5 months, was evaluated in 401 haemodialysis patients in 18 centres by a placebo-controlled, double-blind, randomised trial. The attack-rate of hepatitis B virus (HBV) infections in the control group was 18% over 435 days. The protective efficacy rate of the vaccine was 78% against all HBV infections in the entire study (p = 0.00016), and 94% against HBsAg-positive hepatitis more than 3 months after day 0. Those patients in whom HBV developed showed no evidence of vaccine-acquired anti-HBs. Among 152 similarly randomised staff members receiving three monthly injections, all 5 HBsAg-positive infections occurred in the placebo group (p = 0.022). The vaccine induced anti-HBs in 88% of the patients and 100% of the staff. Immediately after the fourth injection, anti-HBs levels were as high in responding patients as in staff. There were no serious side effects. In the four-dose schedule the vaccine provides dialysis patients with protection of the same order as that given by other hepatitis B vaccines to normal subjects.\n", + "output": "Conclusions: Plasma derived vaccines are more effective than placebo in achieving hepatitis B antibodies, while no statistically significant difference was found between recombinant and plasma vaccines. No statistically significant difference of effectiveness was observed between a reinforced vaccination series versus routine vaccinations of three inoculations of recombinant vaccine." + }, + { + "input": "Study: A comparison of follicular response of ovaries to ovulation induction after laparoscopic ovarian cystectomy or fenestration and coagulation versus normal ovaries in patients with endometrioma. In a comparison of follicular responses to controlled ovarian hyperstimulation (COH) between normal ovaries and ovaries previously treated by different laparoscopic techniques for ovarian endometrioma in 65 patients with unilateral endometrioma, laparoscopic ovarian fenestration and coagulation was performed in 24 cases (group 1) and laparoscopic ovarian cystectomy in the other 41 (group 2). In 16 patients with bilateral endometrioma (group 3), cystectomy was done in one ovary and fenestration and coagulation in the contralateral side. The results indicate that the response of ovaries to COH after laparoscopic ovarian cystectomy or fenestration and coagulation was the same and that there was no difference in response to COH between normal ovaries and those operated on by the laparoscopic techniques mentioned above.\n", + "output": "Conclusions: There is good evidence that excisional surgery for endometriomata provides a more favourable outcome than drainage and ablation with regard to the recurrence of the endometrioma, recurrence of pain symptoms, and subsequent spontaneous pregnancy in women who were previously subfertile. Consequently this approach should be the favoured surgical approach. However in women who may subsequently undergo fertility treatment, insufficient evidence exists to determine the favoured surgical approach." + }, + { + "input": "Study1: High tibial osteotomy with overcorrection of varus malalignment in medial gonarthrosis. Seventy-eight knee joints with varus malalignment were examined preoperatively using three-point measurement. Operation was performed with or without 5 degrees overcorrection of the varus deformity using random selection. The overcorrection group showed significantly better results than the normal-correction group.\nStudy2: Open-wedge osteotomy of the proximal tibia with hemicallotasis. Conventional high tibial osteotomy for losteoarthritis of the medial compartment of the knee with closed-wedge or dome osteotomy (DMO) may produce shortening of the patellar tendon and loss of inclination of the proximal tibial plateau or of the offset of the tibial condyle relative to its bony axis. This can make subsequent total knee arthroplasty technically demanding. We undertook a prospective study comparing these changes after DMO with those after using open-wedge osteotomy hemicallotasis (HCO). A total of 50 knees with arthritis of the medial compartment in 46 consecutive patients was randomly allocated to either DMO or HCO. There were no significant differences between the groups with regard to age, gender, femorotibial angle before operation or the angle of correction. Radiological studies showed that HCO caused little change in the length of the patellar tendon or the inclination angle of the tibial plateau, while after DMO both gradually decreased. The degree of tibial condylar offset increased in both groups, but less so in the HCO group.\nStudy3: Valgus high tibial osteotomy. Comparison between an Ilizarov and a Coventry wedge technique for the treatment of medial compartment osteoarthritis of the knee. A matched-pair comparative analysis was done comparing outcomes between a Coventry-type closing wedge valgus high tibial osteotomy (HTO) and an HTO using an Ilizarov apparatus. Thirty patients were treated with a mean follow-up interval of 28.1 months. Functional outcomes were evaluated using the Western Ontario and McMaster University (WOMAC) osteoarthritis index. Clinical and radiographic assessment of the index knee, complications, and over-all satisfaction of the patients were assessed. The procedures were performed between 1994 and 1997. The two groups were equal with respect to baseline demographics - age, sex, body mass index, smoking status. The patients undergoing an Ilizarov HTO had a significantly greater decrease in pain and increase in function at final follow-up assessment. Eleven of the 15 patients in the Ilizarov group were satisfied with the procedure compared to five in the closing wedge HTO group. The treatment of medial compartment osteoarthritis in genu varum of the knee with an Ilizarov apparatus produces outcomes that are comparable to the standard lateral closing wedge osteotomy.\nStudy4: High tibial osteotomy versus unicompartmental joint replacement in unicompartmental knee joint osteoarthritis: 7-10-year follow-up prospective randomised study. The clinical outcome of patients treated either by high tibial osteotomy or unicompartmental arthroplasty for medial unicompartmental osteoarthritis of the knee was compared in a prospective randomised study. In total, 32 patients received a high tibial osteotomy (HTO) and 28 patients a unicompartmental arthroplasty (UKA). More intra- and postoperative complications were observed after HTO. Patients were assessed at an average of 2.5 (1.6-5), 4.5 (3.6-7), and 7.5 years (6.6-10) after the operation. Using the Knee Society Score, 71% (15) of patients after osteotomy and 65% (13) after replacement had a knee score of excellent or good 7-10 years postoperatively. The Kaplan-Meier survival analysis 7-10 years postoperatively showed a survivorship of 77% for UKA and 60% for HTO. Although the unicompartmental prosthesis used in this series has not shown promising results, we conclude that with the advanced design of unicompartmental prosthesis today, UKA offers better long-term success.\nStudy5: The incidence of thrombosis in high tibial osteotomies with and without the use of a tourniquet. In a prospective randomised study, 65 high tibial osteotomies were performed in cases of varus osteoarthritis of the knee, and the incidence of thrombosis with and without the use of a tourniquet was studied. With an average incidence of thrombosis of 10.8%, no statistically significant differences between these two groups were seen.\nStudy6: Early knee mobilization after osteotomy for gonarthrosis. In a prospective study, 32 knees in 32 patients were randomized to either a cylinder plaster cast (17 knees) or hinged cast-brace (15 knees) after high tibial osteotomy for medial gonarthrosis. At 6 weeks, 3 months, and still 1 year after surgery, the range of motion was better in the cast-brace group. There was no difference in the other clinical results at 3 months and at 1 year after surgery, nor in changes of osseous correction or in the final knee alignment. All the patients in the cast-brace group were satisfied with early motion.\nStudy7: Open-wedge osteotomy by hemicallotasis or the closed-wedge technique for osteoarthritis of the knee. A randomised study of 50 operations. We describe the results of 50 operations carried out on 46 patients with medial osteoarthritis of the knee of Ahlb\u00e4ck grade 1 to 3. Patients were randomised either to a closed-wedge high tibial osteotomy (HTO) or an open-wedge procedure based on the hemicallotasis technique (HCO). Their median age was 55 years (38 to 68). The preoperative median hip-knee-ankle (HKA) angle was 171 degrees (164 to 176) in the HTO group and 173 degrees (165 to 179) in the HCO group. After six weeks, the median HKA angle was 185 degrees (176 to 194) in the HTO group and 184 degrees (181 to 188) in the HCO group. In the HTO group, seven patients were within the range of 182 degrees to 186 degrees compared with 21 in the HCO group (p < 0.001). One year later, ten HTO patients were within this range while the HKA angulation in the HCO group was unchanged. At two years the numbers were 11 and 18, respectively. We evaluated the clinical results on the Hospital for Special Surgery, Lysholm and Wallgren-Tegner activity scores, and patients completed part of the Nottingham Health Profile questionnaire. An impartial observer at the two-year follow-up concluded that all scores had improved, but found no clinical differences between the groups.\nStudy8: Gait and clinical measurements in patients with knee osteoarthritis after surgery: a prospective 5-year follow-up study. The aim of this prospective follow-up study was to determine if gait measurements and/or clinical measurements could detect differences in treatment outcome between two surgical interventions in patients with knee osteoarthritis (OA). The patients were followed for 5 years after surgery. Forty patients, 55-70 years of age, with unilateral knee OA were included. The patients were treated either with a high tibial osteotomy (HTO) (n=18) or a unicompartmental knee arthroplasty (UKA) (n=22). Clinical outcome measures were the British Orthopaedic Association (BOA) score, pain during walking, passive range of knee motion (PROM) and patients' subjective opinion. The gait variables were free walking speed, step frequency, step length and single and double-stance phase for each leg. The patients were examined before surgery and 3 months, 1 year and 5 years after surgery. The time-distance variables of gait could detect differences in treatment outcome, 3 months after surgery, while the clinical outcome measures, as given here, could not detect any differences between the two groups of patients. Measurements of free walking speed could be recommended for clinical evaluation, after surgical interventions, in patients with knee OA.\n", + "output": "Conclusions: Based on 13 studies, we conclude that there is 'silver' level evidence (www.cochranemsk.org) that valgus HTO improves knee function and reduces pain. There is no evidence whether an osteotomy is more effective than conservative treatment and the results so far do not justify a conclusion about effectiveness of specific surgical techniques." + }, + { + "input": "Study1: Controlled trial of hypo-osmalar versus World Health Organization oral rehydration solution. To compare the safety and efficacy of a hyposmolar oral rehydration solution (H-ORS) (245 mmol/liter) with the World Health Organization oral rehydration solution (WHO ORS) in cholera and acute non-cholera diarrhea. Controlled clinical trial. Diarrhea training and treatment unit. Thirty-five culture proven cholera and 135 acute non-cholera diarrheal patients randomly received H-ORS or WHO-ORS. Intake and output were measured every 4 hours. Analysis of the total cases revealed rehydration phase (p=0.048, 95% CI 0.64-0.99) and overall (p=0.046, 95% CI 0.70-0.99) frequency of stools to be significantly less in the H-ORS group. In the severely malnourished, the rehydration phase (p=0.032, 95% CI 0.55-97), maintenance phase (p=0.035, 95% CI 0.51-0.97) and overall (p=0.011; 0.95% CI 0.55-0.93) stool frequency were significantly decreased in the H-ORS group. The amount of ORS consumed in the maintenance phase of the cholera cases was significantly (p=0.04, 95% CI 0.44-0.98) less in the H-ORS group. All other parameters, despite showing a decreasing trend, were statistically comparable in the cholera, non-cholera and total cases. The amount of intravenous fluid needed was significantly more in the noncholera and total cases on H-ORS. In the non-breastfed cases, under two years of age, the total duration of diarrhea was significantly decreased (p=0.03; 95% CI 11.07-11.45) but the need for intravenous fluids significantly increased (p=0.02; 95% CI 109.8-112.1) in the H-ORS group. The proportion of children vomiting, the weight gain, urine passed in 24 hours, serum sodium, caloric intake and failure rate were comparable. H-ORS is as safe and effective as the WHO-ORS and may have some additional benefits in malnourished children.\nStudy2: Efficacy of oral hyposmolar glucose-based and rice-based oral rehydration salt solutions in the treatment of cholera in adults. Recent animal experiments and clinical trials have shown that both osmolarity and rice as the organic components are important factors for net intestinal absorption of an oral rehydration salt solution. In a controlled clinical trial 123 male adult patients with severe cholera, after initial rehydration with intravenous Ringer's lactate solution, were randomly assigned to receive one of the four oral rehydration salt solutions: WHO ORS, ORS containing 70 mmol/l Na+ and 16.2 g/l glucose, rice ORS containing 50 g/l rice and 90 mmol/l Na+, and rice ORS containing 50 g/l rice and 70 mmol/l Na+. All patients received 300 mg of doxycycline as a single dose. Patients who received rice-low-sodium ORS subsequently had lower (P < 0.05) stool output, ORS consumption, and diarrhoea duration than the other three ORS groups. We conclude that rice-based low-sodium ORS is superior for treating adult cholera.\nStudy3: Reduced osmolarity oral rehydration salt in Cholera. In a controlled clinical trial conducted in 34 adults with severe cholera diarrhoea, the use of a relatively dilute oral rehydration salt (ORS) solution (sodium 67, potassium 20, chloride 66, citrate 7, glucose 89 mmol/l, osmolality 249 mOsmol/kg) caused a 29% (p=0.003) reduction in stool output over the first 24 h and a 37% (p=0.001) reduction over the first 48 h compared with 29 controls who received the hyperosmolar WHO/UNICEF ORS. No controls but 3 study-group patients had marked but asymptomatic hyponatraemia (sodium <125 mmol/l) at 24 h. Twenty-four % of controls and 12% of patients receiving the dilute ORS needed unscheduled intravenous therapy for recurrence of dehydration. The ORS intake was twice the 48 h stool volume in controls and 3 times in the study group. The test ORS with a reduced glucose and sodium concentration is more efficient than the WHO/UNICEF ORS in preserving net intestinal fluid balance in severe cholera.\nStudy4: Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group. The effects of oral rehydration solution (ORS) with reduced osmolarity on children with acute watery diarrhoea are known, but little is known about the effects of such ORS on adults with cholera. We aimed to compare the efficacy and safety of an ORS with reduced osmolarity with that of standard WHO ORS in adults with cholera. We undertook a double-blind, controlled clinical trial in adults with severe cholera at the International Centre for Diarrhoeal Disease Research, Bangladesh. Our primary outcomes were mean stool output in the 24 h after randomisation, proportion of patients who needed unscheduled intravenous therapy, and proportion of patients with biochemical hyponatraemia 24 h after randomisation. 147 patients received ORS with reduced osmolarity and 153 received standard WHO ORS. There was no significant difference between the two groups in terms of main outcome variables: mean initial 24 h and total stool output (reduced osmolarity vs standard WHO ORS 212 [SE 8] vs 207 [8] and 284 [13] vs 273 [13] g/kg respectively), duration of diarrhoea (46 [1.5] vs 43 [1.5]). The proportion of patients vomiting during the first 24 h and the proportion who received unscheduled intravenous infusion during the first 24 h was similar between groups. More patients on reduced osmolarity ORS than on standard WHO ORS developed hyponatraemia during the first 24 h, defined as serum sodium concentration below 130 mmol/L (29 of 142 vs 16 of 150; odds ratio 2.1 [95% CI 1.1-4.1]). However, all hyponatraemic patients in both groups were symptom-free and the proportion of patients with serum sodium concentration below 125 mmol/L was similar between groups. There was no difference in clinical outcome between cholera patients treated with reduced osmolarity ORS solution and those treated with standard WHO ORS. The risk of increased incidence of symptom-free hyponatraemia in patients with cholera treated with an ORS with reduced osmolarity should be further assessed by meta-analysis. The risk should be taken into account when choice of ORS is made in areas in which cholera is endemic.\n", + "output": "Conclusions: In people with cholera, ORS \u2264 270 is associated with biochemical hyponatraemia when compared with ORS \u2265 310, but there are no differences in terms of other outcomes. Although this risk does not appear to be associated with any serious consequences, the total patient experience in existing trials is small. Under wider practice conditions, especially where patient monitoring is difficult, caution is warranted." + }, + { + "input": "Study1: A controlled trial of arthroscopic surgery for osteoarthritis of the knee. Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee. A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic d\u00e9bridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated d\u00e9bridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores--three on scales for pain and two on scales for function--and one objective test of walking and stair climbing. A total of 165 patients completed the trial. At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (+/-SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and d\u00e9bridement groups: 48.9+/-21.9, 54.8+/-19.8, and 51.7+/-22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and d\u00e9bridement) and 51.6+/-23.7, 53.7+/-23.7, and 51.4+/-23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference. In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic d\u00e9bridement were no better than those after a placebo procedure.\nStudy2: Articular debridement versus washout for degeneration of the medial femoral condyle. A five-year study. In a prospective randomised trial 76 knees with isolated degenerative changes in the medial femoral condyle of grades 3 or 4 were treated by either arthroscopic debridement (40) or washout (36). All knees were followed up for at least one year and 58 for five years. The mean follow-up time was 4.5 years in the debridement group and 4.3 years in the washout group. At one year 32 of the debridement group and five of the washout group were painfree and at five years 19 of a total of 32 survivors in the debridement group and three of the 26 in the washout group were also free from pain. The mean improvement in a modified Lysholm score was 28 for the debridement group at one year and 21 at five years. In the washout group it was only 5 at one year and 4 at five years. For knees with lesions of the medial femoral condyle of grades 3 or 4, arthroscopic debridement appears to be the treatment of choice with over half the patients free from pain after five years.\n", + "output": "Conclusions: There is 'gold' level evidence that AD has no benefit for undiscriminated OA (mechanical or inflammatory causes)." + }, + { + "input": "Study1: Early inhaled glucocorticoid therapy to prevent bronchopulmonary dysplasia. The safety and efficacy of inhaled glucocorticoid therapy for asthma stimulated its use in infants to prevent bronchopulmonary dysplasia. We tested the hypothesis that early therapy with inhaled glucocorticoids would decrease the frequency of bronchopulmonary dysplasia in premature infants. We conducted a randomized, multicenter trial of inhaled beclomethasone or placebo in 253 infants, 3 to 14 days old, born before 33 weeks of gestation and weighing 1250 g or less at birth, who required ventilation therapy. Beclomethasone was delivered in a decreasing dosage, from 40 to 5 microg per kilogram of body weight per day, for four weeks. The primary outcome measure was bronchopulmonary dysplasia at 28 days of age. Secondary outcomes included bronchopulmonary dysplasia at 36 weeks of postmenstrual age, the need for systemic glucocorticoid therapy, the need for bronchodilator therapy, the duration of respiratory support, and death. One hundred twenty-three infants received beclomethasone, and 130 received placebo. The frequency of bronchopulmonary dysplasia was similar in the two groups: 43 percent in the beclomethasone group and 45 percent in the placebo group at 28 days of age, and 18 percent in the beclomethasone group and 20 percent in the placebo group at 36 weeks of postmenstrual age. At 28 days of age, fewer infants in the beclomethasone group than in the placebo group were receiving systemic glucocorticoid therapy (relative risk, 0.6; 95 percent confidence interval, 0.4 to 1.0) and mechanical ventilation (relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0). Early beclomethasone therapy did not prevent bronchopulmonary dysplasia but was associated with lower rates of use of systemic glucocorticoid therapy and mechanical ventilation.\nStudy2: Inhaled budesonide in ventilator-dependent preterm infants: a randomized, double-blind pilot study. The aim of this randomized, double-blind pilot study was to evaluate the short-term efficacy of early inhalation therapy with budesonide in ventilator-dependent preterm infants. The primary outcome variable was the duration of artificial ventilation; secondary outcome variables were the need for supplemental oxygen and the release of several inflammatory mediators in the tracheobronchial aspirate fluid. The infants of the budesonide group could not be weaned earlier from the ventilator. The ventilatory parameters on day 14 of life and the need for supplemental oxygen were similar in both groups. The release of inflammatory mediators was not reduced in the budesonide group. No adverse side effects were observed in either group. In conclusion, aerosolized budesonide failed to demonstrate significant short-term pulmonary improvement in ventilator-dependent preterm infants.\nStudy3: Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome. To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome. Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications. More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects. These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.\n", + "output": "Conclusions: Based on this updated review, there is no evidence from the trials reviewed that early administration (in the first two weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome." + }, + { + "input": "Study: No beneficial effect of low-dose fetal intravenous gammaglobulin administration in combination with intravascular transfusions in severe Rh D haemolytic disease. Recent observations have shown that treatment with high-dose intravenous gammaglobulin (IVIgG) given to the mother may improve fetal outcome in cases of severe Rh D alloimmunization. Unfortunately, the costs of this new method of treatment are too high for routine use. Therefore, we decided to apply this treatment to the fetus and to investigate whether the effect of IVIgG might be attributable to blockade of the fetal mononuclear phagocyte system. We have performed a randomized study in which 20 fetuses with severe Rh D-haemolytic disease (HDN) were treated with intrauterine intravascular red cell transfusions (IUT). In 10 of these 20 cases transfusions were followed by administration to the fetus of low-dose IVIgG (85.7 +/- 11.6 mg/kg by ultrasound-estimated fetal weight because of fetal vascular volume considerations). We compared the number of IUTs, postnatal exchange transfusions, haematocrit (Ht) and haemoglobulin (Hb) values before and after transfusion (s) needed by the newborns of the two groups. No significant differences in the transfusion requirements of the fetuses and in the clinical outcome could be demonstrated. However, the 95% confidence interval for the difference in the improvement of cord blood Ht was too wide for any conclusions. The 95% confidence interval for the difference in the improvement of Hb levels suggests that any clinically relevant advantage of IVIgG on Hb is unlikely.\n", + "output": "Conclusions: There is little available high quality information from randomised controlled trials to inform the optimal procedural technique when performing fetal intrauterine fetal blood transfusions for women with an anaemic fetus due to red cell alloimmunisation. Further research evaluating the benefits and harms associated with different techniques is required." + }, + { + "input": "Study: Preoperative intraaortic balloon pump enhances cardiac performance and improves the outcome of redo CABG. Reoperative coronary artery bypass grafting (redo CABG) is associated with an increased operative risk compared with primary CABG. Because the hospital mortality in redo CABG is known to be influenced by poor left ventricular function (left ventricular ejection fraction < or = 0.40), unstable angina, and left main stem stenosis greater than or equal to 70%, a preoperative intraaortic balloon pump (IABP) support could be beneficial to improve the outcome in high-risk redo CABG. Between June 1994 and October 1996, 48 high-risk patients underwent redo CABG and were randomized into the following groups: group 1 (24 patients) who received preoperative IABP treatment on average 2 hours before cardiopulmonary bypass, and group 2 (24 patients) who received no preoperative IABP and served as controls. Mean age was 65 years and 90% (43 patients) were men. Forty-one patients had preoperative left ventricular ejection fraction less than or equal to 0.40 (85%), 38% (18 patients) had left main stem stenosis greater than or equal to 70%, and 54% (26 patients) had unstable angina preoperatively. Preoperative patient characteristics did not differ between the groups. The time on cardiopulmonary bypass was shorter in group 1, 86 versus 110 minutes (p = 0.006). There were no hospital deaths in group 1, but four deaths occurred in the control group (p = 0.049). Cardiac index rose significantly preoperatively after introduction of the IABP in group 1. Cardiac index was significantly higher postoperatively in group 1 compared with group 2 and remained significantly higher during the first 24 hours after cardiopulmonary bypass. Significantly fewer patients in the IABP group had postoperative low cardiac output (4 versus 13 patients). Nine patients in group 2 required IABP support postoperatively for 4.1 +/- 1.7 days. Only 2 patients in group 1 needed IABP postoperatively, and their IABPs were successfully removed on the first postoperative day. The preoperative IABP-supported patients had a shorter intensive care unit stay, 2.4 +/- 0.8 days compared with group 2, 4.5 +/- 2.2 days (p = 0.007), as well as a shorter hospital stay. The preoperative IABP treatment was found to be cost-effective. Preoperative treatment with IABP in high-risk redo CABG patients is an effective modality to prepare these patients to have their myocardial revascularization in an as nonischemic situation as possible, which resulted in a significantly lower hospital mortality, fewer instances of postoperative low cardiac output, and shorter stays in both the intensive care unit and the hospital.\n", + "output": "Conclusions: Evidence suggests that preoperative IABP may have a beneficial effect on mortality and morbidity in specific high risk patient groups undergoing coronary artery bypass grafting, however there are many problems with the quality, validity and generalisability of the trials. However, the available evidence is not robust enough to extend the use of IABP to truly elective, high risk patients. Defining more precisely which patient groups may benefit would be the challenge for the future." + }, + { + "input": "Study1: Interferon therapy in disseminated renal cell carcinoma. Twenty patients with pulmonary metastases of renal cell carcinomas have been treated in a randomized study with either leucocyte interferon in daily doses of 3 x 10(6) I.U.i.m or irradiation of both lungs in a calculated mean central dose of 10 Gy in 4 weeks in combination with bleomycin and vincristine. Most patients had a short time to progression of their disease. Three patients in the interferon group had complete response (CR) and partial response (PR) and one patient in the other group had PR. The numbers of patients in both arms of the study are too small to allow any conclusions whether beneficial effects are more frequent in one group than in the other, but there is a more favourable tendency in the interferon group.\nStudy2: Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Surgery is the main treatment for localised renal cell carcinoma, but use of radical nephrectomy for metastatic disease is highly controversial. We aimed to establish whether radical nephrectomy done before interferon-alfa-based immunotherapy improved time to progression and overall survival (primary endpoints) compared with interferon alfa alone. We included 85 patients from June, 1995, to July, 1998: two (one per group) were ineligible. 42 of the 83 participants were randomly assigned combined treatment (study group) and 43 immunotherapy alone (controls). All patients had metastatic renal-cell carcinoma that had been histologically confirmed and was progressive at entry. In study patients, surgery was done within 4 weeks of randomisation, and immunotherapy (5x10(6) IU/m(2) subcutaneously three times per week) started 2-4 weeks later. In controls, immunotherapy was started within 1 working day of randomisation. Follow-up visits were monthly. All analyses were by intention to treat. 40 (53%) of 75 patients received at least 16 weeks of interferon-alfa treatment, which was also the median duration of treatment. Time to progression (5 vs 3 months, hazard ratio 0.60, 95% CI 0.36-0.97) and median duration of survival were significantly better in study patients than in controls (17 vs 7 months, 0.54, 0.31-0.94). Five patients responded completely to combined treatment, and one to interferon alfa alone. Dose modification was necessary in 32% of patients, most commonly because of non-haematological side-effects. Radical nephrectomy before interferon-based immunotherapy might substantially delay time to progression and improve survival of patients with metastatic renal cell carcinoma who present with good performance status.\nStudy3: Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Metastatic renal carcinoma has a 2-year survival of around 20% and is largely resistant to chemotherapy. The use of interferons in the treatment of metastatic renal carcinoma remains controversial. Although non-randomised studies suggest that biological therapy with interferons produces a small number of tumour responses, most clinicians judge such treatment to be ineffective. We have investigated the effect of treatment with interferon-alpha on survival in patients with metastatic renal carcinoma. In a multicentre, randomised trial, patients with metastatic renal carcinoma were randomly assigned subcutaneous interferon-alpha (three doses--5 MU, 5 MU, 10 MU--for the first week, then 10 MU three times per week for a further 11 weeks; n=174) or oral medroxyprogesterone acetate (MPA; 300 mg once daily for 12 weeks; n=176). The primary endpoint was overall survival. Analysis was by intention to treat. The trial used a triangular sequential design for early termination as soon as results were conclusive. The trial was stopped in November, 1997, when data were available for 335 patients (167 interferon-alpha, 168 MPA). A total of 111 patients have died in the interferon-alpha group, and 125 patients have died in the MPA group. There was a 28% reduction in the risk of death in the interferon-alpha group (hazard ratio 0.72 [95% CI 0.55-0.94], p=0.017). Interferon-alpha gave an improvement in 1-year survival of 12% (MPA 31% survival, interferon-alpha 43%), and an improvement in median survival of 2.5 months (MPA 6 months, interferon-alpha 8.5 months). The benefit of treatment with interferon-alpha should be weighed against the drug's toxic effects. Combination regimens of biological therapy and chemotherapy should now be compared with interferon-alpha monotherapy in randomised controlled trials.\nStudy4: A randomized study of low and high doses of leukocyte alpha-interferon in metastatic renal cell carcinoma: the American Cancer Society collaborative trial. A prospective randomized trial of low versus high doses of human leukocyte alpha-interferon (1 X 10(6) units/day for 28 days versus 10 X 10(6) units/day for 28 days) was carried out in 30 patients with metastatic renal cell carcinoma, to test the tolerance and relative antitumor effects of these interferon doses. Both doses were tolerated well, and responses to the human leukocyte alpha-interferon were observed overall in seven individuals, including complete, partial, and minimal tumor regressions. Six of the seven responses occurred in patients who received the high dosage, and three of these responses were major responses. While not statistically significant, this result suggested a dose-response relationship. One minimal response was observed in a patient treated at low dosage. Nine individuals who were stable after 1 month of therapy at low dosage were randomized to a further month of therapy at low or high dosage, during which one of four at high dosage had a partial response, and none of five at low dosage manifested response. Regression of pulmonary disease in one individual was delayed, occurring 3 months after therapy at the high dose and enduring for a period of 28 months. Major objective responses in other patients were of 4 and 15 months duration. Human leukocyte alpha-interferon is an active agent in renal cell carcinoma at the dosage of 10 million units daily. No relationship of toxicity to response was evident in this trial. Optimum dosage and duration of treatment have yet to be established.\nStudy5: Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma. Recombinant human interleukin-12 (rHuIL-12) is a pleiotropic cytokine with anticancer activity against renal cell carcinoma (RCC) in preclinical models and in a phase I trial. A randomized phase II study of rHuIL-12 compared with interferon-alpha (IFN-alpha) evaluated clinical response for patients with previously untreated, advanced RCC. Patients were randomly assigned 2:1 to receive either rHuIL-12 or IFN-alpha2a. rHuIL-12 was administered by subcutaneous (s.c.) injection on days 1, 8, and 15 of each 28-day cycle. The dose of IL-12 was escalated during cycle 1 to a maintenance dose of 1.25 microg/kg. IFN was administered at 9 million units by s.c. injection three times per week. Serum concentrations of IL-12, IFN-gamma, IL-10, and neopterin were obtained in 10 patients treated with rHuIL-12 after the first full dose of 1.25 microg/kg given on day 15 (dose 3) of cycle 1 and again after multiple doses on day 15 (dose 6) of cycle 2. Thirty patients were treated with rHuIL-12, and 16 patients were treated with IFN-alpha. Two (7%) of 30 patients treated with rHuIL-12 achieved a partial response, and the trial was closed to accrual based on the low response proportion. IL-12 was absorbed rapidly after s.c. drug administration, with the peak serum concentration appearing at approximately 12 h in both cycles. Serum IL-12 concentrations remained stable on multiple dosing. Levels of IFN-gamma, IL-10, and neopterin increased with rHuIL-12 and were maintained in cycle 2. rHuIL-12 is a novel cytokine with unique pharmacologic and pharmacodynamic features under study for the treatment of malignancy and other medical conditions. The low response proportion associated with rHuIL-12 single-agent therapy against metastatic RCC was disappointing, given the preclinical data. Further study of rHuIL-12 for other medical conditions is underway. For RCC, the study of new cytokines is of the highest priority.\nStudy6: EORTC (30885) randomised phase III study with recombinant interferon alpha and recombinant interferon alpha and gamma in patients with advanced renal cell carcinoma. The EORTC Genitourinary Group. In the treatment of renal cell carcinoma both complete (CRs) and partial remissions (PRs) have been obtained using recombinant (r) interferon alpha (IFN-alpha), with response rates ranging from 0 to 31% (mean 16%). rIFN-gamma is a potent immunostimulating agent, but the clinical experience of its use is limited and results are conflicting. In a phase II study with the combination of rIFN-alpha 2c (Boehringer Ingelheim) and rIFN-gamma (Genentech, supplied by Boehringer Ingelheim) in 31 eligible patients, a response rate of 25% was recorded. Based on this observation a randomised phase III study was initiated to investigate the possible advantage of the addition rIFN-gamma to rIFN-alpha 2c treatment. Treatment consisted of rIFN-alpha 2c 30 micrograms m-2 = 10 x 10(6) IU m-2 s.c. twice weekly in arm A and the same dose of rIFN-alpha combined with rIFN-gamma 100 micrograms m-2 = 2 x 10(6) IU m-2 in arm B. Eligibility criteria included documented progression of disease; patients with bone lesions only and overt central nervous system metastases were excluded. Between November 1988 and September 1990, 102 patients were entered into the study. An interim analysis showed a response in 7/53 (13%) patients (two CRs and five PRs) in the rIFN-alpha 2c monotherapy arm and in 2/45 (4%) (one CR and one PR) patients in the combination arm. This difference was not statistically significant (P = 0.17). The probability of missing an eventual 10% advantage for the combination is 0.001. The numbers are insufficient to rule out a negative effect of the addition of rIFN-gamma. The dose intensity of IFN-alpha 2c for the two treatment arms was the same. The addition of rIFN-gamma does not improve the response rate of rIFN-alpha 2c monotherapy. A possible detrimental effect cannot be excluded.\nStudy7: Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer. Treatment results in patients with metastatic renal cell cancer (RCC) are still extremely unsatisfactory. Rates of response to IFN-alpha monotherapy and/or IL-2 mono/combination therapy vary between 10% and 20%. Coumarin (Cum) together with cimetidine (Cim) has yielded objective responses in 20%-33% of patients with RCC, according to two recent phase II studies. In the present study 148 patients with metastatic RCC were randomised to receive either IFN-alpha (5 MU 5 x weekly s.c.) + coumarin (100 mg/d p.o.) + cimetidine (3 x 400 mg/d p.o.), or IFN-alpha-monotherapy (5 MU 5 x weekly s.c.). Of the 148 patients in the study 137 were evaluable for response. No differences in remission rates (RR IFN-alpha + Cum + Cim 17.1% and IFN-alpha 20.8%) or survival times (median survival 9 months and 8 months, respectively) were found between these two treatment arms. This study confirms that INFN-alpha has antitumoral activity in RCC. Adding coumarin + cimetidine to IFN-alpha in the dose and regimen prescribed in this study did not increase response rates or survival.\nStudy8: A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma. We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.\nStudy9: [Preoperative subcutaneous immunotherapy with interleukin-2 in renal carcinoma with synchronous metastasis: randomized clinico-biological study. Preoperative use of Il-2 in renal carcinoma]. Despite the efficacy of IL-2 in the treatment of metastatic renal cell carcinoma (RCC), the prognosis of patients with synchronous metastases still remains poor. Nephrectomy itself, as well as other surgical operations, may further suppress the antitumor immune response. Previous studies suggested that the preoperative injection of IL-2 may neutralize surgery-induced lymphocytopenia in advanced colon cancer. On this basis, a pilot randomized study was performed in an attempt to evaluate the effects of a preoperative administration of IL-2 on postoperative lymphocyte numbers and on the survival in advanced RVV patients with more than 3 synchronous metastases. The study included 20 consecutive patients, who were randomized to receive nephrectomy alone or nephrectomy plus preoperative subcutaneous immunotherapy with IL-2 (18 million IU/day for 3 days). Then, all patients underwent postoperative immunotherapy with IL-2 (6 million IU/day for 5 days/week for 6 weeks). Surgery-induced lymphocytopenia was completely abolished by IL-2 preoperative injection. The frequency of postoperative complications was significantly higher in controls than in patients preoperatively treated with IL-2. On the contrary, significant differences between control and patients preoperatively treated with IL-2 were observed neither in the clinical response to IL-2 immunotherapy, nor in the percent of 1-year survival. The results of this preliminary pilot study would suggest that IL-2 preoperative immunotherapy may neutralize surgery-induced lymphocytopenia and reduce the postoperative complications in RCC patients with synchronous metastases, without, however, influencing their prognosis in terms of survival time.\nStudy10: Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P =.048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P =.033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P =.04). Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.\n", + "output": "Conclusions: Interferon-alfa provides a modest survival benefit compared to other commonly used treatments. In fit patients with metastases at diagnosis and minimal symptoms, nephrectomy followed by interferon-alfa gives the best survival strategy for fully validated therapies. The need for more effective specific therapy for this condition is apparent." + }, + { + "input": "Study1: A pilot study to assess the viability of a randomised controlled trial of methods of supplementary feeding of breast-fed pre-term babies. to compare the impact of two methods of supplementary feeding of pre-term babies (bottle vs cup) on subsequent breast feeding and to assess the feasibility of using a randomised controlled trial (RCT) to investigate the topic. small scale prospective RCT. Data on breast feeding, as defined as the exclusive method of feeding, were collected. A range of relevant bio-data was also collected and their impact on breast feeding assessed. a special care baby unit in a District General Hospital in the UK. over a three-month period, all pre-term babies (32-37 weeks' gestation) who fulfilled the inclusion criteria and has been born to mothers who had expressed a pre-partum desire to breast feed, who had consented to take part, were included (n=14). the eligible babies were randomly allocated to supplementary feeding of breast milk, via either a cup or a bottle. Whether or not the baby was being breast fed at discharge was noted. the study suggested that this RCT framework is a viable method of investigating baby feeding. Because of the small-scale nature of the project, the actual database must be treated with extreme caution. No significant differences were found between the two groups in terms of breast feeding. However, the mothers reported high levels of support and also the breast-feeding rates were above the national averages. These two findings could have contributed to the non-significant results observed in this analysis. if the present findings could be supported by further research, then the non-significant results relating method of supplementary feeds to subsequent breast feeding could be explained by reference to three factors. Firstly, there is, in fact, no real effect of method of supplementary feeding and subsequent breast feeding; secondly, the method adopted differed from existing research and thus may be expected to produce non-corroborative results; and finally, the overall levels of breast feeding within the Unit generally were higher than the national average. The relevance of the RCT for investigating this subject is also discussed with reference to the present data set. Further experimental work to develop these ideas and to identify causal links is required. Copyright 2001 Harcourt Publishers Ltd.\nStudy2: Effect of bottles, cups, and dummies on breast feeding in preterm infants: a randomised controlled trial. To determine the effect of artificial teats (bottle and dummy) and cups on breast feeding in preterm infants. Randomised controlled trial. Two large tertiary hospitals, 54 peripheral hospitals. 319 preterm infants (born at 23-33 weeks' gestation) randomly assigned to one of four groups: cup/no dummy (n = 89), cup/dummy (n = 72), bottle/no dummy (n = 73), bottle/dummy (n = 85). Women with singleton or twin infants < 34 weeks' gestation who wanted to breastfeed were eligible to participate. Cup or bottle feeding occurred when the mother was unable to be present to breast feed. Infants randomised to the dummy groups received a dummy on entry into the trial. Full breast feeding (compared with partial and none) and any breast feeding (compared with none) on discharge home. Secondary outcomes: prevalence of breast feeding at three and six months after discharge and length of hospital stay. 303 infants (and 278 mothers) were included in the intention to treat analysis. There were no significant differences for any of the study outcomes according to use of a dummy. Infants randomised to cup feeds were more likely to be fully breast fed on discharge home (odds ratio 1.73, 95% confidence interval 1.04 to 2.88, P = 0.03), but had a longer length of stay (hazard ratio 0.71, 0.55 to 0.92, P = 0.01). Dummies do not affect breast feeding in preterm infants. Cup feeding significantly increases the likelihood that the baby will be fully breast fed at discharge home, but has no effect on any breast feeding and increases the length of hospital stay.\n", + "output": "Conclusions: Cup feeding cannot be recommended over bottle feeding as a supplement to breastfeeding because it confers no significant benefit in maintaining breastfeeding beyond hospital discharge and carries the unacceptable consequence of a longer stay in hospital." + }, + { + "input": "Study1: Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study. Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.\nStudy2: Tianeptine: a novel strategy of psychopharmacological treatment of children with autistic disorder. Many autistic children have problems of eye contact and expressive language that limit the effectiveness of educational and behavioural interventions. Few controlled psychopharmacological trials have been conducted in autistic children to determine which agents may be effective for these associated features. Twelve male children (7.3 +/- 3.3 years) with autistic disorder, diagnosed by ICD-10 criteria, completed a placebo-controlled, double-blind crossover trial of tianeptine, which lasted for 12 weeks. Subjects were included in the study if their eye contact and expressive language was inadaequate for their developmental level. Subjects had not tolerated or responded to other psychopharmacological treatments (neuroleptics, methylphenidate, clonidine or desipramine). Teacher ratings on the aberrant behaviour checklist irritability, stereotypy and inappropriate speech factors were lower during treatment with tianeptine than during treatment with placebo. Clinician ratings (children's psychiatric rating scale autism, anger and speech deviance factors; children's global assessment scale; clinical global impressions efficacy) of videotaped sessions were not significantly different between tianeptine and placebo. Tianeptine were modestly effective in the short-term treatment of irritability in some children with autistic disorder. Copyright 2003 John Wiley & Sons, Ltd.\nStudy3: A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride. Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine. Outpatient clinic. A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study. Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale. Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity. Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.\n", + "output": "Conclusions: Clinicians considering the use of TCAs need to be aware of the limited and conflicting evidence of effect and the side effect profile when discussing this treatment option with people who have ASD and their carers. Further research is required before TCAs can be recommended for treatment of individuals with ASD." + }, + { + "input": "Study: Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. The antiplatelet drug cilostazol is efficacious for prevention of stroke recurrence compared with placebo. We designed the second Cilostazol Stroke Prevention Study (CSPS 2) to establish non-inferiority of cilostazol versus aspirin for prevention of stroke, and to compare the efficacy and safety of cilostazol and aspirin in patients with non-cardioembolic ischaemic stroke. Patients aged 20-79 years who had had a cerebral infarction within the previous 26 weeks were enrolled at 278 sites in Japan and allocated to receive 100 mg cilostazol twice daily or 81 mg aspirin once daily for 1-5 years. Patients were allocated according to a computer-generated randomisation sequence by means of a dynamic balancing method using patient information obtained at registration. All patients, study personnel, investigators, and the sponsor were masked to treatment allocation. The primary endpoint was the first occurrence of stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage). The predefined margin of non-inferiority was an upper 95% CI limit for the hazard ratio of 1\u00b733. Analyses were by full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT00234065. Between December, 2003, and October, 2006, 2757 patients were enrolled and randomly allocated to receive cilostazol (n=1379) or aspirin (n=1378), of whom 1337 on cilostazol and 1335 on aspirin were included in analyses; mean follow-up was 29 months (SD 16). The primary endpoint occurred at yearly rates of 2\u00b776% (n=82) in the cilostazol group and 3\u00b771% (n=119) in the aspirin group (hazard ratio 0\u00b7743, 95% CI 0\u00b7564-0\u00b7981; p=0\u00b70357). Haemorrhagic events (cerebral haemorrhage, subarachnoid haemorrhage, or haemorrhage requiring hospital admission) occurred in fewer patients on cilostazol (0\u00b777%, n=23) than on aspirin (1\u00b778%, n=57; 0\u00b7458, 0\u00b7296-0\u00b7711; p=0\u00b70004), but headache, diarrhoea, palpitation, dizziness, and tachycardia were more frequent in the cilostazol group than in the aspirin group. Cilostazol seems to be non-inferior, and might be superior, to aspirin for prevention of stroke after an ischaemic stroke, and was associated with fewer haemorrhagic events. Therefore, cilostazol could be used for prevention of stroke in patients with non-cardioembolic stroke. Otsuka Pharmaceutical. Copyright \u00a9 2010 Elsevier Ltd. All rights reserved.\n", + "output": "Conclusions: Cilostazol is more effective than aspirin in the prevention of vascular events secondary to stroke. Cilostazol has more minor adverse effects, although there is evidence of fewer bleeds." + }, + { + "input": "Study: Effect of a low-glycemic-index diet during pregnancy on obstetric outcomes. Pregnancy is a condition in which the glycemic index (GI) may be of particular relevance because maternal glucose is the main energy substrate for intrauterine growth. The aim was to compare the effects of low-GI and conventional dietary strategies on pregnancy outcomes in healthy women. Compliance and acceptability were also investigated. The subjects were assigned alternately to receive dietary counseling that encouraged either low-GI (LGI) carbohydrate foods or high-fiber, moderate-to-high GI (HGI) foods and were studied 5 times between <16 wk gestation and delivery. Of the 70 women who met the inclusion criteria, 62 completed the study (32 in the LGI and 30 in the HGI groups). Primary outcomes were measures of fetal size. The mean diet GI fell significantly in the LGI group but not in the HGI group. Compared with the LGI group, women in the HGI group gave birth to infants who were heavier (3408 +/- 78 compared with 3644 +/- 90 g; P = 0.051) and had a higher birth centile (48 +/- 5 compared with 69 +/- 5; P = 0.005), a higher ponderal index (2.62 +/- 0.04 compared with 2.74 +/- 0.04; P = 0.03), and a higher prevalence of large-for-gestational age (3.1% compared with 33.3%; P = 0.01). Women in the LGI group found the diet easier to follow. Because birth weight and ponderal index may predict chronic disease in later life, a low-GI diet may favorably influence long-term outcomes.\n", + "output": "Conclusions: While a low glycaemic index diet was seen to be beneficial for some outcomes for both mother and child, results from the review were inconclusive. Further trials with large sample sizes and longer follow up are required to make more definitive conclusions. No conclusions could be drawn from the high-fibre versus control-diet comparison since the trial involved did not report on many of the outcomes we prespecified." + }, + { + "input": "Study1: Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder. The study was undertaken to determine the safety and efficacy of NIPRISAN, a phytomedicine, developed for the management of patients with Sickle Cell Disorder (SCD). The study design is a placebo-controlled double blind cross-over trial. Eighty-two (82) patients with SCD were recruited and randomised into two groups. An initial 4 month pre-trial study was undertaken to determine the similarity of the groups. The main study was conducted over a twelve-month period with crossover at six months. Safety of the drug was assessed clinically and biochemically. NIPRISAN significantly (P < 0.01) reduced the frequency of SCD crisis associated with severe pains. Acute toxicity to the liver assessed by the activities of liver enzymes, indicate that NIPRISAN is safe. Renal function assessed by the serum levels of creatinine and blood urea nitrogen remained normal. Both the clinical and laboratory results of the present phase IIB (pivot) clinical study suggest that NIPRISAN is a safe and efficacious phytomedicine for the management of patients with Sickle Cell Disorder.\nStudy2: Clinical evaluation of extract of Cajanus cajan (Ciklavit) in sickle cell anaemia. The major pathology in sickle cell anaemia (SCA) is sickling of red cells due to the precipitation of reduced haemoglobin. We report our experience with extract of Cajanus cajan as a possible antisickling agent by determining changes, if any, in clinical and laboratory features of the disease in patients given the extract in a single-blind placebo-controlled study. One hundred patients with steady-state SCA were randomized into treatment and placebo arms. The extract/placebo were administered twice daily to the subjects. Weight, hepatosplenomegaly, blood levels of biliurubin, urea, creatinine, and packed cell volume (PCV) were monitored over a 6-month period. Recall episodes of pain 6 months before enrolment were compared with episodes of pains recorded during the treatment period. Twenty-six cases (55.3 per cent) had hepatomegaly on enrolment. This significantly reduced to 33.3 per cent at 6 months (p = 0.03); but increased in the placebo arm (p > 0.05). The total number of recall painful episodes in cases was 207 (mean 4.4 +/- 10.3 (SD), range 0-60) and fell to 191 (mean 4.2 +/- 4.4 (SD), range 0-16); p = 0.03. Episodes of pain increased from 109 in controls (mean 2.6 +/- 5.0 (SD), range 0-26) to 164 (mean 3.9 +/- 4.3 (SD), range 0-22); p = 0.01. Mean PCV in the cases showed no appreciable changes (p = 0.1) but there was a significant increase in the controls (p = 0.02). In conclusion, the extract may cause a reduction of painful crises and may ameliorate the adverse effects of sickle cell anaemia on the liver. The mechanism of action remains to be determined.\n", + "output": "Conclusions: While Niprisan\u00ae appeared to be safe and effective in reducing severe painful crises over a six-month follow-up period, further trials are required to assess its role in the management of people with SCD and the results of its multicentre trials are awaited. Currently no conclusions can be made regarding the efficacy of Ciklavit\u00ae. Based on the published results for Niprisan\u00ae and in view of the limitations in data collection and analysis of both trials, phytomedicines may have a potential beneficial effect in reducing painful crises in SCD. This needs to be further validated in future trials. More trials are required on the safety and efficacy of phytomedicines used in managing SCD." + }, + { + "input": "Study1: A randomized controlled study of prostaglandin 15-methyl F2 alpha compared with syntometrine for prophylactic use in the third stage of labour. A randomized controlled study of 112 women with singleton pregnancies at term, and no antenatal complications, admitted in spontaneous labour were randomized to receive either an intramuscular injection of 0.5 mg of Syntometrine or an intramuscular injection of 125 ug of prostaglandin 15-methyl F2 alpha at delivery of the anterior shoulder of the baby. Blood lost in the first 2 hours, and subsequent 22 hours postdelivery were collected separately and measured by colourimetric measurement of haemoglobin content. Other parameters in the third stage were measured, including need for transfusion of blood or blood products, length of the third stage, and change in haemoglobin concentration before and 24 hours after delivery. The incidence of side-effects with administration of either prostaglandin 15-methyl F2 alpha or Syntometrine were documented. The prophylactic use of intramuscular prostaglandin 15-methyl F2 alpha (Carboprost) in the active management of the third stage of labour gave similar results to prophylactic intramuscular Syntometrine in terms of length of the third stage of labour, incidence of postpartum haemorrhage and total blood loss in the first 2 hours and subsequent 22 hours after delivery. However it has the disadvantage of higher cost, as well as statistically significant increase in the incidence of profuse and frequent diarrhoea. Based on these results intramuscular injection of prostaglandin 15-methyl F2 alpha offers no advantage over intramuscular Syntometrine for routine prophylactic use to reduce blood loss in the third stage of labour.\nStudy2: Sublingual misoprostol versus methylergometrine for active management of the third stage of labor. To compare the efficacy and side effects of sublingual misoprostol and intravenous methylergometrine for active management of third stage of labor. One hundred twenty low risk pregnant women at term with spontaneous onset of labor were included in the study. The women were randomized to receive either two tablets of misoprostol (200 microg/tablet) sublingually or 1 ml of methylergometrine (200 microg) intravenous injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were: need for additional oxytocic drugs, blood loss >or=500 ml, change in hemoglobin levels and side effects. Postpartum hemorrhage as defined by hemorrhage >or=500 ml occurred in 3.1% of the women in the sublingual misoprostol group but none of the women in the methylergometrine group (P > 0.05). There was a need for additional oxytocic drugs in 5.0% and 8.3% after methylergometrine and misoprostol, respectively (P > 0.05). The change in hemoglobin levels at 24 h postpartum were 0.8 and 0.7 gm% in methylergometrine and misoprostol group, respectively(P > 0.05). In the misoprostol group, 6.6% women developed fever >or=38 degrees C and 21.6% had shivering while in methylergometrine group none experienced these side effects. However, the incidence of other side effects like nausea, vomiting, headache and giddiness were similar in both groups. Sublingual misoprostol appears to be as effective as intravenous methylergometrine in the prevention of postpartum hemorrhage. However, larger randomized studies are needed to advocate its routine use.\nStudy3: The effect of sublingual misoprostol versus intravenous oxytocin in reducing bleeding after caesarean section. In this study, 100 singleton pregnant women underwent a caesarean delivery under general anaesthesia and were studied in terms of postpartum bleeding using oxytocin or misoprostol. Patients were randomly divided into two equal groups. One group received two tabs of misoprostol 200 microg sublingually and the second group took intravenous infusion of 20 units of oxytocin at the rate of 10 cc/min immediately after delivery until full contraction of the uterine. The amount of blood loss was lower in misoprostol group comparing with oxytocin group (608.91 ml vs 673.9 ml) (p = 0.048) and this difference was statistically significant. The need to give additional oxytocin therapy in oxytocin group (36%) was significantly higher than misoprostol group (14%) (p = 0.032). It seems that the efficacy of sublingual misoprostol is equivalent to that of low dose intravenous oxytocin in reducing postpartum haemorrhage at caesarean section. Misoprostol has some other advantages like long shelf -life, stability at room temperature and oral use.\nStudy4: A prospective randomised trial to compare the efficacy and safety of hemabate and syntometrine for the prevention of primary postpartum haemorrhage. In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.\nStudy5: Oral misoprostol for third stage of labor: a randomized placebo-controlled trial. To investigate whether orally administered misoprostol during the third stage of labor is efficient in reducing postpartum blood loss. In a double-masked trial, during vaginal delivery women were randomly assigned to receive a single oral dose of misoprostol (600 microg) or placebo in third stage of labor, immediately after cord clamping. The third stage of labor was managed routinely by early cord clamping and controlled cord traction; oxytocin was administered only if blood loss seemed more than usual. Blood loss was estimated by the delivering physician and differences in hematocrit were measured before and after delivery. Mean (+/- standard error of the mean) estimated blood loss (345 +/- 19.5 mL versus 417 +/- 25.9 mL, P = .031) and hematocrit difference (4.5 +/- 0.9% versus 7.9 +/- 1.2%, P = .014) were significantly lower in women who received misoprostol than those who received placebo. Fewer women in the misoprostol group had postpartum hemorrhage (blood loss of at least 500 mL), but that difference was not statistically significant (7% versus 15%, P = .43). Additional oxytocin before or after placental separation was used less often in the misoprostol group (16% versus 38%, P = .047). There were no differences in the length of third stage of labor (8 +/- 0.9 minutes versus 9 +/- 1 minutes, P = .947). There were no differences in pain during third stage of labor, postpartum fever, or diarrhea, but shivering was more frequent in the misoprostol group. Oral misoprostol administered in the third stage of labor reduced postpartum blood loss and might be effective in reducing incidence of postpartum hemorrhage.\nStudy6: Rectal misoprostol versus intravenous oxytocin for prevention of postpartum hemorrhage. To assess the effectiveness of 800 microg of rectal misoprostol compared with an intravenous infusion of 5 IU of oxytocin as prophylaxis against postpartum hemorrhage (PPH). A total of 514 women in labor were randomized into two groups (257 women in each). Within 1 minute of delivery of the anterior shoulder participants in group 1 received 800 microg of rectal misoprostol and 1 ampoule of normal saline in 5 mL lactated Ringer solution intravenously; group 2 received a rectal placebo tablet and 5 IU of oxytocin in 5 mL lactated Ringer solution intravenously. Both groups were comparable regarding the need for uterotonics, blood transfusion, and hematocrit drop of 10% or greater, 24 hours post partum (P=0.54, P=0.25, and P=0.85, respectively). Fever was significantly higher among misoprostol patients (18.7% vs 0.8%, P<0.001). Routine use of 800 microg of rectal misoprostol was effective in reducing blood loss after delivery. We recommend the regimen for low-resource, busy obstetric settings.\nStudy7: A randomized clinical trial comparing oral misoprostol with synthetic oxytocin or syntometrine in the third stage of labour. This is a multicentre, blocked, randomized trial to compare the efficacy of oral misoprostol 400 microg with current injectable uterotonic agents (oxytocin/ Syntometrine) used prophylactically in the third stage of labour. Main outcome measures were blood loss, use of a second uterotonic agent and difference in haemoglobin level from antepartum to postpartum. Data analysis from 863 women showed a statistically significant increase in both the mean blood loss (p < 0.001) and the rate of postpartum haemorrhage > 500 mL, (RR 2.72: 95% C1 1.73-4.27) in the misoprostol group compared to the oxytocin/Syntometrine group. The use of a second uterotonic agent was higher in the misoprostol group (RR 2.89: 95% Cl 2.00-4.18) as well as a greater decrease in postpartum haemoglobin (p = 0.015). Oral misoprostol 400 microg is significantly less effective than the traditional intramuscular uterotonic agents currently used and therefore cannot be considered as a viable option to these agents in the management of the third stage of labour.\nStudy8: Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled trial. to determine if misoprostol is safe and efficacious in preventing postpartum haemorrhage (PPH) when administered by trained traditional birth attendants (TBA) at home deliveries. a randomised, double-blind, placebo-controlled trial. Chitral, Khyber Pakhtunkhwa Province, Pakistan. a total of 1119 women giving birth at home. from June 2006 to June 2008, consenting women were randomised to receive 600 microg oral misoprostol (n = 534) or placebo (n = 585) after delivery to determine whether misoprostol reduced the incidence of PPH (\u2265 500 ml). the primary outcomes were measured blood loss \u2265 500 ml after delivery and drop in haemoglobin >2 g/dl from before to after delivery. oral misoprostol was associated with a significant reduction in the rate of PPH (\u2265 500 ml) (16.5 versus 21.9%; relative risk 0.76, 95% CI 0.59-0.97). There were no measurable differences between study groups for drop in haemoglobin >2\u2003g/dl (relative risk 0.79, 95% CI 0.62-1.02); but significantly fewer women receiving misoprostol had a drop in haemoglobin >3 g/dl, compared with placebo (5.1 versus 9.6%; relative risk 0.53, 95% CI 0.34-0.83). Shivering and chills were significantly more common with misoprostol. There were no maternal deaths among participants. postpartum administration of 600 microg oral misoprostol by trained TBAs at home deliveries reduces the rate of PPH by 24%. Given its ease of use and low cost, misoprostol could reduce the burden of PPH in community settings where universal oxytocin prophylaxis is not feasible. Continual training and skill-building for TBAs, along with monitoring and evaluation of programme effectiveness, should accompany any widespread introduction of this drug.\nStudy9: Prophylactic intramyometrial carboprost tromethamine does not substantially reduce blood loss relative to intramyometrial oxytocin at routine cesarean section. The influence of intramyometrial injection of 125 micrograms of 15-s-15-methyl prostaglandin F2 alpha (carboprost tromethamine, Prostin/15M) versus 20 U of oxytocin immediately after delivery of placenta on blood loss at cesarean section was investigated by means of a double-blinded, randomized trial. Hematocrit decrease from the day before operation to the third postoperative day was used as an index of blood loss. Decreases in hematocrit were comparable for the oxytocin and carboprost tromethamine groups. Excess blood loss (hematocrit decrease more than 6 vol. %) was significantly associated with the indication for cesarean section (three of four for cephalopelvic disproportion versus 9 of 42 others, p less than 0.01), but not with age, parity, number of prior cesarean sections, or birthweight. Carboprost tromethamine does not appear to be more effective than oxytocin when given by intramyometrial injection at this dose for routine cesarean section; its prophylactic utility in higher doses or in cases at risk for hemorrhage from uterine atony remains to be investigated.\nStudy10: The misoprostol third stage of labour study: a randomised controlled comparison between orally administered misoprostol and standard management. To compare misoprostol with standard oxytocic regimens in the prevention of postpartum haemorrhage. Randomised controlled trial. Obstetric unit in a large teaching hospital. One thousand women randomised to 500 microg misoprostol given orally or to standard oxytocic regimens of oxytocin, oxytocin with ergometrine, or ergometrine. Incidence of postpartum haemorrhage and the incidence and severity of side effects. Postpartum haemorrhage occurred in 12% of women given misoprostol and in 11% of women given standard oxytocic drugs (relative risk (RR) 1.10, 95% confidence interval (CI) 0.79, 1.55). Blood loss of 1000 mL or more occurred in 2% of women in each group. Nausea, headache, dizziness and tiredness were less frequent with misoprostol (RR (95% CI) 0.71 (0.59, 0.84); 0.53 (0.38, 0.74); 0.73 (0.61, 0.87) and 0.88 (0.83, 0.94) respectively). The main side effects of misoprostol were shivering (RR 1.95, 95% CI 1.69, 2.25) and a rise in temperature (difference in mean rise 0.34 degrees C, 95% CI 0.26, 0.42). Oral misoprostol for the prevention of postpartum haemorrhage was comparable to standard oxytocics. Many side effects were less common with misoprostol but shivering and pyrexia were more common. Larger randomised trials are needed before establishing the equivalence between misoprostol and standard oxytocic drugs in the prevention of postpartum haemorrhage.\n", + "output": "Conclusions: Oral or sublingual misoprostol shows promising results when compared with placebo in reducing blood loss after delivery. The margin of benefit may be affected by whether other components of the management of the third stage of labour are used or not. As side-effects are dose-related, research should be directed towards establishing the lowest effective dose for routine use, and the optimal route of administration.\nNeither intramuscular prostaglandins nor misoprostol are preferable to conventional injectable uterotonics as part of the management of the third stage of labour especially for low-risk women; however, evidence has been building for the use of oral misoprostol to be effective and safe in areas with low access to facilities and skilled healthcare providers and future research on misoprostol use in the community should focus on implementation issues." + }, + { + "input": "Study1: A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia (PA). Randomized, double-blind, placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month. Two geriatric hospitals in the North Western Health Care Network, Melbourne, Australia. Thirty-one inpatients with serum vitamin B12 levels between 100 and 150 pmol/L, without PA, other malabsorption disorders, or progressive neurological or terminal illness. The mean age was 81.4 years. After informed consent, a medical and drug history was taken and the Mini-Mental State Examination (MMSE) completed. A dietitian made assessment of oral cobalamin intake. Blood was taken for serum vitamin B12, serum and red cell folate assay, full blood examination, fasting serum gastrin, parietal and intrinsic factor antibodies, fasting serum homocysteine, and creatinine. Patients were then randomized to receive 10 microg oral cyanocobalamin, 50 microg oral cyanocobalamin, or placebo treatment for 1 month, after which the investigations and clinical examinations were repeated. Percentage change in the level of vitamin B12, homocysteine, folate, and red cell parameters and absolute changes in MMSE were calculated and compared between groups. The groups were compared on the number of responders who improved their level of B12 by 20%. Chi-square calculations on changes in serum vitamin B12 concentration were also performed. Mean serum vitamin B12 +/- standard deviation improved by 51.7 +/- 47.1% in the 50-microg group, 40.2 +/- 34.4% in the 10-microg group, and 11.7 +/- 24.5% in the placebo group. The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group (P=.044). The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group (P=.186). Eight of 10 subjects in each treatment group were classified as responders, compared with two of 11 in the placebo group (P=.004). Homocysteine levels fell in patients receiving cyanocobalamin, but this fall failed to reach statistical significance. There were no significant changes in the other parameters measured. Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12. This result has implications for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12.\nStudy2: No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported. A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40-2.00 micromol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later. At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P = 0.43), nor among individuals with only slightly impaired cognitive function (n = 44, total CAMCOG score: P = 0.42). The treatment group did not improve in depression score as compared to the placebo group (P = 0.18). The duration of impaired cognitive function was unknown. A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period.\n", + "output": "Conclusions: Evidence of any efficacy of vitamin B12 in improving the cognitive function of people with dementia and low serum B12 levels is insufficient. The included trials (De La Fourniere 1997; Hvas 2004; Seal 2002) were restricted to a small number of patients with Alzheimer's disease and other types of cognitive impairment. No trials involving people without dementia or using other definitions of vitamin B12 deficiency were found." + }, + { + "input": "Study1: Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. Effective ways to prevent arthropathy in severe hemophilia are unknown. We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI). Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.\nStudy2: Evaluation of prophylactic replacement therapy in haemophilia B. Prophylaxis replacement therapy has been assessed for a period of 12 months in 10 patients with severe haemophilia B showing a high incidence of spontaneous bleeding episodes. Two different schedules of administration of a freeze-dried factor IX concentrate were randomly evaluated: according to scheme A, 7.5 U/kg were administrated biweekly, whereas scheme B was based on the weekly infusion of 15 U/kg. On prophylaxis the frequency of bleeding episodes was significantly reduced (P less than 0.005) when compared with that observed in one-year period preceding the trial. Biweekly infusions were superior to weekly infusion (P less than 0.01), and the benefit appeared to be related to the higher number of days in which measurable levels of factor IX were attained in plasma. Range of motion, which was redeced at the start of the trial in 26 joints, was found to have improved in 23. Favourable changes of the joint radiological picture were observed in 6 cases. Hepatitis and factor IX inhibitors did not develop during the trial period. Side effects were rare and mild.\n", + "output": "Conclusions: There is strong evidence from randomised controlled trials and observational trials that prophylaxis preserves joint function in children with hemophilia as compared to on-demand treatment. There is insufficient evidence from randomised controlled trials to confirm the observational evidence that prophylaxis decreases bleeding and related complications in patients with existing joint damage. Well-designed randomised controlled trials and prospective observational controlled studies are needed to establish the best prophylactic regimen and to assess the effectiveness of prophylactic clotting factor concentrates in adult patients." + }, + { + "input": "Study1: Two-year follow-up of a social-cognitive intervention to prevent substance use. This study presents two-year follow-up results of the Adolescent Decision-Making Program initially implemented when students were in their sixth grade. The intervention was found to maintain a positive effect on mean tobacco use, but no differences were observed for mean alcohol, marijuana, or hard drug use. In a test of the differential effectiveness of the intervention, program students living with married parents reported lower mean tobacco use than control students living with married parents and program and control students living with single parents. Logistic regression analyses examining the proportion of users at follow-up revealed a negative program effect for alcohol and no differences for the other substances. Subsequent attrition analyses strongly suggested that the positive effect for tobacco use at follow-up was most likely even stronger, and that the negative effect for alcohol was spurious. The importance of examining both program and attrition effects when evaluating the impact of longitudinal preventive interventions was emphasized, and the need to consider alternative models to guide the conceptualization and evaluation of adolescent substance use prevention programs was discussed.\nStudy2: Drug abuse prevention among minority adolescents: posttest and one-year follow-up of a school-based preventive intervention. Most drug abuse prevention research has been conducted with predominantly White middle-class adolescent populations. The present study tested a school-based drug abuse preventive intervention in a sample of predominantly minority students (N = 3,621) in 29 New York City schools. The prevention program taught drug refusal skills, antidrug norms, personal self-management skills, and general social skills in an effort to provide students with skills and information for resisting drug offers, to decrease motivations to use drugs, and decrease vulnerability to drug use social influences. Results indicated that those who received the program (n = 2,144) reported less smoking, drinking, drunkenness, inhalant use, and polydrug use relative to controls (n = 1,477). The program also had a direct positive effect on several cognitive, attitudinal, and personality variables believed to play a role in adolescent substance use. Mediational analyses showed that prevention effects on some drug use outcomes were mediated in part by risk-taking, behavioral intentions, and peer normative expectations regarding drug use. The findings from this study show that a drug abuse prevention program originally designed for White middle-class adolescent populations is effective in a sample of minority, economically disadvantaged, inner-city adolescents.\nStudy3: Drug refusal behavior: the relative efficacy of skills-based and information-based treatment. Examined the impact of two treatment strategies on children's drug refusal skills and drug-related information. Fifty-seven third graders were randomly assigned to one of three groups: rehearsal-plus, general information, and control. Children in the rehearsal-plus group were taught drug knowledge, assertiveness skills, decision-making skills, rationale and specific drug refusal skills in the context of a skills-based strategy. At a more global level, the general information group targeted all of the same components with the exception of rationale. Results indicated that children in the skills-based strategy (rehearsal-plus) showed significant improvement in behavioral skills, decision-making, and rationale, while children in the information/education-based strategy (general information) improved most on the measure of general knowledge. At follow-up, gains were generally maintained.\nStudy4: An experimental evaluation of a drug education course. nan\n", + "output": "Conclusions: Skills based programs appear to be effective in deterring early-stage drug use. The replication of results with well designed, long term randomised trials, and the evaluation of single components of intervention (peer, parents, booster sessions) are the priorities for research. All new studies should control for cluster effect." + }, + { + "input": "Study: Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial. A randomized double-blind trial of colchicine vs placebo was conducted in 67 patients with histologically proven alcoholic hepatitis, 33 of whom had cirrhosis. Patients with hepatic encephalopathy, ascites, protracted prothrombin time, severe thrombocytopenia, hepatocellular carcinoma, evident lack of discipline or refusal to participate in the trial were not included. Thirty-three patients received colchicine (1 mg/day) and 34 received placebo for 6 months. Blood parameters including N-terminal peptide of type III procollagen were assessed in the serum, and a percutaneous liver biopsy was performed at the start of the trial and after 3 and 6 months. Alcoholic hepatitis and fibrosis scores were established for each biopsy specimen. Twenty-eight percent of patients were lost to follow-up at 3 months, and fifty-two percent at 6 months. One patient died of liver failure. Fifty-eight percent of patients were abstaining from alcohol at 3 months and fifty percent at 6 months. No significant effect of treatment was noted. Nevertheless, improvement in alcoholic hepatitis core at 3 months was more important in the colchicine group than in the placebo group. No side-effects were noted except transient diarrhea. Our results suggest that colchicine has no important effect on the course of alcoholic hepatitis. A trial including of at least 260 patients might be necessary for the observed alcoholic hepatitis score difference at 3 months, favoring colchicine, to be statistically significant.\n", + "output": "Conclusions: Colchicine should not be used for alcoholic, viral, or cryptogenic liver fibrosis or liver cirrhosis outside randomised clinical trials." + }, + { + "input": "Study1: Psychological support for patients undergoing breast cancer surgery: a randomised study. To evaluate the effect of support from a nurse specialising in breast care and a voluntary support organisation on prevalence of psychological morbidity after surgery for breast cancer. Prospective randomised study. Three teaching hospitals in Glasgow with established breast clinics. 272 women aged less than 70 years undergoing surgery for breast cancer. Patients were randomly allocated to receive routine care from ward staff, routine care plus support from breast care nurse, routine care plus support from voluntary organisation, or routine care plus support from nurse and organisation. Prevalence of psychological morbidity as assessed by self rating scales: 28 item general health questionnaire and its subscales, and hospital anxiety and depression scale. Measurements were made at first postoperative clinic visit and at three, six, and 12 months after surgery. On each self rating scale, psychological morbidity tended to fall over the 12 month period. For each scale, scores were consistently lower in patients offered support from breast care nurse alone compared with the other groups, which were similar to each other. Differences were significant or nearly so: P values were 0.015 (28 item general health questionnaire), 0.027 (anxiety and insomnia), 0.072 (severe depression), 0.053 (somatic symptoms), 0.031 (social dysfunction), 0.093 (hospital anxiety), and 0.003 (hospital depression). Support from breast care nurse can significantly reduce psychological morbidity, as measured by self rating scales, in women undergoing breast cancer surgery.\nStudy2: Nurse-led follow-up on demand or by a physician after breast cancer surgery: a randomised study. The value of routine follow-up with frequent visits to a breast cancer specialist-both in terms of detection of recurrence and patient satisfaction-has been questioned. The aim of this study was to compare nurse-led follow-up on demand versus physician follow-up after breast cancer treatment with regards to patients' well-being, satisfaction, access to medical care and medical safety. Two hundred and sixty-four consecutively selected women with newly diagnosed breast cancer, classified as UICC stage I or stage II, were randomised to follow-up at two hospitals in Sweden, either by routine medical follow-up, the physician group (PG, n=131), or on demand by a specialist nurse, the nurse group (NG, n=133). Measures were done at baseline and twice a year over a period of 5 years by means of a questionnaire containing the Hospital Anxiety and Depression Scale (HAD), and the Satisfaction and Accessibility (SaaC) scale. Number of contacts with the health care services, number of diagnostic procedures, and time to recurrence or death were monitored. The ratings of HAD and SaaC did not show any statistically significant differences between the groups. The levels of anxiety and depression were generally low and levels of patient satisfaction high. There were no differences between the groups concerning time to recurrence or death. This study indicates that women with breast cancer in stages I to II can be followed up by a specialist nurse with high patient satisfaction and good medical safety.\nStudy3: Effect of counselling on the psychiatric morbidity associated with mastectomy. A controlled trial was conducted to determine whether counselling by a specialist nurse prevented the psychiatric morbidity associated with mastectomy and breast cancer. Seventy-five patients were counselled by the nurse and monitored during follow-up, while 77 patients received only the care normally given by the surgical unit. Counselling failed to prevent morbidity, but the nurse's regular monitoring of the women's progress led her to recognise and refer 76% of those who needed psychiatric help. Only 15% of the control group whose condition warranted help were recognised and referred. Consequently, 12 to 18 months after mastectomy there was much less psychiatric morbidity in the counselled group (12%) than in the control group (39%). These findings highlight the high degree of psychiatric morbidity in patients who have undergone mastectomy and indicate the need to find ways of reducing this morbidity.\nStudy4: Effects of a nursing intervention on subjective distress, side effects and quality of life of breast cancer patients receiving curative radiation therapy--a randomized study. The purpose of this randomized study was to investigate whether a nursing intervention using Orem's self-care theory as a framework would affect subjective distress, side effects and quality of life as perceived by breast cancer patients receiving curative radiation therapy. The intervention consisted of five 30-min sessions once a week during the treatment period and two follow-up sessions after completion of treatment. The experimental group consisted of 67 patients, as did the control group. Measurements were collected five times: at baseline before commencement of treatment, at weeks 3 and 5 (completion of treatment) and follow-up periods of 2 weeks and 3 months. No measurable effect of the nursing intervention was found for side effects or quality of life but nursing intervention proved to have a positive effect in minimizing stress reactions (p = < 0.05). It is suggested that a nursing intervention should be implemented for breast cancer patients receiving curative radiation therapy.\nStudy5: Effects of advanced nursing care on quality of life and cost outcomes of women diagnosed with breast cancer. To evaluate quality of life (QOL) and cost outcomes of advanced practice nurses' (APNs') interventions with women diagnosed with breast cancer. Randomized clinical trial. Integrated healthcare system in a midwestern suburban community. 210 women with newly diagnosed breast cancer with an age range of 30-85 years. The control group (n = 104) received standard medical care. The intervention group (n = 106) received standard care plus APN interventions based on Brooten's cost-quality model and the Oncology Nursing Society's standards of advanced practice in oncology nursing QOL was measured using the Functional Assessment of Cancer Therapy, Mishel Uncertainty in Illness Scale and Profile of Mood States at seven intervals over two years. Information about costs (charges and reimbursement) was collected through billing systems. Uncertainty, mood states, well-being, charges, and reimbursement. Uncertainty decreased significantly more from baseline in the intervention versus control group at one, three, and six months after diagnosis (p = 0.001, 0.026, and 0.011, respectively), with the strongest effect on subscales of complexity, inconsistency, and unpredictability. Unmarried women and women with no family history of breast cancer benefited from nurse interventions in mood states and well-being. No significant cost differences were found. APN interventions improved some QOL indicators but did not raise or lower costs. The first six months after breast cancer diagnosis is a critical time during which APN interventions can improve QOL outcomes. More research is necessary to define cost-effective interventions.\n", + "output": "Conclusions: There is limited evidence at this time to support the contention that interventions by BCNs assist in the short-term with the recognition and management of psychological distress for women with breast cancer. Further research is required before the impact of BCNs on aspects of quality of life for women with breast cancer can be known." + }, + { + "input": "Study1: Is in-patient management of diastolic blood pressure between 90 and 100 mm Hg during pregnancy necessary? A randomised controlled trial was performed at the Queen Elizabeth Hospital to compare the effects and acceptance of routine in-patient versus out-patient management of diastolic blood pressure between 90 and 100 mm Hg in pregnant women. There were no significant differences in the establishment of the diagnosis of hypertension, development of severe hypertension or proteinuric hypertension, the number of women requiring obstetric interventions, or the neonatal outcome between the two groups. Antenatal hospital stay for the in-patient group, however, was more than twice as long as for the out-patient group (difference in mean stay, 3.7 days; 95% confidence interval, 1.3-6.2). The number of hospitalisations in the in-patient group was almost four times greater than that in the out-patient group (difference in mean number of hospitalisations, 1.7; 95% confidence interval, 1.2-2.2). The two groups did not differ in their levels of satisfaction of the overall management of blood pressure. Nevertheless, a greater proportion of women preferred to choose the same type of care among the out-patient group than among the in-patient group if they had hypertension in a future pregnancy (83.7% versus 51.2%; P<0.001). More women were dissatisfied about the number of admissions than on the frequency of out-patient care (40.5% versus 16.3%; P<0.001). We conclude that in-patient care, day care, or home monitoring should be individualised.\nStudy2: Does admission to hospital for bed rest prevent disease progression or improve fetal outcome in pregnancy complicated by non-proteinuric hypertension? To test whether a policy of admission to hospital for rest is of value in the management of women with non-proteinuric hypertension during pregnancy. A randomized controlled trial. Harare Maternity Hospital, Zimbabwe. 218 (28 first pregnancies) women with non-proteinuric hypertension and a singleton pregnancy at between 28 and 38 weeks gestation allocated to rest in hospital or routine outpatient care. Admission to hospital for rest. Encouraged to rest in bed although voluntary ambulation around the ward was allowed. The women in the control group were encouraged to continue normal activity at home, to check urine each day for proteinuria. All the women were reviewed weekly. Disease progression was assessed by the development of severe hypertension (greater than or equal to 160/110 mmHg), development of proteinuria, need for induction of labour and number of infants born preterm (less than 37 weeks). Fetal outcome was assessed by birthweight, number of infants small-for-gestational age (SGA), and the number of infants requiring admission to the neonatal unit and their length of stay. The hospital rest group had a decreased risk of developing severe hypertension (blood pressure greater than or equal to 160/110 mmHg [odds ratio 0.47, 95% CI 0.26-0.83]). No differences were found in fetal growth or neonatal morbidity. The mean antenatal stay in hospital was 22.2 (SD 16.5), and 6.5 (SD 7.9) days in the rest and control groups, respectively. Hospital admission for bed rest decreased the risk of developing severe hypertension but no improvement in fetal growth or neonatal morbidity was observed. Fetal monitoring at home and continued outpatient antenatal care provided a safe, alternative policy to hospital admission.\nStudy3: A randomized controlled trial of complete bed rest versus ambulation in the management of proteinuric hypertension during pregnancy. Forty patients participated in a randomized controlled trial of complete bed rest versus ambulation as desired in the management of proteinuric hypertension during pregnancy. Daily increases in serum human placental lactogen and oestriol concentrations were greater in the rested group. An especially 'at risk' group of 10 patients with both hyperuricaemia and severe fetal growth retardation was identified. Strict confinement to bed in these cases seemed to encourage the development of the premonitory symptoms of eclampsia, but was associated with a better prognosis for the fetus.\n", + "output": "Conclusions: Few randomised trials have evaluated rest for women with hypertension during pregnancy, and important information on side-effects and cost implication is missing from available trials. Although one small trial suggests that some bed rest may be associated with reduced risk of severe hypertension and preterm birth, these findings need to be confirmed in larger trials. At present, there is insufficient evidence to provide clear guidance for clinical practice. Therefore, bed rest should not be recommended routinely for hypertension in pregnancy, especially since more women appear to prefer unrestricted activity, if the choice were given." + }, + { + "input": "Study1: Lactational amenorrhea and the recovery of ovulation and fertility in fully nursing Chilean women. The probability of experiencing the first postpartum bleeding, the first ovulation and the risk of pregnancy during exclusive breastfeeding was assessed in a selected group of urban Chilean women. Admission criteria included having had a normal pregnancy and a vaginal term delivery of a healthy infant and the desire to maintain breastfeeding for as long as possible. The risk of bleeding and the recovery of ovulation was assessed in 48 women selected for being amenorrheic and fully nursing at day 75 postpartum and their willingness to participate in the blood sampling protocol. The first bleeding and ovulation was experienced while fully nursing by 28% and 26% of these subjects, respectively, at day 180 postpartum. The probability of experiencing the first bleeding and the probability of pregnancy during full nursing were calculated for 236 women not contracepting who were enrolled during the first month postpartum. The cumulative probability of bleeding and of pregnancy was 52% and 9.4% at day 180 postpartum, respectively. The risk of pregnancy was less than 2% in the subset of amenorrheic cases. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with infertility was too weak to serve as an effective birth spacer, except for the period of lactational amenorrhea. When the first postpartum bleeding took place before the sixth postpartum month in fully nursing women, it had a good predictive value to indicate the onset of a higher risk period.\nStudy2: Clinical study of the lactational amenorrhoea method for family planning. The effect of breastfeeding on fertility is well known; however, its use as a method of family planning was, until recently, untested. In 1988, the Bellagio Consensus Conference proposed guidelines that became the basis for a method of family planning called the lactational amenorrhoea method (LAM). The principle of LAM is that a woman who continues to fully or nearly fully breastfeed her infant and who remains amenorrhoeic during the first 6 months postpartum is protected from pregnancy during that time. We have assessed this method in the context of a breastfeeding support intervention study of 422 middle-class women in urban Santiago, Chile. The cumulative 6-month life-table pregnancy rate was 0.45% among women who relied on LAM as their only family planning method (1 woman pregnant in month 6). The findings indicate that LAM, with its high acceptance and efficacy, is a viable method of family planning and can safely serve as an introductory method for breastfeeding women.\nStudy3: Multicenter study of the Lactational Amenorrhea Method (LAM): I. Efficacy, duration, and implications for clinical application. A multicenter study of the Lactational Amenorrhea Method (LAM) was carried out to test the acceptability and efficacy of the method. Additionally, the data are used to test new constructs for improvement of method criteria. A protocol was designed at the Institute for Reproductive Health (IRH), Department of Obstetrics and Gynecology, Georgetown University Medical Center, a World Health Organization (WHO) Collaborating Center, and was reviewed and modified in collaboration with the co-sponsors, the World Health Organization and the South to South Cooperation for Reproductive Health, and the principal investigators from each site. Data were gathered prospectively on LAM acceptors at 11 sites. Data were entered and cleaned on-site and further cleaned and analyzed at IRH, using country-level and pooled data to produce descriptive statistics and life tables. The 98+% efficacy of LAM is confirmed in a wide variety of settings. In addition, the results yield insight on the possibility of continued use beyond 6 months. LAM is found to be highly effective as an introductory postpartum method when offered in a variety of cultures, health care settings, socio-economic strata, and industrial and developing country locales. In addition, LAM acceptance complements breastfeeding behaviors without ongoing breastfeeding support services. The parameters studied yield high efficacy and method continuation. Therefore, the basic tenets of the 1995 Bellagio consensus on LAM is reconfirmed and it is recommended that LAM be reconfirmed and it is recommended that LAM be incorporated into hospital, maternity, family planning, maternal and child health, and other primary health care settings.\nStudy4: Breast-feeding, return of menses, sexual activity and contraceptive practices among mothers in the first six months of lactation in Onitsha, South Eastern Nigeria. The objective of this study was to determine the exclusive breast-feeding practices, return of menstruation, sexual activity and contraceptive practices among breast-feeding mothers in the first six months of lactation. The study was based in Onitsha, South Eastern Nigeria. A structured questionnaire was used to obtain data from breast-feeding mothers on their age, educational attainment, breast-feeding practices, return of menstruation, sexual activity and contraceptive practices within the first six months of lactation at intervals of 6 weeks, 10 weeks 14 weeks and 6 months post delivery. Analysis of the information obtained showed that out of the 178 mothers who participated in the study 81% of the mothers were within the ages of 20 - 34 years. While all the mothers had formal education, the majority (59%) had secondary education. Seventy-three percent initiated breast-feeding within one hour of delivery. On discharge from hospital, all of them had already established breast-feeding which continued up to six weeks and dropped to 97.8% at six months. Exclusive breast-feeding which was practised by 100% on discharge dropped to 3.9% at six months. The feeding regimen was on demand as practised by 98.9% of the mothers. Menstrual flow had returned in 33.8% of the mothers by 6 weeks of lactation, and had risen to 70.2% at six months. There was more prolonged lactational amenorrheoa in exclusively breast-feeding mothers than in those who were not. By 6 weeks post delivery 31.6% of the mothers had resumed sexual activity and this rose to 93.6% at six months. With the resumption of sexual activity only 5% of the mothers resorted to contraceptive practices other than lactational amenorrhea and this increased to 54% at six months. There was no pregnancy in any of these women during the six months period. While appreciating the role of lactational amenorrhea in child spacing and considering the early return of sexual activity among the mothers the practice of introducing contraceptive practices needs to be encouraged especially in women whose menstruation has returned.\nStudy5: Contraceptive efficacy of lactational amenorrhea in urban Chilean women. The contraceptive efficacy of breastfeeding was assessed in 236 healthy urban women who were followed at monthly intervals during the first postpartum year. Proportional hazard models were used to evaluate the influence of time postpartum, menstrual status and breastfeeding pattern upon the risk of pregnancy. Time and menstrual status had a highly significant effect on this risk. Those women who remained in amenorrhea had cumulative probabilities of pregnancy of 0.9% and 17% at 6 and 12 months postpartum, respectively. In those who recovered menstrual cycles, the risk rose to 36% and 55% at 6 and 12 months, respectively. Milk supplementation also increased significantly the risk when considered alone but not when time and/or menstrual status were included in the analysis. However, amenorrheic women who introduced bottle feeding, had a higher risk of pregnancy after 6 months postpartum than those who remained fully nursing. The analysis was unable to detect a significant influence of the nursing frequency. The results confirm that lactational amenorrhea is an effective contraceptive during the first six months postpartum. The first postpartum bleeding marks a great increase in the risk of pregnancy. Supplementation also increases the risk, particularly in amenorrheic women.\nStudy6: Effectiveness of lactational amenorrhoea in prevention of pregnancy in Manila, the Philippines: non-comparative prospective trail. To determine the contraceptive efficacy of the lactational amenorrhoea method. Non-comparative prospective trial. Urban Manila, the Philippines. 485 lower income, educated women with extensive experience of breast feeding. Women were offered all available contraceptives for use after birth. Those who chose the lactational amenorrhoea method were taught the method, screened for the study, and followed for 12 months to determine the risk of pregnancy when the method was used. Life table pregnancy rates during correct and incorrect use of the method, censored monthly in the event of sexual abstinence or the use of another contraceptive method. The lactational amenorrhoea method was 99% effective when used correctly (that is, during lactational amenorrhoea and full or nearly full breast feeding for up to six months). At 12 months the effectiveness during amenorrhoea dropped to 97%. The lactational amenorrhoea method provided as much protection from pregnancy as non-breast feeding women experience with non-medicated intrauterine devices and barrier methods. The contraceptive effect of lactation cannot be attributed to lactational or postpartum abstinence.\nStudy7: Effectiveness of the lactational amenorrhea method in Pakistan. To determine the efficacy of the lactational amenorrhea method of family planning (amenorrhea during full or nearly full breastfeeding for 6 months postpartum). Prospective noncomparative study. Normal breastfeeding women in Karachi and Multan, Pakistan, most delivered at home by a midwife. Three hundred ninety-nine newly delivered mothers who successfully had breastfed a previous child and chose the lactational amenorrhea method to prevent a subsequent pregnancy, 391 of whom were followed for a full year. Mothers were taught, before or shortly after delivery, to use the method and were interviewed in their homes each month by a Lady Health Visitor. Life-table pregnancy rates. Periods of postpartum or lactational abstinence were excluded in the calculation of the pregnancy rates. During full or nearly full breastfeeding, while the women were amenorrheic and not otherwise contracepting, the rate of pregnancy was 0.6%. The pregnancy rate during lactational amenorrhea alone was 1.1% at 1 year postpartum. The lactational amenorrhea method was found to be highly effective for 6 months. A high degree of contraceptive protection endures for a full year during lactational amenorrhea, but not after the return of menses during breastfeeding.\nStudy8: Santiago Breastfeeding Promotion Program: preliminary results of an intervention study. A prospective intervention study was undertaken in Santiago, Chile, to assess the impact of a breastfeeding promotion program and the acceptance and use of the lactational amenorrhea method for natural child spacing. The intervention study significantly increased the duration of exclusive breastfeeding and amenorrhea. In addition, the use of the lactational amenorrhea method proved highly efficacious, with an unplanned pregnancy rate of less than 0.5% by 6-month cumulative life table. Total family planning coverage at 6 months was increased in the intervention group.\nStudy9: An assessment of the nine-month lactational amenorrhea method (MAMA-9) in Rwanda. This report presents a secondary data analysis based on prospectively collected records gathered during a field assessment that was carried out in Rwanda in August 1993. The assessment used service statistics and follow-up interviews to evaluate the efficacy of a modified lactational amenorrhea method (LAM) as a nine-month introductory postpartum natural family planning method. The program, carried out by Action Familiale Rwandaise (AFR), reflects high efficacy of the method in a compliant sample that sought this method followed by another form of family planning. These results are promising and provide guidance for the extended use of LAM past six months. Programmatic findings suggest that studies be conducted of the contribution of extended LAM to improved weaning practices, the high efficacy of continued reliance on substantial lactation and amenorrhea beyond nine months, and male involvement in LAM and breastfeeding.\nStudy10: Breastfeeding pattern and the duration of lactational amenorrhea in urban Chilean women. The influence of the breastfeeding pattern and several clinical variables upon the duration of postpartum amenorrhea was assessed in a group of healthy women selected for having had a normal pregnancy and delivery and being highly motivated for prolonged breastfeeding on demand. 676 women who were fully nursing at the second month postpartum entered the study. Supplements were administered to 11% and 48% of the infants by the end of the 3rd and 6th month, respectively. The first bleeding was experienced before the end of the sixth month postpartum by 57% of the cases. Supplementation had a strong negative influence while nursing frequency had a significant positive influence upon the length of amenorrhea. Notwithstanding, a frequency of 8+ suckling episodes per 24 h could not maintain amenorrhea in around half of the subjects. Age and parity had a moderate negative influence upon the risk of experiencing the first postpartum bleeding. Maternal weight and ponderal index, infant sex, birth weight and growth rate showed no significant influence upon the length of amenorrhea. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with amenorrhea was weak in comparison with what has been described for other populations. The risk of experiencing the first bleeding was reduced while fully breastfeeding with a high number of nursing episodes per day and night, particularly in older women with higher parity. But even in such situation 25% and 50% of the women had started to cycle by the end of the fifth and eight postpartum month.\n", + "output": "Conclusions: We found no clear differences in life table pregnancy rates between women using LAM and being supported in doing so, and fully breastfeeding amenorrheic women not using any method. Because the length of lactation amenorrhea in women using LAM was very different between the populations studied, and is population specific, it is uncertain whether the LAM extends lactational amenorrhea." + }, + { + "input": "Study: A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization. This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization. This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications. Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain. While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.\n", + "output": "Conclusions: Risperidone appears to have a marginal benefit in terms of clinical improvement compared with placebo in the first few weeks of treatment but data are limited, poorly reported and probably biased in favour of risperidone. The margin of improvement chosen by the researchers as their outcome may not be clinically meaningful. Even after so much use of this drug, we feel that further independent trials can be justified." + }, + { + "input": "Study: Long-term acetyl-L-carnitine treatment in Alzheimer's disease. In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.\n", + "output": "Conclusions: There is evidence for benefit of ALC on clinical global impression as a categorical measure and on MMSE at 24 weeks, but there is no evidence using objective assessments in any other area of outcome. Given the large number of comparisons made, the statistically significant results may be due to chance. At present there is no evidence to recommend its routine use in clinical practice. Many of the trials used rather vague descriptions of dementia and trials using more strictly defined groups may be informative. Individual patient data may add to the findings, as would trials including other outcomes (e.g. mood and caregiver quality of life). However, the evidence does not suggest that ALC is likely to prove an important therapeutic agent. More work on the pharmacokinetics of ALC in humans is also required." + }, + { + "input": "Study1: The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage. To establish the effect of antenatal vitamin K on the incidence and severity of intraventricular hemorrhage, 92 patients destined to deliver infants less than 32 weeks' gestation were, in a prospective fashion, randomly assigned to two groups. Group I received 10 mg of vitamin K1 intramuscularly every 5 days until delivery. Group II received no antenatal vitamin K1 therapy. There were 100 neonates less than 1500 gm, equally divided between groups I and II with respect to gestational age, birth weight, race, sex, presentation, route of delivery, duration of labor, Apgar scores, and arterial umbilical cord acid-base balance. The antenatal use of vitamin K resulted in significant reduction in the prothrombin time (12.7 versus 15.2 seconds) and partial thromboplastin time (42.6 versus 58.9 seconds; p less than 0.05). Furthermore, group I experienced a lower incidence of total (16% versus 36%) and severe (0% versus 11%) grades of intraventricular hemorrhage (p less than 0.05). This study suggests that the antenatal use of vitamin K may result in a reduction and severity of intraventricular hemorrhage in the neonate less than 1500 gm.\nStudy2: Antenatal vitamin K therapy of the low-birth-weight infant. The purpose of our study was to determine whether maternal vitamin K1 administered antenatally improved global coagulation parameters and the levels of specific vitamin K-dependent proteins in low-birth-weight infants. Thirty-three preterm mothers admitted in labor were assigned in a prospective, blinded fashion to receive either intramuscular vitamin K1 (17) or placebo (16). At delivery cord blood samples were tested for prothrombin time, activated partial thromboplastin time, factor II and protein C activity, and antigen levels. Statistical analysis was by Student t test. No statistically significant differences could be demonstrated with regard to group mean values for global tests (prothrombin time, activated partial thromboplastin time) or specific vitamin K-dependent protein levels (factor II, protein C) in newborns whose mothers received antenatal vitamin K compared with those who did not. These results would suggest that antenatal vitamin K1 therapy to mothers < 32 weeks' gestation has no significant effect on the level of vitamin K-dependent factors in the fetus.\nStudy3: Maternal antenatal administration of vitamin K1 results in increasing the activities of vitamin K-dependent coagulation factors in umbilical blood and in decreasing the incidence rate of periventricular-intraventricular hemorrhage in premature infants. Infants less than 35 weeks' gestation age are susceptible to periventricular-intraventricular hemorrhage (PIVH). This may be partially attributable to low concentrations of vitamin K-dependent coagulation factors. The purposes of this study were: (1) to determine the umbilical blood activity levels of vitamin K-dependent coagulation factors II, VII, IX and X; (2) to investigate the change in activities of these factors in premature infants' umbilical blood after prenatal administration of vitamin K1 to the mothers; and (3) to study the prophylactic effects on PIVH after maternal antenatal supplemental vitamin K1. Pregnant women in preterm labor at less than 35 weeks of gestation were randomly selected to receive antenatal vitamin K1 10 mg per day injection intramuscularly or intravenously for 2-7 days (vitamin K1 group, n = 40), or no such treatment (control group, n = 50). At the same period, cord blood samples were collected from thirty full-term neonates to compare the factor levels with those of premature infants. Intracranial ultrasound was performed by the same sonographer to determine the presence and severity of PIVH. The activities of vitamin K-dependent coagulation factors in umbilical blood in the control group were: factor II 25.64+/-9.49%, factor VII 59.00+/-17.66%, factor IX 24.67+/-8.88%, and factor X 30.16+/-5.02%. In full-term infants, the respective values were: factor II 36.70+/-4.88%, factor VII 64.54+/-10.62%, factor IX 30.18+/-5.69%, and factor X 34.32+/-12.63%. In vitamin K1 group these factors were: factor II 36.35+/-6.88%, factor VII 69.59+/-16.55%, factor IX 25.71+/-10.88%, and factor X 39.26+/-8.02%. The data suggest the absence of vitamin K-dependent coagulation factors in preterm infants, and antenatal supplement of vitamin K1 may increase the cord blood activity of factor II, VII and factor X (P < 0.001). In addition, the overall rates of PIVH in the vitamin K1 group and in controls were 32.4 and 52.0%, respectively (P = 0.036), and the frequency of severe PIVH was 5.0 and 20.0%, respectively (P = 0.038). Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation age may result in improved coagulation and may reduce the incidence as well as the severity degree of PIVH.\nStudy4: Maternal administration of vitamin K does not improve the coagulation profile of preterm infants. The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.\nStudy5: Maternal-fetal transport of vitamin K1 and its effects on coagulation in premature infants. We conducted a prospective study to determine (1) the maternal-fetal vitamin K1 transport in premature infants after vitamin K1 was given to the mothers antenatally and (2) the vitamin K1 effects on blood coagulation in the babies. Women in labor at less than or equal to 34 weeks of gestation were randomly selected to receive antenatal vitamin K1, 5 mg given intramuscularly (vitamin K1 group), or no vitamin K1 (control group). Eight infants, including one set of twins, were in the vitamin K1 group and six in the control group. Vitamin K1 concentrations were higher in the vitamin K1 group than in the control group (p = 0.06). Activated partial thromboplastin time was prolonged, and factor II coagulation activity and factor II antigen were proportionately decreased in cord plasma in both groups. The average ratio of factor II coagulation activity to antigen was not decreased in either group. Protein induced by vitamin K absence-II (PIVKA-II) was not detectable in any cord plasma sample in either group. These findings support previous reports that the decreased vitamin K-dependent coagulation activity in premature infants is the result of reduced synthesis of precursor proteins, rather than the result of vitamin K deficiency, and suggest that additional vitamin K1 is not likely to improve coagulation activity. Among those infants who underwent cranial ultrasonography, all four in the vitamin K1 group and one of five in the control group had mild intraventricular hemorrhage. Studies of a larger number of patients are necessary before it can be established that maternal antenatal administration of vitamin K1 results in improvement of coagulation and the prevention of intraventricular hemorrhage in premature infants.\nStudy6: Maternally administered antenatal vitamin K1: effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage. Infants weighing 1500 g or less at birth are susceptible to intraventricular hemorrhage. This may be due in part to low concentrations of vitamin K-dependent clotting factors. Women in labor between 24-34 weeks' gestation were selected, according to their hospital registration number, to receive 10 mg vitamin K1 intramuscularly at least four hours before delivery. Control women received no vitamin K. The study included only infants born of mothers who were in hospital more than four hours before delivery, who weighed 1500 g or less at birth, and were less than 34 weeks' gestation. Twenty vitamin K1 and 33 control infants qualified for the study. Infants in both groups received routine postnatal vitamin K1. On admission, the infant's prothrombin activity and partial thromboplastin time (PTT) were measured. A head ultrasound was done between days 2 and 4 of life. Results demonstrated significantly improved prothrombin activity, a nonsignificant trend toward improved PTT, and a significantly decreased frequency of intraventricular hemorrhage in infants whose mothers had received vitamin K1. The effect of antenatal vitamin K1 on prothrombin activity and PTT appeared to be more pronounced in female infants.\n", + "output": "Conclusions: Vitamin K administered to women prior to very preterm birth has not been shown to significantly prevent PVH in preterm infants or improve neurodevelopmental outcomes in childhood." + }, + { + "input": "Study1: Effects of a comprehensive self-management programme in patients with chronic obstructive pulmonary disease. The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life (HRQoL), symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease (COPD). This study was part of the overall COPD study of the Dept of Pulmonary Medicine, Enschede, which consisted of an inhaled corticosteroid (ICS) trial and a self-management trial. After the ICS trial, all patients were randomised again to a self-management and a control group. The self-management intervention consisted of a skill-oriented patient education programme and a near-home fitness programme, on top of usual care. The control group received usual care by the treating chest physician. HRQoL was measured by the St George's Respiratory Questionnaire (SGRQ) and walking distance by the 6-min walking test. Patients recorded their symptoms in diaries and graded their health status from 1-10 in a weekly report. Altogether, 248 COPD patients were randomly allocated to either an intervention (127) or control (121) group. No differences in the SGRQ scores within and between both groups were observed over 1 yr. Similarly, no differences in symptom scores and 6-min walking distance were found within and between groups. The intervention group reported more exacerbations than the control group. The majority (69%) of the exacerbations in the intervention group were self-treated at home. This study failed to show positive effects of a self-management programme among moderately severe chronic obstructive pulmonary disease patients.\nStudy2: Randomised controlled trial of the effectiveness of a respiratory health worker in reducing impairment, disability, and handicap due to chronic airflow limitation. A randomised controlled trial was undertaken to determine whether a respiratory health worker was effective in reducing the respiratory impairment, disability, and handicap experienced by patients with chronic airflow limitation attending a respiratory outpatient department. The 152 adults (aged 30-75 years) who participated had a prebronchodilator forced expiratory volume in one second (FEV1) below 60% predicted and no other disease. They were randomised to receive the care of a respiratory health worker or the normal services provided by the outpatient department. The respiratory health worker provided health education and symptom and treatment monitoring in liaison with primary care services. After one year there was little difference between the two groups in spirometric values (FEV1 and forced vital capacity before and after salbutamol 200 micrograms), disability (six minute walking distance and paced step test), and handicap (sickness impact profile, hospital anxiety and depression scale). Patients not looked after by the respiratory health worker were more likely to die (relative risk 2.9 (95% confidence limits 0.8, 10.2); when age and FEV1 were controlled for this risk increased to 5.5 (95% confidence limits 1.2, 24.5). Patients looked after by the respiratory health worker attended their general practitioner more frequently and were prescribed a greater range of drugs. This is the third study to have found limited measurable benefit in terms of morbidity from the intervention of a respiratory health worker. This may be due to the ability of such workers to keep frail patients alive.\nStudy3: Controlled trial of respiratory health worker visiting patients with chronic respiratory disability. Seventy five patients with chronic respiratory disability were randomised to a group visited by a respiratory health worker (42) or control group (33). The first group was visited monthly by a respiratory nurse, who gave education and support. The effect of the intervention was assessed in terms of quality of life (by questionnaires), the number and duration of admissions to hospital, and the number of deaths. The questionnaires on quality of life showed no changes in either group during the study, but nearly all of the group visited by a respiratory health worker said that they valued the visits and wished them to continue. Their knowledge about their condition also improved compared with that of the controls. The duration of stay in hospital for respiratory reasons in the group visited by a respiratory health worker was longer than that of control patients. This was explained by their being scored as more ill than the controls on admission. Fewer patients died in the group visited by a respiratory health worker than in the control group (p = 0.11). The patients in the group visited by respiratory health workers may have survived longer because they sought help rather than dying at home. If confirmed this could have implications for the cost of their care.\nStudy4: A randomized trial of two types of nurse-assisted home care for patients with COPD. Whereas pulmonary rehabilitation reduces symptoms and improves the quality of life of patients with COPD and is recommended in management guidelines, few patients have access to rehabilitation services. The purpose of this study was to investigate the effectiveness of increasing access to selected components of pulmonary rehabilitation by providing nurse-assisted home care that was composed of patient education, efforts to improve patient self-management skills, and enhanced follow-up. We conducted a 6-month, randomized, controlled trial. Primary care clinics associated with an urban academic health system. Patients were > or = 45 years of age with a physician diagnosis of COPD, and had a > or = 20-pack-year smoking history, had experienced at least one respiratory symptom during the past 12 months, and had airflow obstruction (ie, FEV1/FVC ratio, < 70%; FEV1, < 80%). Four nurses were trained in the use of the Global Initiative for Chronic Obstructive Lung Disease guidelines, and two of the four nurses received additional training in collaborative management. Patients were randomly assigned to usual care (UC), nurse-assisted medical management (MM), or nurse-assisted collaborative management (CM). The main outcome measures were of generic (Medical Outcome Study 36-item short form [SF-36], illness intrusiveness) and disease-specific (St. George's respiratory questionnaire [SGRQ]) quality of life and self-reported health-care utilization. Overall, 151 patients (UC group, 51 patients; MM group, 49 patients; and CM group, 51 patients) completed the study, their average age was 69 years, and 56.9% were women. The average change in the SF-36 general health domain for the MM group vs the UC group was 1.1 (95% confidence interval [CI], -7.9 to 11.2), and for the CM group vs the UC group the average change was 2.5 (95% CI, -7.0 to 12.3). The corresponding changes in SGRQ total domain were -2.9 (95% CI, -9.8 to 4.1) and -2.6 (95% CI, -9.5 to 4.3). There was no change in the number of self-reported emergency department visits or hospitalizations, but the utilization of these services was infrequent. The findings of our investigation and those from the published literature suggest that interventions to enhance patient education, self-management skills, and follow-up among patients with COPD do not result in clinically meaningful improvements in health status or self-reported health-care utilization. Moreover, future studies of disease management programs for patients with COPD need to evaluate interventions that address associated comorbidities, exercise, and social support.\nStudy5: Care plans for acutely deteriorating COPD: a randomized controlled trial. Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a frequent reason for admission to hospital and are responsible for the majority of the direct economic costs of treating COPD. To test whether an individualized care plan for patients experiencing acute exacerbations of COPD result in reduced health care utilization and improved quality of life for patients. Ninety-two patients with confirmed COPD were selected by general practitioners or district nurses, and randomly assigned to care plan or usual care groups. The care plan was developed in collaboration with general practitioners, secondary care specialists, specialist nurses, ambulance service providers and the after hours clinic. Patients were followed for 12 months, and the primary end-points were frequency of use of primary care services and hospital admissions. There was no significant reduction in hospital admissions or improvement in quality of life in the group of patients who used the care plan compared to controls. The care plan group called out the ambulance service more frequently [2.8 (1.3, 4.3) versus 1.1 (0.7, 1.5) calls per 12 months; P = 0.03], and there was a trend towards greater use of oral prednisone [2.3 (1.4, 3.2) versus 1.3 (0.8, 1.8) courses per 12 months; P = 0.06]. In contrast to asthma, the provision of individualized self-management plans, whose content was enhanced to provide guidance to carers and health care professionals, did not reduce health care utilization or improve overall quality of life during acute exacerbations of COPD. Other strategies are required.\nStudy6: A randomized controlled evaluation of a psychosocial intervention in adults with chronic lung disease. The effect of a stress management program on morbidity and psychosocial and physical function in patients with chronic lung disease was assessed. Adults attending either a VA pulmonary clinic or university hospital pulmonary rehabilitation clinic who met criteria for obstructive or restrictive pulmonary disease were randomly assigned to receive the intervention or to a control group. The intervention was provided by a nurse and included one to three teaching sessions, reading material, audiotapes, and telephone follow-up. The program focused on stress management techniques such as cognitive restructuring, progressive relaxation, breathing exercises, and visual imagery. The 45 experimental subjects were similar to the 49 controls with respect to baseline characteristics. Experimental and control subjects had similar rates of mortality, hospital days, bed-disability days, restricted-activity days, and physician visits during the 12-month follow-up. There were no differences between the two groups in physical or psychosocial function at six months or in levels of stressful life changes, social supports, and self-esteem at six and 12 months. Intervention recipients had better function at 12 months, suggesting a possible benefit of the intervention.\nStudy7: Managing chronic obstructive pulmonary disease in the community. A randomized controlled trial of home-based pulmonary rehabilitation for elderly housebound patients. Pulmonary rehabilitation is essential for managing chronic obstructive pulmonary disease (COPD). Housebound COPD patients are frequently excluded from this treatment because they are unable to access outpatient pulmonary rehabilitation programs because of the severity of their disease. This randomized controlled trial assesses the effects of a 12-week home-based pulmonary rehabilitation program for 60 housebound COPD patients older than 60 years. Intervention patients received an individually tailored supervised walking and arm exercise program as well as individual multidisciplinary education sessions on COPD and its management. Outcomes were assessed using the 6-minute walk test, St George's respiratory questionnaire, and Borg score of perceived breathlessness. Healthcare utilization was assessed using hospital admission rates with exacerbation of COPD and average length of stay at readmission. Complete data for 23 patients in each group were available for analysis. There was no significant difference between groups on baseline measures. Compared with the control group, intervention patients demonstrated a significant improvement in 6-minute walk test (P = .023), Borg score of perceived breathlessness (P = .024), St George's respiratory questionnaire total score (P = .020), and impact subscore (P = .024). At 6 months, the intervention group had a significantly shorter average length of stay at readmission to hospital with exacerbation (P = .035). A 12-week home-based pulmonary rehabilitation is effective in improving exercise tolerance, perception of breathlessness, and quality of life for housebound COPD patients. To manage COPD in the community more effectively, health services should focus on expanding home-based pulmonary rehabilitation.\nStudy8: Reduction of hospital utilization in patients with chronic obstructive pulmonary disease: a disease-specific self-management intervention. Self-management interventions improve various outcomes for many chronic diseases. The definite place of self-management in the care of chronic obstructive pulmonary disease (COPD) has not been established. We evaluated the effect of a continuum of self-management, specific to COPD, on the use of hospital services and health status among patients with moderate to severe disease. A multicenter, randomized clinical trial was carried out in 7 hospitals from February 1998 to July 1999. All patients had advanced COPD with at least 1 hospitalization for exacerbation in the previous year. Patients were assigned to a self-management program or to usual care. The intervention consisted of a comprehensive patient education program administered through weekly visits by trained health professionals over a 2-month period with monthly telephone follow-up. Over 12 months, data were collected regarding the primary outcome and number of hospitalizations; secondary outcomes included emergency visits and patient health status. Hospital admissions for exacerbation of COPD were reduced by 39.8% in the intervention group compared with the usual care group (P =.01), and admissions for other health problems were reduced by 57.1% (P =.01). Emergency department visits were reduced by 41.0% (P =.02) and unscheduled physician visits by 58.9% (P =.003). Greater improvements in the impact subscale and total quality-of-life scores were observed in the intervention group at 4 months, although some of the benefits were maintained only for the impact score at 12 months. A continuum of self-management for COPD patients provided by a trained health professional can significantly reduce the utilization of health care services and improve health status. This approach of care can be implemented within normal practice.\nStudy9: Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease. Exercise rehabilitation is recommended increasingly for patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of exercise and education on 79 older adults (M age = 66.6 +/- 6.5 years; 53% female) with COPD, randomly assigned to 10 weeks of (a) exercise, education, and stress management (EXESM; n = 29); (b) education and stress management (ESM; n = 25); or (c) waiting list (WL; n = 25). EXESM included 37 sessions of exercise, 16 educational lectures, and 10 weekly stress management classes. ESM included only the 16 lectures and 10 stress management classes. Before and after the intervention, assessments were conducted of physiological functioning (pulmonary function, exercise endurance), psychological well-being (depression, anxiety, quality of life), and cognitive functioning (attention, motor speed, mental efficiency, verbal processing). Repeated measures multivariate analysis of variance indicated that EXESM participants experienced changes not observed among ESM and WL participants, including improved endurance, reduced anxiety, and improved cognitive performance (verbal fluency).\nStudy10: Humanistic outcomes in the hypertension and COPD arms of a multicenter outcomes study. To evaluate the effects of pharmaceutical care on selected humanistic outcomes in patients with hypertension or chronic obstructive pulmonary disease (COPD). Clinic patients with hypertension or COPD were randomly assigned to a treatment group (pharmaceutical care) or a control group (traditional pharmacy care) over a six-month period. Clinical pharmacists and pharmacy residents conducted the protocols. There were 133 evaluable patients (63 treatment, 70 control) in the hypertension study arm and 98 evaluable patients (43 treatment, 55 control) in the COPD study arm. The Pharmaceutical Care Questionnaire evaluated patient satisfaction with care. Tests specific to the disease states assessed disease and disease management knowledge. Quality of life (QOL) was evaluated using the Health Status Questionnaire 2.0 (HSQ 2.0) in the COPD arm; in the hypertension arm, the Hypertension/Lipid TyPE Specification Form 5.1 was used. Ambulatory care centers of 10 Department of Veterans Affairs (DVA) medical centers and 1 university medical center. Patient-centered pharmaceutical care model (employing standardized care) implemented by clinical pharmacy residents. Satisfaction with pharmaceutical care, disease and disease management knowledge, and QOL. Statistically significant differences in most satisfaction items were found, with treatment patients expressing greater satisfaction. Treatment groups in both arms strongly agreed that pharmacists helped them with confidence in use of their medication and understanding of their illness, gave complete explanations about their medications, made them feel that their care was a priority, and followed up on their questions and concerns. In the hypertension arm, treatment patients demonstrated significant increases in knowledge scores. Trends in QOL were positive for both hypertension groups, with a significant decrease found in number of treatment patients reporting problems with sexual function. In the COPD arm, improvement trends were significantly stronger for treatment patients. Although patients were not dissatisfied with traditional pharmacy care, they were more satisfied overall with the pharmaceutical care model.\n", + "output": "Conclusions: It is likely that self-management education is associated with a reduction in hospital admissions with no indications for detrimental effects in other outcome parameters. This would in itself already be enough reason for recommending self-management education in COPD. However, because of heterogeneity in interventions, study populations, follow-up time, and outcome measures, data are still insufficient to formulate clear recommendations regarding the form and contents of self-management education programmes in COPD. There is an evident need for more large RCTs with a long-term follow-up, before more conclusions can be drawn." + }, + { + "input": "Study1: Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST) Our objective was to assess the risks and benefits of carotid endarterectomy, primarily in terms of stroke prevention, in patients with recently symptomatic carotid stenosis. This multicentre, randomised controlled trial enrolled 3024 patients. We enrolled men and women of any age, with some degree of carotid stenosis, who within the previous 6 months had had at least one transient or mild symptomatic ischaemic vascular event in the distribution of one or both carotid arteries. Between 1981 and 1994, we allocated 1811 (60%) patients to surgery and 1213 (40%) to control (surgery to be avoided for as long as possible). Follow-up was until the end of 1995 (mean 6.1 years), and the main analyses were by intention to treat. The overall outcome (major stroke or death) occurred in 669 (37.0%) surgery-group patients and 442 (36.5%) control-group patients. The risk of major stroke or death complicating surgery (7.0%) did not vary substantially with severity of stenosis. On the other hand, the risk of major ischaemic stroke ipsilateral to the unoperated symptomatic carotid artery increased with severity of stenosis, particularly above about 70-80% of the original luminal diameter, but only for 2-3 years after randomisation. On average, the immediate risk of surgery was worth trading off against the long-term risk of stroke without surgery when the stenosis was greater than about 80% diameter; the Kaplan-Meier estimate of the frequency of a major stroke or death at 3 years was 26.5% for the control group and 14.9% for the surgery group, an absolute benefit from surgery of 11.6%. However, consideration of variations in risk with age and sex modified this simple rule based on stenosis severity. We present a graphical procedure that should improve the selection of patients for surgery. Carotid endarterectomy is indicated for most patients with a recent non-disabling carotid-territory ischaemic event when the symptomatic stenosis is greater than about 80%. Age and sex should also be taken into account in decisions on whether to operate.\nStudy2: Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group. To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis. Prospective, randomized, multicenter trial. Sixteen university-affiliated Veterans Affairs medical centers. Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization. Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98). At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period. For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.\nStudy3: Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery.\n", + "output": "Conclusions: Endarterectomy is of some benefit for 50% to 69% symptomatic stenosis and highly beneficial for 70% to 99% stenosis without near-occlusion. Benefit in patients with carotid near-occlusion is marginal in the short-term and uncertain in the long-term. These results are generalisable only to surgically-fit patients operated on by surgeons with low complication rates (less than 7% risk of stroke and death). Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other factors, including the delay to surgery after the presenting event." + }, + { + "input": "Study1: Interferon alfa treatment of HCV RNA carriers with persistently normal transaminase levels: a pilot randomized controlled study. Most patients with serum hepatitis C virus (HCV) RNA and persistently normal alanine transaminase (ALT) levels show histological features of mild to moderately active chronic hepatitis. Some cirrhosis has also been reported. To assess whether interferon (IFN) treatment led to long-term HCV suppression in these patients, 31 previously untreated patients (15 men, 16 women; mean age, 44 years) with serum HCV RNA, persistently normal ALT levels on at least four consecutive occasions 2 months apart, and histological features of chronic hepatitis (21 mild activity, 10 moderate activity) were randomized to receive 1FN-alpha-2a, 3 MU three times a week for 6 months (n = 16), or no treatment (n = 15). All patients were followed up for at least 6 months after treatment ended. HCV RNA was tested by nested reverse-transcription polymerase chain reaction (RT-PCR) using 5'-untranslated region complementary primers, quantified by branched-DNA assay, and typed by nested RT-PCR testing for the HCV core region. Treated and untreated patients had similar epidemiological, virological, and histological characteristics. At the end of treatment, serum HCV RNA was still detected in 15 patients (94%) and 14 controls (93%). ALT levels flared up in 10 patients receiving IFN (62%) and in 1 control (62% vs. 7%; P < .005, chi2 test). In conclusion, 6 months' treatment with IFN-alpha-2a did not eradicate HCV RNA from serum in carriers with persistently normal ALT levels but caused ALT flare-ups in two thirds of them. Until more is known about the natural history of HCV RNA carriers with normal ALT levels, these patients should not be treated with IFN.\nStudy2: Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study. To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p = 0.0035) and platelet count (p = 0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71%, whereas that in patients with a serum HCV-RNA level above 10(5) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.\nStudy3: A randomized controlled trial of interferon alfa-2b as therapy for chronic non-A, non-B hepatitis. Eighty patients with chronic non-A, non-B hepatitis completed a randomized controlled trial of the therapeutic efficacy of recombinant interferon alfa-2b. Twenty-nine received 1 million units and 26 received 3 million units of interferon subcutaneously thrice weekly for 6 months, and 25 were controls. Normalization or a significant decrease of alanine aminotransferase values was obtained in 19/29 (66%) patients treated with 1 million units, in 18/26 (69%) patients treated with 3 million units and in one control patient (4%, p less than 0.05). However, when control patients were randomized after the initial 24 weeks to receive 1 or 3 million units of interferon for 48 weeks, 12/14 (86%) patients receiving 3 million units responded to therapy versus 3/11 patients receiving 1 million units (27%, p less than 0.05). After a 1 to 6 months follow-up period post treatment, an alanine aminotransferase relapse was observed in 18/30 (60%) responders to 3 million units and in 17/22 (77%) responders to 1 million units. Cirrhotic patients responded less than patients with non-cirrhotic disease (47 vs. 78%, p less than 0.05). Only responders treated with 3 million units significantly ameliorated their histologic picture (pre-therapy Knodell's index = 8.9, post-therapy = 6.0, p less than 0.05). The data confirm that treatment with interferon is of benefit in patients with chronic non-A, non-B hepatitis.\nStudy4: A double-blind controlled trial of recombinant interferon-alpha 2b in haemodialysis patients with chronic hepatitis C virus infection and abnormal aminotransferase levels. Nephrologists' Group for the Study of HCV infection. The efficacy and safety of recombinant interferon-alpha 2b (rIFN-alpha 2b) was evaluated in a double-blind controlled trial comprising 23 haemodialysis patients with antibodies to hepatitis C virus (anti-HCV), detectable serum HCV RNA by polymerase chain reaction and chronic alanine aminotransferase elevation. The patients were randomly assigned to receive rIFN-alpha 2b at a dose of 1.5 MU (increasing to 3 MU if no response was observed) (Group I: n = 14) or identical placebo (Group II: n = 9), for 6 months. A biochemical response (normal alanine aminotransferase) was observed in 10 patients (71.4%) from Group I and in one patient (11.1%) from Group II (P < 0.01) at the end of therapy, and in four patients from Group I (28.6%) and in none from Group II (NS) 12 months after therapy. Virological response (HCV RNA negative) was observed in four patients (28.6%) from Group I and in none from Group II (NS) at the end of therapy, and in two patients (14.2%) from Group I and in none from Group II (NS) 12 months after therapy. Interferon doses were 1.5 MU in 12 patients and 3 MU in two patients. Therapy interruption owing to severe side-effects was necessary in three patients (21.4%) from Group I and in two patients (22.2%) from Group II. Although long-term statistical differences were not observed, these results suggest that rIFN-alpha 2b at a low dose is a reasonable and well tolerated therapeutic approach for haemodialysis patients with chronic hepatitis C.\nStudy5: A randomized controlled trial of interferon-alpha in patients with cirrhosis caused by 2a/2b genotype hepatitis C virus. nan\nStudy6: Virological response to interferon treatment in hepatitis C virus carriers with normal aminotransferase levels and chronic hepatitis. Hepatitis C virus (HCV) carriers with normal aminotransferase levels often show histological chronic hepatitis. This study was undertaken to determine the effect of interferon (IFN) in such patients. Nineteen HCV carriers with normal aminotransferase activities and chronic hepatitis were randomized to receive IFN-alpha2b (3 million units 3 times weekly for 12 months) or no treatment. Therapy was monitored by qualitative and quantitative determination of viral RNA. Patients who did not clear HCV RNA after 6 months discontinued therapy. In all, 9 patients constituted the control group, while 10 patients were treated. Five of these patients, still viremic after 6 months, stopped IFN. The remaining 5 patients, who cleared the viral RNA within 6 months, completed the 12-month course. Three of these patients relapsed off treatment, and 2 were still free of viremia 12 months after stopping therapy. A transient flare-up of aminotransferase activities was detected in 2 patients during treatment and in 3 patients after. None of the 9 control patients cleared the viral RNA during follow-up. A variable degree of sequence heterogeneity was detected in the hypervariable region before therapy, and IFN treatment decreased sequence diversity in all patients. These results indicate that IFN therapy can be effective in chronic HCV carriers with normal aminotransferase activities, inducing short-term virological response in 3 of 10 patients and sustained response in 2. The effects of treatment on viral load and quasispecies complexity were similar to those reported previously in patients with increased aminotransferase activities.\nStudy7: Transfusion-associated chronic hepatitis C: alpha-n1 interferon for 6 vs. 12 months. To compare the long-term effects of brief and prolonged therapy with alpha-n1 interferon for transfusion-associated chronic hepatitis C. One hundred and sixteen subjects (male/female 48/68, mean age 46.9 years) were studied. Sixty patients were randomised to brief treatment (group 1: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 4 months), and 56 to prolonged treatment (group 2: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 10 months). All were followed for 12 months after stopping interferon. The early response rate was 47.4% (Group 1 [45%], Group 2[50%]. No \"breakthrough\" reactivations were observed. The early response rate was 19% in patients with and 63% in patients without cirrhosis. Twenty-three (19.8%) subjects stopped therapy. Among 54 evaluable early responders, 21 had a sustained response. The rate of sustained response was comparable in group 1 (18.3%) and group 2 (18.2%). All sustained response subjects and some non-responders were HCV-RNA negative at the end of follow-up. Histological improvement was seen only after sustained response. Cirrhosis developed in 20% of non-responders. Overall, interferon induced a long-lasting remission of chronic hepatitis C in about one of every five patients. In a population predominantly infected by hepatitis C virus type 1, 12 months of therapy with high doses of interferon does not confer any additional benefit on the early response or sustained response rates as compared to a 6-month course.\nStudy8: alpha-Interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers. Forty patients with chronic viral hepatitis or active cirrhosis (33 anti-HCV positive) entered a recombinant human alpha 2A interferon randomized trial. Twenty-one subjects were treated with 6 million units (MU) three times per week for 6 months. Nineteen were not treated. Six months later in 12 patients of the treated group (60% of the evaluable 20) with normalized serum aminotransferases levels (responders), fibrogenesis serum markers (NPIIIP and laminin) were significantly lower than baseline. In the untreated patients and in non-responders NPIIIP and laminin were unchanged. Semi quantitative histological evaluation (allotting scores for inflammation, necrosis and fibrosis) confirmed a significant improvement of necro-inflammation in the responders. These data suggest that alpha-IFN treatment may decrease stimuli for fibrogenesis by reducing liver inflammation and necrosis, thus preventing evolution to cirrhosis.\nStudy9: Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: gamma GT levels predictive for response. The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon-alpha treatment in chronic sporadic-type non-A, non-B hepatitis. We also aimed to determine if histological or liver function data could predict either response or relapse. Sixty patients with chronic sporadic-type non-A, non-B hepatitis were randomized in two groups of 30. One group was treated with interferon-alpha (3 MU thrice weekly) for one year; the other group was untreated controls. The treated group was followed for another year after interferon withdrawal. Liver function tests were performed during treatment. Liver biopsy was carried out before and a year after randomization. We evaluated rate of response [normalization of alanine aminotransferase (ALT) levels for at least three consecutive months] and rate of relapse (ALT rebound after therapy suspension). We also looked at possible predictive factors for response and relapse. In the treatment group the rate of response was 55% (16/29). No control patient exhibited ALT normalization. Among the responders, 31% (5/16) relapsed after interferon withdrawal. Low gamma GT and female sex are positive predictive factors of response (P < 0.01 and P < 0.02 respectively). Presence of portal and periportal inflammation at the second liver biopsy was correlated with relapse (P < 0.05). In conclusion, human lymphoblastoid interferon-alpha treatment for one year is beneficial in patients suffering from chronic sporadic-type non-A, non-B hepatitis. Low pretreatment gamma GT levels and female sex are positive predictors of response in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy10: Treatment with interferon(s) of community-acquired chronic hepatitis and cirrhosis type C. The TVVH Study Group. Two hundred and thirty-four patients with chronic non-A, non-B hepatitis, 86% positive for anti-HCV by ELISA, were treated with recombinant interferon-alpha 2a or with natural (human-leukocytes-derived) interferon-alpha using different dosage and periods of administration. Interim analysis of follow-up data indicate that 65-70% of patients treated initially with 6 MU, thrice weekly, of recombinant interferon-alpha 2a achieved a complete biochemical response (normalization of alanine aminotransferase: ALT) during therapy compared to 56-58% of those treated with 3 MU, thrice weekly, of recombinant or natural interferon-alpha. A 12-month schedule of interferon administration appeared superior to a 6-month schedule in reducing the probability of reactivation of liver disease after therapy withdrawal, although further data are needed to confirm such a conclusion. The probability of response to interferon in terms of maintaining normal ALT after withdrawal did not appear to be influenced by sex, while it was significantly higher in patients aged below 45 years and in those without cirrhosis.\n", + "output": "Conclusions: Interferon is effective in achieving viral clearance and improving liver biochemistry and histology in interferon naive patients with chronic hepatitis C. Higher doses and prolonged durations are more effective, but associated with more frequent adverse events. Interferon is associated with similar benefits in patients with cirrhosis, but the efficacy in patients with normal aminotransferases is unproven." + }, + { + "input": "Study: The relative efficacy of two brief treatments for sleep problems in young learning disabled (mentally retarded) children: a randomised controlled trial. Settling and night waking problems are particularly prevalent, persistent, and generally considered difficult to treat in children with a learning disability, although intervention trials are few. Scarce resources, however, limit access to proven behavioural treatments. To investigate the efficacy of a media based brief behavioural treatment of sleep problems in such children by comparing (1) face-to-face delivered treatment versus control and (2) booklet delivered treatment versus controls. The parents of 66 severely learning disabled children aged 2-8 years with settling and/or night waking problems took part in a randomised controlled trial with a wait-list control group. Behavioural treatments were presented either conventionally face-to-face or by means of a 14 page easy to read illustrated booklet. A composite sleep disturbance score was derived from sleep diaries kept by parents. Both forms of treatment were almost equally effective compared with controls. Two thirds of children who were taking over 30 minutes to settle five or more times per week and waking at night for over 30 minutes four or more times per week improved on average to having such settling or night waking problems for only a few minutes or only once or twice per week (H = 34.174, df = 2, p<0.001). These improvements were maintained after six months. Booklet delivered behavioural treatments for sleep problems were as effective as face-to-face treatment for most children in this population.\n", + "output": "Conclusions: These formats of delivering behavioural interventions for carers of children are worth considering in clinical practice. Media-based interventions may, in some cases, be enough to make clinically significant changes in a child's behaviour, and may reduce the amount of time primary care workers have to devote to each case. They can also be used as the first stage of a stepped care approach. Consequently this would increase the number of families who could possibly benefit from these types of intervention, releasing clinician time that can be reallocated to more complex cases. Media-based therapies would therefore appear to have both clinical and economic implications as regards the treatment of children with behavioural problems." + }, + { + "input": "Study1: Respiratory muscle training improves cardiopulmonary function and exercise tolerance in subjects with subacute stroke: a randomized controlled trial. To determine whether two types of exercise--breathing retraining (BRT) and inspiratory muscle training (IMT)--improve on cardiopulmonary functions and exercise tolerance in patients with stroke. A randomized controlled trial. Education and research hospital. Forty-five inpatients with stroke (24 men, 21 women) were recruited for the study. The subjects were randomized into three groups: 15 assigned to receive inspiratory muscle training (IMT); 15 assigned to received breathing retraining, diaphragmatic breathing and pursed-lips breathing (BRT); 15 assigned to a control group. All study groups participated in a conventional stroke rehabilitation programme. For the same period, the IMT and BRT groups trained daily, six times a week, with each session consisting of one half-hour of training for six weeks. Each subject underwent pulmonary function and cardiopulmonary exercise tests. Subjects were also assessed for exertional dyspnoea, stages of motor recovery, ambulation status, activity of daily living and quality of life. After the training programme, the IMT group had significantly improved forced expiratory volume at 1 second (FEV(1)), forced vital capacity (FVC), vital capacity (VC), forced expiratory flow rate 25-75% (FEF 25-75%) and maximum voluntary ventilation (MVV) values compared with the BRT and control groups, although there were no significant differences between the BRT and control groups (P<0.01). Peak expiratory flow rate (PEF) value was increased significantly in the BTR group compared with the IMT and control groups. The IMT group also had significantly higher peak oxygen consumption (Vo(2peak)) than the BRT and control groups, although there were no significant differences between the BRT and control groups (P<0.001). There was a statistically significant increase in maximum inspiratory pressure (PI(max)) and maximum inspiratory and expiratory pressure (PE(max)) in the BRT group and, PI(max) in the IMT group compared with baseline and the control group. In the IMT group, this was associated with improvements in exercise capacity, sensation of dyspnoea and quality of life. Significant short-term effects of the respiratory muscle training programme on respiratory muscle function, exercise capacity and quality of life were recorded in this study.\nStudy2: Inspiratory muscular training in chronic stroke survivors: a randomized controlled trial. To assess the effectiveness of inspiratory muscular training (IMT) on measures of strength, resistance, functional performance, and quality of life (QOL) for chronic stroke survivors. Double-blinded randomized controlled trial. Research laboratory. Subjects (N=21) with stroke (11 men, 10 women; maximal inspiratory pressure [MIP] <90% of predicted values) were randomly assigned to the experimental (n=11) and control groups (n=10); 18 participants completed all testing and training. Interventions were based on home-based training, with resistance adjusted biweekly to 30% of MIP for the experimental group. The control group underwent the same protocol without the threshold resistance valve. Both groups received home training 30 minutes a day 5 times a week for 8 weeks. MIP, inspiratory muscular endurance (IME), functional performance, and QOL. There were significant between-group differences for the MIP and IME measures. Significant changes were observed for only the experimental group for MIP (67.8\u00b114.6 at baseline to 102.2\u00b126.0cmH(2)O at posttraining) and IME (31.8\u00b119.3 to 49.2\u00b121.1cmH(2)O). No statistically significant differences were observed for measures of functional performance and QOL. Significant short-term effects of the IMT program for inspiratory strength and endurance were observed in chronic stroke survivors. These findings gave some indications that IMT may benefit people with stroke, and it is feasible to be included in rehabilitation interventions with this population. Copyright \u00a9 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.\n", + "output": "Conclusions: There is insufficient evidence to support inspiratory muscle training as an effective treatment to improve function after stroke, and no evidence relating to the safety of inspiratory muscle training. Further well-designed RCTs are required." + }, + { + "input": "Study1: Effect of diabetes education on glucose control. After diabetes education, 39 adult diabetic patients were randomized to either an education group or control group. The two groups received identical medical care and follow-up, except that the education group met with their diabetes educator on at least a quarterly basis. Neither group showed any statistically significant change in their glycosylated hemoglobin values, although the education group did have a 4% drop after initial education compared to a 6% rise in the control group. The education group had a lower attrition rate and a better improvement in self-rated dietary compliance. Education remains the cornerstone of diabetes management. Our team identified some trends between the two groups as well as some ideas to improve motivating and developing a stronger and more effective relationship with our patients.\nStudy2: Management of obese patients with diabetes mellitus: comparison of advice education with group management. The purpose of our study was to compare the effect on diabetes control of group management with the advice-educational technique traditionally used in managing obese outpatients with poorly controlled non-insulin-dependent diabetes mellitus (NIDDM). Forty-one patients were randomly assigned to these two treatment programs, and 32 patients completed the 6-mo study. Initially, patients were seen for 1-h sessions at 1- and 2-wk intervals and later at 1-mo intervals. Patients were asked to do home blood glucose monitoring, decrease caloric intake, increase exercise, and if they were taking insulin, to adjust the dose to attain approximate euglycemia and to stabilize food and exercise patterns. The combined groups reduced mean +/- SD glycohemoglobin from 10.9 +/- 3.1 to 9.4 +/- 2.4% (P less than .05). Internal Health Locus of Control Scale was negatively and significantly correlated with initial and subsequent glycohemoglobin values (the more internal, the lower the glycohemoglobin). At the end of the study the patients in the group management program had significantly lower blood glucose levels than those given advice and education, but no significant differences in glycohemoglobin values or percentage overweight were observed. One patient had a normal initial glycohemoglobin, and only 4 patients had values in the normal range of 4-6.8% at the end of the study. Better management programs need to be developed for treating obese outpatients with NIDDM.\nStudy3: Assessment of the function and effect of diabetes education programs in Taiwan. A multi-center prospective study was conducted to assess the function and impact of diabetic education programs on diabetic control. A total of 208 subjects with type 2 diabetes were recruited. Diabetes self-care, assessed by questionnaire, was evaluated before, and 4 months after attending a diabetes education course. A total of 121 subjects who received advanced diabetes education courses were designated as the experimental group. A second group of 87 cases receiving a basic course served as controls. In addition to basic knowledge, the advanced education programs included dietary control, blood glucose monitoring, management of hypoglycemia, medication compliance, foot care and exercise. Diabetes self-care techniques were significantly improved in the experimental group. The overall score for diabetes self-care techniques improved in both groups at the 4th month over baseline values. The change was significant with the controls' (P < 0.001). Multiple regression analysis confirmed the intensity of diabetic education was the only significant variable correlated with the decrease of fasting blood glucose and systolic blood pressure. In conclusion, integrated and intensive diabetes education program in diabetes education centers provides an effective method for improving diabetes self-care techniques and metabolic outcome.\nStudy4: Can medication packaging improve glycemic control and blood pressure in type 2 diabetes? Results from a randomized controlled trial. To assess the impact of calendar blister pack (CBP) use on glycemic and blood pressure control. We conducted an 8-month randomized controlled double-blind study among diabetic patients with poor glucose control (HbA1c >9.0%) in an urban area of South Auckland, New Zealand, with a high proportion of Maori and Pacific Islands people. Subjects included 68 consecutive patients, of whom 50% were prescribed three or more medications per day HbA1c was reduced by 0.95+/-0.22% in the CBP group and 0.15+/-0.25% in the control group (P = 0.026). Diastolic blood pressure decreased 5.8+/-1.5 mm Hg in the CBP group and increased 0.1+/-1.9 mm Hg in the control group (P = 0.0041). Systolic blood pressure did not change significantly CBPs should be considered among diabetic patients with poor glycemic control receiving multiple medications.\nStudy5: Telemedicine improved diabetic management. Effective control of diabetes is known to delay or prevent the end-organ complications of this disease. Can telemedicine improve a patient's ability to self-manage diabetes? Twenty-eight patients entered a study comparing home telemedicine consultation with standard outpatient care. A nurse case manager contacted the telemedicine group once a week under the direction of a primary care physician, who contacted the telemedicine group once a month. Laboratory studies and total body weight were measured at the beginning and at the end of the 3-month study. The hemoglobin A1c (HbA1c) and total body weight improved significantly in the intervention (telemedicine) group, as shown by a 16% reduction in mean HbA1c level (from 9.5 to 8.2%) and a 4% mean weight reduction (from 214.3 to 206.7 pounds). Based on our experience, we present a functionally based telemedicine classification system to improve the application of electronic medicine in future studies.\n", + "output": "Conclusions: Current efforts to improve or to facilitate adherence of people with type 2 diabetes to treatment recommendations do not show significant effects nor harms. The question whether any intervention enhances adherence to treatment recommendations in type 2 diabetes effectively, thus still remains unanswered." + }, + { + "input": "Study1: Prevention of diarrhoea and dysentery by hand washing. A 'non-blind' randomized hand washing intervention study was conducted in a low socioeconomic community in Rangoon to determine if hand washing by 494 children under 5 years old and their mothers could reduce the incidence of diarrhoea and dysentery in these children. Children and mothers in the intervention group were asked to wash their hands after defaecation and before preparing or eating their 3 main meals; 2 bars of plain soap were provided. The control group was left to follow customary practice. Diarrhoea and dysentery incidences in the 2 groups were monitored during 4 months by comparing the incidence density ratios (IDR). The diarrhoeal incidence among the children in the hand washing households was significantly lower than that among those in the control households (IDR = 0.70, 95% confidence interval (CI) = 0.54-0.92). For dysentery incidence, although there was a 40% reduction (IDR = 0.58, 95% CI = 0.22-1.55) in the children under 2 years, there seemed to be no impact in older children (IDR = 1.2, 95% CI = 0.52-2.80). The study indicates that hand washing is effective in reducing the morbidity from diarrhoea and dysentery.\nStudy2: An educational intervention for altering water-sanitation behaviors to reduce childhood diarrhea in urban Bangladesh. II. A randomized trial to assess the impact of the intervention on hygienic behaviors and rates of diarrhea. An educational intervention was designed to improve three water-sanitation behaviors empirically shown to be associated with high rates of childhood diarrhea in Dhaka, Bangladesh: lack of handwashing before preparing food, open defecation by children in the family compound, and inattention to proper disposal of garbage and feces, increasing the opportunity for young children to place waste products in their mouth. Fifty-one communities, each comprising 38 families, were randomized either to receive (n = 25) or not to receive (n = 26) the intervention. During the six months after the intervention, the rate of diarrhea (per 100 person-weeks) in children under six years of age was 4.3 in the intervention communities and 5.8 in the control communities (26% protective efficacy; p less than 0.0001). A corresponding improvement in handwashing practices before preparing food was noted, although no improvement was observed for defecation and waste disposal practices. These data suggest that educational interventions for water-sanitation practices can have an important beneficial effect upon childhood diarrhea in developing countries, particularly when the interventions are designed in a simple way to promote naturally occurring salutory behaviors that are empirically associated with lower rates of childhood diarrhea.\nStudy3: Combining drinking water treatment and hand washing for diarrhoea prevention, a cluster randomised controlled trial. To evaluate the effectiveness of point of use water treatment with flocculent-disinfectant on reducing diarrhoea and the additional benefit of promoting hand washing with soap. The study was conducted in squatter settlements of Karachi, Pakistan, where diarrhoea is a leading cause of childhood death. Interventions were randomly assigned to 47 neighbourhoods. Households in 10 neighbourhoods received diluted bleach and a water vessel; nine neighbourhoods received soap and were encouraged to wash hands; nine neighbourhoods received flocculent-disinfectant water treatment and a water vessel; 10 neighbourhoods received disinfectant-disinfectant water treatment and soap and were encouraged to wash hands; and nine neighbourhoods were followed as controls. Field workers visited households at least once a week from April to December 2003 to promote use of the interventions and to collect data on diarrhoea. Study participants in control neighbourhoods had diarrhoea on 5.2% of days. Compared to controls, participants living in intervention neighbourhoods had a lower prevalence of diarrhoea: 55% (95% CI 17%, 80%) lower in bleach and water vessel neighbourhoods, 51% (95% CI 12%, 76%) lower in hand washing promotion with soap neighbourhoods, 64% lower (95% CI 29%, 90%) in disinfectant-disinfectant neighbourhoods, and 55% (95% CI 18%, 80%) lower in disinfectant-disinfectant plus hand washing with soap neighbourhoods. With an intense community-based intervention and supplies provided free of cost, each of the home-based interventions significantly reduced diarrhoea. There was no benefit by combining hand washing promotion with water treatment.\nStudy4: Occurrence of infectious symptoms in children in day care homes. Transmission of enteric pathogens is facilitated in child day care centers, including family day care homes, by frequent and intimate exposure among susceptible hosts, with diaper changing as the highest-risk procedure for such transmission. The objective of this study was to evaluate the effectiveness of an intervention program in decreasing the incidence of infectious disease symptoms in children attending family day care homes during a 12-month period. Each of 24 family day care homes was randomly assigned to an intervention or control group. The intervention included four components: (1) a handwashing educational program and (2) use of vinyl gloves, (3) use of disposable diaper changing pads, and (4) use of an alcohol-based hand rinse by the day care provider. Symptoms of enteric disease (diarrhea and vomiting) were significantly reduced in intervention family day care homes (p less than or equal to 0.05), whereas respiratory symptoms were not significantly different between intervention and control family day care homes (p = 0.35). Diarrhea was reported in 1 of every 100 child care days, representing one diarrhea episode per month in a typical family day care home.\nStudy5: A cluster-randomized controlled trial evaluating the effect of a handwashing-promotion program in Chinese primary schools. Intensive handwashing promotion can reduce diarrheal and respiratory disease incidence. To determine whether less intensive, more scalable interventions can improve health, we evaluated a school-based handwashing program. We randomized 87 Chinese schools to usual practices: standard intervention (handwashing program) or expanded intervention (handwashing program, soap for school sinks, and peer hygiene monitors). We compared student absence rates, adjusting for cluster design. In control schools, children experienced a median 2.0 episodes (median 2.6 days) of absence per 100 student-weeks. In standard intervention schools, there were a median 1.2 episodes (P = 0.08) and 1.9 days (P = 0.14) of absence per 100 student-weeks. Children in expanded intervention schools experienced a median 1.2 episodes (P = 0.03) and 1.2 days (P = 0.03) of absence per 100 student-weeks. Provision of a large-scale handwashing promotion program and soap was associated with significantly reduced absenteeism. Similar programs could improve the health of children worldwide.\nStudy6: Effect of handwashing on child health: a randomised controlled trial. More than 3.5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year. We undertook a randomised controlled trial to assess the effect of handwashing promotion with soap on the incidence of acute respiratory infection, impetigo, and diarrhoea. In adjoining squatter settlements in Karachi, Pakistan, we randomly assigned 25 neighbourhoods to handwashing promotion; 11 neighbourhoods (306 households) were randomised as controls. In neighbourhoods with handwashing promotion, 300 households each were assigned to antibacterial soap containing 1.2% triclocarban and to plain soap. Fieldworkers visited households weekly for 1 year to encourage handwashing by residents in soap households and to record symptoms in all households. Primary study outcomes were diarrhoea, impetigo, and acute respiratory-tract infections (ie, the number of new episodes of illness per person-weeks at risk). Pneumonia was defined according to the WHO clinical case definition. Analysis was by intention to treat. Children younger than 5 years in households that received plain soap and handwashing promotion had a 50% lower incidence of pneumonia than controls (95% CI (-65% to -34%). Also compared with controls, children younger than 15 years in households with plain soap had a 53% lower incidence of diarrhoea (-65% to -41%) and a 34% lower incidence of impetigo (-52% to -16%). Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap. Handwashing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally-namely, diarrhoea and acute lower respiratory infections. Handwashing with daily bathing also prevents impetigo.\nStudy7: Effect of infection control measures on the frequency of diarrheal episodes in child care: a randomized, controlled trial. Diarrheal infections are common in children who attend child care, and preventing transmission of disease in this setting depends on actions by child care staff. We set out to discover whether transmission of gastrointestinal infections in child care could be reduced by improved infection control procedures. We performed a cluster randomized, controlled trial of an infection control intervention conducted in child care centers for 1 city in Australia. The intervention was training of child care staff about transmission of infection and handwashing and focused on both staff and child behavior. Implementation of the intervention was recorded by an observer. Illness was measured by parent report in telephone interviews every 2 weeks. There were 311 child-years of surveillance for diarrheal episodes. The rate of episodes of diarrhea was 1.9 per child-year in intervention centers and 2.7 per child-year in control centers. Multivariable analysis showed that diarrheal episodes were significantly reduced in intervention center children by 50%. However, the impact of the intervention was confined to children over 24 months of age. For those centers in which children's compliance with handwashing was high, diarrheal episodes were reduced by 66%. This trial supports education about infection control, for staff and children in child care, as a means of reducing transmission of diarrhea. Reduction in episodes of diarrhea in children in child care was limited to children over 24 months of age.\nStudy8: Effect of intensive handwashing in the prevention of diarrhoeal illness among patients with AIDS: a randomized controlled study. Patients with AIDS frequently develop diarrhoeal illness. In this randomized, controlled study, 260 patients were screened for those who had not had diarrhoea in the preceding 3 months and who had received a stable highly active antiretroviral therapy regimen for at least 6 weeks prior to the study enrollment. A total of 148 patients met the inclusion criteria and were enrolled: 75 patients were randomly assigned to an intensive handwashing intervention (i.e. handwashing after defecation, after cleaning infants who had defecated, before preparing food, before eating, and before and after sex) and 73 patients were randomly assigned to the control group. Patients in both groups were called weekly by telephone to determine compliance with handwashing and to determine the number of diarrhoeal episodes for the preceding week. Patients were observed for 1 year. Patients assigned to the intensive handwashing intervention group washed their hands more frequently compared with the control group (seven vs four times a day, respectively; P <0.05) and developed fewer episodes of diarrhoeal illness (1.24+/-0.9 vs 2.92+/-0.6 new episodes of diarrhoea, respectively; P <0.001) during the 1 year observation. The most common pathogens identified in both groups in patients who developed diarrhoeal illness were Giardia lamblia, Cryptosporidium, Entamoeba histolytica and Shigella flexneri. These data suggest that intensive handwashing reduces diarrhoeal illness in patients with AIDS.\nStudy9: [Hand-hygiene and sickness among small children attending day care centers. An intervention study]. The purpose of the study was to evaluate the effect of intensified hygiene with frequent handwashing and several educational procedures in day-care centres. The study was conducted as a controlled trial, with an intervention group and an observation group. There was a 34% reduction in expected sickness in children in the intervention group. In the categories diarrhoea and eye-infection there was a significant drop in sickness. We conclude that broad intervention concerning hand-hygiene has a positive effect on sickness in children attending day-care centres.\nStudy10: Community-based hygiene education to reduce diarrhoeal disease in rural Zaire: impact of the intervention on diarrhoeal morbidity. Diarrhoeal disease is a leading cause of morbidity in young children in rural Zaire. Few diarrhoea prevention programmes have been implemented in Bandundu Province, where available data suggest an annual prevalence rate of 10%. The urgent need to reduce diarrhoeal morbidity in Zaire, together with the potential effectiveness and feasibility of hygiene education as a diarrhoea prevention strategy, led to the development of the present research project. A randomized, controlled trial of an education intervention to reduce diarrhoea through improved personal and domestic hygiene behaviours was conducted in 18 geographically separate village clusters (sites) in rural Zaire. For 12 weeks baseline information on the diarrhoeal morbidity of 2082 children aged 3-35 months was collected at weekly home visits, and structured observations of hygiene practices related to diarrhoea were made on a subset of 300 families. Intervention messages addressed disposal of animal faeces from the yard, handwashing after defecation and before meal preparation and eating, and disposal of children's faeces. Three months after the start of the intervention and exactly 1 year after the baseline studies, a second diarrhoeal morbidity study and a second observational study were conducted in order to evaluate the intervention. Children in intervention communities experienced an 11% reduction in the risk of reporting diarrhoea during the peak diarrhoeal season, compared to controls (P < 0.025). The largest differences were seen among children aged 24-35 months, with those from intervention communities reporting significantly fewer episodes, shorter mean durations and hence fewer days of diarrhoea. There was some evidence that greater reductions in diarrhoea occurred in sites where the quality of the intervention, a scored measure of volunteer efficacy and community participation, was highest. The results of this study suggest that hygiene education may be an effective approach to reduce the incidence and duration of diarrhoeal episodes in rural Zaire. Children aged 2 years appear to benefit the most. A Hawthorne effect of the education may contribute to diarrhoeal reductions.\n", + "output": "Conclusions: Interventions that promote hand washing can reduce diarrhoea episodes by about one-third. This significant reduction is comparable to the effect of providing clean water in low-income areas. However, trials with longer follow up and that test different methods of promoting hand washing are needed." + }, + { + "input": "Study1: The effect of terbutaline sulfate, nitroglycerin, and aminophylline on lower esophageal sphincter pressure and radionuclide esophageal emptying in patients with achalasia. We studied the effects of three smooth muscle relaxants on lower esophageal sphincter (LES) pressure and radionuclide esophageal emptying in 15 untreated patients with achalasia. LES pressures were determined before and after the administration of normal saline subcutaneously, terbutaline sulfate subcutaneously, nitroglycerin sublingually, and aminophylline intravenously. All smooth muscle relaxants significantly decreased LES pressures when compared with normal saline controls and pretreatment baseline pressures (p less than 0.01). However, in normal saline controls, LES pressure actually increased over time (p less than 0.01). Control radionuclide esophageal emptying studies were performed in all patients. Subsequent esophageal emptying studies were carried out only in patients responding to smooth muscle relaxants by decreasing LES pressures by greater than or equal to 25% (terbutaline sulfate, n = 8; nitroglycerin, n = 7; and aminophylline, n = 4). Significant improvement in esophageal emptying was observed after nitroglycerin and terbutaline sulfate (p less than 0.05) but not after aminophylline. We conclude that in patients with achalasia (a) terbutaline sulfate, nitroglycerin, and aminophylline can significantly decrease LES pressure; (b) resting LES pressures vary over time; and (c) terbutaline sulfate and nitroglycerin significantly improve esophageal emptying in some subjects.\nStudy2: Isosorbide dinitrate and nifedipine treatment of achalasia: a clinical, manometric and radionuclide evaluation. The effects of sublingual isosorbide dinitrate (5 mg) and nifedipine (20 mg) were compared in 15 patients with achalasia. The parameters examined included the manometric measurement of the lower esophageal sphincter pressure, the radionuclide assessment of esophageal emptying and the clinical response. The mean basal lower esophageal sphincter pressure fell significantly after both drugs (p less than 0.01), with a maximum fall of 63.5% 10 min after receiving isosorbide dinitrate, but by only 46.7% 30 min after nifedipine. The esophageal radionuclide test meal retention was significantly less (p less than 0.01) only after receiving isosorbide dinitrate. The drug improved initial esophageal emptying by its effect on the lower esophageal sphincter and by relieving the test meal hold-up noted to occur at the junction of the upper and midesophagus. Eight patients cleared their test meal within 10 min after isosorbide dinitrate administration while only two did so after nifedipine. Subjectively, 13 patients had their dysphagia relieved by isosorbide dinitrate and 8 by nifedipine. However, this relief was not confirmed in 4 patients by the radionuclide study and they, as well as the other 3 patients who did not respond to therapy, were referred to pneumatic dilatation. Side effects were more prominent after nitrates. Three of the patients are currently receiving nifedipine and 5 patients received isosorbide dinitrate therapy for 8-14 mo. The radionuclide test meal is currently the best way of objectively evaluating drug therapy in patients with achalasia. Isosorbide dinitrate is more effective than nifedipine in relieving their symptoms.\n", + "output": "Conclusions: From most of the single reports we found, after intake of nitrates (either nitroglycerin or isosorbide dinitrate), there was a fall in lower oesophageal pressure and improvement of radionuclide esophageal emptying compared to the baseline. From the available evidence, we cannot provide any implications for practice. Appropriately designed, parallel group, randomised controlled trials with long term follow-up are needed to determine the effects of nitrates for achalasia." + }, + { + "input": "Study: Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz. In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat. Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine. Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.\n", + "output": "Conclusions: The combination of nevirapine, 3TC and d4T is as efficacious as a combination of efavirenz, 3TC and d4T. Once-daily NVP with twice-daily 3TC and d4T is as efficacious as twice-daily NVP, 3TC and d4T. However, toxicity may be increased in the once-daily NVP regime. Additional trials of sufficient duration are required to provide better evidence for the use of this combination as a first line therapy. Ideally, trials should use standardised assessment measures especially with respect to measuring viral load, so that results can be compared and combined in meta-analyses." + }, + { + "input": "Study1: Augmentation of labor: does internal tocography result in better obstetric outcome than external tocography? Labor was augmented in 250 patients for slow progress. These women were randomized to have uterine contractions recorded by either an external tocotransducer or an intrauterine catheter. Oxytocin was titrated to achieve an optimal frequency of contractions of six to seven every 15 minutes in each group; additional information on active contraction area profiles was available for those patients who had an intrauterine catheter. There was no statistically significant difference between the groups in the length of the post-augmentation period. The mean maximum dose of oxytocin was 11.1 mU/minute in the external tocography group and 11.0 mU/minute in the internal tocography group. Evidence of uterine hyperstimulation requiring temporary reduction of the oxytocin dose occurred in 19 and 20.2% of the patients in the external and internal tocography groups, respectively. Cesarean delivery was necessary in 12.6 and 16.9% of patients in the external and internal tocography groups, respectively, which is a nonsignificant difference. The incidence of low Apgar scores in the neonates and admission to neonatal intensive care was similar in both groups. The incidence of poor Apgar scores was not different between those who had transient hyperstimulation and those who had no hyperstimulation. In the management of augmented labor, monitoring of uterine contractions by intrauterine pressure catheters did not confer any advantage over tocography by external transducers.\nStudy2: Outcomes after internal versus external tocodynamometry for monitoring labor. It has been hypothesized that internal tocodynamometry, as compared with external monitoring, may provide a more accurate assessment of contractions and thus improve the ability to adjust the dose of oxytocin effectively, resulting in fewer operative deliveries and less fetal distress. However, few data are available to test this hypothesis. We performed a randomized, controlled trial in six hospitals in The Netherlands to compare internal tocodynamometry with external monitoring of uterine activity in women for whom induced or augmented labor was required. The primary outcome was the rate of operative deliveries, including both cesarean sections and instrumented vaginal deliveries. Secondary outcomes included the use of antibiotics during labor, time from randomization to delivery, and adverse neonatal outcomes (defined as any of the following: an Apgar score at 5 minutes of less than 7, umbilical-artery pH of less than 7.05, and neonatal hospital stay of longer than 48 hours). We randomly assigned 1456 women to either internal tocodynamometry (734) or external monitoring (722). The operative-delivery rate was 31.3% in the internal-tocodynamometry group and 29.6% in the external-monitoring group (relative risk with internal monitoring, 1.1; 95% confidence interval [CI], 0.91 to 1.2). Secondary outcomes did not differ significantly between the two groups. The rate of adverse neonatal outcomes was 14.3% with internal monitoring and 15.0% with external monitoring (relative risk, 0.95; 95% CI, 0.74 to 1.2). No serious adverse events associated with use of the intrauterine pressure catheter were reported. Internal tocodynamometry during induced or augmented labor, as compared with external monitoring, did not significantly reduce the rate of operative deliveries or of adverse neonatal outcomes. (Current Controlled Trials number, ISRCTN13667534; Netherlands Trial number, NTR285.) 2010 Massachusetts Medical Society\nStudy3: Induction of labour: does internal tocography result in better obstetric outcome than external tocography. A prospective randomized study was undertaken to evaluate the benefit of intrauterine catheters in induced labour. Two hundred and thirty nine women who had induced labour were studied. The patients in one group had intrauterine catheters inserted and oxytocin was titrated to achieve the 75th percentile of uterine activity observed in spontaneous normal labour according to parity. Contractions were assessed by external tocography in the other group and oxytocin was titrated to achieve 6 to 7 contractions per 15 minutes each lasting > 40 seconds. Mean maximum dose of oxytocin, mode of delivery, Apgar score < 7 at 5 minutes, cord arterial blood pH < 7.15 and admission to neonatal intensive care unit did not differ significantly in the 2 groups. In conclusion, women who had intrauterine catheters did not have a shorter duration of labour, lower dose of oxytocin, fewer operative deliveries or fewer babies in poor condition at birth compared with those who had external tocography in induced labour.\n", + "output": "Conclusions: This review found no differences between the two types of monitoring (internal or external tocodynamometry) for any of the maternal or neonatal outcomes. Given that this review is based on three studies (N = 1945 women) of moderate quality, there is insufficient evidence to recommend the use of one form of tocodynamometry over another for women where intravenous oxytocin was administered for induction or augmentation of labour." + }, + { + "input": "Study1: A randomized comparison of primary closure and T-tube drainage of the common bile duct after laparoscopic choledochotomy. Traditionally, the common bile duct (CBD) has been closed with T-tube drainage after laparoscopic choledochotomy and removal of CBD stones. However, insertion of the T-tube is related to some potential postoperative complications, and patients must carry the T-tube for several weeks before its removal. Primary closure of the CBD without drainage has been proposed as a safe alternative to T-tube placement after laparoscopic choledochotomy. This randomized study aimed to compare the postoperative course and final outcome between the two methods applied after LCBDE. Between January 2000 and January 2004, 80 patients treated with laparoscopic choledochotomy for CBD stones were randomly assigned to primary duct closure (n = 40) or T-tube drainage (n = 40). The primary end points were morbidity, operative time, postoperative stay, hospital expenses, and time until return to work. There were no differences in the demographic characteristics or clinical presentations between the two groups. In the primary closure group, the postoperative stay (5.2 +/- 2.2 vs 8.3 +/- 3.6 days) and the time until return to work (12.6 +/- 5.1 vs 20.4 +/- 13.2 days) were significantly shorter, the hospital expenses (8,638 +/- 2,946 vs 12,531 +/- 4,352 yuan) were significantly lower, and the incidences of postoperative complications (15% vs 27.5%) and biliary complications (10% vs 20%) were statistically and insignificantly lower than in the T-tube drainage group. In the primary closure group, six patients experienced postoperative complications, four of whom had biliary complications, compared, respectively, with 11 and 8 patients in the T-tube drainage group. This study showed that primary CBC closure after laparoscopic choledochotomy was a viable alternative to mandatory T-tube drainage.\nStudy2: Is the use of T-tube necessary after laparoscopic choledochotomy? Traditionally, the common bile duct (CBD) is closed with T-tube drainage after choledochotomy and removal of CBD stones. However, the insertion of a T-tube is not without complication. This randomized study was designed to compare the use of T-tube and primary closure of choledochotomy after laparoscopic choledochotomy to determine whether primary closure can be as safe as closure with T-tube drainage. Between February 2006 and June 2009, 122 consecutive patients with proven choledocholithiasis had laparoscopic choledochotomy. They were randomized into two equal groups: T-tube (n = 61) and primary closure (n = 61). Demographic data, intraoperative findings, postoperative complications, and postoperative stay were recorded. There was no mortality in both groups. There were no differences in the demographic characteristics or clinical presentations between the two groups. Compared with the T-tube group, the operative time and postoperative stay were significantly shorter and the incidences of overall postoperative complications and biliary complications were statistically and significantly lower in the primary closure group. Laparoscopic common bile duct exploration with primary closure without external drainage after laparoscopic choledochotomy is feasible, safe, and cost-effective. After verification of ductal clearance, the CBD could be closed primarily without T-tube insertion.\n", + "output": "Conclusions: T-tube drainage appears to result in significantly longer operating time and hospital stay as compared with primary closure without any evidence of benefit after laparoscopic common bile duct exploration. Based on currently available evidence, there is no justification for the routine use of T-tube drainage after laparoscopic common bile duct exploration in patients with common bile duct stones. More randomised trials comparing the effects of T-tube drainage versus primary closure after laparoscopic common bile duct exploration may be needed. Such trials should be conducted with low risk of bias, assessing the long-term beneficial and harmful effects including long-term complications such as bile stricture and recurrence of common bile duct stones." + }, + { + "input": "Study1: Randomised trial of histoacryl blue tissue adhesive glue versus suturing in the repair of paediatric lacerations. To compare histoacryl blue tissue adhesive glue with suturing in the repair of simple paediatric lacerations. Prospective, randomised controlled trial in tertiary paediatric emergency department. Children 4 years old or older with non-ragged lacerations <5 cm in length, <12-h-old and not involving eyelid or mucous membrane. A total of 163 patients were randomly allocated to either glue (83 cases) or sutures (80 controls) to repair their laceration. Primary outcome measures were cosmetic outcome at 3 and 12 months with secondary outcomes-length of time to perform procedure, and pain assessment of procedure by doctor, nurse, parent and child. Cases and controls were similar in age, wound length and width and body part involved, but more females received glue (P = 0.013). Time taken to repair the wound was faster in the glue group (median 0-2 mins vs. 6-10 min suture, P<0.001). Doctors (P = 0.02), nurses (P<0.01) and parents (P = 0.02) but not the children themselves (P = 0.24) rated glue repair as less distressing. Complications at 1 week (wound dehiscence, redness and discharge) were the same for both groups (P>0.2). Cosmetic outcome was the same for both groups at 3 (n = 65) and 12 (n = 65) months (P>0.7). Tissue adhesive glue is faster and probably less painful than suturing. Tissue adhesive glue has the same cosmetic result as suturing when used for the repair of simple lacerations in children.\nStudy2: Evaluation of a new high-viscosity octylcyanoacrylate tissue adhesive for laceration repair: a randomized, clinical trial. Tissue adhesives have recently been approved for skin closure. Their low viscosity may result in inadvertent migration. The authors compared the tendency of the adhesive to migrate after laceration closure with a high- or low-viscosity octylcyanoacrylate (OCA). This was a randomized, clinical trial set in university and community-based emergency departments. Participants included patients with simple traumatic lacerations. Patients were randomized to laceration closure with low- or high-viscosity OCA tissue adhesive. The outcome measured was immediate adhesive migration (interobserver agreement, kappa = 0.90). Data analysis was performed with proportions compared with chi-square and Fisher's exact tests. Eighty-four patients were randomized to low- (n = 42) or high- (n = 42) viscosity OCA tissue adhesive. Groups were similar in baseline patient and wound characteristics. The high-viscosity OCA was less likely to migrate than the lower-viscosity agent (21% vs. 78%, p < 0.001; odds ratio = 0.3, 95% confidence interval = 0.1 to 0.5). The proportion of patients who noted a sensation of heat during OCA application was higher in the high-viscosity groups (44% vs. 26% respectively, p = 0.11); however, all such patients in both groups would use the device again. At 14 days, there were no wound infections in either group. There was one dehiscence in the high-viscosity group. The high-viscosity OCA tissue adhesive was less likely to migrate than the lower-viscosity device. Wound dehiscence and infection rates were acceptably low in both treatment groups.\nStudy3: A randomized, controlled trial comparing a tissue adhesive with suturing in the repair of pediatric facial lacerations. To compare the tissue adhesive Histoacryl Blue with suturing in the repair of pediatric facial lacerations. Prospective, randomized controlled trial. Emergency department of a pediatric teaching hospital. Eighty-one children presenting with clean facial lacerations less than 4 cm in length and 0.5 cm in width. Patients were allocated randomly to have their lacerations repaired with sutures or Histoacryl Blue. The two groups were similar for demographic and clinical characteristics. Photographs taken at three months were rated by two plastic surgeons blinded to the method of closure. There was no difference between groups for appearance scores on a visual analog scale (60.5 mm for Histoacryl Blue versus 57.2 mm for suture, P = .45) or on a categorical scale (Histoacryl Blue versus sutures: unacceptable, 11% versus 13%; acceptable, 59% versus 71%; excellent, 30% versus 16%; P = .76). Measures of observer agreement produced Pearson correlations of .72 and .94 on the visual analog scale and kappa coefficients of .46 and .73 on the categorical scale. Histoacryl Blue was assessed as less painful on a visual analog scale (24.7 versus 43.7 mm, P < .01) and faster (7.9 versus 15.6 minutes, P < .001). Histoacryl Blue is a faster and less painful method of facial laceration repair that has cosmetic results similar to the use of sutures.\nStudy4: Prospective, randomized, controlled trial of tissue adhesive (2-octylcyanoacrylate) vs standard wound closure techniques for laceration repair. Stony Brook Octylcyanoacrylate Study Group. To compare a new tissue adhesive, 2-octylcyanoacrylate, with standard wound closure techniques for the repair of traumatic lacerations. A prospective, randomized, controlled clinical trial enrolled consecutive patients > 1 year of age with non-bite, non-crush-induced lacerations who presented < 6 hours after injury. Structured closed-question data sheets were completed at the time of laceration repair and suture removal. Patients were randomly assigned to treatment with either 2-octylcyanoacrylate or standard wound closure. Infection was determined at the time of suture removal. Long-term cosmetic appearance (> 3 months) was assessed by physicians using a previously validated categorical cosmetic scale and by patients using a 100-mm visual analog scale. There were 63 patients randomized to the octylcyanoacrylate group and 61 patients treated with standard wound closure techniques. The 2 treatment groups were similar with respect to age, gender, race, medical history, and wound characteristics. At the 5-to-10-day follow-up, only 1 wound was infected and only 2 wounds required reclosure due to dehiscence. These 3 patients received treatment with octylcyanoacrylate. At long-term follow-up, the cosmetic appearances were similar according to the patients (octylcyanoacrylate, 83.8 +/- 19.4 mm vs standard techniques, 82.5 +/- 17.6 mm; p = 0.72) and the physicians (optimal cosmetic appearance, 77% vs 80%; p = 0.67). Wounds treated with octylcyanoacrylate and standard wound closure techniques have similar cosmetic appearances 3 months later.\nStudy5: Comparison of tissue adhesive and suturing in the repair of lacerations in the emergency department. The objective of this study was to compare the applications of Histoacryl Blue (HAB) and suturing regarding cosmetic outcome, cost and patient and physician satisfaction in the emergency department (ED). A total of 92 consecutive adult patients with lacerations equal to or shorter than 5 cm were enrolled in the study. Patients were randomized to either HAB or suturing. Ten-day and three-month cosmetic outcomes were evaluated via visual analogue scale (VAS) by a blinded surgeon. Cosmetic outcome, cost and patient and physician satisfaction of both groups were compared. Only 52 patients completed the follow-up at three months. Twenty-eight had been repaired with sutures and 24 with HAB. The differences regarding ten-day and three-month cosmetic outcome scales between the patients repaired with HAB and sutures were not statistically significant. Application of HAB resulted in greater satisfaction of the patient and the physician (p=0.007 and p=0.0001, respectively). Costs of HAB were significantly lower than sutures (p=0.0001). It is concluded that HAB is a cheaper method of laceration repair and results in greater satisfaction of both patients and physicians, while cosmetic outcomes were comparable. These results suggest that HAB is a viable alternative to suturing for selected lacerations in the ED.\nStudy6: Long-term appearance of lacerations repaired using a tissue adhesive. Histoacryl Blue (HAB), a tissue adhesive, has been shown to decrease laceration repair time, cause less pain to the child, eliminate the need for suture removal, and result in a similar short-term cosmetic outcome compared with conventional suturing. Reports suggest that poor correlation can exist between the short-term and long-term cosmetic outcomes for lacerations repaired by conventional suturing. Therefore, this study compares the long-term cosmetic outcome of HAB to conventional suturing for laceration repair in children. Prospective, randomized clinical trial. Children presenting an urban pediatric emergency department for laceration repair between October 1994 and February 1995 were eligible. Patients less than 1 or more than 18 years old, those with lacerations more than 5 cm in length, or in areas of high tension or mobility were excluded. After routine wound management, including subcutaneous closure when deemed necessary, patients were randomized to receive skin sutures or HAB for cutaneous closure. Photographs taken at the 2-month and 1-year follow-up visits were evaluated for cosmetic appearance by two plastic surgeons blinded to the method of repair. Sixty-one children were enrolled: HAB (N = 30), suture (N = 31). Thirty HAB and 25 sutured patients were assessed at 2 months, while 17 HAB and 15 sutured patients were reevaluated at 1 year. Patients that followed-up at 2 months and 1 year were comparable to those with no follow-up in: treatment group (HAB vs suture), demographics, wound characteristics, and initial parental satisfaction. The two plastic surgeons graded the cosmetic appearance of the wounds repaired by HAB to be comparable to those repaired by conventional suturing at both the 2-month and 1-year follow-up. The use of HAB is an ideal alternative to conventional suturing for the cutaneous closure of low tension lacerations in children with a long-term cosmetic outcome comparable to conventional suturing.\nStudy7: Tissue adhesive versus suture wound repair at 1 year: randomized clinical trial correlating early, 3-month, and 1-year cosmetic outcome. To compare the 1-year cosmetic outcome of wounds treated with octylcyanoacrylate tissue adhesive and monofilament sutures and to correlate the early, 3-month, and 1-year cosmetic outcomes. We prospectively randomized 136 cases of traumatic laceration to repair with octylcyanoacrylate tissue adhesive or 5-0 or smaller monofilament suture. A wound score was assigned by a research nurse, and validated by a second nurse blinded to the treatment, at 5 to 10 days after injury (early), 3 months, and 1 year. Standardized photographs were taken at 3 months and 1 year and shown to a cosmetic surgeon blinded to the method of closure, who rated the wounds on a validated cosmesis scale. We were able to examine 77 lacerations at 1 year for follow-up. No differences were found in the demographic or clinical characteristics between groups. Likewise, at 1 year no difference was found in the optimal wound scores (73% versus 68%, P =.60) or in visual analog scale cosmesis scores (69 versus 69 mm, P =.95) for octylcyanoacrylate and sutures, respectively. Agreement was poor between early and 3-month wound scores (kappa=.34; 95% confidence interval [CI],.10 to.58) but a strong association existed between 3-month and 1-year wound scores (kappa=.71; 95% CI,.52 to.90). We noted a moderate correlation between 3-month and 1-year results on the visual analog cosmesis scale (intraclass correlation,.48; 95% CI, .30 to.63). One year after wound repair, no difference is noted in the cosmetic outcomes of traumatic lacerations treated with octylcyanoacrylate tissue adhesive and sutures. The assessment of wounds 3 months after injury and wound repair provides a good measure of long-term cosmetic outcome.\n", + "output": "Conclusions: Tissue adhesives are an acceptable alternative to standard wound closure for repairing simple traumatic lacerations. They offer the benefit of decreased procedure time and less pain, when compared to standard wound closure. A small but statistically significant increased rate of dehiscence with tissue adhesives is observed." + }, + { + "input": "Study1: Cue-based feeding for preterm infants: a prospective trial. We set out to test whether premature infants were able to be fed orally on feeding cues and be discharged home earlier than infants fed by traditional feeding regimens. Attainment of adequate growth, adverse events, and nursing time to provide care were also assessed. After screening, the recruited premature infants (< 36 wks post-conceptual age [PCA]) were divided into two feeding regimens. A control group of 40 infants was fed using an initial combination of scheduled gavage and bottle feeding and then graduating to demand feeds. The intervention group comprised 39 neonates who had gavage feeds discontinued at study entrance and fed orally on cues. Outcomes measured were: weight gain in grams/kg/day, length of stay (in days) after enrollment, PCA on entrance and at discharge, adverse events during feeding, number of cues per feed in the intervention group, and resource utilization using nurse/patient ratios. Differences between groups were evaluated using Mann-Whitney U test, Fisher's exact test, and regression analysis. Two-tailed P values of < 0.05 were considered significant. There was no difference between groups in the mean weight gain; in the control group mean weight gain was 12.5 gm/kg/day and in the intervention group 12.1 gm/kg/day ( P = 0.83). The average length of stay in the control group of 14.5 days was significantly longer than the 10.0 days in the intervention group ( P = 0.009). This difference remained significant after adjusting for gestational age at birth in regression analysis. The average total number of adverse events in the control group (12.5 events) was significantly greater than in the intervention group (3.5 events; P = 0.007). The mean PCA on study entry was 34.4 wks in both groups and on exit 36.5 wks in the control group and 35.8 wks in the intervention group, a significant difference ( P = 0.02), The intervention group elicited 2.8 cues/feed. The nurse to patient ratios was equal in both groups throughout the study period. Cue-based feeding was possible for premature infants with similar weight gain as traditional feeding without affecting workload. Hospitalization and adverse events were decreased.\nStudy2: The effects of prescribed versus ad libitum feedings and formula caloric density on premature infant dietary intake and weight gain. Although feedings that are organized on an ad lib basis (i.e., in response to infant cues of hunger and of satiation) could enhance an infant's self-regulatory capacities for feeding, ad lib feeding of fully nipple-fed premature infants in a special care nursery has not been examined. To study whether the caloric and protein intake and weight change of fully nipple-fed preterm infants differed by the feeding regimen (prescribed or ad lib) and by the caloric density of the formula (20- or 24-kcalories per ounce). The 78 infants who participated in the study were randomized to prescribed or ad lib feeding regimens and, within each regimen, were further randomized to receive either 20-calorie or 24-kcalorie per ounce formula. Dietary intake (volume/kg, caloric intake/kg) and weight change (grams/kg gained or lost) were assessed for each of the 5 study days. Multivariate data analysis was used to examine the effects of feeding regimen and caloric density on dietary intake and weight change, controlling biologic variables (infant gender, race, lung disease diagnosis, treatment with supplemental oxygen, gestational age and weight at birth, and weight on the day prior to full nipple-feeding). Overall, the ad lib feeding regimen had a negative effect on volume intake and caloric intake. Weight gain was influenced by caloric intake, but not by feeding regimen or the caloric density of the diet. With increased full nipple-feeding experience, caloric intake of ad lib feeders approached that of the infants fed on the prescribed regimen. Development of self-regulatory capacities through ad lib feeding experience was indicated by infant regulation of the volume of intake by the caloric density of the formula, an unexpected finding. Furthermore, the approach of the caloric intake of infants on the ad lib regimen to that of infants on the prescribed regimen suggests they had gained skill in regulating intake with experience. Whether or not the trend for similar intakes would continue beyond 5 days is a question for further study.\n", + "output": "Conclusions: Limited evidence exists that feeding preterm infants with ad libitum or demand/semi-demand regimens allows earlier attainment of full oral feeding and earlier hospital discharge. This finding should be interpreted cautiously because of methodological weaknesses in the included trials. A large randomised controlled trial is needed to confirm this finding and to determine if ad libitum of demand/semi-demand feeding of preterm infants affects other clinically important outcomes." + }, + { + "input": "Study1: Prostaglandin F 2 for induction of labor. nan\nStudy2: Biochemical and haematological changes during the induction of labour at term with oxytocin, prostaglandin E-2 and prostaglandin F-2alpha. A total of 75 patients had labour induced near term using intravenous oxytocin, prostaglandin E-2 or prostaglandin F-2alpha. Biochemical and haematological investigations were performed to assess hepatic, renal and adrenocortical function and changes in platelet adhesiveness. In doses which were similarly effective in inducing labour, both prostaglandins were without the water-retaining effect of oxytocin. Adrenocortical stimulation was greatest with oxytocin. No difference between these agents was observed for the other measurements made.\n", + "output": "Conclusions: Intravenous prostaglandin is no more efficient than intravenous oxytocin for the induction of labour but its use is associated with higher rates of maternal side-effects and uterine hyperstimulation.\nNo conclusions can be drawn form the comparisons of combination of prostaglandin F2 alpha and oxytocin compared to oxytocin alone or extra-amniotic and intravenous prostaglandin E2.\n[Note: The two citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]" + }, + { + "input": "Study1: Controlled trial of hypnotherapy in the treatment of severe refractory irritable-bowel syndrome. 30 patients with severe refractory irritable-bowel syndrome were randomly allocated to treatment with either hypnotherapy or psychotherapy and placebo. The psychotherapy patients showed a small but significant improvement in abdominal pain, abdominal distension, and general well-being but not in bowel habit. The hypnotherapy patients showed a dramatic improvement in all features, the difference between the two groups being highly significant. In the hypnotherapy group no relapses were recorded during the 3-month follow-up period, and no substitution symptoms were observed.\nStudy2: Gut-directed hypnotherapy for irritable bowel syndrome: piloting a primary care-based randomised controlled trial. In western populations irritable bowel syndrome (IBS) affects between 10% and 30% of the population and has a significant effect on quality of life. It generates a substantial workload in both primary and secondary care and has significant cost implications. Gut-directed hypnotherapy has been demonstrated to alleviate symptoms and improve quality of life but has not been assessed outside of secondary and tertiary referral centres. To assess the effectiveness of gut-directed hypnotherapy as a complementary therapy in the management of IBS. Randomised controlled trial. Primary care patients aged 18-65 years inclusive, with a diagnosis of IBS of greater than 6 weeks' duration and having failed conventional management, located in South Staffordshire and North Birmingham, UK. Intervention patients received five sessions of hypnotherapy in addition to their usual management. Control patients received usual management alone. Data regarding symptoms and quality of life were collected at baseline and again 3, 6, and 12 months post-randomisation. Both groups demonstrated a significant improvement in all symptom dimensions and quality of life over 12 months. At 3 months the intervention group had significantly greater improvements in pain, diarrhoea and overall symptom scores (P<0.05). No significant differences between groups in quality of life were identified. No differences were maintained over time. Intervention patients, however, were significantly less likely to require medication, and the majority described an improvement in their condition. Gut-directed hypnotherapy benefits patients via symptom reduction and reduced medication usage, although the lack of significant difference between groups beyond 3 months prohibits its general introduction without additional evidence. A large trial incorporating robust economic analysis is, therefore, urgently recommended.\nStudy3: Hypnosis treatment for severe irritable bowel syndrome: investigation of mechanism and effects on symptoms. Hypnosis improves irritable bowel syndrome (IBS), but the mechanism is unknown. Possible physiological and psychological mechanisms were investigated in two studies. Patients with severe irritable bowel syndrome received seven biweekly hypnosis sessions and used hypnosis audiotapes at home. Rectal pain thresholds and smooth muscle tone were measured with a barostat before and after treatment in 18 patients (study I), and treatment changes in heart rate, blood pressure, skin conductance, finger temperature, and forehead electromyographic activity were assessed in 24 patients (study II). Somatization, anxiety, and depression were also measured. All central IBS symptoms improved substantially from treatment in both studies. Rectal pain thresholds, rectal smooth muscle tone, and autonomic functioning (except sweat gland reactivity) were unaffected by hypnosis treatment. However, somatization and psychological distress showed large decreases. In conclusion, hypnosis improves IBS symptoms through reductions in psychological distress and somatization. Improvements were unrelated to changes in the physiological parameters measured.\nStudy4: The treatment of irritable bowel syndrome with hypnotherapy. Previous research from the United Kingdom has shown hypnotherapy to be effective in the treatment of irritable bowel syndrome (IBS). The current study provides a systematic replication of this work in the United States. Six matched pairs of IBS patients were randomly assigned to either a gut-directed hypnotherapy (n = 6) or to a symptom monitoring wait-list control condition (n = 6) in a multiple baseline across subjects design. Those assigned to the control condition were later crossed over to the treatment condition. Subjects were matched on concurrent psychiatric diagnoses, susceptibility to hypnosis, and various demographic features. On a composite measure of primary IBS symptoms, treatment was superior (p = .016) to symptom monitoring. Results from the entire treated sample (n = 11; one subject was removed from analysis) indicate that the individual symptoms of abdominal pain, constipation, and flatulence improved significantly. State and trait anxiety scores were also seen to decrease significantly. Results at the 2-month follow-up point indicated good maintenance of treatment gains. No significant correlation was found between initial susceptibility to hypnosis and treatment gain. A positive relationship was found between the incidence of psychiatric diagnosis and overall level of improvement.\n", + "output": "Conclusions: The quality of the included trials was inadequate to allow any conclusion about the efficacy of hypnotherapy for irritable bowel syndrome. More research with high quality trials is needed." + }, + { + "input": "Study: Clinical benefits of lightweight compression: reduction of venous-related symptoms by ready-to-wear lightweight gradient compression hosiery. Medical-grade compression of class I (20-30 mmHg) and class II (30-40 mmHg) have been shown to be beneficial against venous hypertension or congestion. Relatively few studies address the effects of ready-to-wear (RTW) lightweight gradient compression pantyhose on venous symptoms. To perform a study comparing the effects of two different compression RTW lightweight gradient compression stockings (8-15 mmHg and 15-20 mmHg) on the venous symptoms of flight attendants. A prospective crossover trial of symptom evaluation in 19 flight attendants was performed in which participants rated their symptoms on a visual analog scale. During the initial phase, participants wore no compression for 2 weeks. They then wore 8-15 mmHg and 15-20 mmHg gradient compression support hose while flying over a 4-week period. Symptoms before and after wearing the gradient compression stockings were compared and statistically analyzed. Wearing of 8-15 mmHg gradient hose resulted in statistically significant improvement of discomfort (P < 0.01). Swelling, fatigue, aching, and tightness of the leg were all improved to a statistically significant degree (P < 0.01). For 15-20 mmHg gradient hosiery, symptoms were improved to a statistically significant or almost significant level. The difference between the 8-15 mmHg and 15-20 mmHg compression was not statistically significant. Use of lightweight (low compression) RTW gradient compression hosiery is very effective in improving symptoms of discomfort (P < 0.01), swelling (almost P < 0. 05), fatigue (P < 0.05), aching (P < 0.01), as well as leg tightness. Improvement of symptoms is statistically significant compared to no compression when hosiery was worn regularly during waking hours for 4 weeks.\n", + "output": "Conclusions: Due to the extremely limited number of trials, there is insufficient evidence to draw any conclusions about the effectiveness of non-pharmacological interventions for preventing CVI in standing workers. Further large-scale studies examining all possible non-pharmacological interventions and outcomes are required." + }, + { + "input": "Study1: Open comparative long-term study of vigabatrin vs carbamazepine in newly diagnosed partial seizures in children. To compare vigabatrin with carbamazepine as monotherapy in newly diagnosed children with partial epilepsy in order to evaluate the efficacy and tolerability of both drugs. Open and randomized with a 2-year follow-up period. The Infantile Neuropsychiatric Division of the Regional Pediatric Hospital, Ancona, Italy. Seventy children with newly diagnosed partial epilepsy were treated with vigabatrin (38 patients) or carbamazepine (32 patients). Vigabatrin, 50 to 60 mg/kg per day, or carbamazepine, 15 to 20 mg/kg per day, split into twice-a-day doses. The efficacy and tolerability of vigabatrin were compared with those of the standard treatment (carbamazepine) for this patient group. The efficacy of vigabatrin and carbamazepine was similar, with the suggestion of a better side effect profile with vigabatrin. Vigabatrin monotherapy should be considered as a monotherapeutic treatment option in patients with newly diagnosed epilepsy. However, more studies are needed to evaluate other issues of concern, such as the cognitive and behavioral adverse effects of antiepileptic drugs, to determine the most suitable therapy.\nStudy2: Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy. A randomized, controlled study. To evaluate the efficacy, safety, and cognitive effects of initial vigabatrin monotherapy compared with initial carbamazepine monotherapy in patients with newly diagnosed epilepsy. Open, randomized, controlled design. Follow-up period of 12 months. University hospital with an epilepsy center. A total of 100 patients, aged 15 to 64 years, classified as suffering from partial seizures and/or generalized tonic-clonic seizures were randomized to either vigabatrin or carbamazepine monotherapy. Fifty-nine patients with a single epileptic seizure and no antiepileptic drug treatment served as a control population for objective safety measures. To evaluate the comparative efficacy and toxicity of vigabatrin and carbamazepine, the drug success rate (ie, the proportion of patients continuing successful treatment with the randomly assigned drug) after 12 months of steady-state treatment was used. To evaluate the safety of the drugs in addition to reported side effects, visual evoked potential recordings and neuropsychological evaluation were performed during follow-up. During the 12-month follow-up period, 60% of patients receiving vigabatrin and carbamazepine were treated successfully. Vigabatrin caused fewer side effects that required discontinuation of therapy. However, vigabatrin had to be discontinuated more often owing to lack of efficacy, and fewer of the successfully treated patients receiving vigabatrin achieved total freedom from seizures. Vigabatrin had no detrimental effects on cognitive functions. Retrieval from both episodic and semantic memory and flexibility of mental processing improved significantly in patients successfully treated with vigabatrin. Vigabatrin seems to be an effective and safe antiepileptic drug as primary monotherapy for epilepsy with fewer cognitive side effects than carbamazepine.\n", + "output": "Conclusions: There is currently insufficient data to address the risk-benefit balance of using VGB versus CBZ monotherapy for epilepsy. Considering the high prevalence of visual field defects, reported in an existing systematic review of observational studies (Maguire 2010), the prescribing of VGB monotherapy for epilepsy should be used with caution and not considered as a first-line choice. If necessary, a frequent assessment of visual field is\u00a0needed. Future research should focus on investigating the reasons for visual field defects and exploring the potential prevention strategies. Moreover, future monotherapy studies of epilepsy should report results according to the recommendation of International League Against Epilepsy (ILAE) Commission, and methodological quality should be improved." + }, + { + "input": "Study1: Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. Several studies have demonstrated that diabetic patients with cirrhosis require insulin treatment because of insulin resistance. As chronic alcoholic liver damage is partly due to the lipoperoxidation of hepatic cell membranes, anti-oxidizing agents may be useful in treating or preventing damage due to free radicals. The aim of this study was to ascertain whether long-term treatment with silymarin is effective in reducing lipoperoxidation and insulin resistance in diabetic patients with cirrhosis. A 12-month open, controlled study was conducted in two well-matched groups of insulin-treated diabetics with alcoholic cirrhosis. One group (n=30) received 600 mg silymarin per day plus standard therapy, while the control group (n=30) received standard therapy alone. The efficacy parameters, measured regularly during the study, included fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria levels, glycosylated hemoglobin (HbA1c) and malondialdehyde levels. There was a significant decrease (p<0.01) in fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels already after 4 months of treatment in the silymarin group. In addition, there was a significant decrease (p<0.01) in fasting insulin levels and mean exogenous insulin requirements in the treated group, while the untreated group showed a significant increase (p<0.05) in fasting insulin levels and a stabilized insulin need. These findings are consistent with the significant decrease (p<0.01) in basal and glucagon-stimulated C-peptide levels in the treated group and the significant increase in both parameters in the control group. Another interesting finding was the significant decrease (p<0.01) in malondialdehyde/levels observed in the treated group. These results show that treatment with silymarin may reduce the lipoperoxidation of cell membranes and insulin resistance, significantly decreasing endogenous insulin overproduction and the need for exogenous insulin administration.\nStudy2: Immunomodulatory and hepatoprotective effects of in vivo treatment with free radical scavengers. The hepatoprotective and immunomodulatory effects of silymarin and amino-imidazol-carboxamid-phosphate were studied in 60 patients with compensated alcoholic cirrhosis of the liver in a one month double blind clinical trial. Treatment with both drugs normalized the elevated levels of aspartate aminotransferase, alanine aminotransferase and serum bilirubin, markedly reduced the high level of gamma-glutamyl transferase, increased lectin-induced lymphoblasttransformation, decreased the percentage of CD8+ cells and suppressed lymphocytotoxicity. None of these changes occurred in the placebo-treated group. Thus the hepato-protective effects of silymarin and amino-imidazol-carboxamid-phosphate are accompanied by changes in parameters of cellular immunoreactivity of the treated patients.\nStudy3: Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. The role of silymarin in the treatment of liver cirrhosis is controversial. Clinical outcome,biochemical profile and the antiperoxidative effects of silymarin MZ-80 during 6 months treatment were investigated in patients with alcoholic liver cirrhosis. Sixty consecutive patients with alcoholic liver cirrhosis were randomized to receive either silymarin MZ-80 (S) (150 mg t.i.d. per day) or placebo (P) for periods of 6 months. Erythrocyte total glutathione (GSH) content, platelet malondialdehyde (MDA) and serum amino-terminal propeptide of procollagen Type III (PIIINP) were determined at baseline and at the end of treatment. Forty-nine patients completed the study (24 S and 25 P). The 2 groups were well-matched for demographic as well as baseline clinical and laboratory parameters. Silymarin increased total GSH at 6 months (4.5 +/- 3.4 to 5.8 +/- 4.0 micromol/g Hb) whereas, in the placebo group, GSH remained unchanged (4.1 +/- 3.9 to 4.4 +/- 4.1 micromol/gHb) (p < 0.001), and platelet-derived non-induced MDA decreased by 33% (p < 0.015). A parallel decrease in PIIINP values was seen with silymarin (1.82 1.03 to 1.36 +/- 0.5 U/ml, p < 0.033) but not with placebo (1.31 +/- 0.4 to 1.27 +/- 0.6 U/ml). There were no concurrent changes on laboratory indices of the pathology. Silymarin is well-tolerated and produces a small increase in glutathione and a decrease in lipid peroxidation in peripheral blood cells in patients with alcoholic liver cirrhosis. Despite these effects no changes in routine liver tests were observed during the course of therapy.\nStudy4: Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent. In patients with non-insulin dependent diabetes mellitus (T2DM) and associated chronic liver disease, plasma levels of glucose, insulin and triglycerides are high, lipid peroxidation is increased and natural antioxidant reserves are reduced. Thus, we hypothesised that the re-balancing of cell redox levels and amelioration of liver function could result in a better glucose and lipid metabolism. To study this, we assessed the effect of a new oral formulation of an antioxidant agent - silybin-beta-cyclodextrin (named IBI/S) - in patients with chronic alcoholic liver disease and concomitant T2DM. Sixty outpatients were enrolled in a three-centre, double blind, randomised, IBI/S vs placebo study. Forty-two (21 in the group IBI/S - 135 mg/d silybin per os - and 21 in the placebo group) concluded the 6-month treatment period. The efficacy parameters included fasting and mean daily plasma glucose levels, glycosylated hemoglobin (HbA1c), basal, stimulated C-peptide and insulin levels, total-, HDL-cholesterol and triglycerides levels in addition to conventional liver function tests. Insulin sensitivity was estimated by HOMA-IR. Malondialdehyde (MDA) was also measured before and after treatment as an index of oxidative stress. Fasting blood glucose levels, which were similar at baseline in IBI/S group and in the placebo group (173.9 mg/dl and 177.1 mg/dl, respectively), decreased to 148.4 mg/dl (-14.7% vs baseline; p = 0.03) in the IBI/S group while they were virtually unchanged in the placebo group. The comparison between the groups at mo 6 (T6) also showed a significant reduction of glucose levels in the IBI/S group (p = 0.03). The same trend was observed in mean daily blood glucose levels, HbA1c and HOMA-IR, although differences were not significant. Basal and stimulated C-peptide values showed that only a few changes had occured in both groups. Such results indicate that insulin secretion was virtually unaffected, as confirmed also by the insulinemia data. Plasma triglycerides concentrations dropped from a baseline value of 186 mg/dl to 111 mg/dl (T6) in the IBI/S group, with significant differences at all instances with respect to baseline values. By contrast, triglycerides increased from 159 mg/dl at entry to 185 mg/dl (T6) in the placebo group. The difference between the groups at T6 was highly significant (p < 0.01). Total and HDL cholesterol as well as liver function tests did not change significantly during the study in both groups. MDA decreased significantly only in the group receiving IBI/S. No clinically relevant side effects were observed in either group. Oral administration silybin-beta-cyclodextrin in patients with T2DM and compensated chronic alcoholic liver disease causes a significant decrease in both glucose and triglyceride plasma levels. These effects may be due to the recovery of energy substrates, consistent with a reduced lipid peroxidation and an improved insulin activity.\nStudy5: [Liver-protective action of silymarin therapy in chronic alcoholic liver diseases]. The effects of silymarin (Legalon) therapy on liver function tests, serum procollagen III peptide level and liver histology were studied in 36 patients with chronic alcoholic liver disease in a six month double blind clinical trial. During silymarin treatment serum bilirubin, aspartate aminotransferase and alanin-aminotransferase values have been normalized, while gamma-glutamyl transferase activity and procollagen III peptid level decreased. The changes were significant, and there was a significant difference between post-treatment values of the two groups, as well. In the placebo group only gamma-glutamyl transferase values decreased significantly but to a lesser extent than that in the silymarin group. The histological alterations showed an improvement in the silymarin group, while remained unchanged in the placebo group. These results indicate that silymarin exerts hepatoprotective activity and is able to improve liver functions in alcoholic patients.\nStudy6: Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. Silymarin, the active principle of the milk thistle Silybum marianum, protects experimental animals against various hepatotoxic substances. To determine the effect of silymarin on the outcome of patients with cirrhosis, a double blind, prospective, randomized study was performed in 170 patients with cirrhosis. 87 patients (alcoholic 46, non-alcoholic 41; 61 male, 26 female; Child A, 47; B, 37; C, 3; mean age 57) received 140 mg silymarin three times daily. 83 patients (alcoholic 45, non-alcoholic 38; 62 male, 21 female; Child A, 42; B, 32; C, 9: mean age 58) received a placebo. Non-compliant patients and patients who failed to come to a control were considered as 'drop outs' and were withdrawn from the study. All patients received the same treatment until the last patient entered had finished 2-years of treatment. The mean observation period was 41 months. There were 10 drop outs in the placebo group and 14 in the treatment group. In the placebo group, 37 (+2 drop outs) patients had died, and in 31 of these, death was related to liver disease. In the treatment group, 24 (+4 drop outs) had died, and in 18 of these, death was related to liver disease. The 4-year survival rate was 58 +/- 9% (S.E.) in silymarin-treated patients and 39 +/- 9% in the placebo group (P = 0.036). Analysis of subgroups indicated that treatment was effective in patients with alcoholic cirrhosis (P = 0.01) and in patients initially rated 'Child A' (P = 0.03). No side effects of drug treatment were observed.(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy7: A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis. In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.\nStudy8: [Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients]. A randomized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis, 58 of them with cirrhosis. Patients were not included in case of hepatic encephalopathy, contraindication to percutaneous liver biopsy, hepatocellular carcinoma, evident lack of discipline or refusal to enter the trial. Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months. Biologic parameters were assessed in the serum, and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later. Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists. The 2 groups were comparable at inclusion; 26 p. 100 of patients were lost to follow-up at 3 months, abstinence was obtained in 46 p. 100 of patients at the end of the trial. These percentages were similar in the two groups. Four patients died of hepatic failure during the trial, 3 in the placebo group. Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, was noted in both groups during the trial, irrespective of treatment with silymarin or placebo. No side-effects were noted. Our results suggest that silymarin 420 mg/d is not clinically relevant in the treatment of moderate alcoholic hepatitis.\nStudy9: Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. One hundred and six consecutive patients with liver disease were selected on the basis of elevated serum transaminase levels. The patients were randomly allocated into a group treated with silymarin (treated) and a group receiving placebo (controls). Ninety-seven patients complete the 4-week trial-47 treated and 50 controls. In general, the series represented a relatively slight acute and subacute liver disease, mostly induced by alcohol abuse. There was a statistically highly significantly greater decrease of S-SGPT (S-ALAT) and S-SGOT (S-ASAT) in the treated group than in controls. Serum total and conjugated bilirubin decreased more in the treated than in controls, but the differences were not statistically significant. BSP retention returned to normal significantly more often in the treated group. The mean percentage decrease of BSP was also markedly higher in the treated. Normalization of histological changes occurred significantly more often in the treated than in controls.\nStudy10: [Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres (author's transl)]. In a double blind study carried out under standard conditions at two treatment centers silymarin, 2 sugar-coated tablets 70 mg three times daily, showed a definite therapeutic influence on the characteristic increased serum levels of bilirubin, GOT and GPT associated with acute viral hepatitis. The above mentioned values in 28 patients treated with silymarin were compared with those in 29 patients treated with placebo. The laboratory parameters in the silymarin group regressed more than in the placebo group after the 5th day of treatment. The number of patients having attained normal values after 3 weeks' treatment was higher in the silymarin group than in the placebo group. A statistical comparison revealed a difference between bilirubin and GOT values in the placebo and silymarin groups and a definite trend in the regression of GPT values in favour of silymarin. The course of the immune reaction in HBS Ag patients was not influenced by silymarin. As already proved by other investigators, the use of silymarin in acute viral hepatitis can lead to an accelerated regression in pathological values, thus indicating its use in the treatment of this liver disease.\n", + "output": "Conclusions: Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed." + }, + { + "input": "Study1: Effects of three different stimulations (acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small toe on fetal behavior of breech presentation. The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments.\nStudy2: Moxibustion for correction of breech presentation: a randomized controlled trial. Traditional Chinese medicine uses moxibustion (burning herbs to stimulate acupuncture points) of acupoint BL 67 (Zhiyin, located beside the outer corner of the fifth toenail), to promote version of fetuses in breech presentation. Its effect may be through increasing fetal activity. However, no randomized controlled trial has evaluated the efficacy of this therapy. To evaluate the efficacy and safety of moxibustion on acupoint BL 67 to increase fetal activity and correct breech presentation. Randomized, controlled, open clinical trial. Outpatient departments of the Women's Hospital of Jiangxi Province, Nanchang, and Jiujiang Women's and Children's Hospital in the People's Republic of China. Primigravidas in the 33rd week of gestation with normal pregnancy and an ultrasound diagnosis of breech presentation. The 130 subjects randomized to the intervention group received stimulation of acupoint BL 67 by moxa (Japanese term for Artemisia vulgaris) rolls for 7 days, with treatment for an additional 7 days if the fetus persisted in the breech presentation. The 130 subjects randomized to the control group received routine care but no interventions for breech presentation. Subjects with persistent breech presentation after 2 weeks of treatment could undergo external cephalic version anytime between 35 weeks' gestation and delivery. Fetal movements counted by the mother during 1 hour each day for 1 week; number of cephalic presentations during the 35th week and at delivery. The intervention group experienced a mean of 48.45 fetal movements vs 35.35 in the control group (P<.001; 95% confidence interval [CI] for difference, 10.56-15.60). During the 35th week of gestation, 98 (75.4%) of 130 fetuses in the intervention group were cephalic vs 62 (47.7%) of 130 fetuses in the control group (P<.001; relative risk [RR], 1.58; 95% CI, 1.29-1.94). Despite the fact that 24 subjects in the control group and 1 subject in the intervention group underwent external cephalic version, 98 (75.4%) of the 130 fetuses in the intervention group were cephalic at birth vs 81 (62.3%) of the 130 fetuses in the control group (P = .02; RR, 1.21; 95% CI, 1.02-1.43). Among primigravidas with breech presentation during the 33rd week of gestation, moxibustion for 1 to 2 weeks increased fetal activity during the treatment period and cephalic presentation after the treatment period and at delivery.\nStudy3: Moxibustion for breech version: a randomized controlled trial. To estimate the efficacy of moxibustion between 34 and 38 weeks of gestation to facilitate the cephalic version of fetuses in breech presentation and the acceptability of this method by women. We conducted a randomized controlled trial in a Swiss university hospital maternity unit. We proposed to stimulate the acupoint BL 67 by moxibustion daily for 2 weeks for 212 consenting women between 34 and 36 weeks of gestation with a single fetus in breech presentation. We did the intervention three times weekly in the hospital and a teaching session and information leaflet on the technique for additional daily therapy at home. The control group received expectant management care. The availability of external cephalic version was maintained for both groups. The main outcome measure was the comparison of the proportion of women with cephalic presentation at delivery. Baseline characteristics were similar between groups, except more nulliparous women were randomized to moxibustion. The percentage of versions was similar between groups: 18% in the moxibustion group compared with 16% in the control group (relative risk 1.12, 95% confidence interval 0.62 to 2.03). Adjustment for the imbalance in parity did not change these results. The frequency of cesarean delivery was similar (64% compared with 58% in the moxibustion group and the control group, respectively). Acceptability of the intervention and women's perceptions of moxibustion were favorable. We observed no beneficial effect of moxibustion to facilitate the cephalic version of fetuses in breech presentation. Despite this lack of proven effectiveness, women had positive opinions on the intervention. ClinicalTrials.gov, www.clinicaltrials.gov,NCT00890474. I.\nStudy4: Acupuncture plus moxibustion to resolve breech presentation: a randomized controlled study. In many Western countries breech presentation is an indication for elective Cesarean section. In order to correct fetal presentation, the stimulation of the acupoint BL67 by moxibustion, acupuncture or both has been proposed. Since no studies had previously been carried out on Western populations, pregnant Italian women at 33-35 weeks gestational age carrying a fetus in breech presentation were enrolled in a randomized, controlled trial involving an active BL67 point stimulation and an observation group. A total of 240 women at 33-35 weeks of gestation carrying a fetus in breech presentation were randomized to receive active treatment (acupuncture plus moxibustion) or to be assigned to the observation group. Bilateral acupuncture plus moxibustion was applied at the BL67 acupoint (Zhiyin). The primary outcome of the study was fetal presentation at delivery. Fourteen cases dropped out. The final analysis was thus made on 226 cases, 114 randomized to observation and 112 to acupuncture plus moxibustion. At delivery, the proportion of cephalic version was lower in the observation group (36.7%) than in the active-treatment group (53.6 %) (p = 0.01). Hence, the proportion of Cesarean sections indicated for breech presentation was significantly lower in the treatment group than in the observation group (52.3% vs. 66.7%, p = 0.03). Acupuncture plus moxibustion is more effective than observation in revolving fetuses in breech presentation. Such a method appears to be a valid option for women willing to experience a natural birth.\n", + "output": "Conclusions: This review found limited evidence to support the use of moxibustion for correcting breech presentation. There is some evidence to suggest that the use of moxibustion may reduce the need for oxytocin. When combined with acupuncture, moxibustion may result in fewer births by caesarean section; and when combined with postural management techniques may reduce the number of non-cephalic presentations at birth, however, there is a need for well-designed randomised controlled trials to evaluate moxibustion for breech presentation which report on clinically relevant outcomes as well as the safety of the intervention." + }, + { + "input": "Study1: Effect of dexamethasone on the frequency of postdural puncture headache after spinal anesthesia for cesarean section: a double-blind randomized clinical trial. In this study, we evaluated the effect of dexamethasone used as a prophylaxis for nausea and vomiting on the incidence of postdural puncture headache (PDPH) in pregnant women receiving spinal anesthesia for cesarean section. In a prospective, randomized, double-blind, placebo-controlled study, 372 women under spinal anesthesia received 8 mg of dexamethasone or placebo intravenously just after the umbilical cord was clamped. The rate of PDPH and correlated risk factors were evaluated. The prevalence of nausea and vomiting in the dexamethasone and placebo groups was 54.4 and 51.7%, respectively. There was no statistically meaningful difference between the results (P value = 0.673). The overall incidence rate of PDPH was 10.8%, with 28 cases from the dexamethasone group compared with 11 subjects from the placebo group (P value = 0.006). This effect was most prominent on the first day (P value = 0.046) and disappeared on the second day after spinal anesthesia (P value = 0.678). Prophylactic treatment with 8 mg of dexamethasone not only increases the severity and incidence of PDPH, but is also ineffective in decreasing the prevalence of intra-operative nausea and vomiting during cesarean section. The treatment is a significant risk factor for the development of PDPH.\nStudy2: Postoperative headache in young patients after spinal anaesthesia. Spinal anaesthesia was performed on 247 young adult patients with a 25-G needle. Rectal administration of indomethacin had no significant effect on the incidence of postdural puncture headache, which occurred in 16.8% of patients who received the drug compared to 24.5% who received a placebo. A history of headache pre-operatively did not influence the incidence of postlumbar puncture headache.\nStudy3: PDPH in obstetric anesthesia: comparison of 24-gauge Sprotte and 25-gauge Quincke needles and effect of subarachnoid administration of fentanyl. Postdural puncture headache (PDPH) is a frequent complication of spinal anesthesia. Some investigators have recommended the use of the Sprotte needle to reduce the incidence of this serious complication. This study prospectively compared the incidence of PDPH with two spinal needles of different size and design: the 24-gauge Sprotte (noncutting point) versus the 25-gauge Quincke (diamond, cutting point). The hypothesis that subarachnoid fentanyl will reduce the incidence of PDPH, as suggested in the literature, was also studied. Only patients for emergency or elective cesarean delivery were studied. One hundred ninety four patients were randomly assigned to receive spinal anesthesia with one of the two needles (Sprotte, n = 96; Quincke, n = 98). Simultaneously, each patient was assigned to receive hyperbaric 0.75% bupivacaine local anesthetic or a combination of the same concentration of local anesthetic with 20 micrograms of fentanyl (Sprotte with fentanyl, n = 47; Sprotte without fentanyl, n = 49; Quincke with fentanyl, n = 49; Quincke without fentanyl, n = 49). All patients were evaluated during the first 4 postoperative days, and follow-up telephone interviews were conducted 3 weeks after discharge. Four patients (4.2%) in the Sprotte group and seven (7.1%) in the Quincke group developed PDPH. Three out of four patients with headache in the Sprotte and four out of seven in the Quincke group received fentanyl as an adjunct for spinal anesthesia. Two patients in the Sprotte group required an epidural blood patch as a therapy for PDPH. Two patients in the Quincke group had severe headache and required an epidural blood patch. In the current study, the use of the 24-gauge Sprotte spinal needle resulted in a low incidence of severe PDPH, but was not significantly different when compared with the use of a 25-gauge Quincke needle (oriented parallel to the longitudinal dural fibers). The addition of fentanyl to hyperbaric bupivacaine spinal anesthesia did not reduce the risk of PDPH.\nStudy4: Oral multidose caffeine-paracetamol combination is not effective for the prophylaxis of postdural puncture headache. To investigate the effects of different doses of oral caffeine-paracetamol combinations in postdural puncture headache (PDPH) prophylaxis. Prospective, randomized, placebo-controlled, blinded study. University hospital. A total of 210 ASA physical status I and II patients undergoing lower extremity surgery. Patients were randomly divided into 3 groups. One hour before the spinal anesthesia, the first group (n = 70) received placebo, the second group (n = 70) received 500-mg paracetamol + 75-mg caffeine, and the third group (n = 70) received 500-mg paracetamol + 125-mg caffeine orally. The same doses were repeated every 6 hours for 3 days. Patients were then interviewed on days 1, 2, 3, 4, and 7 to inquire about any PDPH. The interviewer was unaware of the PDPH prophylaxis group members. Patients who were discharged early were interviewed by telephone. Postdural puncture headache occurred in 11 patients (15.7%) in group 1, 10 patients (% 14.28) in group 2, and 10 patients (% 14.28) in group 3. The differences between the groups were insignificant (P > .05). The complications due to spinal anesthesia were similar in the 3 groups. Side effects of caffeine such as lack of sleep, tachycardia, and hypertension were not observed in groups 2 or 3. Prophylactic administration of paracetamol-caffeine combinations at the stated doses does not prevent PDPH.\nStudy5: Effect of subarachnoid morphine on the incidence of spinal headache. The addition of fentanyl to hyperbaric local anesthetics has been shown to reduce the incidence of post dural puncture headache in the obstetric patient. This study was undertaken to evaluate the effects of subarachnoid morphine on the incidence of headache. Eighty-two healthy patients undergoing cesarean delivery with spinal anesthesia were studied. All patients were hydrated with 1500 ml lactated Ringer's solution. Patients were randomly assigned to receive, in a double-blind fashion, 0.2 mg of either morphine (Group 1, n = 40) or saline (Group 2, n = 42) in 0.2 ml volume mixed with 0.75% bupivacaine in 8.25% dextrose plus 0.2 ml 1:1000 epinephrine. Spinal anesthesia was induced using a 25-gauge spinal needle at L3-4 interspace with the bevel, in most cases, parallel to the dural fibers. Patients were followed for three days to evaluate the incidence and severity of headache using a four-category rank scale (none, mild, moderate, severe). Data were analyzed for statistical significance using Student's t-test or chi-square test as appropriate. A p value less than 0.05 was considered significant. Results. The incidence of post dural puncture headache did not differ significantly between groups. Eight patients in Group 1 versus nine patients in Group 2 developed headache (p greater than 0.05). Similarly, the use of blood patch or intravenous caffeine sodium benzoate to treat the headache did not differ significantly between groups. It is concluded from our study that subarachnoid morphine did not decrease the incidence of post dural puncture headache in the obstetric patient.\nStudy6: Cosyntropin for prophylaxis against postdural puncture headache after accidental dural puncture. The aim of the current study was to investigate the effect of administration of cosyntropin after accidental dural puncture (ADP) on the incidence of postdural puncture headache (PDPH) and the need for therapeutic epidural blood patch (EBP). Ninety parturients who suffered an ADP were studied. After delivery, patients were randomly assigned to one of two equal-sized groups. In group I (cosyntropin group), patients received cosyntropin in a dose of 1 mg intravenously. In group II (control group), patients received an equal volume of normal saline. Fifteen patients (33%) in the cosyntropin group suffered from PDPH, compared with 31 patients (68.9%) in the control group (P = 0.001). Significantly fewer patients in the cosyntropin group required an EBP, compared with the control group (5 patients [11.1%] vs. 13 patients [28.9%], respectively; P = 0.035). The Kaplan-Meier curves for the occurrence of PDPH showed a hazard ratio of 0.32 (95% CI = 0.16-0.55, P < 0.0001). The time from ADP to occurrence of PDPH was significantly longer in the cosyntropin group (27.2 [7.7] h) in comparison with the control group (17.5 [4.9] h; P < 0.001). However, there were no statistically significant differences among patients who developed PDPH in both groups with regard to the severity or duration of PDPH or with regard to the need for EBP or for repeat EBP (P > 0.05). Administration of cosyntropin after ADP in parturients was associated with significant reduction in the incidence of PDPH and need for EBP and significant prolongation of the time from ADP to occurrence of PDPH.\nStudy7: Epidural morphine injections for prevention of post dural puncture headache. A prospective, randomised, double-blind trial was conducted to study the effect of epidural morphine in prevention of post dural puncture headache in 25 parturients after inadvertent dural puncture. Women were randomly allocated to receive two epidural injections, 24 h apart, of either 3 mg morphine in 10 ml saline (morphine group) or 10 ml saline (saline group). The incidence of headache and need for therapeutic epidural blood patch were reported. There was a significant difference in the incidence of headache between the two groups: 3/25 (12%) in the morphine group and 12/25 (48%) in the saline group (p = 0.014). Therapeutic epidural blood patches were required in six patients in the saline group and none of the patient in the morphine group (p = 0.022). It was concluded that epidural morphine appears to be a simple and effective technique for prevention of post dural puncture headache after accidental dural puncture in high risk obstetric patients.\n", + "output": "Conclusions: Morphine and cosyntropin have shown effectiveness for reducing the number of participants affected by PDPH of any severity after a lumbar puncture, when compared to placebo, especially in patients with high risk of PDPH, such as obstetric patients who have had an inadvertent dural puncture. Aminophylline also reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention in patients undergoing elective caesarean section. Dexamethasone increased the risk of PDPH, after spinal anaesthesia for caesarean section, when compared to placebo. Morphine also increased the number of participants affected by adverse events (pruritus and nausea and vomiting)\nThere is a lack of conclusive evidence for the other drugs assessed (fentanyl, caffeine, indomethacin and dexamethasone).\nThese conclusions should be interpreted with caution, owing to the lack of information, to allow correct appraisal of risk of bias and the small sample sizes of studies." + }, + { + "input": "Study1: A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network. The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network. Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine. A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings. A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine. The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs.\nStudy2: Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection. With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.\nStudy3: A randomized trial of one-day vs. three-day buprenorphine inpatient detoxification protocols for heroin dependence. Detoxification from opioids remains an important first step in the treatment of many patients with opioid dependence. Several pharmacologic regimens have been used for opioid detoxification. In the United States, the partial mu-opioid agonist, buprenorphine (BUP) is the most recently approved pharmacotherapy for opioid detoxification and replacement. The literature in recent years has described detoxification protocols using a single high dose of BUP and a three-day BUP regimen. In many settings, such as drug-free programs, a single-dose detoxification protocol would be of significant benefit. There have been no prior studies comparing one-day and three-day BUP-assisted opioid withdrawal. In this pilot study, we conducted an open-label, randomized trial of one-day vs. three-day BUP/naloxone sublingual tablet-assisted opioid withdrawal. Twenty patients from a therapeutic community treatment program were randomly assigned to receive either 32 mg sublingual BUP over one hour (one-day group), or 32 mg sublingual BUP over three days (three-day group). Nine of 10 subjects (90 percent) in each group completed seven days in the detoxification protocol. There was no statistically significant difference between the two groups in all other outcome variables, including retention in the treatment program, intensity of withdrawal signs and symptoms, amounts of adjunct medications used, and ability to produce opiate-free urine. This study further validates the feasibility of the single high dose of BUP as a rapid detoxification method.\nStudy4: Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine. Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.\nStudy5: A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification. Eight opioid-dependent individuals were maintained on daily sublingual buprenorphine (8 mg) for 28 days and assigned randomly to one of two outpatient detoxification schedules under double-blind, double-dummy conditions. The two detoxification schedules were buprenorphine gradual (36 days; N = 3) or buprenorphine rapid (12 days; N = 5). Outcome variables were subject- and observer-ratings of opioid withdrawal, treatment retention and illicit-opioid use. Outcome measures were similar for the two groups during buprenorphine maintenance. Increases in subject-rated opioid withdrawal and illicit-opioid use, and a drop in treatment retention occurred during rapid detoxification. Stable subject-rated opioid withdrawal and treatment retention, and less illicit-opioid use occurred during gradual detoxification. These data suggest that gradual reduction in buprenorphine dose is likely to produce superior treatment outcomes than more rapid buprenorphine detoxification.\nStudy6: Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial. The prevalence of heroin and other opioid use has markedly increased among adolescents in the last decade; however, virtually no research has been conducted to identify effective treatments for this population. To evaluate the relative efficacy of 2 pharmacotherapies, the partial opioid agonist buprenorphine hydrochloride and the centrally active alpha(2)-adrenergic blocker clonidine hydrochloride, in the detoxification of opioid-dependent adolescents. A double-blind, double-dummy, parallel-groups randomized controlled trial conducted in a university-based research clinic from October 2001 to December 2003. Patients were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid dependence (ages 13-18 years eligible). Participants were randomly assigned to a 28-day, outpatient, medication-assisted withdrawal treatment with either buprenorphine or clonidine. Both medications were provided along with thrice weekly behavioral counseling and incentives contingent on opiate abstinence. Postdetoxification, all participants were offered the opportunity for continued treatment with the opiate antagonist, naltrexone hydrochloride. Treatment retention, opiate abstinence, and human immunodeficiency virus risk behavior, along with measures of withdrawal and medication effects. A significantly greater percentage of adolescents who received buprenorphine were retained in treatment (72%) relative to those who received clonidine (39%) (P<.05). For those in the buprenorphine group, a significantly higher percentage of scheduled urine test results were opiate negative (64% vs 32%; P = .01). Participants in both groups reported relief of withdrawal symptoms and drug-related human immunodeficiency virus risk behavior. Those in the buprenorphine condition generally reported more positive effects of the medication. No evidence of opioid intoxication or psychomotor impairment was observed. Sixty-one percent of participants in the buprenorphine condition and 5% of those in the clonidine group initiated treatment with naltrexone. Combining buprenorphine with behavioral interventions is significantly more efficacious in the treatment of opioid-dependent adolescents relative to combining clonidine and behavioral interventions.\nStudy7: Three methods of opioid detoxification in a primary care setting. A randomized trial. Opioid detoxification in a primary care setting followed by ongoing substance abuse treatment may be appropriate for selected opioid-dependent patients. To compare three pharmacologic protocols for opioid detoxification in a primary care setting. Randomized, double-blind clinical trial with random assignment to treatment protocols. A free-standing primary care clinic affiliated with drug treatment programs. 162 heroin-dependent patients. Three detoxification protocols: donidine, combined donidine and naltrexone, and buprenorphine. Successful detoxification (that is, when study participants received a full opioid-blocking dose [50 mg] of naltrexone), treatment retention (8 days), and withdrawal symptoms. Overall, 65% of participants (36 of 55) who received clonidine, 81% (44 of 54) who received combined clonidine and naltrexone, and 81% (43 of 53) who received buprenorphine were successfully detoxified. Retention did not differ significantly across the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received combined clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. Participants who received buprenorphine had a significantly lower mean withdrawal symptom score than those who received clonidine or combined clonidine and naltrexone. Participants in the combined clonidine and naltrexone group and those in the buprenorphine group were more likely to complete detoxification, although retention at 8 days did not differ among the groups. Participants who were assigned to the buprenorphine group experienced less severe withdrawal symptoms than those assigned to the other two groups.\nStudy8: Buprenorphine and carbamazepine as a treatment for detoxification of opiate addicts with multiple drug misuse: a pilot study. The growing tendency of opioid addicts to misuse multiple other drugs leads to the investigation of new pharmacostrategies to prevent patients from suffering life-threatening complications and minimize the withdrawal symptoms. The short-term efficacy of a 10-day low-dose buprenorphine/19-day carbamazepine regime (n = 15) to a 14-day oxazepam/19-day carbamazepine regime (n = 12) in an open-labelled 21-day inpatient detoxification treatment was compared. Twenty-seven men and women dependent on opioids and misusing other drugs admitted to a detoxification unit were included in this protocol. Eighteen of 27 patients (67%) completed the study. Four non-completers (27%) received buprenorphine/carbamazepine (four of 15) and five non-completers (42%) were treated with oxazepam/carbamzepine (five of 12), but the difference in the dropout rate between the two treatment strategies was not significant.The buprenorphine/carbamazepine regime provided significantly more effective relief of withdrawal symptoms during the first week of treatment. No severe side effects occurred during treatment in both groups. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than oxazepam/carbamazepine in rapid opioid detoxification in patients with additional multiple drug misuse and both regimens were safe with no unexpected side effects.\nStudy9: Opioid detoxification using high doses of buprenorphine in 24 hours: a randomized, double blind, controlled clinical trial. In recent years, interest in shortening of opioid detoxification has increased with the rising demands to find more cost-effective approaches for treatment of opioid dependence. This study was designed to evaluate the efficacy of administration of high doses of buprenorphine during 24 h in the management of acute opioid withdrawal. A total of 40 treatment-seeking opioid dependents were admitted and randomly assigned to two groups in a double blind, parallel trial. Buprenorphine was administered intramuscularly. Twenty patients received 12 mg buprenorphine in 24 h and the remaining 20 patients treated with conventional doses of buprenorphine tapered down over 5 days. Variables that were assessed included retention in treatment, rates of successful detoxification, the Subjective Opiate Withdrawal Scale (OOWS) scores, the Objective Opiate Withdrawal Scale (SOWS) scores, intensity of craving, drug side effects, and levels of hepatic enzymes (ALT and AST). There was no significant difference between the two groups on most variables. The main difference was in the time that maximal withdrawal symptoms occurred, which in the experimental protocol group appeared early while in the conventional protocol group appeared later during the detoxification period. Moreover, the experimental protocol was not only tolerated well but also accompanied with significantly less elevation in the ALT levels compared to the conventional treatment. However, patients in this group used more indomethacin and trazodone for symptom palliation. This study suggests that administration of high doses of buprenorphine in 24 h may be a reasonable approach for shortening of opioid detoxification. However, a larger study to confirm our results is warranted.\nStudy10: A comparison of buprenorphine and lofexidine for community opiate detoxification: results from a randomized controlled trial. To investigate whether a buprenorphine opiate detoxification regimen can be considered to be at least as clinically effective as a lofexidine regimen. An open-label randomized controlled trial (RCT) using a non-inferiority approach. Non-inferiority is demonstrated if, within a 95% confidence interval, buprenorphine performs within a preset tolerance limit of clinically acceptable difference in outcomes and completion rates between the two treatments. Individuals ready for heroin detoxification were given information about the trial and invited to participate. Consenting participants (n = 210) were then randomized to one of the two treatments. Detoxification was undertaken in a specialist out-patient clinic according to predefined protocols. The primary outcome was whether or not an individual completed the detoxification. Abstinence at 1-month follow-up was used as a secondary outcome measure. Additional secondary outcome measures were substance use, dependence, psychological health, social satisfaction, and treatment satisfaction. Data were also collected for individuals who declined randomization and instead chose their treatment (n = 271). A total of 46% of those on lofexidine and 65% of those on buprenorphine completed detoxification. Of these, 35.7% of the lofexidine and 45.9% of the buprenorphine groups reported abstinence at 1 month. Of those not completing detoxification abstinence was reported at 27.5% and 29.0%, respectively; 271 individuals who opted not to be allocated randomly and instead chose one of the two treatments produced similar results Buprenorphine is at least as effective as lofexidine detoxification treatment. Whether or not individuals were randomized to, or chose, a treatment appeared not to affect the study's outcome.\n", + "output": "Conclusions: Buprenorphine is more effective than clonidine or lofexidine for the management of opioid withdrawal. Buprenorphine may offer some advantages over methadone, at least in inpatient settings, in terms of quicker resolution of withdrawal symptoms and possibly slightly higher rates of completion of withdrawal." + }, + { + "input": "Study: Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m(2) (49 patients) or 75 mg/m(2) (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7. 1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P <.001), as was median survival (7.0 v 4.6 months; log-rank test, P =.047). The difference was more significant for docetaxel 75 mg/m(2) patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P =.010; 1-year survival, 37% v 11%; chi(2) test, P =.003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2), three of whom died, and in one patient treated with docetaxel 75 mg/m(2). Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m(2), the benefits of docetaxel therapy outweigh the risks.\n", + "output": "Conclusions: Definitive recommendations cannot be made since evidence is only available from one randomised controlled trial which, though of reasonable quality had a number of limitations. There is currently no evidence to support second-line treatment of patients with poor performance status. Larger, well-designed controlled trials are needed to further evaluate whether the benefits of second-line chemotherapy to patients with non-small cell lung cancer outweigh its risks and costs." + }, + { + "input": "Study: Improvement of nutritional measures during preoperative parenteral nutrition in patients selected by the prognostic nutritional index: a randomized controlled trial. Patients undergoing major gastrointestinal surgery who had a prognostic nutritional index (PNI) score of greater than 30% were randomized to receive a preoperative course of 10 days of intravenous nutrition or to undergo surgery at the next convenient operation list. Two groups of 17 patients were well matched for age, sex, and nutritional status. Although they underwent diverse operations, the extent of these was similar: 12 +/- 3 days of parenteral nutrition resulted in weight gain, 3.2 +/- 2.3 kg p less than 0.01; increased triceps skinfold, 0.6 +/- 1.2 mm p less than 0.05; improved immunological state, p less than 0.02; and improved PNI, 5.5 +/- 10.1% p less than 0.05. The changes in serum albumin and transferrin were not significant. There were only three major complications with one death in the treatment group but this was not significantly different from the control group which had six major complications and three deaths. This study suggests that patients with demonstrable nutritional depletion who require major gastrointestinal surgery will benefit from a preoperative course of parenteral nutrition, but to conclusively prove this a large and probably multicentre study will be required.\n", + "output": "Conclusions: There have been significant benefits demonstrated with pre-operative administration of IE nutrition in some high quality trials. However, bias was identified which may limit the generalizability of these results to all GI surgical candidates and the data needs to be placed in context with other recent innovations in surgical management (eg-ERAS). Some unwanted effects have also been reported with components of IE nutrition in critical care patients and it is unknown whether there would be detrimental effects by administering IE nutrition to patients who could require critical care support after their surgery. The studies evaluating PN demonstrated that the provision of PN to predominantly malnourished surgical candidates reduced post-operative complications; however, these data may not be applicable to current clinical practice, not least because they have involved a high degree of 'hyperalimentation'. Trials evaluating enteral or oral nutrition were inconclusive and further studies are required to select GI surgical patients for these nutritional interventions." + }, + { + "input": "Study1: Effect of nursing in the head elevated tilt position (15 degrees) on the incidence of bradycardic and hypoxemic episodes in preterm infants. We investigated whether nursing in the head elevated tilt position (HETP), compared with the horizontal position, has any effect on the incidence of bradycardic and hypoxemic episodes in preterm infants. Twelve spontaneously breathing preterm infants with idiopathic recurrent apnea were studied in a randomized controlled crossover trial. Nine infants were treated with aminophylline. Each spent a total of 24 hours in the horizontal prone position and a total of 24 hours in HETP (prone, 15 degrees). The position was changed in random order every 6 hours. Thoracic impedance, heart rate, and arterial oxygen saturation were recorded continuously. The frequency of isolated hypoxemia (arterial saturation <80%), of isolated bradycardia (heart rate <90 beats per minute), and of mixed events was analyzed and compared without knowledge of the allocated position. In total, there were significantly fewer bradycardic and/or hypoxemic episodes (28.2%) in HETP compared with the horizontal position (mean difference, 13.35 episodes/24 hours; 95% confidence interval [CI]: 5.9- 20.8). The decrease was largest for isolated hypoxemic episodes (48.5%; mean difference, 11.74 episodes/24 hours; 95% CI: 6.1-17.4). Isolated bradycardic episodes (mean difference, 2.27 episodes/24 hours; 95% CI: -0.78-5.31) and mixed events were not decreased significantly in HETP. Nursing in a moderately tilted position (15 degrees) reduces hypoxemic events in preterm infants. This intervention is easy to apply, quickly reversible, and can be combined with drugs such as aminophylline.\nStudy2: Effect of positioning on the breathing pattern of preterm infants. Respiration, as judged by gas exchange and pulmonary function, is improved in preterm infants kept in the prone rather than the supine position. The influence of position on the breathing pattern as documented by the pneumogram was studied in 14 stable preterm infants with recent clinical apnoea. Ten of the infants had oximetry and nasal flow studies simultaneously with the impedance pneumogram. Each infant had consecutive nocturnal pneumograms, one in the prone, one in the supine position. The infants were kept for more than six hours in the assigned position. A significant increase in apnoea density and in periodic breathing was found in the supine v the prone position (mean (SE) 4.5 (0.7)% v 2.5 (0.5)%, and 13.6 (3.2)% v 7.7 (2.2)%, respectively). There was no positional difference in the incidence of bradycardia and prolonged apnoea. The examination of obstructive apnoea, mixed apnoea, and cyanotic spells did not reveal a consistent disparity between the two positions. These findings indicate an increase in central apnoea in preterm infants kept predominantly in the supine position. Possible relations of positional changes to lung mechanics are discussed. When evaluating pneumograms, attention must be given to the position in which they were performed.\nStudy3: Does supine positioning increase apnea, bradycardia, and desaturation in preterm infants? The purpose of this study was to determine the effects of prone and supine positioning on the cardiorespiratory stability of preterm infants with apnea and bradycardia. A total of 22 preterm infants with symptomatic apnea and bradycardia (gestational age of 26.9 +/- 1.8 weeks and birth weight of 865 +/- 235 gm) were monitored for 24 hours (in four sequential 6-hour blocks) for apnea, bradycardia, and oxygen desaturation in alternating positions (prone or supine) following randomization. Postconceptional age at the time of study was 31.9 +/- 3.0 weeks. Respiratory rate, heart rate, and transcutaneous oxygen saturation were continuously monitored. All episodes of apnea (> or = 10 seconds), bradycardia (< 100 beats per minute), and oxygen desaturation (< 90%) were recorded on an event monitor. Episodes of apnea, bradycardia, and oxygen desaturation were defined as clinically significant if the following criteria were met: apnea, > or = 15 seconds; bradycardia, < 90 beats per minute; and oxygen desaturation, < 80%. All other recorded episodes were considered mild. The episodes were analyzed for statistical significance using the paired t-test. No significant differences (p > 0.05) in the incidence of clinically significant apnea, bradycardia, or desaturation between supine and prone positions were seen in these preterm infants. Our results suggest that the cardiorespiratory stability of preterm infants is not significantly compromised by supine positioning.\n", + "output": "Conclusions: There is insufficient evidence to determine the role of body positioning on apnoea, bradycardia, oxygen desaturation and oxygen saturation. Large randomised controlled trials are needed to determine the effect of body positioning on cardiorespiratory function in spontaneously breathing preterm infants." + }, + { + "input": "Study1: An objective comparison of the effects of parenterally administered drugs in patients suffering from detrusor instability. Cystometric changes produced by 3 parenterally administered drugs, flavoxate hydrochloride, emepronium bromide and imipramine hydrochloride, have been evaluated in 15 female patients with detrusor instability. Each patient was given 2 of the 3 drugs and cystometric recordings were done 10 and 30 minutes after the administration of each drug. Emepronium bromide was found to be the only drug to cause a significant improvement in bladder capacity and reduction in detrusor pressure.\nStudy2: [Comparative studies of the effect of mictonorm (propiverin hydrochloride) and Spasuret (flavoxate hydrochloride) on the bladder detrusor muscle]. 46 patients suffering from urgency/urge incontinency were treated with Mictonorm and Spasuret in a crossing-over study. In consideration of the placebo effect in this disease both agents were tested versus a non-verum. The application period was 4 weeks and the dosage was 45 mg/d Mictonorm and 300 mg/d Spasuret, respectively. Both with Mictonorm and with Spasuret a significant reduction of micturition frequency and an increase of the compliance could be observed, whereas the placebo was ineffective. A markedly growth of the maximal bladder capacity (16.9%) was obtained only by Mictonorm. Both agents keep likewise to an improvement of the symptoms or urgency/urge incontinency. Side effects could observed in a small size without a breaking-off of the treatment.\n", + "output": "Conclusions: Many of the drugs considered in trials in this review are no longer used in clinical practice (and this includes the most commonly tested - flavoxate). There is inadequate evidence as to determine whether any of the available druge are better or worse than anticholinergic medications. Larger randomised controlled trials in clinical settings are required to further establish the role of these medications in the management of overactive bladder syndrome." + }, + { + "input": "Study: Anxiety levels in women undergoing prenatal maternal serum screening for Down syndrome: the effect of a fast reporting system by mobile phone short-message service. To study the effect of fast reporting by mobile phone short-message service (SMS) on anxiety levels in women undergoing prenatal biochemical screening for Down syndrome. From January 2005 to December 2006, 2782 women undergoing prenatal biochemical serum screening were randomized into fast reporting by SMS (group A) or without mobile phone reporting (group B). Anxiety levels were measured with the Spielberger State-Trait Anxiety Inventory (STAI) before prenatal screen testing, before the appointed clinic (when the SMS report had already been given to group A), and 3 days after the appointed clinic (when the full screening report had been given to groups A and B). For screen-negative women, anxiety scores did not differ between groups before prenatal screen testing and 3 days after the appointed clinic. The state-anxiety scores measured on the second occasion had declined significantly in group A. The state-anxiety scores in both groups increased over the 3-week period after being informed of positive screen results. The trait- and state-anxiety scores at all points did not differ between the two groups of screen-positive women. The provision of a routine reporting system plus additional SMS report revealed some overall benefits in reducing anxiety among women with screen-negative result. 2008 John Wiley & Sons, Ltd\n", + "output": "Conclusions: We found very limited evidence of low quality that communicating results of medical investigations by mobile phone messaging may make little or no difference to women's anxiety overall or in women with positive test results, but may reduce anxiety in women with negative test results. However, with only one study included in this review, this evidence is insufficient to inform recommendations at this time. More research is needed on the effectiveness and user evaluation of these interventions. In particular, more research should be conducted into the potential risks and limitations of these interventions." + }, + { + "input": "Study1: Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of non-small cell lung cancer: a prospective randomized study. Endobronchial brachytherapy (EBBT) is an established modality for the palliation in advanced non-small cell lung cancer. We compared three different schedules using EBBT with or without external radiation (XRT) in this setting. Forty-five patients were randomized to three treatment arms. Arm A received XRT to a dose of 30 Gy/10 fr/2 weeks and two sessions of EBBT 8 Gy each. Arm B received the same XRT and a single session of EBBT 10 Gy at 1 cm. Arm C received only a single fraction of brachytherapy to a dose of 15 Gy at 1 cm without XRT. Symptomatic response rates, duration of symptom palliation, obstruction scores, quality of life outcomes and complications were assessed and compared. The overall symptomatic response rates were 91% for dyspnea, 84% for cough, 94% for hemoptysis and 83% for obstructive pneumonia. There was no significant difference between the arms. The median time to symptom relapse was 4-8 months for all symptoms and the median time to symptom progression was 6-11 months. The results were comparable between groups except for hemoptysis, where a shorter palliation was seen in Arm C that achieved statistical significance (P < 0.01). Quality of life showed significant improvement, with maximum benefit in Arm A. Complication rates were low. Only one patient died of fatal hemoptysis. EBBT is thus a safe and effective palliative tool in advanced non-small cell lung cancer, either alone or in conjunction with XRT. The difference between the treatment arms were not statistically significant in most categories, but patients treated with XRT and two endobronchial sessions of 8 Gy had the most consistent benefit in terms of all the parameters studied.\nStudy2: External irradiation versus external irradiation plus endobronchial brachytherapy in inoperable non-small cell lung cancer: a prospective randomized study. No randomized studies are available on the additional value of endobronchial brachytherapy (EBB) to external irradiation (XRT) regarding palliation of respiratory symptoms (RS). A prospective randomized study was initiated to test the hypothesis that the addition of EBB to XRT provides higher levels of palliation of dyspnea and other RS and improvement of quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) with endobronchial tumour. Patients with previously untreated NSCLC, stages I-IIIb, WHO-performance status of 0-3 and with biopsy proven endobronchial tumour in the proximal airways were eligible. EBB consisted of two fractions of 7.5 Gy at 1 cm on day 1 and 8. XRT started at day 2. The XRT dose was 30 Gy (2 weeks) or 60 Gy (6 weeks). The EORTC QLQ-C30 and QLQ-LC13 were assessed before treatment and 2 weeks, 6 weeks, 3, 6 and 12 months after treatment. Re-expansion of collapsed lung was tested by the inspiratory vital capacity (IVC) and CT scan of the chest. Ninety-five patients were randomized between arm 1 (XRT alone) (n=48) or arm 2 (XRT+EBB) (n=47). The arms were well balanced regarding pre-treatment characteristics and QoL scores. The compliance for QoL-assessment was >90% at all times. No significant difference between the trial arms was observed with respect to response of dyspnea. However, a beneficial effect of EBB was noted concerning the mean scores of dyspnea over time (P=0.02), which lasted for 3 months. This benefit was only observed among patients with an obstructing tumour of the main bronchus. A higher rate of re-expansion of collapsed lung was observed in arm 2 (57%) compared to arm 1 (35%) (P=0.01). The inspiratory vital capacity (IVC) assessed 2 weeks after radiotherapy improved with 493 cm(3) in arm 2 and decreased 50 cm(3) in arm 1 (P=0.03). No difference was noted regarding the incidence of massive haemoptysis (13 vs. 15%). The addition of EBB to XRT in NSCLC is safe and provides higher rates of re-expansion of collapsed lung resulting in a transient lower levels of dyspnea. This beneficial effect was only observed among patients with obstructing tumours in the main bronchus.\nStudy3: Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study. Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy. From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment. There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The disease's progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05). The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups.\n", + "output": "Conclusions: The evidence did not provide conclusive results that EBB plus EBRT improved symptom relief over EBRT alone. We were not able to provide conclusive evidence to recommend EBB with EBRT, EBB in preference to EBRT, chemotherapy or Nd-YAG laser. From heterogeneous information obtained from several small RCTs, we conclude that EBRT alone is more effective for palliation than EBB alone. For patients previously treated by EBRT who are symptomatic from recurrent endobronchial central obstruction, EBB may be considered in selected cases." + }, + { + "input": "Study1: Regular consumption of a flavanol-rich chocolate can improve oxidant stress in young soccer players. The consumption of a diet rich in certain flavonoids, including the flavanol sub-class, has been associated with a reduced risk for vascular disease. We evaluated the effects of the regular consumption (14 d) of a flavanol-containing milk chocolate (FCMC) or cocoa butter chocolate (CBC) on variables related to vascular disease risk, oxidative stress and physical activity. Twenty-eight free-living, young (18-20 years old) male soccer players consumed daily 105 g of FCMC (168 mg of flavanols) or CBC (< 5 mg of flavanols), as part of their normal diet. The consumption of FCMC was significantly associated with a decrease in diastolic blood pressure (- 5 mm Hg), mean blood pressure (- 5 mm Hg), plasma cholesterol (-11%), LDL-cholesterol (-15%), malondialdehyde (- 12%), urate (- 11%) and lactate dehydrogenase (LDH) activity (- 11%), and an increase in vitamin E/cholesterol (+ 12%). No relevant changes in these variables were associated with CBC consumption. No changes in the plasma levels of (-)-epicatechin were observed following analysis of fasting blood samples. In conclusion, FCMC consumption was associated with changes in several variables often associated with cardiovascular health and oxidant stress. The presence of significant quantities of flavanols in FCMC is likely to have been one of the contributing factors to these results.\nStudy2: Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial. Flavanol-rich cocoa products have been reported to lower blood pressure. It has been suggested that theobromine is partially responsible for this effect. We tested whether consumption of flavanol-rich cocoa drinks with natural or added theobromine could lower peripheral and central blood pressure. In a double-blind, placebo-controlled 3-period crossover trial we assigned 42 healthy individuals (age 62\u00b14.5 years; 32 men) with office blood pressure of 130 to 159 mm Hg/85 to 99 mm Hg and low added cardiovascular risk to a random treatment sequence of dairy drinks containing placebo, flavanol-rich cocoa with natural dose consisting of 106 mg of theobromine, or theobromine-enriched flavanol-rich cocoa with 979 mg of theobromine. Treatment duration was 3 weeks with a 2-week washout. The primary outcome was the difference in 24-hour ambulatory systolic blood pressure between placebo and active treatment after 3 weeks. The difference in central systolic blood pressure between placebo and active treatment was a secondary outcome. Treatment with theobromine-enriched cocoa resulted in a mean\u00b1SE of 3.2\u00b11.1 mm Hg higher 24-hour ambulatory systolic blood pressure compared with placebo (P<0.01). In contrast, 2 hours after theobromine-enriched cocoa, laboratory peripheral systolic blood pressure was not different from placebo, whereas central systolic blood pressure was 4.3\u00b11.4 mm Hg lower (P=0.001). Natural dose theobromine cocoa did not significantly change either 24-hour ambulatory or central systolic blood pressure compared with placebo. In conclusion, theobromine-enriched cocoa significantly increased 24-hour ambulatory systolic blood pressure while lowering central systolic blood pressure.\nStudy3: Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease. Because atherosclerosis is considered a low-grade inflammatory disease, some feeding trials have analyzed the effects of cocoa (an important source of flavonoids) on inflammatory biomarkers, but the results have been controversial. The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients. Forty-two high-risk volunteers (19 men and 23 women; mean +/- SD age: 69.7 +/- 11.5 y) were included in a randomized crossover feeding trial. All subjects received 40 g cocoa powder with 500 mL skim milk/d (C+M) or only 500 mL skim milk/d (M) for 4 wk. Before and after each intervention period, cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated. Adherence to the dietary protocol was excellent. No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups. However, in monocytes, the expression of VLA-4, CD40, and CD36 was significantly lower (P = 0.005, 0.028, and 0.001, respectively) after C+M intake than after M intake. In addition, serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower (both P = 0.007) after C+M intake than after M intake. These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease. These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis. This trial was registered in the Current Controlled Trials at London, International Standard Randomized Controlled Trial Number, at controlled-trials.com as ISRCTN75176807.\nStudy4: Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Flavonoids may be partly responsible for some health benefits, including antiinflammatory action and a decreased tendency for the blood to clot. An acute dose of flavanols and oligomeric procyanidins from cocoa powder inhibits platelet activation and function over 6 h in humans. This study sought to evaluate whether 28 d of supplementation with cocoa flavanols and related procyanidin oligomers would modulate human platelet reactivity and primary hemostasis and reduce oxidative markers in vivo. Thirty-two healthy subjects were assigned to consume active (234 mg cocoa flavanols and procyanidins/d) or placebo (< or = 6 mg cocoa flavanols and procyanidins/d) tablets in a blinded parallel-designed study. Platelet function was determined by measuring platelet aggregation, ATP release, and expression of activation-dependent platelet antigens by using flow cytometry. Plasma was analyzed for oxidation markers and antioxidant status. Plasma concentrations of epicatechin and catechin in the active group increased by 81% and 28%, respectively, during the intervention period. The active group had significantly lower P selectin expression and significantly lower ADP-induced aggregation and collagen-induced aggregation than did the placebo group. Plasma ascorbic acid concentrations were significantly higher in the active than in the placebo group (P < 0.05), whereas plasma oxidation markers and antioxidant status did not change in either group. Cocoa flavanol and procyanidin supplementation for 28 d significantly increased plasma epicatechin and catechin concentrations and significantly decreased platelet function. These data support the results of acute studies that used higher doses of cocoa flavanols and procyanidins.\nStudy5: Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension. Essential hypertension is characterized by reciprocal relations between endothelial dysfunction and insulin resistance. Cocoa flavanols stimulate production of the vasodilator nitric oxide from vascular endothelium. The objective was to test the hypothesis that consumption of cocoa may simultaneously lower blood pressure, improve endothelial dysfunction, and ameliorate insulin resistance in subjects with essential hypertension. We conducted a randomized, placebo-controlled, double-blind, crossover trial of a flavanol-rich cocoa drink (150 mL twice a day, approximately 900 mg flavanols/d) in individuals with essential hypertension (n = 20). Antihypertensive medications were discontinued before study enrollment. After a 7-d cocoa-free run-in period, cocoa or flavanol-poor placebo (approximately 28 mg flavanols/d) treatment for 2 wk was followed by a 1-wk washout and then crossover to the other treatment arm. Blood pressure was measured thrice weekly. At baseline and after each treatment period, we assessed insulin sensitivity (hyperinsulinemic-isoglycemic glucose clamp) and insulin-stimulated changes in brachial artery diameter and forearm skeletal muscle capillary recruitment (Doppler ultrasound with or without microbubble contrast). Cocoa treatment for 2 wk increased insulin-stimulated changes in brachial artery diameter when compared with placebo [median percentage increase from baseline (25th-75th percentile): 8.3 (4.2-11.3) compared with 5.9 (-0.3 to 9.6); P < 0.04]. Nevertheless, cocoa treatment did not significantly reduce blood pressure or improve insulin resistance and had no significant effects on skeletal muscle capillary recruitment, circulating plasma concentrations of adipocytokines, or endothelial adhesion molecules. Daily consumption of flavanol-rich cocoa for 2 wk is not sufficient to reduce blood pressure or improve insulin resistance in human subjects with essential hypertension. This trial was registered at clinicaltrials.gov as NCT00099476.\nStudy6: Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults. Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright \u00a9 2009 Elsevier Ireland Ltd. All rights reserved.\nStudy7: Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. Dark chocolate derived from the plant (Theobroma cacao) is a rich source of flavonoids. Cardioprotective effects including antioxidant properties, inhibition of platelet activity, and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids. To investigate the effects of flavonoid-rich dark chocolate on endothelial function, measures of oxidative stress, blood lipids, and blood pressure in healthy adult subjects. The study was a randomized, double-blind, placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins, 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g, 1.6 oz). High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.3 +/- 0.7%) as compared to low-flavonoid chocolate consumption (mean change = -0.96 +/- 0.5%) (p = 0.024). No significant differences were noted in the resistance to LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight or body mass index (BMI) between the two groups. Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group (204.4 +/- 18.5 nmol/L, p < or = 0.001) but not in the low-flavonoid group (17.5 +/- 9 nmol/L, p = 0.99). Flavonoid-rich dark chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults. No changes in oxidative stress measures, lipid profiles, blood pressure, body weight or BMI were seen.\nStudy8: Dark chocolate or tomato extract for prehypertension: a randomised controlled trial. Flavanol-rich chocolate and lycopene-rich tomato extract have attracted interest as potential alternative treatment options for hypertension, a known risk factor for cardiovascular morbidity and mortality. Treatment of prehypertension (SBP 120-139/DBP 80-89 mmHg) may forestall progression to hypertension. However, there has been only limited research into non-pharmacological treatment options for prehypertension. We investigated the effect of dark chocolate or tomato extract on blood pressure, and their acceptability as an ongoing treatment option in a prehypertensive population. Our trial consisted of two phases: a randomised controlled three-group-parallel trial over 12 weeks (phase 1) followed by a crossover of the two active treatment arms over an additional 12-week period (phase 2). Group 1 received a 50 g daily dose of dark chocolate with 70% cocoa containing 750 mg polyphenols, group 2 were allocated one tomato extract capsule containing 15 mg lycopene per day, and group 3 received one placebo capsule daily over 8 weeks followed by a 4-week washout period. In phase 2 the active treatment groups were crossed over to receive the alternative treatment. Median blood pressure, weight, and abdominal circumference were measured 4-weekly, and other characteristics including physical activity, general health, energy, mood, and acceptability of treatment were assessed by questionnaire at 0, 8 and 20 weeks. We analysed changes over time using a linear mixed model, and one time point differences using Kruskal-Wallis, Fisher's-Exact, or t-tests. Thirty-six prehypertensive healthy adult volunteers completed the 6-month trial. Blood pressure changes over time within groups and between groups were not significant and independent of treatment. Weight and other characteristics did not change significantly during the trial. However, a marked difference in acceptability between the two treatment forms (chocolate or capsule) was revealed (p < 0.0001). Half of the participants allocated to the chocolate treatment found it hard to eat 50 g of dark chocolate every day and 20% considered it an unacceptable long-term treatment option, whereas all participants found it easy and acceptable to take a capsule each day for blood pressure. Our study did not find a blood pressure lowering effect of dark chocolate or tomato extract in a prehypertensive population. Practicability of chocolate as a long-term treatment option may be limited. http://www.anzctr.org.au Identifier: ACTRN12609000047291.\nStudy9: Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear. To determine effects of low doses of polyphenol-rich dark chocolate on BP. Randomized, controlled, investigator-blinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006. Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate. Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols. From baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by -2.9 (1.6) mm Hg (P < .001) and diastolic BP by -1.9 (1.0) mm Hg (P < .001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (P < .001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers. Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide. clinicaltrials.gov Identifier: NCT00421499.\nStudy10: Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. nan\n", + "output": "Conclusions: Flavanol-rich chocolate and cocoa products may have a small but statistically significant effect in lowering blood pressure by 2-3 mm Hg in the short term.\nOur findings are limited by the heterogeneity between trials, which was explored by univariate meta-regression and subgroup analyses. Subgroup meta-analysis of trials using a flavanol-free control group revealed a significant blood pressure reducing effect of cocoa, whereas analysis of trials using a low-flavanol control product did not. While it appears that shorter trials of 2 weeks duration were more effective, analysis may be confounded by type of control and unblinding of participants, as the majority of 2-week trials also used a flavanol-free control and unblinding of participants. Results of these and other subgroup analyses based on, for example, age of participants, should be interpreted with caution and need to be confirmed or refuted in trials using direct randomized comparison.\nLong-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products." + }, + { + "input": "Study: The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure. Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events, but the risks and benefits of antithrombotic therapy are unknown. The current study was an open-label, randomized, controlled trial comparing no antithrombotic therapy, aspirin (300 mg/day), and warfarin (target international normalized ratio 2.5) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy. The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study. The primary clinical outcome was death, nonfatal myocardial infarction, or nonfatal stroke. Two hundred seventy-nine patients were randomized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 +/- 1 months. Twenty-six (26%), 29 (32%), and 23 (26%) patients randomized to no antithrombotic treatment, aspirin, and warfarin, respectively, reached the primary outcome (ns). There were trends to a worse outcome among those randomized to aspirin for a number of secondary outcomes. Significantly (P =.044) more patients randomized to aspirin were hospitalized for cardiovascular reasons, especially worsening heart failure. The Warfarin/Aspirin Study in Heart failure (WASH) provides no evidence that aspirin is effective or safe in patients with heart failure. The benefits of warfarin for patients with heart failure in sinus rhythm have not been established. Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy.\n", + "output": "Conclusions: At present there is little evidence from long term RCTs to recommend the use of antiplatelet therapy to prevent thromboembolism in patients with heart failure in sinus rhythm. A possible interaction with ACE inhibitors may reduce the efficacy of aspirin, although this evidence is mainly from retrospective analyses of trial cohorts and two RCTs. There is also no current evidence to support the use of oral anticoagulation (when compared to aspirin/clopidogrel) in patients with heart failure in sinus rhythm. Anticoagulation/antiplatelet therapy should be reserved for heart failure patients with other comorbidities (such as atrial fibrillation or underlying coronary artery disease) who may still benefit from these therapies." + }, + { + "input": "Study1: Retrograde reperfusion via vena cava lowers the risk of initial nonfunction but increases the risk of ischemic-type biliary lesions in liver transplantation--a randomized clinical trial. Initial nonfunction (INF) and biliary complications such as ischemic-type biliary lesion (ITBL) remain two major complications in clinical orthotopic liver transplantation (OLT). The influence of ischemia and reperfusion injury (I/R) as a significant risk factor for both complications is widely unquestioned. A new reperfusion technique that reduces I/R injury should lead to a reduction in both INF and ITBL. One hundred and thirty two OLT patients were included in this study and randomized into two groups. Group A underwent standard reperfusion with anterograde simultaneous arterial and portal reperfusion and group B received retrograde reperfusion via the vena cava before sequential anterograde reperfusion of portal vein and hepatic artery. Serum transaminase level as a surrogate parameter for I/R injury and serum bilirubin level as a parameter for graft function were significantly reduced during the first week after OLT in group B. INF rate was 7.7% in group A and 0% in group B (P = 0.058). ITBL incidence was 4.55% in group A versus 12.3% in group B (P = 0.053). Retrograde reperfusion seemed to be beneficial for hepatocytes, but was detrimental for the biliary epithelium. The unexplained increased incidence of ITBL after retrograde reperfusion will be focus of further investigation.\nStudy2: Randomized controlled trial to evaluate flush and reperfusion techniques in liver transplantation. To determine the impact of different flush and reperfusion techniques on postreperfusion syndrome (PRS) and postoperative graft function, 100 transplants were randomly assigned into four groups as follows: group 1 (n=31), portal vein flush, no vena caval venting; group 2 (n=21), hepatic arterial flush, no vena caval venting; group 3 (n=29), portal vein flush with vena caval venting; and group 4 (n=19), hepatic artery flush with vena caval venting. Donor and recipient characteristics were similar. Extensive intraoperative and postoperative monitoring was performed and measurements were documented immediately before reperfusion and at 1, 5, 15, and 30 min after reperfusion. PRS was defined by three criteria: mean arterial pressure (MAP) <60 mmHg at 1 min after reperfusion, MAP <60 mmHg at 5 min after reperfusion, and a decrease of 30% or more for the MAP percent area under the curve during the initial 5 min after reperfusion (%AUC). Using these definitions, the overall incidence of PRS was 21%, 8%, and 43%, respectively. Group 1 was the most hemodynamically stable; the incidence of PRS in group 1 was 2/31 (7%) at 1 min and 8/31 (25%) using %AUC criteria compared with 7/21 (33%) at 1 min and 12/21 (57%) using %AUC criteria for group 2 (P<0.05). The patients in groups 3 and 4 (vena caval venting) demonstrated smaller percentage increases in serum potassium levels (as determined by %AUC; 4.3+/-6.8 and 0.3+/-5.4, vs. 15.1+/-8.1 for group 1 and 22.9+/-8.2 for group 2). The difference between group 4 and group 2 was statistically significant (P<0.05). The increases in serum potassium did not translate into increased cardiac or hemodynamic instability. Combining all data obtained over the first 30 min after reperfusion, there was no statistically significant difference in hemodynamic or biochemical changes noted among the four groups. Postoperative liver function was similar among the four groups. We conclude that portal vein flush without vena caval venting provided a lower incidence of PRS than any other technique. Vena caval venting decreased the release of potassium into the circulation. Postoperative graft function was not significantly affected by flush and reperfusion techniques.\nStudy3: Hemodynamic profiles during piggyback liver grafts using arterial or portal revascularization. The order of revascularization in human liver grafts is still discussed. This study tries to answer this question in terms of hemodynamic data. Fifty-nine patients were randomized in this study to compare hemodynamic data just before and 15 minutes after revascularization of liver grafts in relation to first hepatic artery (n = 29) or first portal vein (n = 30) revascularization procedure. Hemodynamic variations were significantly greater in the portal vein group than in the hepatic artery group in terms of mean arterial pressure, cardiac index, central venous pressure, pulmonary capillary pressure, and systemic vascular resistance. The latter decreased from 741.8 +/- 390.3 to 659.9 +/- 411.1 dynes/ cm5 (NS) in the hepatic artery group versus 807.7 +/-336.7 to 439.7 +/- 215 dynes/cm5 (p < 0.05) in the portal vein group. Clinical results and postoperative complications, graft characteristics, patient survival, and graft survival were not significantly different between the groups. Initial arterial revascularization of the liver graft leads to a more stable hemodynamic profile during revascularization of the liver graft after vascular unclamping. This technique is always feasible and has become our reference procedure.\nStudy4: Hemodynamic profile and tissular oxygenation in orthotopic liver transplantation: Influence of hepatic artery or portal vein revascularization of the graft. We performed a prospective, randomized study of adult patients undergoing orthotopic liver transplantation, comparing hemodynamic and tissular oxygenation during reperfusion of the graft. In 30 patients, revascularization was started through the hepatic artery (i.e., initial arterial revascularization) and 10 minutes later the portal vein was unclamped; in 30 others, revascularization was started through the portal vein (i.e., initial portal revascularization) and 10 minutes later the hepatic artery was unclamped. The primary endpoints of the study were mean systemic arterial pressure and the gastric-end-tidal carbon dioxide partial pressure (PCO(2)) difference. The secondary endpoints were other hemodynamic and metabolic data. The pattern of the hemodynamic parameters and tissue oxygenation values during the dissection and anhepatic stages were similar in both groups At the first unclamping, initial portal revascularization produced higher values of mean pulmonary pressure (25 +/- 7 mm of Hg vs. 17 +/- 4 mm of Hg; P < 0.05) and wedge and central venous pressures. At the second unclamping, initial portal revascularization produced higher values of cardiac output and mean arterial pressure (87 +/- 15 mm of Hg vs. 79 +/- 15 mm of Hg; P < 0.05) and pulmonary blood pressure. Postreperfusion syndrome was present in 13 patients (42.5%) in the arterial group and in 11 patients (36%) in the portal group. During revascularization, the values of gastric and arterial pH decreased in both groups and recovered at the end of the procedure, but were more accentuated in the initial arterial revascularization group. In conclusion, we found that initial arterial revascularization of the graft increases pulmonary pressure less markedly, so it may be indicated for those patients with poor pulmonary and cardiac reserve. Nevertheless, for the remaining patients, initial portal revascularization offers more favorable hemodynamic and metabolic behavior, less inotropic drug use, and earlier normalization of lactate and pH values. (c) 2006 AASLD\nStudy5: Sequential versus contemporaneous portal and arterial reperfusion during liver transplantation. Although sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (OLT), contemporaneous portal and hepatic artery revascularization (CPAr) has been used to reduce arterial ischemia to the bile ducts. The aim of this study was to prospectively compare SPAr (group 1; n=19) versus CPAr (group 2; n=21) among 40 consecutive OLT from heart-beating donors. There were no differences in the demographics characteristics, Model for End-stage Liver Disease scores, indication for OLT and donor parameters between the groups. OLT was performed using the piggyback technique. The biliary anastomosis was performed in all cases by a duct-to-duct technique with a T-tube in 32% versus 29% of cases without a T tube (P=.83). In the CPAr group, the liver was reperfused simultaneously via the portal vein and hepatic artery. CPAr showed a longer warm ischemia (66 \u00b1 8 vs 37 \u00b1 7 minutes; P<.001), while SPAr had a longer arterial ischemia 103 \u00b1 42 vs 66 \u00b1 8 minutes (P=.0004). Recovery of graft function was similar. There was no primary nonfunction and delayed graft function occurred among 10% versus 9%. Liver function tests were similar between the two groups up to 90 days case of follow-up- One-year graft and patient survivals were, respectively, 89% and 95% versus 94% and 100% (P=.29). At a median follow-up of 13 \u00b1 6 versus 14 \u00b1 7 months, biliary complications included anastomotic stenoses in 15% versus 19% (P=.78) and intrahepatic non-anastomotic biliary strictures in 26% versus none (P=.01) for SPAr and CPAr, respectively. CPAr was safe and feasible, reducing the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts. Copyright \u00a9 2011 Elsevier Inc. All rights reserved.\n", + "output": "Conclusions: There is currently no evidence to support or refute the use of any specific technique of flushing or reperfusion during liver transplantation. Due to the paucity of data, absence of evidence should not be confused with evidence of absence of any differences. Further well designed trials with low risk of systematic error and low risk of random errors are necessary." + }, + { + "input": "Study1: Efficacy of amodiaquine alone and combined with sulfadoxine-pyrimethamine and of sulfadoxine pyrimethamine combined with artesunate. The safety and the efficacy of amodiaquine (AQ) alone, AQ plus sulfadoxine-pyrimethamine (SP) (AQ plus SP), and artesunate (ART) plus SP (ART plus SP), three possible alternatives to chloroquine (CQ), were investigated in 379 Rwandan children 6-59 months old with uncomplicated Plasmodium falciparum malaria who visited one urban/peri-urban health center and two rural health centers. The three treatment regimens were well tolerated and no serious adverse effects were observed. Children treated with AQ plus SP had less clinical failures than those treated with ART plus SP (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.06-0.81, P = 0.01) or AQ alone (OR = 0.33, 95% CI = 0.07-1.10, P = 0.08). Even after new infections were excluded, AQ plus SP was still significantly more efficacious than ART plus SP (P = 0.05). At day 14, the mean packed cell volume was significantly higher in the AQ plus SP group compared with the ART plus SP group (P = 0.02) and with the AQ alone group (P = 0.01). In Rwanda, AQ plus SP has been chosen to replace CQ as a first-line treatment. However, this is considered an interim measure and new combinations, possibly co-formulated, should be identified and tested.\nStudy2: Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial. New antimalarial treatments are urgently needed in sub-Saharan Africa. Improved therapies should decrease failure rates in the short term, but their effect on incidence of subsequent episodes of malaria is little studied. We aimed to compare the short-term and long-term effectiveness of three antimalarial regimens in children from Kampala, Uganda. We randomly allocated healthy children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine plus either placebo, 25 mg/kg amodiaquine, or 12 mg/kg artesunate. Participants were followed up for 1 year and received the same preassigned treatment for every new episode of uncomplicated malaria diagnosed during follow-up. Recrudescent and new infections were distinguished by comparison of polymorphisms in merozoite surface protein 2 (MSP2). Our primary endpoint was the total number of treatments for malaria per time at risk. Analyses were done per protocol. 183 (61%) of 316 participants were diagnosed with at least one episode of uncomplicated malaria. A total of 577 episodes of uncomplicated Plasmodium falciparum malaria were treated with study drugs; all regimens were safe and well tolerated. Clinical treatment failure after 14 days was significantly more frequent in the sulfadoxine/pyrimethamine group (38 of 215, 18%) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group (two of 164, 1%; p<0.0001) or sulfadoxine/pyrimethamine plus artesunate group (one of 198, 1%; p<0.0001). After 28 and 42 days, patients in the sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely to develop malaria than were those in the other groups. Overall, sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent treatments for malaria by 54% (95% CI 36-66, p<0.0001) compared with sulfadoxine/ pyrimethamine alone and by 37% (12-54, p=0.007) compared with sulfadoxine/pyrimethamine plus artesunate. Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive regimen to decrease the rate of subsequent episodes of malaria.\nStudy3: Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria. This paper reports a two-phase study in Manhi\u00e7a district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6-59 months with axillary body temperature > or = 37.5 degrees C and non-complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up.\n", + "output": "Conclusions: SP plus AQ performed better at controlling treatment failure at day 28, but was not as good as SP plus AS at reducing gametocyte carriage at day seven. Careful consideration of local resistance patterns is required because resistance to sulfadoxine-pyrimethamine and amodiaquine are high in many areas. In order to delay development of resistance to artesunate, the combination with sulfadoxine-pyrimethamine should only be considered where both drugs are known to be effective. Data on adverse events are still lacking." + }, + { + "input": "Study: Pin site care during circular external fixation using two different protocols. Treatment of tibial fractures with Ilizarov external fixation is a valuable treatment alternative; however, development of problems at the pin site is one of the major drawbacks of this technique. Moreover, there is no general agreement regarding pin site care. The purpose of this study was to compare the efficacy of two different pin site care techniques after treatment of tibial fractures with an Ilizarov external fixator. Prospective randomized study. Department of Orthopaedic Surgery of education and research hospital. In this prospective randomized study, we followed up 610 pin sites in 39 cases using two different pin site care protocols. For the first 15 days, patients in both groups cleaned each pin site using sterile gauze impregnated with 10% polyvinylpyrrolidone iodine (Polyod) every 3 days. After 15 days, patients in group 1 (20 cases, 310 pin sites) were advised to perform pin care by daily showering and brushing the pin sites with soap and an ordinary soft toothbrush, whereas patients in group 2 (19 cases, 300 pin sites) were advised to perform pin care by daily showering and cleaning the crusts using sterile gauze impregnated with 10% polyvinylpyrrolidone iodine (Polyod). Each pin site was denominated according to location. Pin sites were inspected and graded on a scale of 0 to 5 according to slight modification of the system of Dahl described by Gordon et al during outpatient visits on the 5th, 10th, 15th, 30th, 45th, 60th, 75th, 90th, 120th, and 150th days of follow up after the operation until fixator removal. Grade 1 and grade 2 infections were categorized as minor infection not requiring any extra pin site care and grade 3 and above infections as major infection. Minor infection rate of all pin sites was determined as 50.7% in group 1 and 43.6% in group 2. Major infection rate was determined as 3.5% in group 1 and 3.7% in group 2. No statistically significant difference was noted between the two groups (all P > 0.05). Pin site care can be performed without impairing patient comfort and without prohibition of showering. Pin site care can be self-managed by the patients without complex sterilization techniques.\n", + "output": "Conclusions: The available trial evidence was not extensive, was very heterogeneous and generally of poor quality, so there was insufficient evidence to be able to identify a strategy of pin site care that minimises infection rates. Adequately-powered randomised trials are required to examine the effects of different pin care regimens, and co-interventions - such as antibiotic use - and other extraneous factors must be controlled in the study designs." + }, + { + "input": "Study1: KR 339 in the treatment of Parkinsonian tremor. nan\nStudy2: A CRITICAL ANALYSIS OF THE EFFECTS OF TRIHEXYPHENIDYL (ARTANE) ON THE COMPONENTS OF THE PARKINSONIAN SYNDROME. nan\nStudy3: [Bornaprine in the treatment of parkinsonian tremor]. We report the results of a double-blind placebo controlled study of bornaprine, an anticholinergic drug, in the treatment of Parkinson's disease. We studied 17 patients presenting persistent tremor in spite of a stable long-term L-Dopa therapy. The bornaprine, in doses of 8 mg/die, compared with placebo significantly improves tremor. Only mild side effects occurred. We think the bornaprine may be of value in the treatment of parkinsonian tremor.\n", + "output": "Conclusions: As monotherapy or as an adjunct to other antiparkinsonian drugs, anticholinergics are more effective than placebo in improving motor function in Parkinson\u00b4s disease. Neuropsychiatric and cognitive adverse events occur more frequently on anticholinergics than on placebo and are a more common reason for withdrawal than lack of efficacy.Results regarding a potentially better effect of the anticholinergic drug on tremor than on other outcome measures are conflicting and data do not strongly support a differential clinical effect on individual parkinsonian features.Data is insufficient to allow comparisons in efficacy or tolerability between individual anticholinergic drugs." + }, + { + "input": "Study1: A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome. To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS). We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques. The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants. Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.\nStudy2: Neonatal respiratory care and infant mortality in emerging countries. nan\nStudy3: A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. National Institute of Child Health and Human Development Neonatal Research Network. To compare the efficacy of two surfactants, Exosurf Neonatal (Burroughs Wellcome Co.) and Survanta (Ross Laboratories), for the treatment of neonatal respiratory distress syndrome. Multicenter randomized trial. Eleven tertiary care university neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. Newborn infants (n = 617) weighing 501 to 1500 gm with respiratory distress syndrome who were receiving assisted ventilation with 30% oxygen or more within 6 hours of birth were enrolled between January 1991 and January 1992. Infants were randomly assigned to receive up to four intratracheal doses of either Exosurf Neonatal (n = 309) or Survanta (n = 308). The occurrence of death or bronchopulmonary dysplasia 28 days after birth and the average fraction of inspired oxygen (FIO2) and mean airway pressure (MAP) during the first 72 hours after treatment. Death or bronchopulmonary dysplasia occurred in 67% of the infants in the Exosurf group and 62% of those in the Survanta group (adjusted relative risk, 1.07; 95% confidence interval, 0.96 to 1.20). During the 72 hours after the first surfactant dose, the average FIO2 (+/- SEM) was 0.50 +/- 0.01 for Exosurf and 0.42 +/- 0.01 for Survanta (difference, 0.08; 95% confidence interval, 0.05 to 0.11); the average MAP (+/- SEM) was 7.64 +/- 0.21 cm H2O for Exosurf and 6.93 +/- 0.21 cm H2O for Survanta (difference, 0.71 cm H2O; 95% confidence interval, 0.13 to 1.29 cm H2O). There was no difference between the groups in the incidence of other neonatal morbidities or in the duration of hospitalization, assisted ventilation, or supplemental oxygen administration. We found no difference between treatment groups in the incidence of death or bronchopulmonary dysplasia, although we did observe a difference in the initial response to treatment as measured by FIO2 and MAP.\nStudy4: Randomized trial comparing natural and synthetic surfactant: increased infection rate after natural surfactant? The efficacy of a natural porcine surfactant and a synthetic surfactant were compared in a randomized trial. In three neonatal intensive care units, 228 neonates with respiratory distress and a ratio of arterial to alveolar partial pressure of oxygen <0.22 were randomly assigned to receive either Curosurf 100 mgkg-1 or Exosurf Neonatal 5 ml.kg-1. After Curosurf, the fraction of inspired oxygen was lower from 15 min (0.45 +/- 0.22 vs 0.70 +/- 0.22, p = 0.0001) to 6 h (0.48 +/- 0.26 vs 0.64 +/- 0.23, p = 0.0001) and the mean airway pressure was lower at 1 h (8.3 +/- 3.2 mm H20 vs 9.4 +/- 3.1 mm H20, p = 0.01). Thereafter the respiratory parameters were similar. The duration of mechanical ventilation (median 6 vs 5 d) and the duration of oxygen supplementation (median 5 vs 4 d) were similar for Curosurf and Exosurf. After Curosurf, C-reactive protein value over 40 mg l-1 occurred in 45% (vs 12%; RR 3.62, 95%CI 2.12-6.17, p = 0.001), leukopenia in 52% (vs 28%; RR 1.85, 95% CI 1.31-2.61, p = 0.001) and bacteraemia in 11% (vs 4%; RR 3.17, 95% CI 1.05-9.52, p < 0.05). We conclude that when given as rescue therapy Curosurf had no advantage compared with Exosurf in addition to the more effective initial response. Curosurf may increase the risk of infection.\nStudy5: Modified bovine surfactant (Survanta) versus a protein-free surfactant (Exosurf) in the treatment of respiratory distress syndrome in preterm infants: a pilot study. We undertook a prospective, randomized, non-blinded pilot study to determine whether infants with respiratory distress syndrome (RDS) who were treated with protein-containing bovine surfactant (Survanta, Ross/Abbott Laboratories, Columbus, Ohio) had earlier and larger responses in gas exchange when compared with similar infants treated with a synthetic surfactant (Exosurf, Burroughs Wellcome, Research Triangle Park, North Carolina). Forty-one infants weighing between 600 g and 1750 g at birth with RDS of sufficient severity to require assisted ventilation with an FiO2 > 0.39 were enrolled in the study and treated with surfactant from 1 to 8 hours after birth. Infants were randomly selected to receive treatment with either Exosurf or Survanta. Despite randomization, the Survanta group was overrepresented with factors associated with greater severity of RDS (lower birthweight, more males, and fewer African Americans). No statistically significant difference was found in the primary outcome measure (arterial/alveolar PaO2 > 0.3 at 24 hours) by univariate or multivariate analysis. The percentage of responders in the Survanta-treated group was significantly increased 24 hours after treatment in two of four secondary measures of oxygenation when analyzed by univariate tests using one-tailed P values. Based on these results, we anticipate that acute outcomes after Survanta or Exosurf will approximate those found in this trial and that differences in measures of oxygenation between treatment groups will approximate 30% to 50% 24 hours after initial treatment.\n", + "output": "Conclusions: Both natural surfactant extracts and synthetic surfactant extracts are effective in the treatment and prevention of respiratory distress syndrome. Comparative trials demonstrate greater early improvement in the requirement for ventilator support, fewer pneumothoraces, and fewer deaths associated with natural surfactant extract treatment. Natural surfactant may be associated with an increase in intraventricular hemorrhage, though the more serious hemorrhages (Grade 3 and 4) are not increased. Despite these concerns, natural surfactant extracts would seem to be the more desirable choice when compared to currently available synthetic surfactants." + }, + { + "input": "Study1: A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation. The success of liver transplantation in this decade has become the stimulus to extend the donor and recipient pool. Reducing early posttransplant morbidity to maintain our success, as we expand our frontiers, has led us to focus on balanced testing of multidrug immunosuppression regimens. A prospective trial in orthotopic liver transplantation using Mycophenolate Mofetil and an identical steroid taper with randomization of patients to Neoral (N) or Tacrolimus (FK) is the basis of this report. This was an intent-to-treat study designed to compare the 6-month primary endpoints of rejection and infection and to compare the 6-month secondary endpoints of liver function, renal function, bone marrow function, hypertension, and serum cholesterol levels. Ninety-seven patients completed the 6-month follow-up period (N=49, FK=48). The actual 6-month patient and graft survival rates were 98% and 94%, respectively. There was no difference in the number of patients with rejection episodes (N=11, FK=8) (P=0.61). There were 24 infections (3 cytomegalovirus) in the FK group and 30 infections (9 cytomegalovirus) in the N group. The cholesterol levels at 6 months were not significantly different (P=0.07) between the groups. The other secondary 6-month endpoints were not significantly different, except total bilirubin, which was lower in the FK arm (P=0.02). The use of Mycophenolate Mofetil with N or FK and an identical steroid taper after orthotopic liver transplantation is associated with excellent graft and patient survival, and at 6 months, only 191% of the patients experienced rejection, with a 48% overall infection rate.\nStudy2: Early steroid withdrawal after liver transplantation: the Canadian tacrolimus versus microemulsion cyclosporin A trial: 1-year follow-up. Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone /=12 years of age symptomatic on a low dose of an inhaled corticosteroid (ICS). The study consisted of a 2-week screening period on low dose ICS; a 4-week open-label FP 250 mcg twice daily (BID) run-in; a 52-week double-blind period (FP/salmeterol [FSC] 100/50 mcg [n=239] or FP 100 mcg [n=236] BID), and a 4-week FP 250 mcg BID run-out period. Annualized exacerbation rate was the primary outcome for comparing the two treatments. Other measures of asthma control included peak expiratory flow, asthma symptoms, and albuterol use. Safety was assessed through adverse events. Exacerbation rates were not significantly different in those treated with FSC 100/50 mcg (0.449 per year) compared with FP 100 mcg (0.529 per year, p=0.169). When the per-protocol analysis was applied, the rates were 0.465 and 0.769 per year for FSC 100/50 mcg and FP 100 mcg, respectively. Treatment with FSC 100/50 mcg provided statistically greater improvements in lung function measures and nighttime awakenings (p 0.05). Prolonged operative time in group A was 85.7 +/- 25.2 min vs group B 48.0 +/- 13.9 min (p < 0.001). Postoperative bowel function recovery with toleration of a regular diet in group A was faster than group B (45.6 +/- 19.2 hrs vs 55.2 +/- 11.0 hrs, p < 0.001). The need for postoperative narcotic drugs with demerol injection was less in group A (40%) than group B (86%) (p < 0.001). The total cost for group A was NT $42139 +/- 7135 and for group B was NT $38085 +/- 7578 (p > 0.05). The interval of return to full activity for group A was shorter than group B (12.8 +/- 8.8 days vs 35.9 +/- 20.6 days respectively p < 0.001). Recurrent symptoms within the 6 to 13 month postoperative follow up period was 8% in group A and 11.7% in group B (p > 0.05). Only one patient in group B was proved to have a recurrent common bile duct stone by endoscopic retrograde cholangiography and received choledocholithotomy again.\nStudy8: Comparative evaluation of the inflammatory mediators in patients undergoing laparoscopic versus conventional cholecystectomy. Injury induces systemic inflammatory response. The degree of response is proportionate to the trauma. Patients with ultrasound-proven gall stones posted for operation were randomized into two groups. Laparoscopic cholecystectomy was performed in one group while the other group underwent conventional cholecystectomy. Peripheral venous blood samples for inflammatory mediators, namely tumour necrosis factor, C-reactive protein, oxygen release from monocytes and polymorphonuclear leucocytes were drawn 1 day before surgery and repeated on the first and third days after surgery. Partial pressure of arterial oxygen was also measured in both groups. Only patients who met selection criteria and had uncomplicated postoperative courses were included in the study. There was a total of 40 patients for the final analysis, 20 in each group. There was no significant difference (P > 0.1) in age, sex or body mass index in both groups of patients. The level of all of the inflammatory mediators was elevated on the first postoperative day; however, the elevation was significantly less following laparoscopic cholecystectomy compared to conventional cholecystectomy (P < 0.01). Although the values came down on the third postoperative day, they remained above the respective controls. Postoperative hypoxaemia was significantly more in patients of conventional than laparoscopic cholecystectomy (P < 0.001). Trauma-induced inflammatory response is significantly less following laparoscopic cholecystectomy compared to conventional cholecystectomy. It appears to be related to degree of trauma.\nStudy9: Laparoscopic and open cholecystectomy. A prospective, randomized study. To compare laparoscopic with open cholecystectomy. Prospective random control trial. Central Hospital of Akershus, Nordbyhagen, Norway. 74 consecutive patients due to undergo elective cholecystecomy between October 1990 and June 1991. Two patients were excluded from randomisation, and two were withdrawn after randomisation. The remaining 70 were randomly allocated to open or laparoscopic cholecystectomy (n = 35 in each group). Duration of operation and postoperative stay in hospital, amount of postoperative pain, incidence of complications, and duration of convalescence and sick leave. Laparoscopic cholecystectomy took twice as long as open (median [range] 100 [52-180] minutes compared with 50 [15-115], p < 0.01), but patients stayed in hospital half the time (2 [1-9] days compared with 4 [2-22], p < 0.01); required less opiate analgesia (4 [0-20] doses compared with 6 [0-13], p = 0.02; took less sick leave (11 [4-267] days (n = 18) compared with 34 [20-48] (n = 22), p < 0.01); and spent less time in convalescence (8 [3-40] days (n = 17) compared with 49 [10-247] (n = 12), p < 0.01). There were six complications in the laparoscopy group and seven in the open cholecystectomy group. Because of the significant differences between laparoscopic and open cholecystectomy we have now adopted the laparoscopic method as our standard, but we think that we can improve our results further by refining our operative techniques and giving our patients more information.\nStudy10: Systemic stress response after laparoscopic or open cholecystectomy: a randomized trial. Surgical injury induces a systemic endocrine-metabolic response which is proportional to the severity of surgical stress. Laparoscopic cholecystectomy is associated with a favourable clinical outcome compared with open cholecystectomy suggesting that surgical injury is reduced. In a randomized clinical trial of 41 patients undergoing laparoscopic cholecystectomy and 42 patients undergoing open cholecystectomy, the neuroendocrine and metabolic stress responses were compared. Plasma levels of cortisol, adrenaline, noradrenaline, glucose, interleukin (IL) 6 and C-reactive protein (CRP) were measured before, during and at 4, 8 and 24 h after operation. Plasma levels of cortisol and catecholamines increased during and after both laparoscopic and open cholecystectomy; however, their postoperative responses during and after both laparoscopic and open cholecystectomy; however, their postoperative responses were significantly higher (P < 0.05) after open cholecystectomy. Glucose, IL-6 and CRP levels also increased after operation and were significantly higher (P < 0.05) in the open cholecystectomy group. The neuroendocrine stress response and inflammatory response following laparoscopic cholecystectomy were significantly reduced compared with those after open cholecystectomy.\n", + "output": "Conclusions: No significant differences were observed in mortality, complications and operative time between laparoscopic and open cholecystectomy. Laparoscopic cholecystectomy is associated with a significantly shorter hospital stay and a quicker convalescence compared with the classical open cholecystectomy. These results confirm the existing preference for the laparoscopic cholecystectomy over open cholecystectomy." + }, + { + "input": "Study1: Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. The DAMAD Study Group. In a double-blind randomized controlled clinical trial conducted in two French and two United Kingdom centers, the effect of antiplatelet agents, i.e., aspirin alone (330 mg 3 times daily) or in combination with dipyridamole (75 mg 3 times daily), was tested versus placebo in 475 patients with early diabetic retinopathy. The assessment of retinopathy was based on change in the number of microaneurysms (MAs) present in the macular field, as seen on fluorescein angiograms, over 3 yr. Forty-one patients did not complete the study. At least three readable initial and yearly angiograms were available on 420 patients (266 treated with insulin and 154 not treated); the results reported are based on these patients. The mean yearly increase in definite MAs was similar in insulin-treated and non-insulin-treated diabetic patients. There was no significant difference between the aspirin-alone group (0.69 +/- 5.1 mean +/- SD, n = 145) and the aspirin-plus-dipyridamole group (0.34 +/- 3.0, n = 142). In the placebo group the mean yearly increase (1.44 +/- 4.5, n = 133) was significantly higher than in the treated group (P = .02, 1-tailed t test). There was a clear relationship between the deterioration in ophthalmological signs and the increase in mean yearly MAs (clinically stable, 0.38 +/- 3.96, n = 293; deteriorating, 1.79 +/- 4.89, n = 127; P = .002, 2-tailed t test). We conclude that aspirin alone and in conjunction with dipyridamole significantly slows the progression of MA evolution in early diabetic retinopathy.\nStudy2: Dipyridamole: a controlled trial of its effect in acute myocardial infarction. A controlled trial of oral dipyridamole in 103 patients with acute myocardial infarction showed no difference in the number of complications or deaths in either the control or the treated groups. It is concluded that dipyridamole has no benefit in acute myocardial infarction.\nStudy3: Dipyridamole in chronic stable angina pectoris; a randomized, double blind, placebo-controlled, parallel group study. Oral dipyridamole induces accumulation of endogenous adenosine, which in a hypoxic milieu exerts experimentally an angiogenic effect on coronary collateral circulation. A meta-analysis of 13 randomized placebo-controlled trials published between 1960 and 1992 showed evidence of benefit for dipyridamole in the treatment of angina pectoris, especially with longer duration of treatment. Aim To assess the efficacy and safety of dipyridamole in the treatment of patients with chronic stable angina in a large scale, international, randomized, placebo-controlled, parallel group study. Four hundred patients with chronic stable angina pectoris and a positive treadmill exercise test were randomized to receive either modified release dipyridamole (200 mg b.i.d. p.o., n=198) or corresponding placebo (n=202), for 24 weeks as an add-on to conventional antianginal therapy and for 4 additional weeks as monotherapy--the latter after withdrawal of standard treatment with calcium antagonists and/or beta-blockers and/or long-acting (prophylactic) nitrates. Of the 198 patients randomized to dipyridamole, 134 completed the add-on and only 12 the monotherapy phase. Of the 202 patients randomized to placebo, 162 reached the add-on and only 12 the monotherapy phase. Serious adverse events occurred in 15 patients with dipyridamole and in 12 with placebo (7.6% vs 6.0, P=0.52). Increase over the baseline treadmill exercise test was similar in the treatment groups at each stage of the trial for all the main efficacy parameters: total treadmill exercise test duration; time to first anginal pain (except for a -13 s difference in favour of placebo at week 24;P=0.040); time to ST segment depression >0.1 mVolt (except for a +21 s difference in favour of dipyridamole at week 8;P=0.024; this latter difference was totally attributable to patients with lower exercise tolerance--Bruce stage II at study entry). In patients with chronic stable angina treated with regular antianginal background medication, the use of oral dipyridamole is safe and well tolerated. Antianginal and antiischaemic efficacy, as assessed by exercise testing, is comparable to placebo, except for a beneficial effect on time to ischaemia after 2 months, totally attributable to patients with lower exercise tolerance at study entry. Copyright 2001 The European Society of Cardiology.\nStudy4: Treatment of claudication with dipyridamole and aspirin. nan\nStudy5: [Ischemic cerebrovascular disease: treatment with various anti-platelet aggregation drugs. Clinical follow-up of 80 patients (22-34 months)]. Personal experience in the treatment of Ischaemic Cerebrovascular Disease with platelet suppressant drugs is reported. 80 patients were treated with 5 different protocols: 1) group \"A\": dipyridamol (14 patients); 2) group \"B\": acetylsalicylic acid (ASA) (14 patients); 3) group \"C\": dipyridamol and ASA (22 patients); 4) group \"D\": ditazol (15 patients); 5) group \"E\": isoxsuprine resinate (15 patients) and followed-up for 22-34 months. The evolution of the disease is discussed and recurrences evaluated on the basis of initial clinical features and particular treatment given.\nStudy6: [Prevention of recurrences of cerebral ischemic vascular accidents by platelet antiaggregants. Results of a 3-year controlled therapeutic trial]. nan\nStudy7: Persantine-Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin. In the Persantine-Aspirin Reinfarction Study, Part II (PARIS II), 3,128 persons who had recovered from myocardial infarction, suffered from 4 weeks to 4 months previously, were randomized into two groups: dipyridamole (Persantine) plus aspirin (n = 1,563) and placebo (n = 1,565). The average length of follow-up was 23.4 months. Prespecified primary end points were coronary incidence (definite nonfatal myocardial infarction plus death due to recent or acute cardiac event), coronary mortality (death due to recent or acute cardiac event) and total mortality, each at 1 year of patient follow-up and at the end of the study. Coronary incidence in the Persantine plus aspirin group was significantly lower than in the placebo group, both at 1 year (30% reduction) and at the end of the study (24% reduction). The statistically significant differences in coronary incidence, at 1 year and at the end of the study, in favor of the combination treatment remained after adjustment for multiple baseline variables and adjustment for multiple testing (three end points for two time periods). Although there were reductions for other end points, these differences were not statistically significant. Coronary mortality was 20% lower in the Persantine plus aspirin group compared with the placebo group at 1 year, and 6% lower overall. Total mortality in the treated group compared with the placebo group was 11% lower at 1 year and 3% lower overall. The reduced rates of coronary incidence largely reflected lower rates of definite nonfatal myocardial infarction in the Persantine plus aspirin group. Several subgroups were defined a priori and at the end of the study. The beneficial effect of Persantine plus aspirin compared with placebo for coronary incidence tended to be greater for the following groups of patients: those who had a non-Q wave infarct; those who were not taking digitalis; those who were receiving beta-receptor blocking drugs at baseline; those who were in New York Heart Association functional class I; those who had had only one myocardial infarction; or those who were enrolled in the study early, that is within 85 days of the qualifying myocardial infarction.\nStudy8: Dipyridamole in the treatment of angina pectoris. A double-blind evaluation. nan\nStudy9: Persantine Aspirin Trial in cerebral ischemia. Part II: Endpoint results. The American-Canadian Co-Operative Study group. The Persantine Aspirin Trial focused on the question of whether the administration of the combination of aspirin and dipyridamole (Persantine) would result in a lower incidence of cerebral or retinal infarction or death than the administration of aspirin alone for persons with a history of recent carotid territory transient ischemic attacks (TIAs). Fifteen centers in the United States and Canada participated and 890 individuals were admitted and randomly allocated to either aspirin (325 mg) plus placebo or aspirin (325 mg) plus Persantine (75 mg) four times daily. Ninety eight percent of the subjects were followed for at least one year; many were followed for four to five years. The results of life table analysis indicate that the overall endpoint rates for the \"aspirin only\" and \"aspirin plus Persantine\" groups are identical. Thus, for TIA patients taking aspirin, the addition of Persantine contributes nothing. There was a clustering of stroke endpoints during the first month after randomization. Deaths from all causes were essentially equally divided between the two treatment groups.\nStudy10: Treatment of angina pectoris with dipyridamole: a double-blind study. nan\n", + "output": "Conclusions: For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug reduced the risk of vascular death, though it reduces the risk of further vascular events. This benefit was found only in patients presenting after cerebral ischaemia. There was no evidence that dipyridamole alone was more efficacious than aspirin." + }, + { + "input": "Study: Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: randomised controlled trial. To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day. Randomised controlled trial. Setting: Copenhagen, Denmark. 42 alcoholic patients without liver disease admitted for elective colorectal surgery. Withdrawal from alcohol consumption for 1 month before operation (disulfiram controlled) compared with continuous drinking. Postoperative complications requiring treatment within the first month after surgery. Perioperative immunosuppression measured by delayed type hypersensitivity; myocardial ischaemia and arrhythmias measured by Holter tape recording; episodes of hypoxaemia measured by pulse oximetry. Response to stress during the operation were assessed by heart rate, blood pressure, serum concentration of cortisol, and plasma concentrations of glucose, interleukin 6, and catecholamines. The intervention group developed significantly fewer postoperative complications than the continuous drinkers (31% v 74%, P=0.02). Delayed type hypersensitivity responses were better in the intervention group before (37 mm2 v 12 mm2, P=0.04), but not after surgery (3 mm2 v 3 mm2). Development of postoperative myocardial ischaemia (23% v 85%) and arrhythmias (33% v 86%) on the second postoperative day as well as nightly hypoxaemic episodes (4 v 18 on the second postoperative night) occurred significantly less often in the intervention group. Surgical stress responses were lower in the intervention group (P5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy. Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05). Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.\nStudy4: Role of atypical bacteria and azithromycin therapy for children with recurrent respiratory tract infections. The aim of this study of 352 patients, 1-14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences. The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates. Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). Short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. In contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria. Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.\n", + "output": "Conclusions: There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children." + }, + { + "input": "Study1: Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument. Adjuvant chemotherapy versus observation and chemotherapy at progression was evaluated in 162 patients in a prospective randomized multicenter study. We also evaluated DNA-measurements as an additional prognostic factor. Patients received adjuvant carboplatin AUC 7 every 28 days for six courses (n = 81) or no adjuvant treatment (n = 81). Eligibility included surgically staged and treated patients with FIGO stage I disease, grade 1 aneuploid or grade 2 or 3 non-clear cell carcinomas or clear cell carcinomas. Disease-free (DFS) and disease-specific (DSS) survival were end-points. Median follow-up time was 46 months and progression was observed in 20 patients in the treatment group and 19 in the control group. Estimated five-year DFS and DSS were 70% and 86% in the treatment group and 71% and 85% in the control group. The hazard ratio was 0.98 (95% confidence interval (95% CI): 0.52-1.83) regarding DFS and 0.94 (95% CI: 0.37-2.36) regarding DSS. No significant differences in DFS or DSS could be seen when the log-rank test was stratified for prognostic variables. Therefore, data from both groups were pooled for the analysis of prognostic factors. DNA-ploidy (P = 0.003), extracapsular growth (P = 0.005), tumor rupture (P = 0.04), and WHO histologic grade (P = 0.04) were significant independent prognostic factors for DFS with P < 0.0001 for the model in the multivariate Cox analysis. FIGO substage (P = 0.01), DNA ploidy (P < 0.05), and histologic grade (P = 0.05) were prognostic for DSS with a P-value for the model < 0.0001. Due to the small number of patients the study was inconclusive as regards the question of adjuvant chemotherapy. The survival curves were superimposable, but with wide confidence intervals. DNA-ploidy adds objective independent prognostic information regarding both DFS and DSS in early ovarian cancer.\nStudy2: Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P). G.I.C.O.G.: Gruppo Interregionale Collaborativo in Ginecologia Oncologica. From 1983 to 1990, 271 consecutive patients with stage I ovarian cancer entered two randomised trials, aimed at assessing the role of adjuvant chemotherapy after radical surgery in early stages of ovarian cancer. Trial I compared cisplatin (50 mg/m2 with repeated courses every 28 days for 6 cycles) to no further therapy in F.I.G.O. stage Ia & b Grade II-III patients; trial II compared cisplatin (same dose and schedule) to 32P in Iaii & bii and Ic patients. Both studies were multicentric and centrally randomized. Treatment was allocated by phone and stratified by center. All patients satisfying major eligibility criteria (histological and grade, no previous neoplasms) were analysed according to treatment allocated by randomisation. With a median observation time of 76 months, cisplatin significantly reduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14-0.89, p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI = 0.19-0.77, p = 0.007; Cox Model) in trial II. Survival was not significantly different (trial I - Kaplan-Meier overall 5-year survival: cisplatin = 88%, control = 82%, HR = 1.15; 95% CI = 0.44-2.98; p = 0.773; Cox Model); trial II - overall 5-year survival: cisplatin = 81%, 32P = 79%, HR = 0.72; 95% CI = 0.37-1.43; p = 0.354; Cox model). In both studies the risk of dying after relapse increased for patients originally randomized to the cisplatin arms: in trial I, 6 of 7 patients in the cisplatin relapsed arm and died of tumor compared with 8 of 14 patients in the control arm. In trial II 11 of 12 patients on cisplatin, and 18 of 26 on 32P succumbed to tumor recurrence. Adjuvant cisplatin treatment in early ovarian cancer significantly prevents relapse in comparison to 32P in stage IC patients or to no immediate treatment in earlier stage women. The impact of cisplatin adjuvant treatment on survival remains, however, unclear.\n", + "output": "Conclusions: Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease.\u00a0Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where optimal staging is not normally performed/achieved. In such settings, adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade 1 serous and endometrioid carcinoma and offered to all others with early stage disease." + }, + { + "input": "Study: Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM. To assess whether antibiotic administration changes the rate of materno-fetal infectious morbidity in premature rupture of membranes occurring later than 35 weeks of gestation. A prospective, randomized and multicentric study in the Perinatology Units of eleven hospitals in Spain. Women were randomized to either antibiotic administration or control group. All were induced, if labor had not started spontaneously after 12 hours of ruptured membranes. Main outcome measures were maternal infection (chorioamnionitis and endometritis) and neonatal infectious morbidity (neonatal sepsis, meningitis and bronchopneumonia). Seven hundred and thirty-three patients were enrolled in the study, 371 in the antibiotics group and 362 in the control group. The incidence of chorioamnionitis and puerperal endometritis were reduced but the differences are statistically nonsignificant. However, the incidence of neonatal sepsis was significantly lower in newborns to mothers who had received antibiotics, 1 vs. 7 cases (Fisher's exact test, p<0.007). The study strongly suggests that prophylactic use of antibiotics in premature rupture of membranes occurring at 36 or more weeks of gestation reduces the risk of neonatal sepsis and probably maternal endometritis.\n", + "output": "Conclusions: No clear practice recommendations can be drawn from the results of this review on this clinically important question, related to a paucity of reliable data. Further well-designed randomised controlled trials are needed to assess the effects of routine use of maternal antibiotics for women with prelabour rupture of the membranes at or near term." + }, + { + "input": "Study: alpha1-Proteinase inhibitor therapy for the prevention of chronic lung disease of prematurity: a randomized, controlled trial. An imbalance between increased neutrophil elastase and a decreased antiprotease shield has been suggested as a factor contributing to the development of chronic lung disease (CLD). We hypothesized that administration of alpha1-proteinase inhibitor (A1PI), also known as alpha1-antitrypsin, to premature neonates would prevent CLD. A randomized, placebo-controlled, prospective study of A1PI supplementation was performed. Neonates <24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory distress syndrome (RDS) were eligible. Intravenous A1PI (60 mg/kg) or placebo was infused on days 0, 4, 7, and 14. Primary outcome was CLD in survivors, defined as the need for supplemental oxygen on day 28. A total of 106 patients were recruited. There were no significant differences between groups in birth weight or incidence of RDS. The incidence of CLD in survivors was lower in the treated group, but the difference did not reach statistical significance (relative risk [RR], 0.79; confidence interval [CI], 0.60-1.02). This beneficial trend persisted at 36 weeks corrected gestational age (RR, 0.48; CI, 0.23-1.00). The incidence of pulmonary hemorrhage was lower in the treated group (RR, 0.22; CI, 0.05-0.98). Other complications were not significantly different between groups. In this, the first trial of a protease inhibitor for the prevention of CLD in premature infants, the infusions were well-tolerated. A1PI therapy may impede the development of CLD and appears to reduce the incidence of pulmonary hemorrhage in some neonates born prematurely.\n", + "output": "Conclusions: Prophylactic administration of a1PI did not reduce the risk of CLD at 36 weeks or long term adverse developmental outcomes in preterm neonates." + }, + { + "input": "Study1: Theophylline versus caffeine: comparative effects in treatment of idiopathic apnea in the preterm infant. nan\nStudy2: Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants. The purpose of our prospective randomized study was to compare the efficacy of theophylline ethylenediamine and caffeine sodium citrate in the treatment of idiopathic apnea in premature infants. Sixteen infants with three or more severe apneic attacks were studied. Twenty-four-hour cardiorespiratory recordings immediately before and after randomization and four days later showed similar significant decreases of the apnea frequency in both theophylline- (group 1, n = 8) and caffeine-treated infants (group 2, n = 8). No undesirable side effects were observed, except for tachycardia in one infant in group 1. We suggest reasons for preferring caffeine to theophylline in the control of idiopathic apnea in premature infants: caffeine is as efficient and easier to administer.\nStudy3: The effect of caffeine compared with theophylline in the treatment of idiopathic apnea in premature infants. nan\nStudy4: Caffeine or theophylline for neonatal apnoea? Caffeine, in the dose usually recommended (12.5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controlled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. All three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours. The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response.\n", + "output": "Conclusions: Caffeine appears to have similar short-term effects on apnea/bradycardia as does theophylline although caffeine has certain therapeutic advantages over theophylline. Theophylline is associated with higher rates of toxicity. The possibility that higher doses of caffeine might be more effective in extremely preterm infants needs further evaluation in randomized clinical trials." + }, + { + "input": "Study1: The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study. Polycystic ovary syndrome (PCOS) is associated with increased risk of cardiovascular morbidity, whereas statins are proven to reduce cardiovascular mortality and morbidity through lipid-lowering and perhaps through their pleiotropic effects. Statins can also reduce testosterone in vitro by inhibiting ovarian theca-interstitial cell proliferation and steroidogenesis and reducing inflammation in vivo. Our objective was to assess the effect of atorvastatin on inflammatory markers, insulin resistance, and biochemical hyperandrogenemia in patients with PCOS. We conducted a randomized, double-blind, placebo-controlled study at a tertiary care setting in United Kingdom. Patients included 40 medication-naive patients with PCOS and biochemical hyperandrogenemia. Patients were randomized to either atorvastatin 20 mg daily or placebo. The primary endpoint of the study was a change in the inflammatory marker high-sensitivity C-reactive protein. The secondary endpoints were a change in insulin resistance and total testosterone. Results: After 12 wk atorvastatin, there was a significant reduction (mean +/- sem) in total cholesterol (4.6 +/- 0.2 vs. 3.4 +/- 0.2 mmol/liter, P < 0.01), low-density lipoprotein cholesterol (2.9 +/- 0.2 vs. 1.8 +/- 0.2 mmol/liter, P < 0.01), triglycerides (1.34 +/- 0.08 vs. 1.08 +/- 0.13 mmol/liter, P <0.01), high-sensitivity C-reactive protein (4.9 +/- 1.4 vs. 3.4 +/- 1.1 mg/liter, P = 0.04), free androgen index (13.4 +/- 0.6 vs. 8.7 +/- 0.4, P < 0.01), testosterone (4.1 +/- 0.2 vs. 2.9 +/- 0.1 nmol/liter, P < 0.01) and insulin resistance as measured by homeostasis model assessment for insulin resistance (HOMA-IR) (3.3 +/- 0.4 vs. 2.7 +/- 0.4). There was a significant increase in SHBG (31.1 +/- 1.0 vs. 35.3 +/- 1.2 nmol/liter, P < 0.01). There was a positive correlation between the reduction in HOMA-IR in the atorvastatin group with the reduction in triglycerides and the reduction of free androgen index. There was a significant deterioration of HOMA-IR in the placebo group (3.0 +/- 0.4 vs. 3.8 +/- 0.5). This study suggests that atorvastatin is effective in reducing inflammation, biochemical hyperandrogenemia, and metabolic parameters in patients with PCOS after a 12-wk period.\nStudy2: Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism; it is also associated with increased cardiovascular risks such as adverse lipid profile and endothelial dysfunction. Metformin and, more recently, statins have been shown to improve endocrine and metabolic aspects of PCOS. The aim of the study was to compare effects of simvastatin and metformin on PCOS. In a prospective trial, women with PCOS (n = 136) were randomized to simvastatin (S), metformin (M), or simvastatin plus metformin (SM) groups. Evaluations were performed at baseline and after 3 months. The study was conducted at an academic medical center. The change of serum total testosterone was measured. The study was completed by 113 subjects. Total testosterone decreased significantly and comparably in all groups: by 17.1, 13.6, and 15.1%, respectively, in the S, M, and SM groups. Significant decreases were also observed in all groups with respect to body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1. DHEAS declined significantly only in the S group. None of the treatments were associated with significant changes in LH or FSH. Total cholesterol and low-density lipoprotein cholesterol significantly declined only in S and SM groups. Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone.\nStudy3: Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial. To test the hypothesis that statins improve hyperandrogenemia in women with polycystic ovary syndrome (PCOS). Prospective, randomized trial. Academic medical center. Forty-eight women with PCOS. Subjects were randomized to a statin group (simvastatin, 20 mg daily plus oral contraceptive pill [OCP]; n = 24) or an OCP group (OCP alone; n = 24). Serum T. Baseline parameters of both groups were comparable. After 12 weeks of treatment, serum T levels declined by 41% in the statin group and by 14% in the OCP group. In the statin group, there was a greater decrease of LH (43% decrease vs. 9% in the OCP group) and a greater decline of LH/FSH ratio (44% vs. 12%). In the statin group, total cholesterol declined by 10% and low-density lipoprotein (LDL) by 24%. In the OCP group, total cholesterol increased by 8%, and LDL was unchanged. This is the first study demonstrating that statin decreases T levels and normalizes gonadotropin levels in women with PCOS. Statin therapy might offer a novel approach, providing endocrine and cardiovascular benefits.\n", + "output": "Conclusions: Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes." + }, + { + "input": "Study1: A randomized, controlled trial comparing two different continuous positive airway pressure systems for the successful extubation of extremely low birth weight infants. To determine whether the use of the Infant Flow continuous positive airway pressure (IF CPAP) system reduces the rate of extubation failure among extremely low birth weight (ELBW) infants (infants with birth weight <1000 g) when compared with conventional CPAP delivered with a conventional ventilator and nasal prongs. A prospective, unmasked, randomized, controlled clinical trial was conducted in 162 eligible intubated ELBW infants who were hospitalized in 2 intensive care nurseries in Winston-Salem, North Carolina, between July 1997 and November 2000. Successful extubation was defined as no need for reintubation for any reason for at least 7 days after the first extubation attempt. The individual extubation success rates were 61.9% (52 of 84) in the conventional CPAP group and 61.5% (48 of 78) in the IF CPAP group. There were no significant differences in the extubation success rate in any birth weight subset between the 2 cohorts. The most common cause of extubation failure was apnea/bradycardia. Infants who were randomized to IF CPAP had fewer days on supplemental O(2) and shorter hospital stays. Extubation failure is a common problem, occurring in nearly 40% of ELBW infants who require mechanical ventilation. IF CPAP was as effective but no more effective than conventional CPAP in preventing extubation failure among ELBW infants. New strategies are needed to identify predictors of extubation success and to treat apnea/bradycardia, the most common cause of extubation failure, thereby reducing the likelihood of prolonged intubation in this high-risk cohort of premature infants.\nStudy2: Advantages and disadvantages of different nasal CPAP systems in newborns. To compare three different systems of continuous positive airway pressure (CPAP): the naso-pharyngeal tube and two-prong systems in newborns, focusing on duration of CPAP, side effects and cost. Randomized clinical study. Between July 2000 and September 2001 newborns were randomized to three different CPAP systems. Forty infants in two weight groups (>2500 g and 1250-2500 g; 20 patients in each group) were included. In the group >2500 g the median duration of CPAP was 1.1 days (range 0.25-14.3 days). The median time on a naso-pharyngeal CPAP was 1 day (range 0.25-14.3 days), on Hudson prongs 1.6 days (range 0.5-3.3 days) and on the Infant Flow system 0.7 days (range 0.3-13.6 days; p>0.05 for comparison between groups, Fisher's exact test). With naso-pharyngeal CPAP, 2 patients developed moderate nasal injuries. On Hudson, 2 patients developed moderate and three mild nasal injuries. One patient on the Infant Flow showed mild and one moderate nasal injuries. In the weight group 1250-2500 g the median duration of CPAP was 1.1 days (range 0.1-7.0 days). The median time on the naso-pharyngeal tube was 0.9 days (range 0.1-7 days), on Hudson prongs 1.1 days (range 0.7-6.6 days) and on the Infant Flow system 1.3 days (range 0.25-5.9 days; p>0.05 for comparison between groups, Fisher's exact test). With a naso-pharyngeal tube, one infant developed mild and one moderate nasal injuries. On Hudson prongs, two had moderate nasal injuries. On Infant Flow, one newborn showed a severe nasal injury and two mild injuries. None of the patients developed a pneumothorax. The naso-pharyngeal tube is an easy, safe and economical CPAP system usable with every common ventilator. For very low birth weight newborns, a prong system may have advantages.\nStudy3: Comparison of two nasal prongs for application of continuous positive airway pressure in neonates. OBJECTIVE: Few studies have compared the performance of nasal prongs used for applying continuous positive airway pressure. The present study compared the tolerance and efficacy with the Argyle and Hudson nasal prongs. DESIGN: A prospective, randomized clinical study. SETTING: A tertiary neonatal intensive care unit in a university hospital. PATIENTS: A total of 99 preterm infants weighing /=1500 g was significantly higher than for those using the Argyle catheter (p =.03). CONCLUSION: Considering the difference in gestational age for the patients weighing 1500-2500 g, we conclude that the two prongs tested are equally effective for nasal continuous positive airway pressure, but the Argyle prong is more difficult to keep in the nostrils of active patients, and nasal hyperemia, the first sign of tissue aggression, occurs more frequently among infants using this prong.\nStudy4: A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants. To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome. Randomised controlled study. Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated. Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant. IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial.\n", + "output": "Conclusions: Short binasal prong devices are more effective than single prongs in reducing the rate of re-intubation. Although the Infant Flow Driver appears more effective than Medicorp prongs the most effective short binasal prong device remains to be determined. The improvement in respiratory parameters with short binasal prongs suggests they are more effective than nasopharyngeal CPAP in the treatment of early RDS. Further studies incorporating longer-term outcomes are required. Studies are also needed to determine the optimal pressure source for the delivery of NCPAP." + }, + { + "input": "Study1: Functional adaptation skills training (FAST): a pilot psychosocial intervention study in middle-aged and older patients with chronic psychotic disorders. Developing behavioral interventions to improve functioning of older patients with schizophrenia and other chronic psychoses has the potential to significantly increase the patients' independence and quality of life. The authors evaluated a psychosocial intervention designed to improve everyday living skills of middle-aged and older outpatients with very chronic psychotic disorders (mean duration of illness: 21 years). Forty patients who resided in board-and-care facilities were randomly assigned to either a 24-session functional adaptation skills training (FAST) group therapy program targeting problem areas identified in previous work as being problematic for this population (e.g., using public transportation) or treatment-as-usual. Almost all the participants also received antipsychotics. Compared with the patients randomized to the treatment-as-usual condition, FAST-treated patients' performance on everyday living skills improved significantly immediately post-intervention and was still significantly better at a 3-month maintenance follow-up period. There was no significant change in psychopathology. Results suggest that older patients with longstanding psychotic disorders may benefit from participation in this skills-training program.\nStudy2: Life skills training for chronic schizophrenics. This research evaluates the effectiveness of training chronic schizophrenic patients in interpersonal and instrumental skills for coping adequately in community living situations. The subjects were male, chronic schizophrenic inpatients with histories of multiple rehospitalizations. Twenty-eight volunteers were randomly assigned to either the life skills training or to a traditional Veterans Administration rehabilitation program. The life skills program included 7 weeks of training in interpersonal and instrumental skills considered important for community tenure: interpersonal communication skills, nutrition, health, finance, time management, and utilization of community resources. Acquisition of skills was assessed by means of a Life Skills Inventory (LSI) and five attitudinal and affective measures pretreatment and post-treatment. The results of the comparison of outcome measures showed the treatment group superior to the control in interpersonal skills, finance, health, use of community resources, and total LSI score. They also showed greater improvement on most of the attitudinal and affective measures. Patients are being followed to measure duration of community placement and maintenance of skills.\n", + "output": "Conclusions: Currently there is no good evidence to suggest life skills programmes are effective for people with chronic mental illnesses. More robust data are needed from studies that are adequately powered to determine whether life skills training is beneficial for people with chronic mental health problems." + }, + { + "input": "Study1: School-based prevention of depression: a randomised controlled study of the beyondblue schools research initiative. Depressive disorders are experienced by 3-5% of the adolescent population at any point of time. They adversely affect adolescent development in a range of areas and greatly increase risk for suicide. The present study investigated the effectiveness of a universal intervention designed to reduce depressive symptoms among students commencing high school. Twenty-five pairs of secondary schools matched on socio-economic status were randomly assigned to either an intervention or a comparison group (n = 5,634 Year 8 students). The intervention extended over a 3-year period and utilised a comprehensive classroom curriculum programme, enhancements to the school climate, improvements in care pathways, and community forums. A range of measures completed by students, average age at baseline = 13.1 years (SD = .5), and teachers was used to assess changes in depressive symptoms, risk and protective factors relevant to depression, and the quality of the school environment. Changes in the level of depressive symptoms and in the levels of risk and protective factors experienced by students in the two groups did not differ significantly over the 3 years of the study. Furthermore, statistically significant differences in the ratings of school climate across this time period were found only for staff-rated assessments. Despite using an extensive, structured programme, based on best evidence to increase protective factors and reduce risk factors at the individual and school levels, the intervention did not reduce levels of depressive symptoms among participating adolescents. The results draw attention to the difficulties faced when implementing large-scale, school-based, universal preventive interventions. These include the need to develop methods to effectively train teachers across large geographical regions to deliver new interventions with fidelity, the difficulty of engaging young adolescents with prevention programmes, and the long period of time required to implement policy and practice changes at 'whole-school' levels.\nStudy2: The prevention of depressive symptoms in rural school children: a randomized controlled trial. A controlled trial was conducted to evaluate a prevention program aimed at reducing depressive and anxious symptoms in rural school children. Seventh-grade children with elevated depression were selected. Nine primary schools (n = 90) were randomly assigned to receive the program, and 9 control schools (n = 99) received their usual health education classes. Children completed questionnaires on depression, anxiety, explanatory style, and social skills. Parents completed the Child Behavior Checklist (T. M. Achenbach, 1991). No intervention effects were found for depression. Intervention group children reported less anxiety than the control group after the program and at 6-month follow-up and more optimistic explanations at postintervention. Intervention group parents reported fewer child internalizing and externalizing symptoms at postintervention only.\nStudy3: Prevention of depression among Icelandic adolescents. Major depression and dysthymia are frequent, debilitating, and chronic disorders, whose highest rate of initial onset is during the late adolescent years. The effectiveness of a program designed to prevent an initial episode of major depression or dysthymia among adolescents was investigated. Participants were 171 fourteen-year-old \"at risk\" Icelandic adolescents who were randomly assigned to a prevention program or a treatment-as-usual assessment only control group. They were identified as \"at risk\" by reporting the presence of depressive symptoms or a negative attributional style. The program was based on a developmental psychosocial model of enhancement of resilience to factors associated with the occurrence of mood disorders. The results indicated that the prevention program resulted in a significantly lower rate of major depression and dysthymia than did the control group. The study demonstrated that school personnel in the school setting can implement such prevention programs.\nStudy4: An experimental evaluation of theory-based mother and mother-child programs for children of divorce. This study evaluated the efficacy of 2 theory-based preventive interventions for divorced families: a program for mothers and a dual component mother-child program. The mother program targeted mother-child relationship quality, discipline, interparental conflict, and the father-child relationship. The child program targeted active coping, avoidant coping, appraisals of divorce stressors, and mother-child relationship quality. Families with a 9- to 12-year-old child (N = 240) were randomly assigned to the mother, dual-component, or self-study program. Postintervention comparisons showed significant positive program effects of the mother program versus self-study condition on relationship quality, discipline, attitude toward father-child contact, and adjustment problems. For several outcomes, more positive effects occurred in families with poorer initial functioning. Program effects on externalizing problems were maintained at 6-month follow-up. A few additive effects of the dual-component program occurred for the putative mediators; none occurred for adjustment problems.\nStudy5: Brief cognitive-behavioral depression prevention program for high-risk adolescents outperforms two alternative interventions: a randomized efficacy trial. In this depression prevention trial, 341 high-risk adolescents (mean age = 15.6 years, SD = 1.2) with elevated depressive symptoms were randomized to a brief group cognitive-behavioral (CB) intervention, group supportive-expressive intervention, bibliotherapy, or assessment-only control condition. CB participants showed significantly greater reductions in depressive symptoms than did supportive-expressive, bibliotherapy, and assessment-only participants at posttest, though only the difference compared with assessment controls was significant at 6-month follow-up. CB participants showed significantly greater improvements in social adjustment and reductions in substance use at posttest and 6-month follow-up than did participants in all 3 other conditions. Supportive-expressive and bibliotherapy participants showed greater reductions in depressive symptoms than did assessment-only controls at certain follow-up assessments but produced no effects for social adjustment and substance use. CB, supportive-expressive, and bibliotherapy participants showed a significantly lower risk for major depression onset over the 6-month follow-up than did assessment-only controls. The evidence that this brief CB intervention reduced risk for future depression onset and outperformed alternative interventions for certain ecologically important outcomes suggests that this intervention may have clinical utility. Copyright 2008 APA, all rights reserved.\nStudy6: School-based intervention to promote coping in rural teens. To evaluate a program designed to help high school students with depressive symptomology to effectively cope. Two-phase experimental study. Rural high school students (N = 222), ages 14 through 19 years, were surveyed to identify teens with depressive symptomatology, identify stressful life events and coping styles of at-risk subjects, and evaluate a cognitive-behavioral group intervention to enhance students' coping and affect levels of depression. Students with depressive symptomatology were randomized into control (n = 18) or intervention (n = 23) groups. Intervention subjects were treated with a nurse-led, 8-week cognitive skills group, conducted at school. On posttesting, the intervention groups demonstrated reduced depressive symptoms in females and a wider range of coping compared with controls. School-based nurses are in an ideal position to provide assessment, referral, and intervention programs in the natural setting of the school. Results of this study indicate that such programs can be implemented successfully in schools and have the potential to promote mental health in teenagers.\nStudy7: The YouthMood Project: a cluster randomized controlled trial of an online cognitive behavioral program with adolescents. The aim in the current study was to investigate the effectiveness of an online, self-directed cognitive-behavioral therapy program (MoodGYM) in preventing and reducing the symptoms of anxiety and depression in an adolescent school-based population. A cluster randomized controlled trial was conducted with 30 schools (N = 1,477) from across Australia, with each school randomly allocated to the intervention or wait-list control condition. At postintervention and 6-month follow-up, participants in the intervention condition had significantly lower levels of anxiety than did participants in the wait-list control condition (Cohen's d = 0.15-0.25). The effects of the MoodGYM program on depressive symptoms were less strong, with only male participants in the intervention condition exhibiting significant reductions in depressive symptoms at postintervention and 6-month follow-up (Cohen's d = 0.27-0.43). Although small to moderate, the effects obtained in the current study provide support for the utility of universal prevention programs in schools. The effectiveness of booster sessions should be explored in future research.\nStudy8: Peer-group support intervention improves the psychosocial well-being of AIDS orphans: cluster randomized trial. Accumulating evidence suggests that AIDS orphanhood status is accompanied by increased levels of psychological distress such as anxiety, depression, intense guilt, shame, and anger. However, few studies have examined the possible reduction of psychological distress in AIDS orphans through the help of interventions that promote well-being. The objective of the study was to evaluate the effects of a school-based peer-group support intervention combined with periodic somatic health assessments and treatment on the psychosocial well-being of AIDS orphans in the Mbarara District of southwestern Uganda. In a cluster randomized controlled design, 326 AIDS orphans aged 10-15 years were assigned to either peer-group support intervention combined with monthly somatic healthcare (n=159) or control group (n=167) for follow-up assessment. Baseline and 10 week follow-up psychological assessments were conducted in both groups using self-administered Beck Youth Inventories. Complete data were available for 298 orphans. After adjusting for baseline scores, follow-up scores for the intervention group in comparison with controls showed significant improvement in depression, anger, and anxiety but not for self-concept. This study demonstrated that peer-group support intervention decreased psychological distress, particularly symptoms of depression, anxiety and anger. Thus, the use of peer-group support interventions should be incorporated into existing school health programs.\nStudy9: Preventing depression among early adolescents in the primary care setting: a randomized controlled study of the Penn Resiliency Program. This study evaluated the Penn Resiliency Program's effectiveness in preventing depression when delivered by therapists in a primary care setting. Two-hundred and seventy-one 11- and 12-year-olds, with elevated depressive symptoms, were randomized to PRP or usual care. Over the 2-year follow-up, PRP improved explanatory style for positive events. PRP's effects on depressive symptoms and explanatory style for negative events were moderated by sex, with girls benefiting more than boys. Stronger effects were seen in high-fidelity groups than low-fidelity groups. PRP did not significantly prevent depressive disorders but significantly prevented depression, anxiety, and adjustment disorders (when combined) among high-symptom participants. Findings are discussed in relation to previous PRP studies and research on the dissemination of psychological interventions.\nStudy10: Efficacy of Interpersonal Psychotherapy-Adolescent Skills Training: an indicated preventive intervention for depression. Indicated interventions for adolescents with elevated depressive symptoms may help decrease rates of depression. The current study reports on the efficacy of Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST), a group indicated preventive intervention. Forty-one adolescents with elevated depression symptoms were randomized to receive either IPT-AST or school counseling (SC) as delivered by guidance counselors and social workers. Adolescents in the two intervention conditions were compared on depression symptoms, overall functioning, and depression diagnoses post-intervention and at 3-month and 6-month follow-up. Adolescents who received IPT-AST had significantly fewer depression symptoms and better overall functioning post-intervention and at follow-up. Adolescents in IPT-AST also reported fewer depression diagnoses than adolescents in usual care. These results provide preliminary evidence of the efficacy of IPT-AST as an intervention for adolescents with subthreshold depression. Future research is needed to confirm the efficacy of IPT-AST in a larger and more diverse sample and to determine its long-term impact on depression symptoms and depression diagnoses.\n", + "output": "Conclusions: There is some evidence from this review that targeted and universal depression prevention programmes may prevent the onset of depressive disorders compared with no intervention. However, allocation concealment is unclear in most studies, and there is heterogeneity in the findings.\u00a0The persistence of findings suggests that this is real and not a placebo effect." + }, + { + "input": "Study1: Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial. Bacterial infection may adversely affect the hemostasis of patients with gastroesophageal variceal bleeding (GEVB). Antibiotic prophylaxis can prevent bacterial infection in such patients, but its role in preventing rebleeding is unclear. Over a 25-month period, patients with acute GEVB but without evidence of bacterial infection were randomized to receive prophylactic antibiotics (ofloxacin 200 mg i.v. q12h for 2 days followed by oral ofloxacin 200 mg q12h for 5 days) or receive antibiotics only when infection became evident (on-demand group). Endoscopic therapy for the GEVB was performed immediately after infection work-up and randomization. Fifty-nine patients in the prophylactic group and 61 patients in the on-demand group were analyzed. Clinical and endoscopic characteristics of the gastroesophageal varices, time to endoscopic treatment, and period of follow-up were not different between the two groups. Antibiotic prophylaxis decreased infections (2/59 vs. 16/61; P <.002). The actuarial probability of rebleeding was higher in patients without prophylactic antibiotics (P =.0029). The difference of rebleeding was mostly due to early rebleeding within 7 days (4/12 vs. 21/27, P =.0221). The relative hazard of rebleeding within 7 days was 5.078 (95% CI: 1.854-13.908, P <.0001). The multivariate Cox regression indicated bacterial infection (relative hazard: 3.85, 95% CI: 1.85-13.90) and association with hepatocellular carcinoma (relative hazard: 2.46, 95% CI: 1.30-4.63) as independent factors predictive of rebleeding. Blood transfusion for rebleeding was also reduced in the prophylactic group (1.40 +/- 0.89 vs. 2.81 +/- 2.29 units, P <.05). There was no difference in survival between the two groups. In conclusion, antibiotic prophylaxis can prevent infection and rebleeding as well as decrease the amount of blood transfused for patients with acute GEVB following endoscopic treatment.\nStudy2: Infectious sequelae after endoscopic sclerotherapy of oesophageal varices: role of antibiotic prophylaxis. In order to determine the incidence of infection following sclerotherapy and the role of antimicrobial prophylaxis, a prospective randomized control study was performed comparing i.v. imipenem/cilastatin, with an infusion of dextrose-saline as a control group. One hundred patients with bleeding esophageal varices were included. All episodes of infection were documented during admission to the unit. Ninety-seven patients were evaluable. Post-sclerotherapy bacteremia developed in six (5.6%) of 107 sclerotherapy sessions in the control group and one (1.1%) of the 88 sclerotherapy sessions in the imipenem/cilastatin group (P < or = 0.1, NS): six of these seven post-sclerotherapy bacteremias occurred after emergency sclerotherapy. Infection within 7 days of the procedure was documented after 43 (22.1%) of the 195 sclerotherapy sessions, 18 (20.5%) in the imipenem/cilastatin group and 25 (23.4%) in the control group (P = NS). These infections were significantly more common after emergency sclerotherapy, 40 (34.8%) of 115 sessions, than after elective sclerotherapy, three (3.8%) of 80 sessions (P < or = 0.0001). A short prophylactic antibiotic regime does not reduce the risk of early bacteremia or the frequency of infection after sclerotherapy. The higher risk of infection after emergency sclerotherapy may be therefore related more to the gastrointestinal hemorrhage and its associated effects than to sclerotherapy.\nStudy3: Variceal bleeding in portal hypertension: bacterial infection and comparison of efficacy of intravenous and per-oral application of antibiotics--a randomized trial. To determine the prevalence of bacterial infection in patients admitted to hospital with variceal bleeding in comparison with patients with liver cirrhosis admitted because of another reason. To compare the effect of orally administered antibiotics vs. intravenous antibiotics. Bacteriological investigation of blood culture, urine, throat smear, perianal smear and ascites (polymorphonuclear count as well in ascites) was made in 46 cirrhotic patients admitted to hospital with variceal bleeding and 48 cirrhotic patients admitted because of another reason. Bleeders were treated endoscopically (sclerotization) and pharmacologically (terlipressin 1 mg every 4 h for 5 days), and were randomly allocated to the treatment with oral norfloxacin (25 patients) or intravenous ampicillin/sulbactam (21 patients). Early and late mortalities were evaluated. The incidence of infection was high in both groups (63.0% bleeders vs. 54.2% controls), but bleeding patients more often had positive blood culture (17.3% vs. 8.6%) and statistically significantly more positive findings in the throat smears (36.9% vs. 17.3%, P=0.04), which gives the evidence of increased pathological colonization in these patients. No difference in survival was seen in patients with per-oral or intravenous administration of antibiotics. Bacterial infection was demonstrated in high percentage in patients with liver cirrhosis admitted to hospital. The administration of antibiotics is indicated in these patients. Intravenous application is probably of the same efficacy as per-oral one.\nStudy4: Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage. To investigate if oral, nonabsorbable antibiotics prevent bacterial infections in cirrhotics with gastrointestinal hemorrhage, 140 consecutive patients were randomly allocated into two groups: 68 patients (Group I) were given oral, non absorbable antibiotics (gentamicin + vancomycin + nystatin or neomycin + colistin + nystatin) from the inclusion into the trial up to 48 hr after cessation of the hemorrhage, or until emergency surgery or death in those cases who continued bleeding; and 72 patients (Group II) did not receive oral, nonabsorbable antibiotics. Both groups were similar in relation to clinical and laboratory data and characteristics of the hemorrhage. The incidence of infection was significantly lower in Group I than in Group II (11 patients in Group I and 25 in Group II developed proved infections; p less than 0.025). This difference was due to the fact that spontaneous bacteremia and peritonitis and urinary tract infection caused by enteric bacteria occurred almost exclusively in Group II. Two patients of Group I and 10 of Group II developed spontaneous bacteremia and/or peritonitis caused by enteric bacteria (p less than 0.025). These results indicate that prophylactic administration of oral, nonabsorbable antibiotics markedly reduces the incidence of infections caused by enteric bacteria in cirrhotic patients with gastrointestinal hemorrhage.\nStudy5: Prophylactic antibiotics in cirrhotics with upper gastrointestinal hemorrhage: a prospective, controlled trial. Infections are a frequent complication in cirrhotics, and gastrointestinal bleeding may increase the infection rate. Nonabsorbable antibiotics or quinolone have been employed to decrease the incidence of infection. Since most of these studies were performed in western countries, it is still unclear whether this holds true in our Taiwan cirrhotic patients. Thus we conducted this study using a different formula of antibiotics to evaluate the efficacy of reducing infection rates in cirrhotics with upper gastrointestinal bleeding. From July 1999 to August 2000, all cirrhotic in-patients presenting with upper gastrointestinal bleeding but without infection were enrolled. The patients should not have received antibiotics within 2 weeks before admission and should have expected life expectance more than 7 days. Eligible patients who had received endoscopy within 12 hours of hospitalization were randomly allocated into 2 groups. Group A received intravenous cefazolin 1 gm every 8 hours started before endoscopy. After 3 days of prophylactic parenteral antibiotics, antibiotics were shifted to oral cephalexin of 500 mg every 6 hours for 4 days. Group B served as control subjects. All patients received chest X-ray, blood and urine cultures, and ascites culture and sputum culture if ascites and sputum were found. Patients were excluded when initial blood, urine or ascites culture was positive for bacterial growth. Ninety-seven patients were included. Group A was comprised of 47 patients and Group B comprised of 50 patients. There was no significant difference in age, sex, Child-Pugh's score or initial hemoglobin between the 2 groups. Proved infection developed in 6 patients of Group B. By contrast, no proved infection was found in Group A. Three organisms belonged to gram-negative bacilli and 3 organisms were gram-positive cocci. The incidence of proved infection during hospitalization was 0% in Group A and 12.0% in Group B (p = 0.027). If possible infection cases (patient's body temperature more than 38 degrees C for more than 2 days) were included, the infection rate was 6.4% in Group A and 26% in Group B (p = 0.013). Infection-related mortality occurred in 2 patients in Group B, but none in Group A. Our prophylactic antibiotic treatment proved safe and effective in reducing the infection rate in cirrhotics with upper gastrointestinal bleeding.\nStudy6: Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding. Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients. Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission. Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2. These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.\nStudy7: Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage. To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group 2 (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = 0.001), bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P less than 0.05), and urinary infections (0% vs. 18.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.8%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage.\nStudy8: Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Oral norfloxacin is the standard of therapy in the prophylaxis of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. However, during the last years, the epidemiology of bacterial infections in cirrhosis has changed, with a higher incidence of infections caused by quinolone-resistant bacteria. This randomized controlled trial was aimed to compare oral norfloxacin vs intravenous ceftriaxone in the prophylaxis of bacterial infection in cirrhotic patients with gastrointestinal bleeding. One hundred eleven patients with advanced cirrhosis (at least 2 of the following: ascites, severe malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n = 57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the trial was the prevention of bacterial infections within 10 days after inclusion. Clinical data were comparable between groups. The probability of developing proved or possible infections, proved infections, and spontaneous bacteremia or spontaneous bacterial peritonitis was significantly higher in patients receiving norfloxacin (33% vs 11%, P = .003; 26% vs 11%, P = .03; and 12% vs 2%, P = .03, respectively). The type of antibiotic used (norfloxacin), transfusion requirements at inclusion, and failure to control bleeding were independent predictors of infection. Seven gram-negative bacilli were isolated in the norfloxacin group, and 6 were quinolone resistant. Non-enterococcal streptococci were only isolated in the norfloxacin group. No difference in hospital mortality was observed between groups. Intravenous ceftriaxone is more effective than oral norfloxacin in the prophylaxis of bacterial infections in patients with advanced cirrhosis and hemorrhage.\nStudy9: The effect of ciprofloxacin in the prevention of bacterial infection in patients with cirrhosis after upper gastrointestinal bleeding. Cirrhotic patients with upper gastrointestinal bleeding are prone to bacterial infection. The aim of this study was to investigate the efficacy of prophylactic intestinal decontamination with oral ciprofloxacin for the prevention of bacterial infections in cirrhotic patients with upper gastrointestinal bleeding. A total of 120 cirrhotic patients with acute upper gastrointestinal bleeding were enrolled. Sixty patients received ciprofloxacin 500 mg twice daily given orally or through nasogastric tube immediately after upper gastrointestinal endoscopic examination; drug administration continued for 7 days. The remaining 60 patients, who received placebo, served as controls. The incidence of proven bacterial infection in the ciprofloxacin-treated group was significantly lower than that of placebo group (10% vs 45%, p < 0.001). The incidences of bacteremia, spontaneous bacterial peritonitis, and urinary tract infection in the ciprofloxacin-treated group were significantly lower than those in the placebo group (0% vs 23%, 3.3% vs 13%, and 5% vs 18%, respectively; p < 0.05, respectively). Multivariate logistic regression analysis showed that a lack of prophylactic treatment with ciprofloxacin and severity of cirrhosis were the independent significant predictors for cirrhotic patients with acute gastrointestinal bleeding with infection. Prophylactic intestinal decontamination with oral ciprofloxacin is effective in the prevention of bacterial infections in patients with cirrhosis who were suffering from acute upper gastrointestinal hemorrhage.\nStudy10: Antibiotic prophylaxis using third generation cephalosporins can reduce the risk of early rebleeding in the first acute gastroesophageal variceal hemorrhage: a prospective randomized study. Bacterial infection may be a critical trigger for variceal bleeding. Antibiotic prophylaxis can prevent rebleeding in patients with acute gastroesophageal variceal bleeding (GEVB). The aim of the study was to compare prophylactic third generation cephalosporins with on-demand antibiotics for the prevention of gastroesophageal variceal rebleeding. In a prospective trial, patients with the first acute GEVB were randomly assigned to receive prophylactic antibiotics (intravenous cefotaxime 2 g q 8 hr for 7 days, prophylactic antibiotics group) or to receive the same antibiotics only when infection became evident (on-demand group). Sixty-two patients in the prophylactic group and 58 patients in the on-demand group were included for analysis. Antibiotic prophylaxis decreased infection (3.2% vs. 15.5%, p=0.026). The actuarial rebleeding rate in the prophylactic group was significantly lower than that in the on-demand group (33.9% vs. 62.1%, p=0.004). The difference of rebleeding rate was mostly due to early rebleeding within 6 weeks (4.8% vs. 20.7%, p=0.012). On multivariate analysis, antibiotic prophylaxis (relative hazard: 0.248, 95% confidence interval (CI): 0.067-0.919, p=0.037) and bacterial infection (relative hazard: 3.901, 95% CI: 1.053-14.448, p=0.042) were two independent determinants of early rebleeding. In conclusion, antibiotic prophylaxis using third generation cephalosporins can prevent bacterial infection and early rebleeding in patients with the first acute GEVB.\n", + "output": "Conclusions: Prophylactic antibiotic use in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and seems to have reduced all-cause mortality, bacterial infection mortality, rebleeding events, and hospitalisation length. These benefits were observed independently of the type of antibiotic used; thus, no specific antibiotic can be preferred. Therefore, antibiotic selection should be made considering local conditions such as bacterial resistance profile and treatment cost." + }, + { + "input": "Study1: In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial. Elective single embryo transfer (eSET) in a selected group of patients (i.e. young patients with at least one good quality embryo) reduces the number of multiple pregnancies in an IVF programme. However, the reduced overall multiple pregnancy rate (PR) is still unacceptably high. Therefore, a randomized controlled trial (RCT) was conducted comparing eSET and double embryo transfer (DET) in an unselected group of patients (i.e. irrespective of the woman's age or embryo quality). Consenting unselected patients were randomized between eSET (RCT-eSET) (n = 154) or DET (RCT-DET) (n = 154). Randomization was performed just prior to the first embryo transfer, provided that at least two 2PN zygotes were available. Non-participants received our standard transfer policy [SP-eSET in a selected group of patients (n = 100), otherwise SP-DET (n = 122)]. The ongoing PR after RCT-eSET was significantly lower as compared with RCT-DET (21.4 versus 40.3%) and the twin PR was reduced from 21.0% after RCT-DET to 0% after RCT-eSET. The ongoing PRs after SP-eSET and SP-DET did not differ significantly (33.0 versus 30.3%), with an overall twin PR of 12.9%. To avoid twin pregnancies resulting from an IVF treatment, eSET should be applied in all patients. The consequence would be a halving of the ongoing PR as compared with applying a DET policy in all patients. The transfer of one embryo in a selected group of good prognosis patients leads to a less drastic reduction in PR but maintains a twin PR of 12.9%.\nStudy2: How many embryos should be transferred in in vitro fertilization? A prospective randomized study. To maintain the rate of pregnancy, while suppressing high rank multiple pregnancies by limiting the number of fresh embryos transferred after IVF, in a population selected for potential success. A prospective, randomized study. D\u00e9partement de Gyn\u00e9cologie Obst\u00e9trique, Centre Hospitalo Universitaire, Paris VI, France. There were two groups of 28 couples. Women were < or = 35 years of age, with > or = 70% cleavage rate and at least four morphologically regular embryos. On the day of ET, either four fresh embryos were transferred (group 1) or two fresh embryos were transferred and two were frozen for later transfer (group 2). Pregnancy rate and multiple pregnancy. The pregnancy rate was the same in the two groups with one-third of the high rank pregnancies in group 1 and no pregnancies in group 2. Only two fresh embryos need to be transferred in this selected population.\n", + "output": "Conclusions: In a single fresh IVF cycle, SET is associated with a lower LBR than DET. However there is no significant difference in CLBR following SET+ 1FZET and the LBR following a single cycle of DET. MPR are lowered following SET compared with other transfer policies. There are insufficient data on the outcome of two versus three and four embryo transfer policies." + }, + { + "input": "Study: Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation. This was a randomized, double-blind, placebo-controlled trial. Forty-eight healthy smokers who smoked at least one pack per day were studied at an outpatient smoking cessation research clinic. The subjects ranged in age from 20 to 40 years. Intervention with the nicotine skin patch (6 to 8 weeks) plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks) was compared to nicotine patch plus placebo. Mecamylamine treatment began 2 weeks before smoking cessation. The primary outcome was continuous abstinence through 7 weeks after cessation (1 week after treatment), confirmed by expired air carbon monoxide measurements. Secondary measures included point abstinence at 7 weeks, continuous abstinence at 6- and 12-month follow-up, and self-reported withdrawal symptoms. The continuous abstinence rate at 7 weeks was three times higher in the mecamylamine condition: 50% versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58% for mecamylamine versus 29% for placebo, p = 0.044. At follow-up, continuous abstinence remained higher for mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and 37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine also significantly reduced craving for cigarettes, negative affect, and appetite. Agonist-antagonist therapy, consisting of the nicotine patch with oral mecamylamine, may substantially improve current smoking cessation treatment.\n", + "output": "Conclusions: Data from two small studies suggest that the combination of nicotine and mecamylamine may be superior to nicotine alone in promoting smoking cessation. However, these results require confirmation in larger studies before the treatment can be recommended clinically." + }, + { + "input": "Study1: Tolerability and side-effects of post-exposure prophylaxis for HIV infection. A study of HIV post-exposure prophylaxis in 28 recipients showed that indinavir-containing regimens were poorly tolerated. This finding has implications for compliance and efficacy of the currently recommended combinations.\nStudy2: Drug-induced aminotransferase alterations during antiretroviral HIV post-exposure prophylaxis. In 655 individuals receiving HIV postexposure prophylaxis (PEP), drug-induced aminotransferase alterations were frequent and severe in the nevirapine-including regimen, rare and mild-to-moderate in other combinations, and always reversible. Grade 3-4 incidence in protease inhibitor or nevirapine PEP was 0.5 and 25.0 per 100 person-months, respectively. Apart from nevirapine, continuing PEP appears to be safe even in the case of aminotransferase alterations. The usefulness of routine monitoring of liver function during PEP could be re-considered.\nStudy3: Effect of short-course of antiretroviral agents on serum triglycerides of healthy individuals. nan\nStudy4: A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52). The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective.\nStudy5: Postexposure HIV prophylaxis regimen. nan\n", + "output": "Conclusions: The use of occupational PEP is based on limited direct evidence of effect. However, it is highly unlikely that a definitive placebo-controlled trial will ever be conducted, and, therefore, on the basis of results from a single case-control study, a four-week regimen of PEP should be initiated as soon as possible after exposure, depending on the risk of seroconversion. There is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV. However, due to the success of combination therapies in treating HIV-infected individuals, a combination of antiretroviral drugs should be used for PEP. Healthcare workers should be counseled about expected adverse events and the strategies for managing these. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion. A randomized controlled clinical trial is neither ethical nor practical. Due to the low risk of HIV seroconversion, a very large sample size would be required to have enough power to show an effect. More rigorous evaluation of adverse events, especially in the developing world, are required. Seeing that current practice is partly based on results from individual primary animal studies, we recommend a formal systematic review of all relevant animal studies." + }, + { + "input": "Study1: The use of a ward-based educational teaching package to enhance nurses' compliance with infection control procedures. Obtaining study leave is becoming difficult for clinical nurses in the current economic climate, but the need to develop new clinical skills and to maintain existing good practice remains of prime importance to patient care and will become mandatory with the advent of post-registration education and practice (PREP) in the UK. The ward is widely acknowledged as the best venue for learning clinical skills by nurse educationalists and for many nurses is the preferred learning environment. The feasibility of using a ward-based teaching package to enhance nurses' compliance with key infection control precautions (hand decontamination, the use of gloves and the safe handling and disposal of sharp instruments) was tested in a quasi-experimental research study conducted on matched surgical wards in a teaching hospital, controlling for variables likely to influence performance (knowledge, availability of resources to perform infection control, previous opportunity to develop infection control expertise and nursing workload). Nurses on two wards received the intervention (experimental group). The remaining wards, which received no intervention, operated as controls. The ward-based sessions consisted of a carefully planned sequence of theory and practical demonstration delivered to qualified nurses in the clinical environment at convenient times selected by the ward managers. Performance of infection control precautions was audited before the intervention and 3 months afterwards. The sessions were well evaluated and the clinical environment was considered suitable for teaching by the nurses, but heavy and unpredictable workload prevented the teaching programme from being implemented as planned. The analysis of covariance failed to detect any changes in performance between nurses in the control and experimental groups. The implications of the study findings are discussed to help develop creative new ways of strengthening ward-based educational programmes.\nStudy2: Three successful interventions in health care workers that improve compliance with hand hygiene: is sustained replication possible? Hand hygiene (HH) compliance by health care workers has been universally disappointing. Two major programs (Washington and Geneva) have demonstrated interventions that induce sustained improvement. The introduction of alcohol-based hand rub (AHR) together with education also has been reported to improve compliance. These interventions were replicated concurrently for 2 years in selected wards of an 800-bed university teaching hospital, with compliance assessed only within, not between, programs. No significant improvement in HH compliance was observed after the introduction of AHR (incidence rate ratio [IRR] = 1.11; 95% confidence interval [CI] = 0.93 to 1.33; P = .238) or substitution of AHR for a similar product (IRR = 1.10; 95% CI = 0.91 to 1.32; P = .328) with concomitant education. The Washington program achieved a 48% (IRR = 1.48, 95% CI = 1.20 to 1.81; P < .001) improvement in compliance, sustained over 2 years. The Geneva program failed to induce a significant increase in HH compliance in 3 wards, but achieved a 56% (IRR = 1.56; 95% CI = 1.29 to 1.89; P < .001) improvement over the already high HH rate in 1 ward (infectious disease unit). The Washington program demonstrated effectiveness in achieving sustained improved HH compliance, whereas the effect of the Geneva program was limited in those wards without strong medical leadership. Introduction of AHR without an associated behavioral modification program proved ineffective.\n", + "output": "Conclusions: The quality of intervention studies intended to increase hand hygiene compliance remains disappointing. Although multifaceted campaigns with social marketing or staff involvement appear to have an effect, there is insufficient evidence to draw a firm conclusion. There remains an urgent need to undertake methodologically robust research to explore the effectiveness of soundly designed and implemented interventions to increase hand hygiene compliance." + }, + { + "input": "Study1: Fetal pulse oximetry and cesarean delivery. Knowledge of fetal oxygen saturation, as an adjunct to electronic fetal monitoring, may be associated with a significant change in the rate of cesarean deliveries or the infant's condition at birth. We randomly assigned 5341 nulliparous women who were at term and in early labor to either \"open\" or \"masked\" fetal pulse oximetry. In the open group, fetal oxygen saturation values were displayed to the clinician. In the masked group, the fetal oxygen sensor was inserted and the values were recorded by computer, but the data were hidden. Labor complicated by a nonreassuring fetal heart rate before randomization was documented for subsequent analysis. There was no significant difference in the overall rates of cesarean delivery between the open and masked groups (26.3% and 27.5%, respectively; P=0.31). The rates of cesarean delivery associated with the separate indications of a nonreassuring fetal heart rate (7.1% and 7.9%, respectively; P=0.30) and dystocia (18.6% and 19.2%, respectively; P=0.59) were similar between the two groups. Similar findings were observed in the subgroup of 2168 women in whom a nonreassuring fetal heart rate was detected before randomization. The condition of the infants at birth did not differ significantly between the two groups. Knowledge of the fetal oxygen saturation is not associated with a reduction in the rate of cesarean delivery or with improvement in the condition of the newborn. (ClinicalTrials.gov number, NCT00098709 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.\nStudy2: A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns. Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status. A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation. A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation. The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.\nStudy3: Intrapartum management of nonreassuring fetal heart rate patterns: a randomized controlled trial of fetal pulse oximetry. We tested if fetal pulse oximetry in addition to electronic fetal monitoring (CTG) and scalp blood sampling improves the accuracy of fetal assessment and allows safe reduction of operative deliveries (-50%) and scalp blood sampling (-50%) performed because of nonreassuring fetal status. Study design A randomized controlled trial was conducted in 146 patients with term pregnancies in active labor and abnormal fetal heart rate patterns: 73 had electronic fetal heart rate monitoring (CTG) and fetal scalp blood sampling (control group), 73 had CTG, fetal scalp blood sampling, and continuous fetal pulse oximetry (study group). There was a reduction of -50% in operative deliveries and fetal scalp blood sampling performed because of nonreassuring fetal status in the study group: operative deliveries, study versus control 25/49 (P