{
    "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=3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B.                 At the end of week 4, 54% of patients achieved serum phosphorus control at dosages <or=3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication.                 Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden.\nStudy8: Calcium acetate versus calcium carbonate as phosphate binders in hemodialysis patients. We conducted a randomized unblinded parallel clinical trial to compare the effectiveness, side effects and tolerance between calcium acetate (CA) and calcium carbonate (CC) in 80 stable chronic hemodialysis patients selected on the basis of their acceptable control of serum phosphorus (P) levels with aluminum hydroxide (AH). All patients were dialyzed against the same calcium dialyzate (1.62 mmol/l). The serum analytical tests included: calcium corrected to total protein, P, PTH (intact molecule) and bicarbonate. The study was divided into the following periods: P0: baseline measurements; P1: washout (withdrawal of AH for 15 days); P2: random allocation to CA and CC treatment at doses equivalent to 75 mEq of elemental calcium, stratified according to previous doses of AH (2 months); P3: adjustment of doses until control P (2 months). CA was poorly tolerated in 7 patients and CC in 2 (NS). The changes in serum P levels between P0 and P2 periods were lower in the CA group (1.73 +/- 0.25 vs. 1.80 +/- 0.50 mmol/l; p = 0.26) than in the CC group (1.77 +/- 0.35 vs. 1.93 +/- 0.48 mmol/l; p = 0.03, paired t test). Serum calcium was hardly modified by CA (2.42 +/- 0.20 vs. 2.47 +/- 0.17 mmol/l; NS) while in the CC group, it rose significantly (2.40 +/- 0.12 vs. 2.55 +/- 0.22 mmol/l; p = 0.0004). There were no differences in the control of PTH or bicarbonate.(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy9: Magnesium carbonate for phosphate control in patients on hemodialysis. A randomized controlled trial. Magnesium salts bind dietary phosphorus, but their use in renal patients is limited due to their potential for causing side effects. The aim of this study was to evaluate the efficacy and safety of magnesium carbonate (MgCO(3)) as a phosphate-binder in hemodialysis patients.                 Forty-six stable hemodialysis patients were randomly allocated to receive either MgCO(3) (n=25) or calcium carbonate (CaCO(3)), (n=21) for 6 months. The concentration of Mg in the dialysate bath was 0.30 mmol/l in the MgCO(3) group and 0.48 mmol/l in the CaCO(3) group.                 Only two of 25 patients (8%) discontinued ingestion of MgCO(3) due to complications: one (4%) because of persistent diarrhea, and the other (4%) because of recurrent hypermagnesemia. In the MgCO(3) and CaCO(3) groups, respectively, time-averaged (months 1-6) serum concentrations were: phosphate (P), 5.47 vs. 5.29 mg/dl, P=ns; Ca, 9.13 vs. 9.60 mg/dl, P<0.001; Ca x P product, 50.35 vs. 50.70 (mg/dl)(2), P=ns; Mg, 2.57 vs. 2.41 mg/dl, P=ns; intact parathyroid hormone (iPTH), 285 vs. 235 pg/ml, P<0.01. At month 6, iPTH levels did not differ between groups: 251 vs. 212 pg/ml, P=ns. At month 6 the percentages of patients with serum levels of phosphate, Ca x P product and iPTH that fell within the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines were similar in both groups, whereas more patients in the MgCO(3) group (17/23; 73.91%) than in the CaCO(3) group (5/20, 25%) had serum Ca levels that fell within these guidelines, with the difference being significant at P<0.01.                 Our study shows that MgCO(3) administered for a period of 6 months is an effective and inexpensive agent to control serum phosphate levels in hemodialysis patients. The administration of MgCO(3) in combination with a low dialysate Mg concentration avoids the risk of severe hypermagnesemia.\nStudy10: Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermined secondary end point of a randomized clinical trial designed to assess progression of coronary artery calcium (CAC) scores in the two treatment arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects randomized to calcium-containing phosphate binders and 11 in subjects randomized to sevelamer. Baseline CAC score was a significant predictor of mortality after adjustment for age, race, gender, and diabetes with increased mortality proportional to baseline score (P=0.002). Mortality was borderline significantly lower in subjects randomized to sevelamer (5.3/100 patient years, confidence interval (CI) (2.2-8.5) compared to those randomized to calcium-containing binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality. Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders.\n",
            "output": "Conclusions: Available phosphate-binding agents have been shown to reduce phosphorus levels in comparison to placebo. However, there are insufficient data to establish the comparative superiority of novel non-calcium binding agents over calcium-containing phosphate binders for patient-level outcomes such as all-cause mortality and cardiovascular end-points in CKD."
        },
        {
            "input": "Study1: Transcutaneous electrical nerve stimulation in rheumatoid arthritis. The therapeutic effect of once weekly transcutaneous electrical nerve stimulation in patients with rheumatoid arthritis was compared with placebo in a randomised, double-blind, non-crossover study lasting three weeks. Thirty-two patients with classic or definite rheumatoid arthritis and wrist involvement were evaluated. Transcutaneous electrical nerve stimulation was better than the placebo in relieving pain at rest and while gripping. In addition, grip strength, measured as power and work done, immediately improved following transcutaneous electrical nerve stimulation but returned almost to initial values between assessments. No significant improvement was shown for the placebo group.\nStudy2: Optimal stimulation duration of tens in the management of osteoarthritic knee pain. This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation (TENS) for relieving osteoarthritic knee pain and the duration (as measured by half-life) of post-stimulation analgesia.                 Thirty-eight patients received either: (i) 20 minutes (TENS20); (ii) 40 minutes (TENS40); (iii) 60 minutes (TENS60) of TENS; or (iv) 60 minutes of placebo TENS (TENS(PL)) 5 days a week for 2 weeks.                 A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation.                 By Day10, a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 (83.40%) and TENS60 (68.37%) groups than in the TENS20 (54.59%) and TENS(PL) (6.14%) groups (p < 0.000), such a group difference was maintained in the 2-week follow-up session (p < 0.000). In terms of the duration of post-stimulation analgesia period, the duration for the TENS40 (256 minutes) and TENS60 (258 minutes) groups was more prolonged than in the other 2 groups (TENS20 = 168 minutes, TENS(PL) = 35 minutes) by Day10 (p < 0.000). However, the TENS40 group produced the longest pain relief period by the follow-up session.                 40 minutes is the optimal treatment duration of TENS, in terms of both the magnitude (VAS scores) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis.\nStudy3: TNS and osteo-arthritic pain. Preliminary study to establish a controlled method of assessing transcutaneous nerve stimulation as a treatment for the pain caused by osteo-arthritis of the knee. nan\nStudy4: Transcutaneous nerve stimulation in a group of patients with rheumatic disease involving the temporomandibular joint. The effect of transcutaneous nerve stimulation (TNS) was evaluated and compared with placebo TNS in 19 patients (17 women, mean age 33 years) with orofacial functional pain and rheumatic disease involving the temporomandibular joint. In two double-blind noncrossover experiments, high frequency TNS (100 Hz) and low frequency TNS (2 Hz) were evaluated by comparison of the patients' functional and rest pain, muscle and joint tenderness, and jaw function. A significant treatment effect was obtained for all treatment methods regarding functional and rest pain and muscle and joint tenderness. None of the parameters except functional pain, which improved significantly more after high frequency TNS than placebo TNS, revealed any difference between the methods. Jaw function, however, revealed a few differences between high frequency TNS and placebo TNS.\nStudy5: Transcutaneous electrical nerve stimulation in osteoarthrosis: a therapeutic alternative? Thirty patients with chronic pain due to osteoarthrosis (OA) of the knee were enrolled in a randomised double-blind cross-over trial of self-administered transcutaneous electrical nerve stimulation (TENS) and placebo TENS. Medication was standardised to paracetamol tablets only. As measured on visual analogue scales for pain relief 46% of patients responded to active therapy and 43% to placebo. The length of pain relief during active therapy was significantly longer than that during placebo. At the end of the trial more patients wanted to continue using active TENS in preference to placebo or their original medication. Although most of the parameters observed favoured active TENS, it was not possible to establish its clear superiority over placebo, because the response rate to placebo TENS was high and sustained for at least 3 weeks. This trial suggests that a longer study is required to establish the role of TENS as a therapeutic agent in the treatment of the pain of chronic arthritis.\nStudy6: A pilot investigation of the hypoalgesic effects of transcutaneous electrical nerve stimulation upon low back pain in people with multiple sclerosis. To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) upon low back pain (LBP) in people with multiple sclerosis (MS).                 A randomized double-blind placebo controlled clinical pilot study.                 Fifteen people with MS were recruited and randomly allocated to one of the following groups under double blind conditions (n = 5 per group): TENS 1 (4 Hz, 200 micros), TENS 2 (110 Hz, 200 micros), placebo TENS.                 Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up.                 The following outcome measures were taken at weeks 1, 6, and 10: visual analogue scale (VAS) (for current LBP, right leg pain, left leg pain); Leeds Multiple Sclerosis Quality of Life Questionnaire; Roland Morris Disability Questionnaire; Short Form-36 (SF-36) Version 1; and the McGill Pain Questionnaire (MPQ). VAS for current LBP, right and left leg pain were also taken before and after treatment, and once a week during the follow-up period.                 Analysis showed no statistically significant effects for any of the data. However, both active treatment groups showed a trend of improvement in the majority of the outcome measures.                 Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant. Further work in this area is warranted and should include a larger number of participants in the form of a randomized controlled clinical trial to determine the efficacy of this modality.\nStudy7: Comparative effectiveness of different stimulation modes in relieving pain. Part I. A pilot study. In this pilot study, to assess the optimal stimulation parameters, 3 different forms of transcutaneous electrical nerve stimulation were performed in 27 patients. Conventional continuous stimulation with a constant frequency of 70 Hz, burst stimulation (90 msec trains of pulses with an internal frequency of 100 Hz repeated at 2 Hz, each train consisting of 10 pulses), and frequency-modulated stimulation (continuous pulses changed from 90 Hz to 55 Hz over 90 msec) were randomly delivered to the patients for half an hour in 3 separate sessions. The patients were blind to the modes of stimulation. This pilot study demonstrated that patients preferred modulated stimulation modes such as frequency modulation and burst rather than conventional constant mode.\nStudy8: Transcutaneous electrical nerve stimulation (TNS) for painful osteoarthrosis of the knee. nan\nStudy9: Outcome of transcutaneous electrical nerve stimulation in chronic pain: short-term results of a double-blind, randomised, placebo-controlled trial. The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation (TENS) treatment in chronic pain with respect to pain intensity and patients' satisfaction with treatment results. We therefore performed a randomised controlled trial comparing TENS and sham TENS. Patients, researchers and therapists were blinded for treatment allocation. One hundred and sixty-three patients with chronic pain referred to the Pain Centre entered the study. Conventional TENS and sham TENS were applied in the segments of pain, for a period of ten days. Outcome measures were pain intensity (visual analogue scale) and patients' satisfaction with treatment result (yes or no). The proportions of patients satisfied with treatment result differed significantly for TENS compared to sham TENS (58 and 42.7% respectively, chi(2)=3.8, p=0.05). However, no differences in pain intensity were found for patients treated with TENS or sham TENS. Only for patients satisfied with treatment results pain intensity gradually decrease equally both for TENS and sham TENS with repeated treatment application.\nStudy10: Pain reducing effect of three types of transcutaneous electrical nerve stimulation in patients with chronic pain: a randomized crossover trial. Transcutaneous electrical nerve stimulation (TENS) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive. Several types of TENS, based on different combinations of frequency, pulse duration and intensity, exist. The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear. To compare the effectiveness of three types of TENS we conducted a randomized, single blinded crossover trial. Patients received two times a 2-week period of daily TENS treatment, separated by a washout period of 2 weeks. In total, 180 chronic pain patients were randomized into three groups. In group 1, high frequency, low intensity TENS (HFT) was compared with high frequency, high intensity TENS (HIT). In groups 2 and 3, HFT and HIT were compared with a control TENS (COT). The order of applying the different modalities of TENS in each group was also randomized. Primary outcome was the patient's overall assessment of effectiveness and pain reduction (VAS). No differences were found in patient's assessment or pain reducing effect between the three groups, indicating no superiority of one type of TENS. In total, 56% continued TENS after the 2-week treatment period. At 6 months, 42% of all patients still used TENS. We concluded that there were no differences in effectiveness for the three types of TENS used in this study. Because no placebo group was included, no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made.\n",
            "output": "Conclusions: Since the last version of this review, new relevant studies have not provided additional information to change the conclusions. Published literature on the subject lacks the methodological rigour or robust reporting needed to make confident assessments of the role of TENS in chronic pain management. Large multi-centre RCTs of TENS in chronic pain are still needed."
        },
        {
            "input": "Study: Performance-based physician reimbursement and influenza immunization rates in the elderly. The Primary-Care Physicians of Monroe County. To investigate the effect of performance-based financial incentives on the influenza immunization rate in primary care physicians' offices.                 Randomized controlled trial during the 1991 influenza immunization season.                 Rochester, New York, and surrounding Monroe County during the Medicare Influenza Vaccine Demonstration Project.                 A total of 54 solo or group practices that had participated in the 1990 Medicare Demonstration Project.                 All physicians in participating practices agreed to enumerate their ambulatory patients aged 65 or older who had been seen during the 1990 or 1991 calendar years, and to track the immunization rate on a weekly basis using a specially designed poster from September 1991 to January 1, 1992. Additionally, physicians agreed to be randomized, by practice group, to the control group or to the incentive group, which could receive an additional $.80 per shot or $1.60 per shot if an immunization rate of 70% or 85%, respectively, was attained.                 The main outcome measures are the 1991 immunization rate and the improvement in immunization rate from the 1990 to 1991 influenza seasons for each group practice.                 For practices in the incentive group, the mean immunization rate was 68.6% (SD 16.6%) compared with 62.7% (SD 18.0%) in the control group practices (P = .22). The median practice-specific improvement in immunization rate was +10.3% in the incentive group compared with +3.5% in the control group (P = .03).                 Despite high background immunization rates, this modest financial incentive was responsible for approximately 7% increase in immunization rate among the ambulatory elderly.\n",
            "output": "Conclusions: The evidence from the studies identified in this review is not of sufficient quality or power to obtain a clear answer to the question as to whether target payment remuneration provides a method of improving primary health care. Additional efforts should be directed in evaluating changes in physicians' remuneration systems. Although it would not be difficult to design a randomised controlled trial to evaluate the impact of such payment systems, it would be difficult politically to conduct such trials."
        },
        {
            "input": "Study1: Primary repair of colon injuries: a prospective randomized study. Due to the results of a 6-year experience with civilian penetrating colon injuries at Mount Carmel/Grace Hospital, in Detroit, Michigan, which had favored primary repair of colon injuries, a prospective randomized study was performed. Seventy-one patients with penetrating colon injuries were entered in a prospective randomized study. Forty-three patients were treated with primary repair or resection and anastomosis, and 28 patients were treated with diversion. The average Penetrating Abdominal Trauma Index score was 25.5 for the primary repair and 23.4 for the diversion groups. The majority of injuries as assessed by the Colon Injury Score (CIS) for the primary repair group were grades 2 (58%) and 3 (28%). The diversion group predominantly had grades 2 (64%) and 3 (25%). There was no significant difference between the two groups. There were 8 (19%) patients with colon and noncolon-related complications in the primary repair group, and 10 (36%) patients with colon, noncolon, and colostomy-related complications in the diversion group. In addition, there were 2 (7%) patients with complications following colostomy reversal. Independent risk factors for adverse outcomes were compared and used to calculate the probability for adverse outcomes with respect to the mode of treatment. The probability for adverse outcomes was statistically greater in the diversion group. An analysis was also made within the primary repair group comparing the subgroups of primary repair with, and without, resection of colon. It appears that the primary repair with resection of colon may have fewer complications; however, this conclusion is based on a statistically insufficient sample size. The authors contend that primary repair or resection with anastomosis is the method of choice for treatment of all penetrating colon injuries in the civilian population despite any associated risk factors for adverse outcomes.\nStudy2: Randomized clinical trial to determine if delay from time of penetrating colonic injury precludes primary repair. There is often a delay of more than 12 h in transferring patients with penetrating colonic injury from outlying hospitals to a regional referral centre. The aim of this prospective study was to determine whether primary suture of a penetrating colonic injury in the presence of delayed presentation, shock, peritoneal contamination or associated injuries leads to increased morbidity and mortality rates.                 Patients with penetrating colonic injuries were randomized to primary closure or colostomy. Patients were compared with regard to interval from injury to operation, associated injuries, duration of operation, postoperative complications and hospital stay.                 Two hundred and forty patients were seen over a 69-month period. The interval from injury to operation ranged from 3 to 56 h, and was similar in the two treatment groups. Postoperative complications were similar in the two groups but there were significant differences in operation time (mean(s.d.) 127.1(45.8) min for primary repair and 142.3(43.0) min for colostomy; P = 0.009) and length of hospital stay (mean (range) 9 (6-56) versus 26 (13-64) days respectively; P < 0.001).                 Delay from time of penetrating colonic injury is not a contraindication to primary repair. :\nStudy3: Colorectal trauma: primary repair or anastomosis with intracolonic bypass vs. ostomy. This prospective, randomized, controlled study was undertaken to compare primary repair or anastomosis with intracolonic bypass vs. ostomy in severe colon and intraperitoneal rectal injury. Patients were randomized at surgery following confirmation of injury. Data collected included demographics, mechanism and location of injury, trauma score (TS), injury severity score (ISS), penetrating abdominal trauma index (PATI), complications, length of hospital stay, and hospital charges. Twenty-two patients were studied: 11 with intracolonic bypass and 11 controls. The experimental and control groups were statistically similar in demographics and mechanism of injury, severity of injury (TS = 13.8 vs. 12.8; ISS = 27.5 vs. 24.2; PATI = 40.5 vs. 35.0), and complication rate. Length of stay (12.2 days vs. 20.7 days) and charges $27,885 vs. $53,599) tended to be greater in controls, and the comparison did not include subsequent colostomy closure. This study supports intracolonic bypass as a safe alternative to ostomy in severe colon and intraperitoneal rectal trauma.\nStudy4: Management of penetrating colon injuries. A prospective randomized trial. Fifty-six patients with penetrating colon injuries were entered into a randomized prospective study. Management of the colon injury was not dependent on the number of associated injuries, amount of fecal contamination, shock, or blood requirements. Twenty-eight patients were treated with primary repair or resection and anastomosis and 28 patients were treated by diversion (24 colostomy, 3 ileostomy, 1 jejunostomy). The average Penetrating Abdominal Trauma Index score was 23.9 for the diversion group and 26 for the primary repair group. There were five (17.9%) septic-related complications in the diversion group. This included four intra-abdominal abscesses and one subcutaneous wound infection. There were six (21.4%) septic-related complications in the primary repair group. This included one wound infection, two positive blood cultures, and three intra-abdominal abscesses. There were no episodes of suture line failure in the primary repair/anastomosis group. The authors conclude that, independent of associated risk factors, primary repair or resection and anastomosis should be considered for treatment of all patients in the civilian population with penetrating colon wounds.\n",
            "output": "Conclusions: Meta-analysis of currently published randomized controlled trials favors primary repair over fecal diversion for penetrating colon injuries."
        },
        {
            "input": "Study1: Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.\nStudy2: The value of preoperative radiotherapy in esophageal cancer: results of a study by the EORTC. nan\nStudy3: Preoperative radiotherapy for carcinoma of the esophagus. From 21 March to 22 June 1976, 124 patients with squamous cell carcinoma of the esophagus were randomized for inclusion in a prospective trial of preoperative irradiation. Fifteen patients were excluded because of inoperability. Sixty-seven patients were randomly selected to receive 4,000 rads of cobalt radiation for eight days prior to operation; 57 patients were operated upon without receiving radiation therapy. No significant differences were noted between the two groups with regard to age, sex, tumor site, experience of the surgeon, method of approach or surgical technique. Eight esophageal resections were performed upon 47 of the 62 irradiated patients and 33 of the 47 nonirradiated patients. Of the 62 irradiated patients, 14 died during operation, compared with 11 of the 47 nonirradiated patients, the difference between the two groups not being statistically significant. Irradiation was associated with a higher mortality for lesions in the mid third part of the esophagus, 11 of 29 versus four of 19, but again, the difference was not significant. In the irradiated patients, the five year actuarial postoperative survival rate was 9.5 versus 11.5 per cent for the nonirradiated patients. In conclusion, preoperative radiation therapy does not produce a statistically significant short term or long term benefit in the management of squamous cell carcinoma of the esophagus.\nStudy4: Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of esophageal carcinoma: report on 206 patients. From June 1977 to May 1985, a prospective randomized clinical trial on pre-operative radiation for esophageal carcinoma was carried out in 206 patients. Lesions under 8 cm in length and patients younger than 65 years, at least on semi-liquid diet and not contra-indicated for surgery were randomized into a combined group (104 patients) or a surgery alone group (102 patients). Eight MV X ray units were used for the pre-operative radiation using A-P portals to deliver 4,000 cGy to the whole mediastinum and the left gastroepiploic lymphatic chain. Surgery was carried out after 2 to 4 week's rest. The immediate results of the combined group and the surgery alone group were: resection rate 93% and 85%, operative mortality 5% and 6%, intra-thoracic anastomotic leak 0% and 1%, positive pathology at the esophageal stump 0% and 2%, and lymph nodes metastasis 27% and 35% respectively. The 5-year survival rates of the combined group and the surgery alone group were 35% and 30%. We have noticed that those patients with lesions showing radiation reaction of grade III gave a 5-year survival of 50% (12/24). Because intra- and extra-thoracic lymphnode metastasis caused failures (41% and 34% of these two groups), increasing the preoperative tumor dose to 60 Gy or designing post-operative irradiation to cover the bilateral supraclavicular areas was necessary. The whole mediastinum and the left gastroepiploic lymphatics could further improve the results of surgery. Further studies are needed.\n",
            "output": "Conclusions: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%)."
        },
        {
            "input": "Study1: Sublingual misoprostol 100 microgram versus 200 microgram for second trimester abortion: a randomised trial. To compare the efficacy of repeated doses of 100 microg vs. 200 microg misoprostol given sublingually for induction of second trimester abortion.                 One hundred and sixty-two women at 15-22 weeks' gestation were randomized to receive every 2 h either 100 microg (group 1; n = 81) or 200 microg (group 2; n = 81) misoprostol sublingually. The primary outcome measure was the abortion rate within 24 h. The secondary outcome measures were the induction-abortion interval, the total misoprostol dose required, and side effects of the regimen.                 There was no significant difference between the two groups with regard to the abortion rates within 12 h (43.2% in group 1 vs. 48.1% in group 2; p = 0.52; relative risk [RR]: 0.81; 95% confidence interval [CI]: 0.4-1.5) and 24 h (92.6% in group 1 vs. 91.4% in group 2; p = 0.77; RR: 1.11; 95% CI: 0.37-3.6). The induction-abortion intervals in the two groups were of similar length (885 minutes in group 1 vs. 912 minutes in group 2; p = 0.72). When the total dose of misoprostol was compared between the two groups, women belonging to group 2 on average had received significantly more misoprostol than those in group 1 (1274 +/- 592 microg [7 +/- 3 doses] vs. 614 +/- 432 microg [6 +/- 4 doses], respectively; p = 0.000).                 Sublingual administration of repeated doses of 100 microg misoprostol for abortion induction appears to be equally effective to that of repeated doses of 200 microg.\nStudy2: A comparison of misoprostol with and without laminaria tents for induction of second-trimester abortion. Our purpose was to determine whether intracervical placement of laminaria tents would improve the effectiveness of the prostaglandin analog misoprostol for the elective termination of pregnancies in the second trimester.                 Sixty-eight women between 12 and 22 weeks of gestation with either an intrauterine fetal death (n = 40) or medical or genetic indications for pregnancy termination (n = 30) were randomized to receive 200 micrograms of misoprostol administered vaginally every 12 hours with or without intracervical placement of laminaria concurrently with the first dose of misoprostol.                 The rate of abortion 24 hours after initiation of treatment was 69.7% in the 33 women receiving misoprostol alone and 68.6% in the 35 women treated with misoprostol and laminaria. The abortion rates 48 hours after initiation of treatment were 84.8% and 91.4%, respectively, an insignificant difference. The complete abortion rate was also similar between women receiving misoprostol alone (39.3%) and the group receiving misoprostol and laminaria (37.5%). There were no significant differences in the incidence of fever, vomiting, diarrhea, or pain. The mean interval from initiation of treatment to abortion was also similar, 15.7 hours in those receiving misoprostol alone and 17.4 hours in those treated with misoprostol and laminaria. In both groups women who had live fetuses at the start of the procedure had a higher failure rate of abortion and a longer time interval to abortion than women whose fetus was dead.                 Laminaria tents inserted concurrently with the first dose of misoprostol do not significantly improve the abortifacient effect of vaginal misoprostol in the second trimester of pregnancy.\nStudy3: Second-trimester termination of pregnancy by extra-amniotic prostaglandin F2alpha or endocervical misoprostol. A comparative study. To compare the efficacy and side effects of extra-amniotic prostaglandin F2alpha with intracervical misoprostol for midtrimester termination of pregnancy                 Forty women were randomized to receive either intracervical misoprostol or extra-amniotic prostaglandin F2alpha for termination of pregnancy for congenital abnormalities or intrauterine fetal death. Induction-abortion interval and the incidence of side effects were analyzed for both groups.                 All women in the PGF2alpha group; aborted within 28 hours, 16 (80%) of which aborted within 20 hours. Medical termination of pregnancy was complete in 13 cases (65%). In the misoprostol group; all women aborted within 20 hours, 18 (90%) of which aborted within 13 hours. Medical termination of pregnancy was complete in 17 cases (85%). The induction to abortion intervals for the extra-amniotic PGF2alpha and intracervical misoprostol were 16+/-5.9 hours, and 10.3+/-4 hours (mean+/-s.d.) respectively. This was statistically significant (p=0.001). The incidence of prostaglandin-associated pyrexia, vomiting and diarrhea were significantly increased in the PGF2alpha group (p<0.05). Abdominal pain was similar in both groups. There was no post-abortive hemorrhage or infection.                 Misoprostol is an effective, easy to use, safe and cheap drug for termination of second trimester pregnancy. Intracervical administration of misoprostol appears to be effective and well-tolerated with less side effects and no complications. Larger, randomized comparative studies should be carried out to assess its potential advantages.\nStudy4: Oral misoprostol vs. vaginal misoprostol for termination of pregnancy with intrauterine fetal demise in the second-trimester. nan\nStudy5: Vaginal misoprostol versus concentrated oxytocin and vaginal PGE2 for second-trimester labor induction. To compare the efficacy, side effects, and complications of high-dose vaginal misoprostol with concentrated intravenous oxytocin plus low-dose vaginal prostaglandin (PGE(2)) for second-trimester labor induction.                 One hundred twenty-six consenting women with maternal or fetal indications for pregnancy termination and no prior cesarean delivery were randomly assigned to receive either vaginal misoprostol 600 microg 1x, 400 microg every 4 hours 5x (misoprostol group, n = 60) or escalating-dose concentrated oxytocin infusions (277-1,667 mU/min) plus vaginal PGE(2) 10 mg every 6 hours 4x (oxytocin group, n = 66). Both groups received concurrent extra-amniotic saline infusion for cervical ripening. Women who failed their assigned regimen received 20 mg of PGE(2) suppositories every 4 hours until delivery. Analysis was by intent to treat.                 Demographic characteristics were similar between study groups. Median induction-to-delivery interval was significantly shorter in the misoprostol group (12 hours) than in the oxytocin group (17 hours; P <.001). There was a higher induction success rate at 24 hours in the misoprostol group (95%) than in the oxytocin group (85%; P =.06), although this difference did not reach statistical significance. The incidence of live birth (25% versus 17%), chorioamnionitis (5% versus 2%), and postpartum hemorrhage greater than 500 mL (3% versus 3%) were similar between the misoprostol and oxytocin groups, respectively. Diarrhea (2% versus 11%; P =.04), nausea/emesis (25% versus 42%; P =.04), and retained placenta requiring curettage (2% versus 15%; P =.008) were significantly less common in the misoprostol group when compared with the oxytocin group, respectively. Isolated intrapartum fever, however, was more frequent in the misoprostol group (67%) than in the oxytocin group (21%; P <.001).                 Compared with concentrated oxytocin plus low-dose vaginal PGE(2), high-dose vaginal misoprostol is associated with significantly shorter induction-to-delivery intervals, fewer side effects, a lower incidence of retained placenta, and comparable incidence of live birth.\nStudy6: Vaginal versus oral misoprostol for second-trimester pregnancy termination: a randomized trial. The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination. Sixty women in second trimester of gestation with indications for pregnancy termination were randomly assigned in two equal groups to receive either vaginal or oral misoprostol. The dosing regimen was 400 microg as the initial dose followed by 400 microg up to 3 doses (1200 microg) if needed in each group. Efficacy and side effects were compared. The percentage of women who delivered was significantly higher in vaginal group than the oral group (86.7 vs. 43.3 p = 0.0006). No significant differences in complication rates and induction to delivery interval were noted between the two groups. Vaginal administration of misoprostol resulted in a higher success rate for second trimester pregnancy termination, whereas, no significant differences in induction to delivery time and complication rates were noted between vaginal and oral groups.\nStudy7: A comparison between two doses of intravaginal misoprostol and gemeprost for induction of second-trimester abortion. To compare the abortifacient efficacies of two intravaginally administered misoprostol doses and gemeprost in termination of second-trimester pregnancy.                 Eighty-one women between 12 and 24 weeks' gestation requesting abortion were randomized to receive intravaginally either 100 micrograms of misoprostol at 6-hour intervals (n = 27), 200 micrograms of misoprostol at 12-hour intervals (n = 26), or 1.0 mg of gemeprost at 3-hour intervals (n = 28). The regimen was continued until abortion, or for 36 hours, with assessment of the rate of complete and incomplete abortions as well as side effects within 48 hours from the start of the treatment.                 The final rates of terminations were 74% in the 100-microgram misoprostol group, 92% in the 200-microgram misoprostol group, and 89% in the gemeprost group. Abortion was complete in 37%, 61%, and 32% in each group, respectively (P = .03, when the 200-microgram misoprostol group was compared with the two other groups). The induction-to-abortion interval was longer (P = .001) in the misoprostol groups (mean 23.1 hours for the 100-microgram and 27.8 hours for the 200-microgram dose) than in the gemeprost group (14.5 hours). There was less pain (P = .01), diarrhea (P = .001), and vomiting (P = .01) in the misoprostol groups than in the gemeprost group. The mean blood loss in the misoprostol groups was lower than in the gemeprost group (P = .001).                 Intravaginal application of 200 micrograms of misoprostol at 12-hour intervals in induction of second-trimester abortion is equally effective to a standard gemeprost regimen. Misoprostol causes fewer side effects and is cheaper and more practical to use.\nStudy8: A randomized controlled trial comparing two protocols for the use of misoprostol in midtrimester pregnancy termination. Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy.                 Women seen for midtrimester pregnancy termination were randomly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours. The protocol was followed for 24 hours, after which time further management was at the discretion of the attending physician. The primary outcome measure was the induction-to-delivery interval. Sample size was calculated a priori. Statistical analysis was performed with the t test for continuous variables and the chi(2) test for categorical variables. P <.05 was considered significant.                 One hundred fourteen women were randomized, with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol. The two groups were comparable with respect to maternal age, parity, indication for pregnancy termination, gestational age, and maternal weight. The mean induction-to-delivery interval was significantly shorter for the vaginal group (19.6 +/- 17.5 hours vs 34.5 +/- 28.2 hours, P <.01). Length of stay was also shorter in the vaginal group (32.3 +/- 17.3 hours vs 50.9 +/- 27.9 hours, P <.01). Significantly more patients in the vaginal group were delivered within 24 hours (85.1% vs 39.5%, P <.01), and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours (38.2% vs 7%, P <.01). The only complication was an increase in febrile morbidity in the vaginal group (25% vs 6.7%, P =.046). This did not result in an increased use of antibiotics, and all the fevers resolved post partum without further complications.                 Vaginal administration of misoprostol resulted in a shorter induction-to-delivery interval. The shorter length of stay should result in improved patient care.\nStudy9: A comparison of oral misoprostol with vaginal misoprostol administration in second-trimester pregnancy termination for fetal abnormality. To compare the clinical efficacy and side effects of oral misoprostol with vaginal misoprostol for second-trimester pregnancy termination.                 A randomized clinical trial of medical pregnancy termination between 14 and 26 weeks' gestation was conducted. Three misoprostol regimens were compared: 400 microg vaginally at 6-hour intervals (group 1), 400 microg orally at 3-hour intervals (group 2), and a loading dose of 600 microg vaginally followed by 200 microg orally at 3-hour intervals (group 3). A sample size of 225 women was required for equivalence of the three regimens, with an interim safety analysis planned at 80 women.                 A significant difference between the groups was evident at the interim safety analysis and the study ceased. The subset of 84 women recruited before the study closure is described. There was a significant difference in the median time to achieve delivery among the three groups: group 1, 14.5 hours (95% confidence interval 12.0, 16.9), versus group 2, 25.5 hours (13.5, 23.8), versus group 3, 16.4 hours (interquartile range 14.2-37.3) (P =.042). Within 24 hours of commencement 85.7% of women in group 1, 44.8% in group 2, and 74.1% in group 3 delivered (P =.003). At 48 hours 0% in group 1, 20.7% in group 2, and 3.7% in group 3 were undelivered (P =.011). There was no difference in women's perceptions of the termination process.                 In second-trimester pregnancy termination, a vaginal misoprostol regimen of 400 microg every 6 hours was 1.9 times more likely to result in delivery within 24 hours from commencement than an oral regimen of 400 microg every 3 hours.\nStudy10: [Tocographic pattern induced by misoprostol]. nan\n",
            "output": "Conclusions: The use of vaginal misoprostol in the termination of second and third trimester of pregnancy is as effective as other prostaglandin preparations (including cervagem, prostaglandin E2 and prostaglandin F2alpha), and more effective than oral administration of misoprostol. However, important information regarding maternal safety, and in particular the occurrence of rare outcomes such as uterine rupture, remains limited. Future research efforts should be directed towards determining the optimal dose and frequency of administration, with particular attention to standardised reporting of all relevant outcomes and assessment of rare adverse events. Further information is required about the use of sublingual misoprostol in this setting."
        },
        {
            "input": "Study1: [Does low intensity, pulsed ultrasound speed healing of scaphoid fractures?]. Since pulsed low-intensity ultrasound (frequency: 1.5 MHz, pulsed by 1 kHz, signal burst width: 200 microseconds, intensity: 30 mW/cm2) has been proven to stimulate fracture healing both clinically and experimentally, our question was whether this therapy also accelerates healing of fresh stable scaphoid fractures. Addressing this question, we did the following prospective randomized clinical trial. Regarding the results of former clinical fresh fracture studies by Heckman and Kristiansen, we postulated that low intensity ultrasound accelerates healing by about 30%. Based on this thesis, we calculated that 30 patients divided into two groups would be necessary to show significant differences between the standard treatment (treated by casting) and an adjunctive ultrasound treatment (treated by casting and additional daily 20 minutes ultrasound treatment) if present. Diagnosis and healing was assessed by CT scans every two weeks. CT's were analyzed by two independent radiologists and one hand surgeon. Furthermore, areas of cancellous bone bridging in correlation to the diameter of the scaphoid was measured in each CT scan. The results showed ultrasounded fractures healing in 43.2 +/- 10.9 days versus 62 +/- 19.2 days in the control group (p < 0.01). Trabecular bridging six weeks after injury showed 81.2% +/- 10.4% healed in the ultrasound-stimulated fractures versus 54.6% +/- 29% in the control (p < 0.05). Our study results confirm those of Heckman and Kristiansen and show a similar acceleration of bone healing. Low intensity ultrasound is successful in accelerating the healing of fresh scaphoid fractures.\nStudy2: Effect of ultrasound therapy on bone healing of lateral malleolar fractures of the ankle joint fixed with bioabsorbable screws. We investigated the effect of low-intensity ultrasound on bone healing in bioabsorbable self-reinforced poly-L: -lactic acid (SR-PLLA) screw-fixed lateral malleolar fractures. The study design was prospective, randomized, double-blind, and placebo-controlled.                 A total of 22 fractures were fixed with one SR-PLLA screw. All the patients were instructed to use an ultrasound device 20 min daily for 42 days without knowing whether it was active or inactive. Eleven patients had active and eleven sham ultrasound devices. The causes of error during treatment with head module placement and attachment to the convex surface of the lateral distal fibula were minimized by careful targeting and using coupling gel. Radiological fracture healing was assessed by radiographs and multidetector computed tomography (CT) scans in a blinded manner by a radiologist and orthopedic surgeons.                 The overall compliance to the daily ultrasound treatments was good. All wounds healed uneventfully, and no foreign body reactions were observed. No difference was observed between the groups regarding either fracture line visualization or callus formation assessed by plain radiographs. In the CT images at 9 weeks, the share of the endosteal united fracture line compared to the non-united fracture line was slightly higher in the active ultrasound device group than in the sham ultrasound device group, but the difference was not statistically significant.                 The study indicates that the biocompatibility of ultrasound therapy and bioabsorbable SR-PLLA screw fixation is good. There was no obvious effect of low-intensity ultrasound on lateral malleolar fracture healing. However, the relatively small number of patients must be kept in mind when interpreting our results. It is also important to limit any conclusions based on the present study to malleolar fractures fixed with the SR-PLLA screw.\nStudy3: Low-intensity pulsed ultrasound (LIPUS) in fresh clavicle fractures: a multi-centre double blind randomised controlled trial. Several randomised trials have been published on the effect of low-intensity pulsed ultrasound (LIPUS) on fracture healing in both distal radius and tibia fractures. Most studies showed a positive effect on time to clinical and radiological healing. We hypothesised that LIPUS has a beneficial effect on the healing of fresh clavicle fractures as well and studied its effect in non-operatively treated shaft fractures.                 We conducted a randomised double blind, placebo-controlled multi-centre trial in 101 adult patients with a non-operatively treated fresh clavicle shaft fracture. Of these patients, 49 used a placebo transducer and 52 patients had an active transducer with ultrasound stimulation (Exogen 2000). Data were analysed on intention to treat basis. Baseline parameters of both groups were not significantly different.                 There were no differences in time to subjective clinical fracture healing, resumption of daily activities, sports or professional work, Visual Analogue pain Scores (VAS) and use of pain medication.                 Our findings did not confirm that LIPUS accelerates clinical healing time of fresh clavicle shaft fractures.                 Level 1 evidence that low-intensity pulsed ultrasound does not accelerate clinical fracture healing in non-operatively treated fresh midshaft clavicle fractures.\nStudy4: Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound. Sixty-seven closed or grade-I open fractures of the tibial shaft were examined in a prospective, randomized, double-blind evaluation of use of a new ultrasound stimulating device as an adjunct to conventional treatment with a cast. Thirty-three fractures were treated with the active device and thirty-four, with a placebo control device. At the end of the treatment, there was a statistically significant decrease in the time to clinical healing (86 +/- 5.8 days in the active-treatment group compared with 114 +/- 10.4 days in the control group) (p = 0.01) and also a significant decrease in the time to over-all (clinical and radiographic) healing (96 +/- 4.9 days in the active-treatment group compared with 154 +/- 13.7 days in the control group) (p = 0.0001). The patients' compliance with the use of the device was excellent, and there were no serious complications related to its use. This study confirms earlier animal and clinical studies that demonstrated the efficacy of low-intensity ultrasound stimulation in the acceleration of the normal fracture-repair process.\nStudy5: Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound. A clinical study was conducted to investigate the effect of low-intensity pulsed ultrasound (US) stimulation (LIPUS) on the healing of complex tibial fractures. Thirty complex tibial fractures were randomly assigned to the treatment with LIPUS (n = 16) or by a dummy machine (sham-exposed: n = 14). The fractures were immobilized by either internal or external fixations according to the clinical indications. LIPUS was given 20 min/day for 90 days. Fracture healing was monitored by clinical, radiological, densitometric and biochemical assessments. The LIPUS-treated group showed statistically significantly better healing, as demonstrated by all assessments. Complications were minimal in the LIPUS group. There were two cases of delayed union, with one in each group. There were two cases of infection in the control group. The delayed-union cases were subsequently treated by LIPUS and the infection cases were treated with standard protocol. Fracture healing in these patients was again treated by LIPUS.\nStudy6: The effect of pulsed ultrasound in the treatment of tibial stress fractures. Tibial stress fractures commonly occur in athletes and military recruits. This prospective, randomized, double-blind clinical study sought to determine whether pulsed ultrasound reduces tibial stress fracture healing time. Twenty-six midshipmen (43 tibial stress fractures) were randomized to pulsed ultrasound or placebo treatment. Twenty-minute daily treatments continued until patients were asymptomatic with signs of healing on plain radiographs. The groups were not significantly different in demographics, delay from symptom onset to diagnosis, missed treatment days, total number of treatments, or time to return to duty. Pulsed ultrasound did not significantly reduce the healing time for tibial stress fractures.\nStudy7: Accelerated healing of distal radial fractures with the use of specific, low-intensity ultrasound. A multicenter, prospective, randomized, double-blind, placebo-controlled study. A multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to test the efficacy of a specifically programmed, low-intensity, non-thermal, pulsed ultrasound medical device for shortening the time to radiographic healing of dorsally angulated fractures (negative volar angulation) of the distal aspect of the radius that had been treated with manipulation and a cast. Sixty patients (sixty-one fractures) were enrolled in the study within seven days after the fracture. The patients used either an active ultrasound device (thirty fractures) or a placebo device (thirty-one fractures) daily for twenty minutes at home for ten weeks. The two types of devices were identical except that the placebo devices emitted no ultrasound energy. Clinical examination was performed and radiographs were made at one, two, three, four, five, six, eight, ten, twelve, and sixteen weeks after the fracture by each site investigator. The time to union was significantly shorter for the fractures that were treated with ultrasound than it was for those that were treated with the placebo (mean [and standard error], 61 +/- 3 days compared with 98 +/- 5 days; p < 0.0001). Each radiographic stage of healing also was significantly accelerated in the group that was treated with ultrasound as compared with that treated with the placebo. Compared with treatment with the placebo, treatment with ultrasound was associated with a significantly smaller loss of reduction (20 +/- 6 per cent compared with 43 +/- 8 per cent; p < 0.01), as determined by the degree of volar angulation, as well as with a significant decrease in the mean time until the loss of reduction ceased (12 +/- 4 days compared with 25 +/- 4 days; p < 0.04). We concluded that this specific ultrasound signal accelerates the healing of fractures of the distal radial metaphysis and decreases the loss of reduction during fracture-healing.\nStudy8: No effect of low-intensity ultrasound on healing time of intramedullary fixed tibial fractures. To determine whether stimulation with low-intensity ultrasound will reduce the radiologic healing time of fresh tibial shaft fractures fixed with a reamed and statically locked intramedullary rod.                 Prospective, randomized, double blinded, and placebo controlled.                 Thirty-two adult patients were included, fifteen in the active ultrasound group and seventeen in the placebo group. They all used an ultrasound device twenty minutes daily for seventy-five days without knowing whether it was active or inactive. Standardized radiographs were taken every third week until healing and at six and twelve months. All radiographs were assessed blinded and independently by a radiologist and an orthopaedic surgeon. The codes were not broken until all fractures had healed and all radiographs had been evaluated.                 The time until the first visible callus averaged 40+/-3 days for the active group and 37+/-3 days for the placebo (p=0.44). The healing time, defined as radiologic bridging of three cortices, was on average 155+/-22 days (median 113 days) for the active treatment group and 125+/-11 days (median 112 days) for the placebo group (p=0.76) as assessed by the radiologist and 128+/-13 days for the active group and 114+/-9 days for the placebo group (p=0.40) as evaluated by the orthopaedic surgeon.                 We conclude that low-intensity ultrasound treatment did not shorten healing time in fresh tibial fractures treated with a reamed and statically locked intramedullary nail. Our results are not in accordance with previous findings reporting reduced healing time in nonoperatively treated tibial shaft fractures when subjected to ultrasound.\nStudy9: The effects of extracorporeal shockwave on acute high-energy long bone fractures of the lower extremity. High-energy long bone fractures of the lower extremity are at risk of poor fracture healing and high rate of non-union. Extracorporeal shockwave was shown effective to heal non-union of long bone fracture. However, the effect of shockwave on acute fractures is unknown. The purpose of this study was to investigate the effects of shockwave on acute high-energy fractures of the lower extremity.                 Between January and October 2004, 56 patients with 59 acute high-energy fractures were enrolled in this study. Patients were randomly divided into two groups with 28 patients with 28 fractures in the study group and 28 patients with 31 fractures in the control group. Both groups showed similar age, gender, type of fracture and follow-up time. Patients in the study group received open reduction and internal fixation and shockwave treatment immediately after surgery on odd-numbered days of the week, whereas, patients in the control group received open reduction and internal fixation without shockwave treatment on even-numbered days of the week. Postoperative managements were similarly performed in both groups including crutch walking with non-weight bearing on the affected limb until fracture healing shown on radiographs. The evaluation parameters included clinical assessments of pain score and weight bearing status of the affected leg and serial radiographs at 3, 6 and 12 months. The primary end-point is the rate of non-union at 12 months, and the secondary end point is the rate of fracture healing at 3, 6 and 12 months.                 At 12 months, the rate of non-union was 11% for the study group versus 20% for the control group (P < 0.001). Significantly, better rate of fracture healing was noted in the study group than the control group at 3, 6 and 12 months (P < 0.001).                 Extracorporeal shockwave is effective on promoting fracture healing and decreasing the rate of non-union in acute high-energy fractures of the lower extremity.\n",
            "output": "Conclusions: While a potential benefit of ultrasound for the treatment of acute fractures in adults cannot be ruled out, the currently available evidence from a set of clinically heterogeneous trials is insufficient to support the routine use of this intervention in clinical practice. Future trials should record functional outcomes and follow-up all trial participants."
        },
        {
            "input": "Study: Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial. Our purpose was to determine whether aggressive or expectant management of severe preeclampsia at 28 to 32 weeks is more beneficial to maternal and neonatal outcome.                 Ninety-five eligible patients were randomly assigned to either aggressive (n = 46) or expectant management (n = 49). Aggressive management patients were prepared for delivery, either by cesarean or induction, 48 hours after glucocorticoids were administered. Expectant management patients were managed with bed rest, oral antihypertensives, and intensive antenatal fetal testing.                 At the time of randomization there were no differences between the two groups in mean systolic blood pressure (170 +/- 9.7 vs 172 +/- 9.4 mm Hg), diastolic blood pressure (110 +/- 5.4 vs 112 +/- 4.2 mm Hg), proteinuria (3.0 +/- 2.3 vs 3.6 +/- 2.3 gm per 24 hours), and gestational age (30.4 +/- 1.6 vs 30.7 +/- 1.5 weeks) for the aggressive and expectant management groups. The average latency period in the expectant management group was 15.4 days (range 4 to 36), and this period was not affected by the amount of proteinuria at randomization. There was no eclampsia or perinatal death in either group. The two groups had similar incidences of abruptio placentae (4.1% vs 4.3%) and similar days of postpartum hospital stay. The expectant management group had a significantly higher gestational age at delivery (32.9 +/- 1.5 vs 30.8 +/- 1.7 weeks, p < 0.0001), higher birth weight, lower incidence of admission to the neonatal intensive care unit (76% vs 100%, p = 0.002), lower mean days of hospitalization in the intensive care unit (20.2 +/- 14 vs 36.6 +/- 17.4, p < 0.0001), and lower incidence of neonatal complications.                 Expectant management, with close monitoring of mother and fetus at a perinatal center, reduces neonatal complications and neonatal stay in the newborn intensive care unit.\n",
            "output": "Conclusions: There are insufficient data for any reliable recommendation about which policy of care should be used for women with severe early onset pre-eclampsia. Further large trials are needed.\n[Note: The citation in the awaiting classification section of the review may alter the conclusions of the review once assessed.]"
        },
        {
            "input": "Study1: Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment.                 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797.                 Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05).                 Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.\nStudy2: A clinical retrospective and a double-blind study of betamethasone in severe closed brain injuries [proceedings]. nan\n",
            "output": "Conclusions: In the absence of a meta-analysis, we feel most weight should be placed on the result of the largest trial. The increase in mortality with steroids in this trial suggest that steroids should no longer be routinely used in people with traumatic head injury."
        },
        {
            "input": "Study1: Modified TC for MICA offenders: crime outcomes. The study randomly assigned male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders to either modified therapeutic community (MTC) or mental health (MH) treatment programs. On their release from prison, MICA inmates who completed the prison MTC program could enter the MTC aftercare program. The results, obtained from an intent-to-treat analysis of all study entries, showed that inmates randomized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group. The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes (i.e. any criminal activity, and alcohol or drug related criminal activity) are consistent and significant, and persist after an examination of various threats to validity (e.g. initial motivation, duration of treatment, exposure to risk). This study provides some support for the effectiveness of the prison TC only condition. The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders, although qualified by the possibility that selection bias (i.e. differences in motivation on entry into aftercare) may be operating. Nevertheless, given the available evidence and the need for effective programming for MICA offenders, program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders.                 Copyright 2004 John Wiley & Sons, Ltd.\nStudy2: Drug abuse day treatment: a randomized clinical trial comparing day and residential treatment programs. Clients entering a therapeutic community (TC)-oriented drug treatment program were randomly assigned to day or residential conditions and interviewed at 2 weeks and 6 months after admission. Outcomes included Addiction Severity Index composite scores and summary scores for the Beck Depression Inventory, Symptom Checklist-90-R, and a social support scale. Only clients who remained in treatment for at least 2 weeks were included. The mean age of the sample (N = 261) was 32.9 (SD = 6.7 years) and the mean education level was 12.1 years (SD = 1.9 years); 30% were women. Comparison of outcome scores at 6 months between groups, while controlling for baseline values, indicated greater improvement for residential clients on social problems and psychiatric symptoms. The groups were similar on the 8 remaining outcomes, including measures of alcohol and drug problems. Overall, the level of improvement among day treatment clients was not significantly different from that of residential clients.\nStudy3: Outcomes of homeless mentally ill chemical abusers in community residences and a therapeutic community. The feasibility and effectiveness of treating homeless mentally ill chemical abusers in community residences compared with a therapeutic community were evaluated.                 A total of 694 homeless mentally ill chemical abusers were randomly referred to two community residences or a therapeutic community. All programs were enhanced to treat persons with dual diagnoses. Subjects' attrition, substance use, and psychopathology were measured at two, six, and 12 months.                 Forty-two percent of the 694 referred subjects were admitted to their assigned program and showed up for treatment, and 13 percent completed 12 months or more. Clients retained at both types of program showed reductions in substance use and psychopathology, but reductions were greater at the therapeutic community. Compared with subjects in the community residences, those in the therapeutic community were more likely to be drug free, as measured by urine analysis and self-reports, and showed greater improvement in psychiatric symptoms, as measured by the Center for Epidemiological Studies--Depression Scale and the Brief Psychiatric Rating Scale. Their functioning also improved, as measured by the Global Assessment of Functioning scale.                 Homeless mentally ill chemical abusers who are retained in community-based residential programs, especially in therapeutic communities, can be successfully treated.\nStudy4: The effectiveness of alternative planned durations of residential drug abuse treatment. Randomized controlled trials were conducted at two residential drug abuse treatment facilities to compare programs that differed in planned duration. One trial compared a 6-month and a 12-month therapeutic community program (n = 184), and the second compared a 3-month and a 6-month relapse prevention program (n = 444). Retention rates over comparable time periods differed minimally by planned treatment duration, and the longer programs had lower completion rates. There was no effect in either trial of planned treatment duration on changes in psychosocial variables between admission and exit or on rates or patterns of drug use at follow-up between 2 and 6 months after exit.\nStudy5: The effects of planned duration of residential drug abuse treatment on recovery and HIV risk behavior. This study assessed the effects of planned duration of residential drug abuse treatment on recovery from drug use and on human immunodeficiency virus (HIV) risk behaviors.                 Two concurrent randomized controlled trials of programs differing in planned duration were conducted: 6-month vs 12-month versions of a traditional therapeutic community program, and 3-month vs 6-month versions of a modified therapeutic community incorporating a relapse prevention and health education program. Outcomes, measured at least 16.5 months after admission, included time from admission to first drug use; severity of drug, alcohol, legal, and employment problems; and risky drug injection and sexual behaviors.                 Among 539 clients (86% of those enrolled), there were no significant effects of planned duration of treatment upon Addiction Severity Index scores or HIV risk behavior. In the relapse prevention program, clients randomized to the 6-month program had a longer time to first drug use than those in the 3-month program (hazard ratio = 0.74; 95% confidence interval = 0.58, 0.93). Employment problems at follow-up were significantly less severe among clients treated in the therapeutic community than among those in the relapse prevention program.                 No overall benefit of extending treatment beyond 6 months was found.\nStudy6: Treatment refusal/attrition among adults randomly assigned to programs at a drug treatment campus: The New Jersey Substance Abuse Treatment Campus, Seacaucus, NJ. The New Jersey Substance Abuse Treatment Campus was funded to assess the feasibility of establishing a new model for delivering substance abuse treatment services and to serve as a research laboratory for conducting comparative evaluations of those services. The 350-bed campus was designed to improve treatment effectiveness by providing special services needed by underserved populations, and reduce treatment costs by serving large numbers of clients, centralizing services, and sharing facilities. First-time clients who met preliminary eligibility requirements during phone screening were randomly assigned to therapeutic community and chemical dependency programs. We used data collected on 1,573 adults who were ultimately accepted for admission to analyze treatment refusals and attrition during the 25 days after admission. Only 6.4% of the clients refused admission when informed of their treatment assignment. Planned duration of the residential phase of treatment, gender, and language spoken (English/Spanish) interacted with one another and differentially predicted treatment refusal/attrition. These findings may be useful for understanding treatment refusal and attrition in substance abuse treatment programs.\nStudy7: Comparing the impact of standard and abbreviated treatment in a therapeutic community. Findings from the district of Columbia treatment initiative experiment. This study examines the efficacy of providing Enhanced Abbreviated or Standard Inpatient treatment and Outpatient treatment to drug-abusing clients. The experiment randomly assigned 412 clients to two therapeutic community programs, which differed primarily in planned duration. This study addressed limitations of prior research, as it used random assignment of clients to treatment programs, achieved high follow-up rates and used objective measures of drug use and criminal history. Self-reports and objective measures of criminal activity and substance abuse were collected at pre- and posttreatment interviews. Completing the entire 12-month program (inpatient and outpatient) was more important than duration of inpatient program attended. Regardless of program, completers had substantial reductions in posttreatment drug abuse and arrests. A 12-month course of treatment including at least 6 months in a therapeutic community followed by outpatient treatment can produce marked reductions in drug abuse and crime among persons who complete both phases.\n",
            "output": "Conclusions: There is little evidence that TCs offer significant benefits in comparison with other residential treatment, or that one type of TC is better than another. Prison TC may be better than prison on it's own or Mental Health Treatment Programmes to prevent re-offending post-release for in-mates. However, methodological limitations of the studies may have introduced bias and firm conclusions cannot be drawn due to limitations of the existing evidence."
        },
        {
            "input": "Study1: Interpreting positive signs of the supraspinatus test in screening for torn rotator cuff. The purpose of this study was to investigate the validity of the supraspinatus test as a screening test for detecting torn rotator cuff and to determine what its valuable positive signs were. Both the empty-can test and full-can test were performed on 200 shoulders diagnosed by magnetic resonance imaging (MRI)-and in some cases, surgical findings-to have full-thickness or partial-thickness torn rotator cuff s, or no tear in the rotator cuff . During the maneuver, the presence of pain or weakness or both pain and weakness were recorded as positive signs, and the distribution of these signs were analyzed according to the degree of tear. The predictive values were calculated in 2 ways by considering (1) only full-thickness tears as tears and (2) both full- and partial-thickness tears as tears. The 2 tests and the 2 ways of considering partial-thickness tears were compared. Pain and weakness were severity-dependent, and the empty-can test had a higher incidence of pain. The sensitivities of the 2 supraspinatus tests in all positive signs were higher when including partial-thickness tears in the tear group ; however, their specificities were higher when excluding partial-thickness tears. Both pain and weakness were interpretive for the supraspinatus test, and both tests were sensitive to full- and partial- thickness tears and specific for full-thickness tears.\nStudy2: Transdeltoid palpation (the rent test) in the diagnosis of rotator cuff tears. The purpose of this study was to assess the diagnostic accuracy of transdeltoid palpation (the rent test) for the diagnosis of full thickness rotator cuff tear. Clinical and arthroscopic findings were documented prospectively for 109 consecutive patients undergoing shoulder arthroscopy by the senior author. A retrospective analysis was then performed on these data to assess the accuracy of transdeltoid palpation in the diagnosis of full thickness rotator cuff tear. Transdeltoid palpation was found to have a sensitivity of 95.7% and specificity of 96.8% for the diagnosis of full thickness rotator cuff tear. The positive and negative predictive values for transdeltoid palpation were 95.7% and 96.8%, respectively. Overall, the diagnostic accuracy of transdeltoid palpation was 96.3%. We conclude that transdeltoid palpation is highly accurate for the clinical diagnosis of full thickness rotator cuff tear.\nStudy3: Specificity of the Speed's test: arthroscopic technique for evaluating the biceps tendon at the level of the bicipital groove. A positive Speed's test result is usually thought to suggest inflammation or lesions related to the biceps/labral complex. The specificity, sensitivity, and positive and negative predictive values are determined for the Speed's test. A prospective study design was developed for all patients with shoulder pain who presented between October 1, 1994 and February 28, 1995. The clinical results of the Speed's test were correlated with biceps/labral pathology by direct arthroscopic visualization. A neuroprobe is used to pull the biceps tendon into the articular portion of the glenohumeral joint so as to visualize the biceps tendon at the level of the bicipital groove. Forty-six shoulders in 45 patients, 31 men (average age, 53 years; range, 16 to 76 years) and 14 women (average age, 64 years; range, 30 to 80 years) with 26 dominant and 20 nondominant extremities were operated on during this time interval. The clinical evaluation showed that the speed's test was positive in 40 shoulders. Biceps/labral complex pathology was present in 10 of these patients. A specificity of 13.8%, a sensitivity of 90%, a positive predictive value of 23%, and a negative predictive value of 83% were calculated. Thus, it is concluded that the Speed's test is a nonspecific but sensitive test for macroscopic biceps/labral pathology. This clinical examination is positive with a various number of other pathological shoulder problems.\nStudy4: The bear-hug test: a new and sensitive test for diagnosing a subscapularis tear. It was our intent to devise a new clinical test that would more accurately diagnose subscapularis tears than the current clinical tests. This new test is called the bear-hug test. The purpose of this study was to assess the bear-hug test and compare it with the current tests of subscapularis function (lift-off, belly-press, and Napoleon tests).                 Between January 2004 and March 2004, 68 consecutive patients scheduled for an arthroscopic procedure were evaluated preoperatively; the preoperative clinical examination findings were then correlated with arthroscopic findings. Lift-off, belly-press, Napoleon, and bear-hug tests were included in the examination. Furthermore, for the belly-press and bear-hug tests, the strength was precisely quantified by means of an electronic digital tensiometer (Kern HBC). Diagnostic arthroscopy was the reference that determined the actual pathologic lesions.                 Subscapularis tears occurred with a prevalence rate of 29.4%. Of the subscapularis tears, 40% were not predicted by preoperative assessment by use of all of the tests. The bear-hug test was found to be the most sensitive test (60%) of all of those studied (belly-press test, 40%; Napoleon test, 25%; and lift-off test, 17.6%). In contrast, all 4 tests had a high specificity (lift-off test, 100%; Napoleon test, 97.9%; belly-press test, 97.9%; and bear-hug test, 91.7%). No statistically significant difference was found between the area under the receiver operating characteristic curve of the bear-hug test and that of the belly-press test in diagnosing a torn subscapularis. However, the areas under the receiver operating characteristic curve for both the bear-hug test and the belly-press test were significantly greater than those for the lift-off and Napoleon tests (P < .05). Positive bear-hug and belly-press tests suggest a tear of at least 30% of the subscapularis, whereas a positive Napoleon test indicates that greater than 50% of the subscapularis is torn. Furthermore, a positive lift-off test is not found until at least 75% of the subscapularis is torn.                 The bear-hug test optimizes the chance of detecting a tear of the upper part of the subscapularis tendon. Moreover, because the bear-hug test represents the most sensitive test, it can be considered to be the most likely clinical test to alert the surgeon to a possible subscapularis tear. Performing all of the subscapularis tests is useful in predicting the size of the tear.                 Level I, diagnostic study: testing of previously developed criteria in a series of consecutive patients with arthroscopy used as the criterion standard.\nStudy5: Accuracy of the Speed's and Yergason's tests in detecting biceps pathology and SLAP lesions: comparison with arthroscopic findings. The purpose of this study was to explore and describe reasons for variation in diagnostic accuracy of clinical tests using Yergason's and Speed's tests in predicting biceps tendon pathology and SLAP lesions. Shoulder arthroscopy was used as the gold standard.                 Prospective blinded study of consecutive patients with a wide spectrum of shoulder conditions.                 One hundred fifty-two subjects (65 women and 87 men) with complaints of shoulder pain were examined. Fifty subjects (16 women and 34 men) ranging in age from 24 to 79 years (mean age, 50 years; SD = 14.36) met the criteria for surgery. The validity of the Yergason's and Speed's tests was evaluated against findings at surgery.                 The surgical findings related to biceps pathology and SLAP lesions were as follows: 2 bicipital tendonitis, both associated with significant rotator cuff pathology; 10 biceps partial tears; and 2 complete ruptures. Fifteen patients had SLAP lesion type I, 12 type II, and 1 type IV. The sensitivity, specificity, and positive and negative predictive values were 43%, 79%, 60%, and 65% for Yergason's test and 32%, 75%, 50%, and 58% for Speed's test, respectively. The likelihood ratios were 1.28 and 0.91 for Speed's test and 2.05 and 0.72 for Yergason's test. These ratios were provided to assist clinicians in calculating the probability of biceps pathology and SLAP lesions for a single patient with a different history-specific prevalence of having the pathology.                 Although Speed's and Yergason's tests are moderately specific, they do not generate a large change in the post-test probability and are unlikely to make a significant change in the pretest diagnosis. Clinicians should understand that clinical examination tests do not perform consistently and have variable predictive values in different patient populations and settings.                 Level I diagnostic study: testing of previously developed criteria in a series of consecutive patients (using surgery as gold standard).\nStudy6: Diagnostic values of clinical diagnostic tests in subacromial impingement syndrome. Subacromial impingement syndrome (SIS) is a frequent cause of shoulder pain. The aim of this study was to investigate the diagnostic values of clinical diagnostic tests, in patients with SIS.                 72 female, 48 male patients with shoulder pain were included in the study. Five had bilateral shoulder pain, so 125 painful shoulders were evaluated. Details were recorded about the patients' ages and sexes, as well as characteristics of pain and related problems. Detailed physical examination and routine laboratory tests were performed. Conventional radiography and subsequent magnetic resonance imaging of the shoulder region of all patients were performed. Patients were divided into two groups according to the results of subacromial injection test, a reference standard test for SIS. Test positive patients constituted SIS group and test negative patients the non-SIS group. Sensitivity, specificity, accuracy, positive and negative predictive values of some clinical diagnostic tests such as Neer, Hawkins, horizontal adduction, painful arc, drop arm, Yergason and Speed tests for SIS were determined by using 2 x 2 table.                 The most sensitive diagnostic tests were found to be Hawkins test (92.1%), Neer test (88.7%) and horizontal adduction test (82.0%). Tests with highest specificity were drop arm test (97.2%), Yergason test (86.1%) and painful arc test (80.5%) consecutively.                 The highly sensitive tests seem to have low specificity values and the highly specific ones to have low sensitivity values. Although this finding suggests that these diagnostic tests are insufficient for certain diagnosis, it is suggested they play an important part in clinical evaluation.\n",
            "output": "Conclusions: There is insufficient evidence upon which to base selection of physical tests for shoulder impingements, and local lesions of bursa, tendon or labrum that may accompany impingement, in primary care. The large body of literature revealed extreme diversity in the performance and interpretation of tests, which hinders synthesis of the evidence and/or clinical applicability."
        },
        {
            "input": "Study1: THE VALUE OF LUNG PHYSIOTHERAPY IN THE TREATMENT OF ACUTE EXACERBATIONS IN CHRONIC BRONCHITIS. nan\nStudy2: [Physiotherapy in chronic obstructive pulmonary disease: oscillatory breathing with flutter VRP1]. Chronic obstructive pulmonary disease (COPD) is characterized by sputum production and cough. It has been shown that mucus hypersecretion predisposes to recurrent bronchial infection and that reduction in airway secretions is associated with clinical improvement. Recently a new pipe-shaped device for chest physiotherapy, the flutter VRP1 (\"VarioRaw:\" Aubonne, Switzerland), was introduced in order to help clear bronchial hypersecretion. We determined the long-term efficacy of daily chest physiotherapy with the VRP1 in COPD and bronchial hypersecretion. 13 men and 7 women with COPD and sputum hypersecretion were studied; 10 were assigned to the physiotherapy group, and 10 to the control group getting sham therapy. After 3 months of physiotherapy, FVC, FEV1 and distance walked in 12 minutes increased in the treated group, but were almost unchanged in the sham-treated group. Arterial blood gases, the maximum voluntary ventilation, and respiratory rate at rest were unchanged in both groups. There was also an overall significant improvement in COPD symptoms in the physiotherapy group compared to baseline (p < 0.05). We conclude that long-term home physiotherapy with the flutter VRP1 is effective in COPD in improving airflow, functional ability and symptoms.\nStudy3: Active cycle of breathing techniques in non-invasive ventilation for acute hypercapnic respiratory failure. We hypothesised that applying the active cycle of breathing techniques (ACBT) in patients with acute hypercapnic respiratory failure undergoing non-invasive ventilation would improve patient outcome. Thirty-four patients were randomised so that 17 patients with acute hypercapnic respiratory failure received the ACBT and non-invasive ventilation (ACBT group), and 17 patients received non-invasive ventilation alone (control group). The primary outcome measure was length of time requiring non-invasive ventilation, and secondary outcome measures were change in acute physiology score, change in arterial blood gas values, total duration of non-invasive ventilation, and length of stay in the intensive care unit. Although not significant, there was a greater decrease in arterial carbon dioxide pressure in the ACBT group compared to the control group (-21.41 mmHg vs -17.45 mmHg, p = 0.27). Total duration of ventilation tended to be shorter in the ACBT group than in the control group (64.9 hours vs 84.1 hours, p = 0.15). Length of time in need of non-invasive ventilation was significantly lower in the ACBT group than in the control group (5.0 days vs 6.7 days, p = 0.03). There was no significant difference in length of stay in the intensive care unit between the two groups (8.0 vs 9.4 days, p = 0.31). The use of ACBT may have positive effects in the treatment of patients with acute hypercapnic respiratory failure, resulting in a shorter length of time requiring non-invasive ventilation.\nStudy4: Treatment of chronic bronchitis with terbutaline inhaled from a cone spacer with and without positive expiratory pressure. Patients with chronic bronchitis were randomly allocated to 4 weeks treatment with terbutaline 0.5 mg inhaled through a cone spacer with an expiratory resistance creating a positive expiratory pressure (+PEP group) or without (-PEP group). The patients recorded their symptoms in a diary and peak expiratory flow (PEFR) was measured before and after each inhalation. PEFR increased significantly after inhaled terbutaline both with and without PEP. The mean increase in PEFR after terbutaline inhalations was significantly greater (p less than 0.0001) in the +PEP group (24 L/min) compared to the -PEP group (17 L/min). The +PEP group had less sputum and less difficulty with coughing up sputum compared to the -PEP group. This study showed a small but significant enhancement of the bronchodilation and a beneficial effect on symptoms when inhalation of beta-2-agonist was combined with PEP in patients with chronic bronchitis.\nStudy5: PEEP-masks in patients with severe obstructive pulmonary disease: a negative report. Positive pressure during expiration by face masks applied by the patient has gained wide acceptance in the treatment of chronic bronchitis, but the efficacy is still unproven. The effect of 6 months of treatment with PEEP-masks (positive end-expiratory pressure) was therefore studied in 47 patients with severe irreversible obstructive pulmonary disease (forced expiratory volume in one second (FEV1) about 1 l), and mucus hypersecretion. Patients were double-blindly randomized to at least 45 min daily treatment with PEEP-masks with either 10 or 0 cm water pressure. After 6 months of treatment, no statistical difference was found between the two groups in change of median values (month 6 - month 0) of FEV1, forced vital capacity (FVC), arterial oxygen tension (PaO2), amount of sputum or dyspnoea. Median values of arterial carbon dioxide tension (PaCO2) decreased significantly (0.03 kPa) in the placebo group. Cough intensity and dyspnoea during walking on staircases improved significantly in the placebo group. No difference among groups was found in number of days bedridden, hospitalized, number of exacerbations or antibiotic consumption. We conclude, that the use of PEEP-masks in these patients is without clinical documentation and cannot be recommended.\nStudy6: Physiotherapy and intermittent positive-pressure ventilation of chronic bronchitis. Patients aged over 45 admitted to hospital with exacerbations of chronic bronchitis alone or in association with cor pulmonale, pneumonia, or respiratory failure were placed in one of three groups (men with hypoxia, men without hypoxia, and women). Patients within these groups were then randomly allocated to receive either standard drug treatment alone or standard drug treatment plus intermittent positive-pressure ventilation (IPPV). No significant differences occurred between the controls and patients receiving physiotherapy and IPPV in any group. We conclude that when a patient with chronic bronchitis and respiratory failure is deteriorating emphasis should be on correct diagnosis, fluid electrolyte balance, and nutrition together with oxygen treatment when necessary, rather than on additional physiotherapy.\n",
            "output": "Conclusions: Evidence from this review indicates that airway clearance techniques are safe for individuals with COPD and confer small beneficial effects on some clinical outcomes. Consideration may be given to the use of airway clearance techniques for patients with COPD in both acute and stable disease, however current studies suggest that the benefits achieved may be small."
        },
        {
            "input": "Study1: Placement of venous stents: clinical experience with a self-expanding prosthesis. A self-expanding vascular prosthesis was used to treat 20 venous stenoses or occlusions in 13 patients. The lesions were caused by tumor (n = 5), postoperative fibrous scars (n = 2), and chronic hemodialysis fistulas (n = 13). Follow-up ranged between 6 weeks and 53 months (mean follow-up, 14.9 months). Acute occlusion occurred in two stents, one within a tumor stenosis and one in a dialysis shunt after 3 days and 2 days, respectively. Balloon angioplasty, thrombolysis, and aspiration in the first case and balloon angioplasty and thrombolysis in the second case successfully restored patency. Definite occlusion occurred in these two patients after 8 weeks and 5 months, respectively. Ten secondary interventions were performed in three patients with 10 restenoses who had stenotic arm veins in chronic hemodialysis at presentation. Five of seven patients who received treatment for stenoses associated with hemodialysis underwent successful kidney transplantation 5-27 months after placement of vascular stents. Both patients who received treatment for benign strictures had patent stents at follow-up examinations performed at 45 and 53 months, respectively. Four of five stents placed for malignant stenoses were patent at venography (n = 3) or autopsy (n = 1).\nStudy2: Superior vena cava syndrome due to non--small-cell lung cancer. Resolution with chemotherapy alone. Three patients with superior vena cava syndrome due to non--small-cell lung cancer were treated with chemotherapy alone. Symptomatic relief began within three days of treatment and substantial resolution of the syndrome occurred in all three patients. One patient had complete remission of tumor and the other two had more than a 50% tumor reduction within the first month of therapy. These are the first case reports indicating that combination chemotherapy may be effective as initial management of the superior vena cava syndrome due to non--small-cell lung cancer.\nStudy3: Superior vena cava syndrome revisited. A clinical review with analysis of prognostic factors, including the impact of the initial management modality, was conducted on 137 patients with superior vena cava syndrome (SVCS) seen at the Veterans General Hospital-Taipei between 1989 and 1993. Malignant diseases account for most of the SVCS in our Chinese patients. Patients received diagnostic intervention for their underlying diseases without obvious complications. Whether or not there is a development of SVCS in lung cancer patients, showed prognostic significance in non-small cell lung cancer (NSCLC) and no significance in small cell lung cancer (SCLC). Those with SVCS as the initial manifestation of malignant disease had a poor prognosis compared to those who developed SVCS later. Survival is best in lymphoma/leukemia patients, followed by malignant thymoma and SCLC, and worst in NSCLC and metastatic cancer. The rapid onset of symptoms from SVCS had a short median survival in lung cancer and significantly compromised survival in SCLC. The overall survival of SCLC with SVCS was not affected, regardless of whether the initial therapy had been radiotherapy or chemotherapy.\nStudy4: Palliative effectiveness of radiation therapy in the treatment of superior vena cava syndrome. A study was made of 34 patients concerning the palliation effect of radiation therapy in the treatment of superior vena cava syndrome (SVCS). They were seen between 1986-1993, at the Department of Radiotherapy in Middelheim General Hospital, Belgium, Antwerp. All patients had a syndrome of superior vena cava obstruction secondary to malignancy. The histologic diagnosis delivered an equal distribution of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). All patients with a SCLC received chemotherapy as initial treatment, but showed no response, relapse or evolution during treatment. Each treatment began with rapid-high dose irradiation, to continue after re-evaluation with rapid high-dose in cases of poor response or with the conventional fractionation of 2 Gy daily in patients showing good relief of symptoms. The initial rapid-high dose schedules depended on the performance status of the patients. Seventy-six percent of the patients with NSCLC showed good relief of their symptoms. It was very unexpected but the majority of NSCLC patients responded more quickly than SCLC patients, within three days after initiating treatment. In SCLC, 94% of the patients responded up until death. The palliation index defined as the ratio of the symptom-free period on the total survival which is 1 in ideal circumstances, was 0.55 in NSCLC and 0.90 in SCLC. In this last group, death was mainly due to disease progression in distant sites.\nStudy5: Case report: superior vena caval obstruction treated by thrombolysis, mechanical thrombectomy and metallic stents. We describe a case of superior vena caval obstruction (SVCO) due to bronchial carcinoma which was complicated by extensive central venous thrombosis. Partial clot lysis was achieved with thrombolytic agents, but therapy had to be discontinued due to bleeding from the gastrointestinal tract and puncture sites. Clot dissolution was completed using the Amplatz Thrombectomy Device, and the subsequent placement of a Gianturco Z-stent resulted in prolonged symptomatic relief.\nStudy6: [Venous angioplasty and Wallstent implantation in emergency treatment of superior vena cava syndrome caused by tumor]. A 58-year-old man was hospitalized because of threatened asphyxia resulting from massive obstruction to neck vein flow and increased venous markings over the ventral and dorsal thorax. The previous year he had received radiotherapy (total of 55.8 Gy) for squamous cell carcinoma in the right upper lobe of the lung (primary stage T2 N2 M0). The signs of venous congestion had developed over several months.                 Emergency phlebography demonstrated obstruction to superior vena cava (SVC) flow by tumour compression.                 It was possible to pass the SVC obstruction with a hydrophilic guide-wire and then perform a balloon angioplasty, followed later by implantation of two intraluminal expandable stents (\"Wallstent\"). The dyspnoea quickly improved after the successful recanalization. The day after the intervention palliative radiotherapy of the SVC obstruction was begun. But increased venous markings over the thorax recurred, but without dyspnoea, after 4 1/2 months free of signs of venous congestion. Repeat phlebography again demonstrated complete obstruction of the SVC by the tumour. Recanalization by balloon angioplasty was again achieved.                 This case underlines the value of percutaneous balloon angioplasty with stent implantation as supplementary treatment in the late stages of SVC obstruction by tumour.\nStudy7: [Radiotherapy in locoregional treatment of inoperable non-small cell lung cancer: results from a series of 381 patients]. The prognosis of inoperable non-small cell lung cancer (NSCLC) is poor and thoracic radiation therapy is usually the main step of the therapeutic approach. The results of a retrospective analysis of a series of 381 patients treated from 1977 to 1990 for an inoperable NSCLC are reported.                 Three hundred and twenty two men and 59 women were included into the study. Their mean age was 66 years. A squamous cell carcinoma was observed in 276 cases (72%). A superior vena cava syndrome or a Pancoast's syndrome were present in 21 and 26 patients, respectively. Fifty-two per cent of the patients had a WHO performance status > 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 </=9 days of age to a control formula with no AA or DHA (n = 77) or 1 of 2 otherwise identical formulas containing AA+DHA (AA, 0.46% and DHA, 0.14% of total fatty acids) from either egg-derived triglyceride (egg-DTG [n=80]) or fish oil and fungal oil (fish/fungal [n = 82]) at levels similar to the average in breast milk samples as measured in the reference group. All formulas contained 50% of energy from fat with the essential dietary fatty acids, linoleic acid (20% fatty acids) and alpha-linolenic acid (2% fatty acids). The main study outcomes were AA and DHA levels in plasma and red blood cells, and multiple measures of infant development at multiple ages from birth to 14 months: growth, visual acuity, information processing, general development, language, and temperament.                 AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups. No developmental test results distinguished these groups. Expected differences in family demographics associated with breastfeeding were found, but no advantages to breastfeeding on any of the developmental outcome demonstrated.                 These findings do not support adding AA+DHA to formulas containing 10% energy as linoleic acid and 1% energy as alpha-linolenic acid to enhance growth, visual acuity, information processing, general development, language, or temperament in healthy, term infants during the first 14 months after birth.infant development, breast feeding, infant formula, long-chain polyunsaturated fatty acids, docosahexaenoic acid.\nStudy4: Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Ross Pediatric Lipid Study. The CNS and the retina are enriched in long chain polyunsaturated (LCP) fatty acids, specifically docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are present in human milk but not in most infant formulas. In the present study of 134 formula-fed and 63 breast-fed infants, we prospectively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell (RBC) phospholipid levels of these fatty acids, enhance visual function, or affect growth during the first year. Healthy term infants < 7 d old were randomized to be fed formulas containing linoleic acid (approximately 10% kcal) and alpha-linolenic acid (approximately 1% kcal) plus (1) no added LCP fatty acids (control formula), (2) DHA (0.12 wt% fatty acids) and AA (0.43 wt%) from egg yolk phospholipid (AA + DHA formula), or (3) DHA (0.2 wt%) from fish oil (DHA formula). A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo. Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2, 4, 6, 9, and 12 mo. Infants fed the control formula had 10-40% lower RBC levels of DHA and AA than infants in the breast-fed group. Infants fed the AA + DHA formula had levels of both LCP within approximately 10% of the values for infants in the breast-fed group, and infants fed the DHA formula had 25-55% higher DHA levels and 15-40% lower AA levels. There were no differences in growth or in visual function during this 12-mo feeding study.\n",
            "output": "Conclusions: Majority of the RCTS have not shown beneficial effects of LCPUFA supplementation on the neurodevelopmental outcomes of term infants. The beneficial effects on visual acuity have not been consistently demonstrated. Routine supplementation of term infant milk formula with LCPUFA can not be recommended."
        },
        {
            "input": "Study1: A prospective randomised trial comparing spinal anaesthesia using hyperbaric cinchocaine with general anaesthesia for lower limb vascular surgery. One hundred and one patients were randomly allocated to have their peripheral vascular surgery performed under general anaesthesia (51 patients) or spinal anaesthesia (50 patients). Intraoperative haemodynamic changes were markedly different between the two groups with a higher incidence of hypotension in the spinal group (72% vs 31%) and a higher incidence of hypertension in the general anaesthesia group (22% vs 0%). Blood loss was significantly less in the spinal group (560, SD 340, ml vs 792, SD 440, ml). Postoperatively three patients from the general anaesthesia group died from causes unrelated to the anaesthesia, and one had a myocardial infarct. Two patients in the spinal group had myocardial infarcts, both had been treated for bradycardia and hypotension intraoperatively, and one died. There was a significantly higher incidence of postoperative chest infection in the general anaesthesia group (33% vs 16%). There was no significant difference between the groups in the incidence of postoperative confusion, or lower limb amputation rate or need for further surgery prior to hospital discharge.\nStudy2: Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia. Despite evidence that regional anesthesia may be associated with fewer perioperative complications than general anesthesia, most studies that have compared cardiac outcome after general or regional anesthesia alone have not shown major differences. This study examines the impact of anesthetic choice on cardiac outcome in patients undergoing peripheral vascular surgery who have a high likelihood of associated coronary artery disease.                 Four hundred twenty-three patients, between 1988 and 1991, were randomly assigned to receive general (n = 138), epidural (n = 149), or spinal anesthesia (n = 136) for femoral to distal artery bypass surgery. All patients were monitored with radial artery and pulmonary artery catheters. Postoperatively, patients were in a monitored setting for 48-72 h and had daily electrocardiograms for 4-5 days and creatine phosphokinase/isoenzymes every 8 h x 3, then daily for 4 days. Cardiac outcomes recorded were myocardial infarction, angina, and congestive heart failure.                 Baseline clinical characteristics were not different between anesthetic groups. Overall, the patient population included 86% who were diabetic, 69% with hypertension, 36% with a history of a prior myocardial infarction, and 41% with a history of smoking. Cardiovascular morbidity and overall mortality were not significantly different between groups when analyzed by either intention to treat or type of anesthesia received. In the intention to treat analysis, incidences of cardiac event or death for general, spinal, and epidural groups were 16.7%, 21.3%, and 15.4%, respectively. The absolute risk difference observed between general and all regional anesthesia groups for cardiac event or death was -1.6% (95% confidence interval -9.2%, 6.1%) This reflected a nonsignificant trend for lower risk of postoperative events with general anesthesia.                 The choice of anesthesia, when delivered as described, does not significantly influence cardiac morbidity and overall mortality in patients undergoing peripheral vascular surgery.\n",
            "output": "Conclusions: There was insufficient evidence available from the included trials that compared neuraxial anaesthesia with general anaesthesia to rule out clinically important differences for most clinical outcomes. Neuraxial anaesthesia may reduce pneumonia. No conclusions can be drawn with regard to mortality, myocardial infarction and rate of lower-limb amputation, or less common outcomes."
        },
        {
            "input": "Study1: Do Colles' fracture patients benefit from routine referral to physiotherapy following cast removal? Colles' fracture patients who received physiotherapy immediately following cast removal were compared with patients who received no active therapy following cast removal in a prospective randomised study. Patients who attended physiotherapy achieved significantly greater increases in wrist extension and grip strength after 6 weeks compared to patients who received no active therapy.\nStudy2: Ice and pulsed electromagnetic field to reduce pain and swelling after distal radius fractures. To examine the relative effectiveness of ice therapy and/or pulsed electromagnetic field in reducing pain and swelling after the immobilization period following a distal radius fracture.                 A total of 83 subjects were randomly allocated to receive 30 minutes of either ice plus pulsed electromagnetic field (group A); ice plus sham pulsed electromagnetic field (group B); pulsed electromagnetic field alone (group C), or sham pulsed electromagnetic field treatment for 5 consecutive days (group D). All subjects received a standard home exercise programme. A visual analogue scale was used for recording pain; volumetric displacement for measuring the swelling of the forearm; and a hand-held goniometer for measuring the range of wrist motions before treatment on days 1, 3 and 5.                 At day 5, a significantly greater cumulative reduction in the visual analogue scores as well as ulnar deviation range of motion was found in group A than the other 3 groups. For volumetric measurement and pronation, participants in group A performed better than subjects in group D but not those in group B.                 The addition of pulsed electromagnetic field to ice therapy produces better overall treatment outcomes than ice alone, or pulsed electromagnetic field alone in pain reduction and range of joint motion in ulnar deviation and flexion for a distal radius fracture after an immobilization period of 6 weeks.\nStudy3: [The importance of early exercise therapy in the treatment of Colles' fracture. A clinically controlled study]. Forty patients participated in a study of the importance of early occupational therapy for the prognosis in stable Colles' fractures. Seventeen patients were treated by an occupational therapist 1-3 days after the injury, and the need for appliances and home-care was estimated. Twenty-three patients completed the usual treatment. Five weeks after the injury, we found significantly (p less than 0.05) better function of the hand in the 17 patients with early occupational therapy. This difference in function could not be found after 13 weeks. The rate of complications was the same in the two groups. The results indicate that contact with the occupational therapist shortly after the injury is valuable in patients with stable Colles' fractures.\n",
            "output": "Conclusions: The available evidence from randomised controlled trials is insufficient to establish the relative effectiveness of the various interventions used in the rehabilitation of adults with fractures of the distal radius."
        },
        {
            "input": "Study1: Role of intraoperative thermoablation combined with resection in the treatment of hepatic metastasis from colorectal cancer. Thermoablation, either cryosurgical ablation (CSA) or radiofrequency ablation (RFA), combined with resection is effective in the treatment of extensive bilobar colorectal metastasis.                 Retrospective analysis of a prospective hepatobiliary surgical database.                 Tertiary care referral center.                 Consecutive patients with colorectal hepatic metastases selected for surgical treatment.                 All patients underwent hepatic resection combined with CSA or RFA.                 Local recurrence rates at ablation sites, overall survival, disease-free survival, and hepatic disease-free survival.                 Between January 1, 1998, and December 31, 2003, 665 patients with colorectal metastases underwent hepatic resection. Of these, 39 (5.9%) had additional intraoperative thermoablative procedures (19 RFA, 20 CSA). There was 1 (3%) postoperative death not directly associated with the ablation, and the total morbidity rate was 41% (16 of 39). No RFA-related complication occurred; however, 3 patients developed an abscess at cryoablation sites. Actuarial 3-year survival was 47% for the entire group, with a median follow-up of 21.1 months (range, 0.5-71.4 months). The median disease-free survival was 12.3 months (range, 8.4-16.2 months). Overall, the local in situ recurrence rate according to number of ablated tumors was 14% for RFA and 12% for CSA. Tumor size correlated directly with recurrence (P = .02) in RFA-treated lesions.                 Ablation combined with hepatic resection is rarely necessary or applicable. However, in selected patients whose tumors were otherwise unresectable, additional use of ablation allows effective clearance of disease. In these patients with extensive bilobar disease, recurrence rates are high, but long-term survival is encouraging and may be improved with aggressive postoperative chemotherapy.\nStudy2: Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. To examine recurrence and survival rates for patients treated with hepatic resection only, radiofrequency ablation (RFA) plus resection or RFA only for colorectal liver metastases.                 Thermal destruction techniques, particularly RFA, have been rapidly accepted into surgical practice in the last 5 years. Long-term survival data following treatment of colorectal liver metastasis using RFA with or without hepatic resection are lacking.                 Data from 358 consecutive patients with colorectal liver metastases treated for cure with hepatic resection +/- RFA and 70 patients found at laparotomy to have liver-only disease but not to be candidates for potentially curative treatment were compared (1992-2002).                 Of 418 patients treated, 190 (45%) underwent resection only, 101 RFA + resection (24%), 57 RFA only (14%), and 70 laparotomy with biopsy only or arterial infusion pump placement (\"chemotherapy only,\" 17%). RFA was used in operative candidates who could not undergo complete resection of disease. Overall recurrence was most common after RFA (84% vs. 64% RFA + resection vs. 52% resection only, P < 0.001). Liver-only recurrence after RFA was fourfold the rate after resection (44% vs. 11% of patients, P < 0.001), and true local recurrence was most common after RFA (9% of patients vs. 5% RFA + resection vs. 2% resection only, P = 0.02). Overall survival rate was highest after resection (58% at 5 years); 4-year survival after resection, RFA + resection and RFA only were 65%, 36%, and 22%, respectively (P < 0.0001). Survival for \"unresectable\" patients treated with RFA + resection or RFA only was greater than chemotherapy only (P = 0.0017).                 Hepatic resection is the treatment of choice for colorectal liver metastases. RFA alone or in combination with resection for unresectable patients does not provide survival comparable to resection, and provides survival only slightly superior to nonsurgical treatment.\nStudy3: Solitary colorectal liver metastasis: resection determines outcome. Hepatic resection (HR) and radiofrequency ablation (RFA) have been proposed as equivalent treatments for colorectal liver metastasis.                 Recurrence patterns after HR and RFA for solitary liver metastasis are similar.                 Analysis of a prospective database at a tertiary care center with systematic review of follow-up imaging in all of the patients.                 Patients with solitary liver metastasis as the first site of metastasis treated for cure by HR or RFA were studied (patients received no prior liver-directed therapy). Prognostic factors, recurrence patterns, and survival rates were analyzed.                 Of the 180 patients who were studied, 150 underwent HR and 30 underwent RFA. Radiofrequency ablation was used when resection would leave an inadequate liver remnant (20 patients) or comorbidity precluded safe HR (10 patients). Tumor size and treatment determined recurrence and survival. The local recurrence (LR) rate was markedly lower after HR (5%) than after RFA (37%) (P<.001). Treatment by HR was associated with longer 5-year survival rates than RFA, including LR-free (92% vs 60%, respectively; P<.001), disease-free (50% vs 0%, respectively; P = .001), and overall (71% vs 27%, respectively; P<.001) survival rates. In the subset with tumors 3 cm or larger (n = 79), LR occurred more frequently following RFA (31%) than after HR (3%) (P = .001), with a 5-year LR-free survival rate of 66% after RFA vs 97% after HR (P<.001). Patients with small tumors experienced longer 5-year overall survival rates after HR (72%) as compared with RFA (18%) (P = .006).                 The survival rate following HR of solitary colorectal liver metastasis exceeds 70% at 5 years. Radiofrequency ablation for solitary metastasis is associated with a markedly higher LR rate and shorter recurrence-free and overall survival rates compared with HR, even when small lesions (< or = 3 cm) are considered. Every method should be considered to achieve resection of solitary colorectal liver metastasis, including referral to a specialty center, extended hepatectomy, and chemotherapy.\nStudy4: Radiofrequency ablation as first-line treatment in patients with early colorectal liver metastases amenable to surgery. Aiming at avoidance of futile surgery, we have tested whether radiofrequency ablation (RFA) may be used as first-line treatment in patients with colorectal metastases (CRLM) occurring within the first year after colorectal surgery.                 Surgical resection is the standard treatment in patients with CRLM. Major retrospective analyses have identified the interval between colorectal surgery and the occurrence of CRLM to be of prognostic importance. So far, it is unknown whether survival of the respective patients is hampered if RFA is used as first-line treatment.                 According to a clinical pathway, we have treated patients with CRLM detected within the first year after colorectal surgery preferentially by RFA (n=28). Resection (n=82) was performed in patients who were deemed not amenable to RFA due to number, size, or location of metastatic lesions. The diameter of lesions differed between the groups. All other characteristics of patients and lesions were comparable. Local recurrence and new hepatic lesions were treated with repeated RFA or surgery whenever possible.                 Local recurrence at the site of ablation or resection occurred in 32% and 4% (P<0.001), new metastases apart from the site of previous treatment in 50% and 34% (P=0.179), and systemic recurrence in 32% and 37% (P=0.820) of the patients after RFA and surgery, respectively. Time to progression was significantly shorter in patients primarily treated with RFA (203 vs. 416 days; P=0.017). After primary treatment, 9 RFA patients and 8 surgery patients were amenable to repeated RFA or repeated surgery resulting in identical rates of disease-free patients and identical 3-year overall survival in both treatment groups: 67% and 60%, respectively; P=0.93.                 Despite striking differences in local tumor recurrence and shorter time to progression, survival in patients with early CRLM does not depend on the mode of primary hepatic treatment.\nStudy5: Feasibility of adjuvant hepatic arterial infusion of chemotherapy after radiofrequency ablation with or without resection in patients with hepatic metastases from colorectal cancer. The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases.                 Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil. Surgical complications, treatment-related toxicities, and patient outcomes were recorded.                 Fifty patients were treated with RFA and HAI with or without resection. A median of two lesions per patient, with a median greatest diameter of 2.0 cm, were treated with RFA. Postoperative complications, including 1 death, occurred in 11 of 50 patients. Toxicity from HAI was relatively mild. At 20 months' median follow-up, 32% of patients remained disease free. Ten percent of patients had recurrences at the site of RFA, 30% developed new liver metastases, and 48% developed extrahepatic disease.                 RFA of CRC liver metastases followed by HAI is feasible and is associated with acceptable complication and toxicity rates. The high rate of disease recurrence in our patients indicates that novel combinations of regional and systemic therapies are needed to improve patient outcomes.\nStudy6: Long-term outcomes following hepatic resection and radiofrequency ablation of colorectal liver metastases. Recently some have called for randomized controlled trials comparing RFA to hepatic resection, particularly for patients with only a few small metastases. The objectives were to compare local recurrence and survival following RFA and hepatic resection for colorectal liver metastases. This was a retrospective review of open RFA and hepatic resection for colorectal liver metastases between January 1998 and May 2007. All patients who had RFA were considered to have unresectable disease. 58 patients had hepatic resection and 43 had RFA. A 5-year survival after resection was 43% compared to 23% after RFA. For patients with solitary lesions, a 5-year survival was 48% after resection and 15% after RFA. Sixty percent of patients suffered local recurrences after RFA compared to 7% after hepatic resection. RFA is inferior to resection. The results observed in this study support the consensus that RFA cannot be considered an equivalent procedure to hepatic resection.\nStudy7: Comparative analysis of radiofrequency ablation and surgical resection for colorectal liver metastases. To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection for the treatment of colorectal liver metastasis (CRLM).                 Between 1996 and 2008, 177 patients underwent RFA, 278 underwent hepatic resection and 27 underwent combination therapy for CRLM. Comparative analysis of clinical outcomes was performed including number of liver metastases, tumor size, and time of CRLM.                 Based on multivariate analysis, overall survival (OS) correlated with the number of liver metastases and the use of combined chemotherapy (P < 0.001, respectively). Disease-free survival (DFS) also correlated with the number of liver metastases (P < 0.001). In the 226 patients with solitary CRLM < 3 cm, OS and DFS rates did not differ between the RFA group and the resection group (P = 0.962 and P = 0.980). In the 70 patients with solitary CRLM \u2265 3 cm, DFS was significantly lower in the RFA group as compared with the resection group (P = 0.015).                 The results indicate that RFA may be a safe alternative treatment for solitary CRLM less than 3 cm, with outcomes equivalent to those achieved with hepatic resection. A randomized controlled study comparing RFA and resection for patients with single small metastasis would help to determine the most efficient treatment modalities for CRLM.\nStudy8: Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases. Liver resection is the treatment of choice for patients with solitary colorectal liver metastases. In recent years, however, radiofrequency ablation has been used increasingly in the treatment of colorectal liver metastases. In the absence of randomized clinical trials, this study aimed to compare outcome in patients with solitary colorectal liver metastases treated by surgery or by radiofrequency ablation.                 Solitary colorectal liver metastases were treated by radiofrequency destruction in 25 patients. The indications were extrahepatic disease in seven, vessel contiguity in nine and co-morbidity in nine patients. Outcome was compared with that of 20 patients who were treated by liver resection for solitary metastases and had no evidence of extrahepatic disease. Most patients in both groups also received systemic chemotherapy.                 Median survival after liver resection was 41 (range 0-97) months with a 3-year survival rate of 55.4 per cent. There was one postoperative death and morbidity was minimal. Median survival after radiofrequency ablation was 37 (range 9-67) months with a 3-year survival rate of 52.6 per cent.                 Survival after resection and radiofrequency ablation of solitary colorectal liver metastases was comparable. The latter is less invasive and requires either an overnight stay or day-case facilities only.                 Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.\nStudy9: Clinical outcomes of hepatic resection and radiofrequency ablation in patients with solitary colorectal liver metastasis. The role of the radiofrequency ablation (RFA) in treatment of solitary liver metastasis has not been established yet. Both hepatic resection (HR) and RFA have been used increasingly in the treatment of colorectal liver metastases.                 A systemic review was performed to determine the impact of treatment modality of solitary liver metastasis on recurrence patterns, disease-free survival, and overall survival (OS) rates.                 Solitary liver metastases were treated by HR in 116 patients (75.8%) and 37 patients (24.2%) were treated with RFA. Prognostic factors, recurrence rate, recurrence patterns, and survival rates were analyzed. The cumulative 3-year and 5-year local recurrence free survival rates were markedly higher in the HR group (88.0% and 84.6%) as compared with those in the RFA group [53.3% and 42.6%, respectively (P</=0.001)]. The 5-year OS rate was lower in the RFA group as compared with the HR group without statistical significance (5-year OS, 65.7% in the HR, 48.5% in the RFA group, P=0.227).                 Despite of higher local recurrence rate, RFA may be considered as a therapeutic option for patients who are considered unsuitable for conventional surgical treatment. Randomized prospective controlled trials comparing the therapeutic outcome of RFA and HR are definitely warranted.\nStudy10: Comparative study of resection and radiofrequency ablation in the treatment of solitary colorectal liver metastases. We compared outcomes in patients with solitary colorectal liver metastases treated by either hepatic resection (HR) or radiofrequency ablation (RFA).                 A retrospective analysis from a prospective database was performed on 67 consecutive patients with solitary colorectal liver metastases treated by either HR or RFA.                 Forty-two patients underwent HR and 25 patients underwent RFA. The 5-year overall and local recurrence-free survival rates after HR (50.1% and 89.7%, respectively) were higher than after RFA (25.5% and 69.7%, respectively) (P = .0263 and .028, respectively). In small tumors less than 3 cm (n = 38), the 5-year survival rates between HR and RFA were similar, including overall (56.1% vs 55.4%, P = .451) and local recurrence-free (95.7% vs 85.6%, P = .304) survival rates. On multivariate analysis, tumor size, metastases treatment, and primary node status were significant prognostic factors.                 HR had better outcomes than RFA for recurrence and survival after treatment of solitary colorectal liver metastases. However, in tumors smaller than 3 cm, RFA can be recommended as an alternative treatment to patients who are not candidates for surgery because the liver metastases is poorly located anatomically, the functional hepatic reserve after a resection would be insufficient, the patient's comorbidity inhibits a major surgery, or extrahepatic metastases are present.\n",
            "output": "Conclusions: This systematic review gathers information from several controlled clinical trials and observational studies which are vulnerable to different types of bias. The imbalance between characteristics of patients in the allocated groups appears to be the main concern. Only one randomised clinical trial (published as an abstract), comparing 60 patients receiving RFA plus CT versus 59 patients receiving CT alone, was identified. This study showed that PFS was significantly higher in the group that received RFA. However, it was not able to provide information on overall survival. In conclusion, evidence from the included studies are insufficient to recommend RFA for a radical oncological treatment of CRLMs."
        },
        {
            "input": "Study: The use of cranial electrotherapy stimulation in the treatment of closed-head-injured patients. This double-blind study sought to discover if cranial electrotherapy stimulation (CES), which is a known treatment of depression, anxiety and insomnia in non-head-injured patients, could be an effective, drug-free treatment of stress-related symptoms in the closed-head-injured (CHI) patient. In this study 10 CHI patients treated for 45 min daily, 4 days a week for 3 weeks, responded significantly on all negative mood factors of the Profile Of Mood States, while five sham-treated and six placebo controls did not. While the majority of the patients were known seizure cases, no patient suffered a seizure during CES therapy. No placebo effects were found, nor were any negative effects from CES treatment seen.\n",
            "output": "Conclusions: No evidence was provided to support the use of CES treatment for inertia, a component of apathy. Between-group statistical analyses were not conducted and it was therefore not possible to determine the efficacy of the treatment relative to no treatment or sham treatment. Results regarding the effectiveness of treatment can only be inferred, and this evidence is based on only one trial with a small sample size. More randomised controlled trials evaluating different ways of treating apathy would be valuable. Trials should have larger sample sizes and use rigorous research designs and statistical analyses appropriate for examining between-group differences."
        },
        {
            "input": "Study1: Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery. The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.\nStudy2: Ibuprofen arginate provides effective relief from postoperative dental pain with a more rapid onset of action than ibuprofen. Ibuprofen is a safe and effective analgesic, but some formulations have a slow onset of action. Ibuprofen arginate is a rapidly absorbed salt designed to promote more rapid onset of analgesia. A clinical trial was conducted in 226 patients with postoperative dental pain to assess the analgesic efficacy and speed of onset of the arginine salt of ibuprofen compared with one of the commercially available forms of ibuprofen. Patients were administered a single dose of either ibuprofen arginate (200 mg or 400 mg), ibuprofen (200 mg or 400 mg), or placebo in this double-blind, randomized trial. To determine the onset of action of the study medication patients were required to note time to \"any\" pain relief and then time to \"meaningful\" pain relief, using the two-stopwatch method. Pain intensity and relief were assessed using traditional categorical scales over a 6-h period. Meaningful pain relief was achieved in 42 min and 24 min for ibuprofen arginate 200 mg and 400 mg, respectively, compared with 50 min and 48 min for ibuprofen 200 mg and 400 mg, respectively ( P<0.05). The results for the measurements of analgesic effectiveness [sum of pain intensity difference, total pain relief (TOTPAR), peak pain relief and overall evaluation of treatment] all showed that both doses of ibuprofen arginate and both doses of ibuprofen were significantly better than placebo and both 200-mg and 400-mg ibuprofen arginate doses were significantly better than ibuprofen 200 mg for peak pain relief. Mean plasma ibuprofen concentrations at 30 min and 60 min, respectively, were: ibuprofen arginine 200 mg, 13.9 micro g/ml and 15.7 micro g/ml; ibuprofen arginine 400 mg, 29.5 micro g/ml and 29.3 micro g/ml; ibuprofen 200 mg 2.5 micro g/ml and 5 micro g/ml; ibuprofen 400 mg, 2.3 micro g/ml and 7.4 micro g/ml. ( P<0.05). Adverse event profiles were similar across treatment groups. These results overall suggest that ibuprofen arginate when taken at doses equivalent to commercially available ibuprofen formulations produces analgesia that is faster in onset.\nStudy3: Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief of postoperative pain. The objective of this double-masked, parallel-group, multicenter, inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery. In the 8-hour, single-dose phase, 238 patients received single oral doses of bromfenac (50 or 100 mg), acetaminophen 650 mg/oxycodone 10 mg, ibuprofen 400 mg, or placebo. In the multiple-dose phase, 204 patients received bromfenac, acetaminophen/oxycodone, or ibuprofen for up to 5 days. In the single-dose phase, both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone, but the responses to bromfenac were longer lasting. Bromfenac produced significantly better overall (8-hour) analgesic summed scores than acetaminophen/oxycodone. Ibuprofen was less efficacious than the other analgesics. The remedication rate was lower in both bromfenac groups than in the other treatment groups. The acetaminophen/oxycodone group reported more somnolence and vomiting. Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination, with a longer duration of action. Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this study.\nStudy4: Single dose and multidose analgesic study of ibuprofen and meclofenamate sodium after third molar surgery. The purpose of this study was to compare the analgesic efficacy and safety of meclofenamate sodium with ibuprofen after dental impaction surgery. This study was double-blind and used a unique methodology. Patients (N = 254) were first randomized into the single dose phase of the study that included placebo, meclofenamate 50 mg, meclofenamate 100 mg, ibuprofen 200 mg, and ibuprofen 400 mg, followed by a 7-day multidose phase in which patients in the placebo group were rerandomized into one of the active treatment cells. In the single dose phase, all active treatments were significantly more efficacious than placebo for every summary analgesic measure. A positive dose-response was seen for both active drugs with meclofenamate 100 mg and ibuprofen 400 mg exhibiting the greatest efficacy for pain relief, pain reduction, time to remedication, and overall evaluation. Side effects were reported by 26 patients. They were evenly distributed among treatment groups with headache and drowsiness being the most common. During the multidose phase, there were only small differences in efficacy measures among active treatment groups. However, meclofenamate produced a higher incidence of stomach cramps and diarrhea than did ibuprofen (8.8% and 7.2% versus 0.8% and 0.8%). This study indicates that higher doses of nonsteroidal anti-inflammatory drugs are most effective immediately after surgery and that lower doses of these drugs can be used after the first postoperative day. The side effect profile of nonsteroidal anti-inflammatory analgesics is best observed with the use of a multidose study design.\nStudy5: Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: a randomized, placebo- and active-comparator-controlled clinical trial. Pain is a common complaint, often occurring in conjunction with inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesic agents in ambulatory patients. In recent studies, the cyclooxygenase-2 (COX-2) inhibitor rofecoxib demonstrated analgesic effects similar to those of NSAIDs in the treatment of acute pain and primary dysmenorrhea. The present randomized, single-dose, double-blind, double-dummy, placebo- and active-comparator-controlled, parallel-group study was undertaken to compare the analgesic efficacy of the COX-2 inhibitors rofecoxib 50 mg and celecoxib 200 mg with that of ibuprofen 400 mg and placebo in patients with postoperative dental pain. Two hundred and seventy-two patients experiencing pain after the removal of > 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: BET<BET+SLS; p < 0.005 and eating difficulties: BET<BET+SLS; p = 0.02; BET<reference; p = 0.003). The BET paste relieved dry mouth symptoms in 44% of the xerostomic patients, the corresponding figures for the other pastes being BET+SLS 22% (p = 0.002 as compared with BET), SLS 18% (p = 0.022), and reference 7% (p = 0.000). In conclusion, all the mildly flavoured toothpastes used in this study were well accepted by the xerostomic subjects. Thus, other toothpaste components may be more mucosa-irritating than just SLS, or else they enhance the effect of SLS. The detergent-free, BET-containing toothpaste appeared to be associated with relief of some symptoms of dry mouth.\nStudy4: Comparison of the effect of the linseed extract Salinum and a methyl cellulose preparation on the symptoms of dry mouth. The effect of a linseed extract Salinum and a sodium carboxymethyl cellulose preparation called MAS-84 was compared with regard to its effect on the symptoms of dry mouth. Twenty patients with xerostomia, who had been treated for cancer in the head and neck by radiation were recruited from the clinic for maxillofacial surgery, Malmo University Hospital. Following radiation treatment the salivation was severely reduced. The symptoms of a general feeling of a dry mouth, difficulties in chewing and swallowing, taste disturbances, problems with speech and mouth burning were registered on a subjective verbal rating scale. In addition plaque index and gingival bleeding were determined. The study design was crossover and performed single blind. The experimental period was 7 weeks. The patients were randomly divided into 2 groups. One group used Salinum and the other MAS-84 for 3 weeks. The fourth week was a wash out period and for the next three weeks the patients shifted preparation. Each of the preparations was used ad libitum. Registrations of the various parameters were undertaken on days 0, 7 and 21 of the respective period. At the initial examination all patients reported considerable disturbances from mouth-dryness. These symptoms were reduced in 15 patients during the Salinum period and in 9 during the MAS-84 period. The relief was significantly more pronounced during the use of Salinum compared to that during the use of the methyl cellulose preparation. On day 21 plaque and gingival bleeding were significantly reduced during the Salinum period but not during the MAS-84 period. The results of the present study confirm those of a previous pilot study and indicate that the linseed mucilage significantly reduced the symptoms of dry mouth. This effect increased with increasing time of saliva substitute use. The linseed mucilage Salinum appeared to be a suitable saliva replacement in mouth dry patients.\nStudy5: Treatment of xerostomia with polymer-based saliva substitutes in patients with Sj\u00f6gren's syndrome. To determine the efficacy of 3 types of polymer-based saliva substitutes in reducing oral dryness in patients with Sj\u00f6gren's syndrome (SS).                 Subjective efficacy of 3 different saliva substitutes (determined by self-administered questionnaire) was evaluated in a double-blind, placebo-controlled trial in 43 patients with primary and secondary SS. High-viscosity versus low-viscosity xanthan gum-based saliva substitutes were also compared in 33 SS patients. Salivary flow rates (SFR) were determined to examine correlations between the SFR and the subjective efficacy of the saliva substitute.                 Neither the saliva substitutes nor the placebo was truly effective. Preference for a particular saliva substitute over placebo was equally distributed among the 3 types of substitutes. The SFR of patients who preferred polyacrylic acid-based saliva substitutes was lower than that in patients who preferred the porcine mucin-based substitute (P < 0.05). Patients whose oral dryness was reduced by low-viscoelastic substitutes had a low stimulated SFR ( < 0.20 ml/minute; P < 0.05).                 The optimal properties of a saliva substitute are not the same for all patients with SS, but are dependent on such parameters as the individual SFR. Thus, to determine the best saliva substitute for a particular patient, it is necessary to have the patient try a number of substitutes of different viscoelastic properties.\nStudy6: Safety and effectiveness of topical dry mouth products containing olive oil, betaine, and xylitol in reducing xerostomia for polypharmacy-induced dry mouth. Polypharmacy is a common cause of salivary hypofunction, producing symptoms of dry mouth or xerostomia, especially among older populations. As the number of older people continues to increase, polypharmacy-induced salivary hypofunction is becoming an increasing problem. Many over-the-counter products are available for relieving symptoms of dry mouth, but few have been tested in controlled clinical investigations. The purpose of this investigation was to evaluate the safety and efficacy of a group of topical dry mouth products (toothpaste, mouth rinse, mouth spray and gel) containing olive oil, betaine and xylitol. Forty adults were entered into this single-blinded, open-label, cross-over clinical study and 39 completed all the visits. Subjects were randomly assigned at baseline to using the novel topical dry mouth products daily for 1 week, or to maintain their normal dry mouth routine care. After 1 week, they were crossed over to the other dry mouth regimen. The results demonstrated that the use of the novel topical dry mouth products increased significantly unstimulated whole salivary flow rates, reduced complaints of xerostomia and improved xerostomia-associated quality of life. No clinically significant adverse events were observed. These data suggest that the daily use of topical dry mouth products containing olive oil, betaine and xylitol is safe and effective in relieving symptoms of dry mouth in a population with polypharmacy-induced xerostomia.\nStudy7: The cholinesterase inhibitor physostigmine for the local treatment of dry mouth: a randomized study. Application of physostigmine to the oromucosal surface with the aim of stimulating underlying mucin-producing glands while reducing cholinergic systemic effects might be a strategy for treating dry mouth. Subjects suffering from dry mouth and with hyposalivation participated in a crossover, double-blind, randomized study. A gel containing physostigmine (0.9, 1.8, 3.6, and 7.2 mg) or placebo was applied to the inside of the lips and distributed with the tongue. The feeling of dryness was assessed using a visual analogue scale (VAS) (where a score of 100 = extremely dry) and systemic effects were registered. Based on assessments of efficacy and safety, the dose of 1.8 mg of physostigmine was selected for use in the second part of the study to make objective measurements of saliva volumes. Physostigmine (1.8 mg) produced long-lasting (120 min) relief (evident as a score reduction of 25 on the VAS) in the feeling of dryness. Judging from AUC values related to baseline over 180 min, the improvement for both mouth and lips in response to physostigmine was six times greater than that to placebo. At higher doses of physostigmine, gastrointestinal discomfort predominantly occurred. The volume of saliva collected in response to physostigmine was five times higher over 180 min than that collected in response to placebo. Physostigmine, applied locally, therefore appears to be a promising modality for dry-mouth treatment.\nStudy8: Subjective assessment of a new moisturizing mouth spray for the symptomatic relief of dry mouth. A randomized clinical trial (Study 1) and consumer usage test (Study 2) were conducted to evaluate the acceptability and efficacy of OASIS Mouth Moisturizing Spray in subjects experiencing dry mouth.                 Study 1: A randomized, single-blind, four-arm crossover clinical trial was conducted in 24 subjects, ranging from 50-84 years of age, to evaluate OASIS Mouth Moisturizing Spray and two experimental mouth spray formulations, and compare their performance to a reference (marketed) mouth spray, SALIVEZE. Following a three-day acclimatization phase, subjects used all four products at home for three days. Each treatment phase was separated by a three-day washout period. Study 2: One-hundred twenty subjects participated in a three-week home usage consumer test using OASIS Mouth Moisturizing Spray, after which they completed a 52-question online survey exploring sensory, efficacy, and resultant quality of life attributes of the product.                 Study 1: On average, subjects used the four test products 2-3 times per day. OASIS Mouth Moisturizing Spray was found to be effective in relieving dry mouth in the study population, as evidenced by a statistically significant feeling of coating the mouth (p < 0.05), and statistically significantly longer dry mouth relief (p < 0.005) than the commercial control. The OASIS Mouth Moisturizing Spray was statistically significantly (p < 0.05) better and preferred over the other product tested. All the products used in the study were well-tolerated. Study 2: On a five-point scale, 73% of respondents perceived the OASIS Mouth Moisturizing Spray as \"very good\" or \"excellent,\" and more than 60% gave the product an \"excellent\" or \"very good\" rating on sensory, efficacy, and quality of life attributes.                 These studies show that OASIS Mouth Moisturizing Spray helped provide dry mouth relief and was well liked by the study population.\nStudy9: Controlled study of lactoperoxidase gel on oral flora and saliva in irradiated patients with oral cancer. The aim of this study was to determine if radiotherapy induces hyposalivation altering oral microbial flora. The purpose of this placebo-controlled, single-blind study was to determine beneficial effects of a saliva substitute and an oral hygiene product on irradiated patients with oropharyngeal cancer. Eighteen patients were assigned to the test group (Biot\u00e8ne Oral Balance gel [Lacl\u00e9de Incorporated Healthcare Products, Gardena, CA] and toothpaste used daily), and another 18 were put on a conventional daily regimen (carboxymethylcellulose gel and Oral-B toothpaste [Laclede Pharmaceuticals, Gardena, CA]). Cultures for identifying and quantitating microorganisms, whole unstimulated saliva, and visual analog measurements for comfort were obtained before mucositis occurred and after treatment. Daily use of Biot\u00e8ne products enhanced control of microbial flora, improved salivary flow, and increased oral comfort as compared with control subjects. Four weeks after mucositis, some aerobic isolates disappeared in the test group; periodontal-associated bacteria were markedly decreased in the test group; and candidal species were significantly lowered in the test group. Although baseline saliva was lower in the test group (P = 0.001), after 4 weeks, no difference between groups existed; comfort was greater in the test group (P = 0.007). Use of enzyme-engineered Biot\u00e8ne products that assist in control of the oral microbial flora as well as supporting oral comfort through lubrication appear to be useful aids for irradiated patients with oropharyngeal cancer.\nStudy10: Management of xerostomia in older patients : a randomised controlled trial evaluating the efficacy of a new oral lubricant solution. Xerostomia is a subjective sensation of mouth dryness that may frequently occur in older patients.                 To compare the clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray taken five times daily with that of a commercially available saliva substitute Saliveze in the treatment of xerostomia.                 Forty-one institutionalised patients (28 women, 13 men; mean age 84 +/- 7 years) were randomly assigned to receive either OGT or Saliveze in a 2-week, randomised, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness using a self-rated, 10cm long visual analogue scale (VAS), objective assessment of oral tissue condition using a four-point ordinal scale and subjective assessment of symptoms of xerostomia using dichotomous responses to a questionnaire. The primary endpoint was the day (D) 14 patient-based mouth dryness score measured on a self-rated VAS.                 At D14, OGT resulted in significantly greater efficacy with respect to mouth dryness (mean between-treatment difference 2.1 +/- 0.1, 95% CI 1.9, 2.3; p = 0.001), swallowing difficulty (1.8 +/- 0.3, 95% CI 1.5, 2.1; p = 0.001), speech difficulty (1.1 +/- 0.2, 95% CI 1.0, 2.4; p = 0.04) and overall sensation of symptom relief (2.7 +/- 1.2, 95% CI 1.9, 3.8; p = 0.001). Objective assessment of oral tissues also showed significantly better improvement with OGT spray with respect to dryness (p = 0.01), stickiness (p = 0.005) and dullness (p = 0.001) of oral mucosa; severity of mucositis (p = 0.01); and thickening of the tongue (p = 0.03). A significant difference in taste acceptability was also noted in favour of OGT (1.4 +/- 0.6, 95% CI 1.2, 1.9; p = 0.04).                 OGT lubricant oral spray was superior to Saliveze in improving xerostomia and oral tissue condition in older institutionalised patients.\n",
            "output": "Conclusions: There is no strong evidence from this review that any topical therapy is effective for relieving the symptom of dry mouth. OGT spray is more effective than an aqueous electrolyte spray (SMD 0.77, 95% CI 0.38 to 1.15) which is approximately equivalent to a mean difference of 2 points on a 10-point VAS scale for mouth dryness. Chewing gums appear to increase saliva production in those with residual secretory capacity and may be preferred by patients, but there is no evidence that gum is better or worse than saliva substitutes. Integrated mouthcare systems and oral reservoir devices may be helpful but further research is required to confirm this. Well designed, adequately powered randomised controlled trials of topical interventions for dry mouth, which are designed and reported according to CONSORT guidelines, are required to provide evidence to guide clinical care. For many people the symptom of dry mouth is a chronic problem and trials should evaluate whether treatments are palatable, effective in reducing xerostomia, as well as the long-term effects of treatments on quality of life of those with chronic dry mouth symptoms."
        },
        {
            "input": "Study: Randomized trial of breast self-examination in Shanghai: final results. Among women who practice breast self-examination (BSE), breast cancers may be detected when they are at an earlier stage and are smaller than in women who do not practice BSE. However, the efficacy of breast self-examination for decreasing breast cancer mortality is unproven. This study was conducted to determine whether an intensive program of BSE instruction will reduce the number of women dying of breast cancer.                 From October 1989 through October 1991, 266,064 women associated with 519 factories in Shanghai were randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women). Initial instruction in BSE was followed by reinforcement sessions 1 and 3 years later, by BSE practice under medical supervision at least every 6 months for 5 years, and by ongoing reminders to practice BSE monthly. The women were followed through December 2000 for mortality from breast cancer. Cumulative risk ratios of dying from breast cancer were estimated using Cox proportional hazards models. All statistical tests were two-sided.                 There were 135 (0.10%) breast cancer deaths in the instruction group and 131 (0.10%) in the control group. The cumulative breast cancer mortality rates through 10 to 11 years of follow-up were similar (cumulative risk ratio for women in the instruction group relative to that in the control group = 1.04, 95% confidence interval = 0.82 to 1.33; P =.72). However, more benign breast lesions were diagnosed in the instruction group than in the control group.                 Intensive instruction in BSE did not reduce mortality from breast cancer. Programs to encourage BSE in the absence of mammography would be unlikely to reduce mortality from breast cancer. Women who choose to practice BSE should be informed that its efficacy is unproven and that it may increase their chances of having a benign breast biopsy.\n",
            "output": "Conclusions: Data from two large trials do not suggest a beneficial effect of screening by breast self-examination but do suggest increased harm in terms of increased numbers of benign lesions identified and an increased number of biopsies performed. At present, screening by breast self-examination or physical examination cannot be recommended."
        },
        {
            "input": "Study: The dorzolamide/timolol combination versus timolol plus pilocarpine: patient preference and impact on daily life. United States Patient Preference Study Group. International Patient Preference Study Group. To compare the 2.0% dorzolamide/0.5% timolol fixed combination (COSOPT; Merck & Co., Whitehouse Station, NJ) to 0.5% timolol plus 2.0% pilocarpine given concomitantly, and to determine patient preference, tolerability, and impact on daily life in patients with elevated intraocular pressure (IOP).                 Two multi-center, randomized, cross-over, observer masked studies were conducted, one in the United States (97 patients) and one in Europe (93 patients). The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from study medications. Intraocular pressure was measured before and 2 hours after the morning dose of study medication (hour 0 and hour 2).                 In both studies, among patients with a preference, the combination was preterred to timolol plus pilocarpine by a ratio of 4 to 1. The most commonly cited reason for this preference was side effects. Patients in both studies also reported that the combination interfered significantly less with daily life in terms of side effects and activity limitations. They also reported missing significantly fewer doses of study medication while taking the combination and being significantly more satisfied with it. The efficacy of these two treatments was not significantly different, based on IOP measurements at hour 0 and 2 hours after administration. Patients reported significantly more adverse events while receiving timolol plus pilocarpine in both studies, and in the U.S. study, significantly more patients discontinued therapy while receiving timolol plus pilocarpine than while receiving the combination.                 Compared with timolol plus pilocarpine, patients preferred the combination of 2% dorzolamide/0.5% timolol, and reported less interference in daily activities, better tolerability, and better compliance with therapy.\n",
            "output": "Conclusions: Although complex interventions consisting of patient education combined with personalised behavioural change interventions, including tailoring daily routines to promote adherence to eye drops, may improve adherence to glaucoma medication, overall there is insufficient evidence to recommend a particular intervention. The interventions varied between studies and none of the included studies reported on the cost of the intervention. Simplified drug regimens also could be of benefit but again the current published studies do not provide conclusive evidence. Future studies should follow up for at least one year, and could benefit from standardised outcomes."
        },
        {
            "input": "Study: Evaluation of the UCL diabetes self-management programme (UCL-DSMP): a randomized controlled trial. Self-management has been described as the cornerstone of care for diabetes. Many self-management studies are limited by poor methodology and poor descriptions of the intervention. The current study developed a theoretically based self-management programme for patients with type 2 diabetes, which was evaluated via a randomized controlled trial. At immediate post-intervention and three-month follow-up the intervention group showed significant improvement relative to controls on self-management behaviours, quality of life and illness beliefs. A trend towards improved HbA1c was also observed. Documentation in a manual and development of a training programme for facilitators ensures the programme is replicable.\n",
            "output": "Conclusions: Education programmes appear to have beneficial effects on improving patients' knowledge of diabetes and some self-management behavioural changes for patients with diabetes on dialysis or with microalbuminuria. Educational programmes appear to have beneficial effects on improving patients' self-efficacy and result in some beliefs changes for patients with diabetes and microalbuminuria. However, only two studies with small sample sizes and inadequate quality were included in this review. There is, therefore, inadequate evidence to support the beneficial effects of education programmes for people with DKD."
        },
        {
            "input": "Study1: Successful treatment of scabies with oral ivermectin in Nigeria. Currently, several topical scabicides are available but there is yet no oral or parenteral drug which has been established for the treatment of scabies in Nigeria. Ivermectin which is a modified avermectin, known to be an ectoparasiticidal agent in animals, has been used in adults for systemic parasitosis. In Nigeria, 25% benzyl benzoate is being extensively used for the treatment of scabies in adults. It is effective and readily available. The present study was carried out to evaluate the efficacy and safety of ivermectin in the treatment of patients with scabies at the skin clinic of the University of Nigeria Teaching Hospital, Enugu. Fifty-eight patients with scabies were recruited for the study; 13 (22.4%) were children aged between 5-14 years. Oral ivermectin was given in a single dose of 200 [microg/kg body weight to 29 patients. The remaining 29 patients had to apply 25% benzyl benzoate emulsion. All patients received a full physical and dermatological examination prior to onset of treatment and weekly for 4 weeks. Skin scrapings were taken to confirm the diagnosis of scabies. There was a 93% resolution of pruritus with ivermectin and 48% with benzyl benzoate. No side effects were observed with ivermectin. Our results show that oral ivermectin is a promising, effective and safe alternative in both children and adults of Nigeria when compared to 25% benzyl benzoate topical application.\nStudy2: Equivalent therapeutic efficacy and safety of ivermectin and lindane in the treatment of human scabies. To compare the therapeutic efficacy and safety of ivermectin and lindane for the treatment of human scabies.                 Randomized, prospective, controlled, double-blind, \"double-dummy,\" and parallel clinical study.                 A single department of dermatology at a hospital in Buenos Aires, Argentina.                 Patients were outpatients, hospitalized patients, and those referred to our hospital from nursing homes and asylums. Fifty-three patients had clinical signs and symptoms compatible with scabies.                 Patients received either a single oral dose of ivermectin (150-200 microg/kg of body weight) or a topical application of 1% lindane solution. Treatment was repeated after 15 days if clinical cure had not occurred.                 Clinical healing and adverse effects.                 Of 53 patients, 43 (81%) completed the study, 19 in the group treated with ivermectin and 24 in the group treated with lindane. At day 15, 14 patients (74%; 95% confidence interval, 48.8%-90.8%) in the group receiving ivermectin showed healing of their scabies and 13 patients (54%; 95% confidence interval, 32.8%-74.4%) in the group treated with lindane were healed. At 29 days, both treatments resulted in statistically equivalent therapeutic efficacy: 18 patients (95%; 95% confidence interval, 74.0%-99.9%) were healed with ivermectin and 23 patients (96%; 95% confidence interval, 78.9%, 99.9%) were healed with lindane (P<.02). Adverse effects from the treatments were few, mild, and transient. Results from laboratory tests showed no major abnormalities and no difference between treatments.                 Ivermectin is as effective as lindane for the treatment of scabies. Ivermectin is simpler to use and, therefore, is a promising tool to improve compliance and to control infestations.\nStudy3: Comparative study of 5% permethrin cream and 1% lindane lotion for the treatment of scabies. A multicenter, randomized, investigator-blind controlled trial was conducted to compare the safety and efficacy of a single, whole-body application of 5% permethrin cream with that of 1% lindane lotion for the treatment of scabies in 467 patients. At 14 +/- 3 days after treatment, the mean active lesion count decreased from pretreatment levels of 85 (range, 4 to 600) in both treatment groups to 14 (range, 0 to 133) in the permethrin group and to 15 lesions (range, 0 to 500) in the lindane group. At 28 +/- 7 days after treatment, complete resolution had occurred in 181 (91%) of 199 patients treated with permethrin and in 176 (86%) of 205 patients given lindane. Pruritus due to scabies persisted at 28 +/- 7 days in 14% of the permethrin group and in 25% of the lindane group. The most frequent adverse effects were new or increased pruritus and mild, transient burning or stinging; the latter was slightly more frequent following permethrin treatment and appeared to be related to severity of infestation. Because of a lower potential for neurologic toxicity, permethrin may be preferable to lindane for the treatment of scabies particularly in children.\nStudy4: Efficacy and tolerability of a new synergized pyrethrins thermofobic foam in comparison with benzyl benzoate in the treatment of scabies in convicts: the ISAC study (Studio Della scabbia in ambiente carcerario). Scabies is a very common skin infection in convicts. The SIMSPE Society (Societ\u00e0 Italiana di Medicina e Sanit\u00e0 Penitenziaria) has organized and conducted a multicentre, randomized, comparative, parallel group, investigator-blinded trial to evaluate the efficacy and tolerability of synergized pyrethrins foam (PF) in comparison with benzyl benzoate (BB) lotion.                 A total of 240 convicted patients, enrolled in eight National Jail Institutions, with a clinical diagnosis of scabies, were treated with PF (n = 120) for three consecutive days or BB (n = 120) for five consecutive days. Primary study endpoints were the clinical cure rate and the local tolerability. Secondary endpoints were clinical evolution of scabietic lesions and itching intensity. Study outcomes were assessed using appropriate semiquantitative scores at baseline and after 2 and 4 weeks. A second treatment cycle was applied if after 2 weeks the patient was not judged clinically cured.                 At week 2, a total of 75% (95% CI: 66-82%) and 71% (95% CI: 62-78%) of patients showed a complete clinical cure rate in the PF and BB groups, respectively. At week 4, the percentage of totally cured patients increased up to 95% (95% CI: 89-97%) and 91% (95% CI: 83-94%) in the PF and BB groups, respectively (P = NS between groups). At week 4, 5% in the PF group and 9% in the BB group complained of itching. Burning and irritation after treatment applications were more common in the BB group in comparison with the PF group. The tolerability score was better in the PF group in comparison with to BB group (2.9 vs. 2.2; P = 0.0001). A total of 95% of patients in the PV group had a good tolerability score (i.e. = 3) in comparison with 41% in the BB group.                 Our results show that a 3-day treatment with pyrethrins thermofobic foam is at least as effective as a 5-day treatment with benzyl benzoate lotion in convicted subjects with scabies. The foam formulation is better tolerated than the benzyl benzoate lotion.\nStudy5: Permethrin versus crotamiton and lindane in the treatment of scabies. nan\nStudy6: Permethrin 5% dermal cream: a new treatment for scabies. Permethrin 5% dermal cream (Burroughs Wellcome Co.) was compared in an investigator-blinded, randomized study against lindane 1% lotion (Kwell) for the treatment of microscopically confirmed scabies. Eleven of twenty-three patients treated with permethrin cream were cured in 2 weeks (48%). Only two patients had scabies 1 month following a single treatment with this product, giving a cure rate of 91%. One of these two patients was considered to have a reinfestation. Only three of twenty-three (13%) patients treated with 1% lindane lotion (Kwell) were free of scabies 2 weeks after a single treatment and fifteen of twenty-three (65%) were cured at 1 month. The unusually high percentage of treatment failures (35%) following lindane therapy may have been related to extensive use of this agent for head lice and scabies in this village during the preceding 5 years. The higher cure rate at 1 month seen with permethrin cream was significant (p less than 0.025). Permethrin 5% dermal cream offers a new, cosmetically elegant alternative to lindane therapy and was effective in a community in which lindane demonstrated an unacceptable level of treatment failures.\nStudy7: Efficacy and tolerability of natural synergised pyrethrins in a new thermo labile foam formulation in topical treatment of scabies: a prospective, randomised, investigator-blinded, comparative trial vs. permethrin cream. We compared in a prospective, randomised, investigator-blinded trial, the efficacy and tolerability of a new synergised-pyrethrins thermo-labile foam (F) formulation with permethrin 5 % cream (P) in 40 patients with scabies. Clinical evolution of scabetic lesions (Clinical grading = CG) and itching intensity (IS) were assessed, using a 5-point semi-quantitative score, at baseline, at week 2 and 4. F and P were equally effective in the clinical resolution of scabetic lesions. As compared to baseline, P reduced CG and IS from 3.4 0.7 and 3.1 0.4 to 0.2 0.6 and 1.4 1, at week 2, and to 0.0 0.0 and 0.1 0.3 at week 4, respectively (P < 0.001). F reduced CG and IS from 3.3 0.5 and 3.2 0.4 to 0.05 0.2 and 0.4 0.6 (week 2) and to 0.0 0.0 and 0.0 0.0 (week 4), respectively (P < 0.0001). As compared to P group, the IS in F group, at week 2, was significantly lower (0.4 0.6 vs. 1.4 1.1) (P < 0.0013). This foam formulation was at least as effective as permethrin 5 % cream in the treatment of scabies. In comparison with permethrin the foam induced a more rapid and complete resolution of itching.\n",
            "output": "Conclusions: Topical permethrin appears to be the most effective treatment for scabies. Ivermectin appears to be an effective oral treatment. More research is needed on the effectiveness of malathion, particularly when compared to permethrin, and on the management of scabies in an institutional setting and at a community level."
        },
        {
            "input": "Study1: Speech therapy and Parkinson's disease: a review and further data. A review is undertaken of recent experimental studies of the effects of speech therapy offered to patients with Parkinson's disease. In contrast to earlier opinions based upon clinical impressions, the results of these studies indicate that the immediate gains from therapy measured within the clinical setting are readily detected, that these are perceived by patient's relatives and that there is reasonable evidence that benefits persist for some period after treatment. A further study is reported which tests the effects of a less intensive treatment regimen. This also gave positive results. Although questions remain regarding the most efficient form of treatment and the extent of its benefits outside the clinic, the existing results warrant greater optimism about the benefits of speech therapy offered to patients with Parkinson's disease.\nStudy2: Changes in vocal loudness following intensive voice treatment (LSVT) in individuals with Parkinson's disease: a comparison with untreated patients and normal age-matched controls. This study assessed the impact of the Lee Silverman Voice Treatment (LSVT) on vocal loudness [sound pressure level (SPL)] in a group of dysarthric individuals with idiopathic Parkinson's disease (IPD). Pre- to post-treatment changes in SPL in the treated group were compared with changes in voice SPL during the same time in two control groups: individuals with IPD not treated with the LSVT and in non-disordered individuals, age-matched to the patients. All subjects produced the same voice and speech tasks--sustaining vowel phonation, reading the \"Rainbow Passage,\" producing a short monologue, and describing a picture. These tasks were recorded at three different occasions: just prior to treatment, just after treatment, and 6 months following treatment. The individuals treated with LSVT increased voice SPL from baseline to post-treatment by an average of 8 dB and from baseline to 6 months follow-up by an average of 6 dB. These changes were statistically significant and perceptibly audible. No significant changes in SPL were observed in the control groups during the time corresponding to the treatment and follow-up. Differences in SPL between the treated and untreated patients at post-treatment and follow-up were statistically significant for all voice and speech tasks. These findings, along with others, provide additional support for the efficacy of the LSVT.\n",
            "output": "Conclusions: Although improvements in speech impairments were noted in these studies, due to the small number of patients examined, methodological flaws, and the possibility of publication bias, there is insufficient evidence to conclusively support or refute the efficacy of SLT for speech problems in Parkinson's disease. A large well designed placebo-controlled RCT is needed to demonstrate SLT's effectiveness in Parkinson's disease. The trial should conform to CONSORT guidelines. Outcome measures with particular relevance to patients with Parkinson\u2019s disease should be chosen and patients followed for at least six months to determine the duration of any improvement."
        },
        {
            "input": "Study: Early intervention for low birthweight, premature infants: participation and intellectual development. The Infant Health and Development Program was an eight-site randomized controlled trial of comprehensive early intervention for low birthweight, premature infants during the first 3 years of life in which intellectual development was an outcome of major importance. At 24 and 36 months, but not at 12 months, higher Mental Development Index and IQ were associated with higher levels of participation in the intervention. In a longitudinal analysis of these data, we found that the intellectual development of children in the intervention group was associated with each of the three intervention modalities (the number of home visits received, days attended at child centers, and the number of parent meetings attended) but not with children's background characteristics (i.e., maternal education, birthweight). We suggest that these findings represent a dose-response relation between intervention and outcome.\n",
            "output": "Conclusions: Day care has beneficial effect on children's development, school success and adult life patterns. To date, all randomised trials have been conducted among disadvantaged populations in the USA. The extent to which the results are generaliseable to other cultures and socioeconomic groups has yet to be evaluated."
        },
        {
            "input": "Study1: The effects of hospitalization for bed rest on duration of gestation, fetal growth and neonatal morbidity in triplet pregnancy. Nineteen women attending a special multiple pregnancy antenatal clinic with a triplet pregnancy were randomly allocated to either bed rest in hospital from 24 weeks gestation onwards until delivery, or to continue conventional outpatient management. Conclusions are limited by the trial size, but the study suggests that routine hospitalization for bed rest decreases the incidence of preterm delivery and light-for-gestational age infants and reduces the need for intensive neonatal care. Although still compatible with change variation, the observations, if confirmed in a larger randomized study, would have considerable implications for clinical practice. The policy needs further evaluation in a large multicentered collaborative study.\nStudy2: Routine hospital admission in twin pregnancy between 26 and 30 weeks' gestation. Of 141 women with twin pregnancies, 72 were randomly assigned to outpatient care and 69 to hospital admission between 26 and 30 weeks' gestation. There were no differences between the groups in the frequencies of major maternal complications in pregnancy and labour but more of those admitted to hospital than of the outpatient group had to be admitted after 30 weeks. There were no differences between the groups in the mean birthweights of the twins by birth order, or in their mean gestation at birth whether analysed by intention to treat or by the treatment given. 22 infants were delivered before 32 weeks' gestation in the inpatient group compared with 10 in the outpatient group. With the exception of small-for-dates infants, any trend towards greater morbidity or mortality was seen in the inpatient group. The policy of routine hospital admission of women with twin pregnancies from 26 weeks' gestation is not beneficial to mother or babies and should be abandoned.\n",
            "output": "Conclusions: There is currently not enough evidence to support a policy of routine hospitalisation for bed rest in multiple pregnancy. No reduction in the risk of preterm birth or perinatal death is evident, although there is a suggestion that fetal growth may be improved. For women with an uncomplicated twin pregnancy the results of this review show no benefit from routine hospitalisation for bed rest. Until further evidence is available, the policy cannot be recommended for routine clinical practice."
        },
        {
            "input": "Study: Prevention of urinary retention after general surgery: a controlled trial of carbachol/diazepam versus alfusozine. Postoperative urinary retention is a common complication after surgical procedures. It can cause bladder dilatation, infection, and even sepsis. Carbachol/diazepam and alfusozine have been reported to lower the incidence of postoperative urinary retention, but no study showed the benefits of these drugs in a randomized, placebo-controlled trial.                 We used a double blind, placebo-controlled trial in which 249 patients with postoperative urinary retention were randomly assigned to receive carbachol/diazepam (n = 72), alfusozine (n = 82), or placebo (n = 95). The primary endpoint was miction within 2 hours after taking the medication.                 There was no significant difference in miction frequency after taking the medication among the three groups (p = 0.31). The miction rate was 60% for patients in the alfusozine group, 61% in the carbachol/diazepam group, and 51% in the placebo group.                 Alfusozine and carbachol/diazepam had no apparent benefit on the incidence of postoperative urinary retention.\n",
            "output": "Conclusions: Whilst it may appear that cholinergic agents and intravesically administered prostaglandin offer most promise in the treatment of post-operative urinary retention, the evidence is weak. There is a need for further research into pharmacological alternatives to catheterisation in the treatment of this common surgical complication."
        },
        {
            "input": "Study1: Thoracic radiation therapy added to chemotherapy for small-cell lung cancer: an update of Cancer and Leukemia Group B Study 8083. To provide a 10-year update of the experience of the Cancer and Leukemia Group B (CALGB) in the addition of thoracic radiation therapy to chemotherapy in limited-stage small-cell lung cancer.                 Three hundred ninety-nine patients with limited-stage small-cell lung cancer were randomized to receive thoracic radiation therapy that started on day 1 (arm I) or day 64 of chemotherapy treatment (arm II), or chemotherapy alone with cyclophosphamide, vincristine, and etoposide (later, doxorubicin). Thoracic radiation therapy consisted of 4,000 rad to the tumor and mediastinum with a 1,000-rad boost. All patients received prophylactic cranial radiation to a dose of 3,000 rad.                 Arm I patients had a median survival of 13.04 months, arm II patients 14.54 months, and arm III patients 13.58 months (log-rank test, P = .0072). Median time to clinical failure was 11 months in arm I, 11.21 months in arm II, and 8.7 months in arm III (log-rank test, P = .0004).                 With 10 years of follow-up, the two arms that included thoracic radiation therapy remain superior to chemotherapy alone. The addition of thoracic radiation therapy to combination chemotherapy improved both complete response rates and survival, with increased but acceptable toxicity.\nStudy2: Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT.                 We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm.                 Concurrent radiotherapy yielded better survival than sequential radiotherapy (P =.097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm.                 This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.\nStudy3: Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. The importance of the timing of thoracic irradiation (TI) in the combined modality therapy of limited-stage small-cell lung cancer (SCLC) was assessed in a randomized trial.                 All 308 eligible patients received cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) every 3 weeks for three cycles of each chemotherapy regimen. Patients randomized to early TI received 40 Gy in 15 fractions over 3 weeks to the primary site concurrent with the first cycle of EP (week 3), and late TI patients received the same radiation concurrent with the last cycle of EP (week 15). After completion of all chemotherapy and TI, patients without progressive disease received prophylactic cranial irradiation (25 Gy in 10 fractions over 2 weeks).                 Although complete remission rates were not significantly different between the two arms, progression-free survival (P = .036) and overall survival (P = .008) were superior in the early TI arm. Patients in the late TI arm had a higher risk of brain metastases (P = .006).                 The early administration of TI in the combined modality therapy of limited-stage SCLC is superior to late or consolidative TI.\nStudy4: Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC).                 Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17.                 The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity.                 Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration.\nStudy5: Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group. To evaluate if the timing of chest irradiation with respect to chemotherapy would influence survival and local and distant control in patients with limited-stage small-cell lung cancer (LSCLC).                 From 1981 to 1989, 199 consecutive patients with LSCLC were randomly allocated to receive initial chest irradiation (ICI; n = 99) or late chest irradiation (LCI; n = 100) given 18 weeks delayed. Both groups received the same nine cycles of combination chemotherapy: three cycles of cisplatin and etoposide and six cycles of cyclophosphamide, doxorubicin, and vincristine. In the first part of the study, prophylactic cranial irradiation (PCI) was only given to patients randomized to ICI, but after inclusion of 42 patients in the LCI arm, the protocol was changed, so that all patients received PCI independent of the timing of the chest irradiation (CI). A total of 157 patients received PCI with a radiation dose of 25 Gy in 11 fractions.                 The timing of radiotherapy had no significant effect on the 2-year overall survival rate (20% after ICI v 19% after LCI, P = .4) or the 2-year in-field recurrence rate (72% after ICI v 68% after LCI, P = .2). Median survival durations were 10.5 (ICI) and 12.0 (LCI) months. Similarly, no difference in the 2-year incidence of CNS recurrences was found between the 2 arms in patients who received PCI (19% after ICI v 13% after LCI, P = .24). Bone marrow toxicity was acceptable, as 15% developed World Health Organization (WHO) grade 4 leukocytopenia and 4% grade 4 thrombocytopenia. Grade 4 leukocytopenia was more pronounced in the ICI group. There was no difference in the frequency and severity of other toxicities between the 2 groups.                 Timing of CI did not significantly influence the incidence of in-field recurrences, CNS recurrences, or overall survival.\nStudy6: Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy.                 To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response.                 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded.                 Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question.\nStudy7: Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta-analysis. To replicate an earlier National Cancer Institute of Canada (NCIC) trial that examined the effect on survival of the timing of thoracic radiotherapy (TRT) in patients with limited disease small-cell lung cancer (SCLC).                 Patients received three cycles of cyclophosphamide, doxorubicin, and vincristine alternating with three cycles of etoposide and cisplatin. Three hundred twenty five chemotherapy- and radiotherapy-na\u00efve patients were randomly assigned to either early TRT administered concurrently in the second cycle or late TRT administered concurrently with the sixth cycle; the dose was 40 Gy in 15 fractions over 3 weeks.                 TRT was received by 92% and 82% of patients in the early and late arms, respectively (P = .01). Sixty-nine percent of patients in the early arm received all six courses of chemotherapy compared with 80% in the late arm (P = .003). There was no evidence of a survival difference; median overall survival time was 13.7 and 15.1 months in the early and late arms, respectively (P = .23). In a meta-analysis of all eight trials that compared early and late TRT, there were three in which the proportion of patients who completed their planned chemotherapy was similar between the TRT arms (hazard ratio [HR] = 0.73; 95% CI, 0.62 to 0.86) and five in which proportionally fewer patients in the early TRT arm completed their chemotherapy (HR = 1.06; 95% CI, 0.97 to 1.17).                 This study failed to show a survival advantage for early TRT with chemotherapy in limited-stage SCLC, unlike the NCIC trial. However, the results of a meta-analysis suggest that it is essential to ensure that the delivery of chemotherapy is optimal when administered with early TRT.\n",
            "output": "Conclusions: At present, it is uncertain whether the timing of chest radiotherapy as such is important for survival. The optimal integration of chemotherapy and chest radiotherapy in patients with limited-stage small cell lung cancer is unknown. Further research is needed to establish the best combination of radiotherapy and chemotherapy in this disease."
        },
        {
            "input": "Study1: Evaluation of glyceryl trinitrate, misoprostol, and prostaglandin E2 gel for preinduction cervical ripening in term pregnancy. To compare the efficacy of glyceryl trinitrate (GTN), dinoprostone and misoprostol for preinduction cervical ripening in primigravida at term.                 Sixty-five term primigravida, each with an unfavorable cervix (Bishop score </=5), were randomized to receive GTN (0.5 mg perivaginally, n = 21), dinoprostone gel (0.5 mg intracervically, n = 21) and misoprostol (50 microg perivaginally, n = 23) for a maximum of two doses, 6 h apart. Statistical analysis included paired t-tests to compare pre- and post-treatment Bishop scores, one-way analysis of variance (anova) tests to compare quantitative variables and chi-squared tests to compare the proportion of subjects achieving favorable Bishop scores.                 Baseline Bishop scores were similar in the GTN (3.4 +/- 0.9), dinoprostone (3.4 +/- 1.0) and misoprostol groups (3.2 +/- 1.2). The final outcome was favorable (Bishop score >6) 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 </=3), treatment with misoprostol led to a favorable response in 61.6% of patients compared with 45.6% in the misoprostol group and 33.3% in the GTN group. A significant improvement was noted in the Bishop score of all three groups (P < 0.001) but the increase in Bishop score was greater in misoprostol (3.5 +/- 2.1) and dinoprostone groups (2.8 +/- 1.5), compared with the GTN group (2.0 +/- 1.0, ANOVA F = 4.8, P = 0.01). Hyperstimulation and tachysystole were observed only in the misoprostol (9% and 4.3%) and dinoprostone groups (4.7% and 16.2%). The most common adverse effect in the GTN group was headache, which was observed in 47.6% of this group's subjects.                 The findings of the present study suggest that GTN is safer, but less efficacious, compared with prostaglandins for preinduction cervical ripening at term.\nStudy2: Randomized trial of isosorbide mononitrate versus misoprostol for cervical ripening at term. To assess the adverse effects of isosorbide mononitrate (IMN) compared with misoprostol for cervical ripening at term.                 One hundred and seven women with term pregnancies referred for induction of labor with Bishop scores of 6 or less were randomly allocated to receive either a 40-mg IMN tablet vaginally (n = 55) or 50 microg misoprostol vaginally (n = 52) every 6 h for a maximum of three doses. They were sent to the labor ward for amniotomy or oxytocin if either their Bishop scores were more than 6 or their cervices were not ripe 24 h after the treatment. Adverse effects, progress, and outcomes of labor were assessed.                 Isosorbide mononitrate was associated with fewer adverse effects especially uterine tachysystole (0 vs. 19.2%, P < 0.01) and hyperstimulation (0 vs. 15.4%, P < 0.01). The time from start of medication to vaginal delivery in IMN group was significantly longer (25.6 +/- 6.1 vs. 14 +/- 6.9 h, P < 0.01). Oxytocin was needed in 51 women (92%) of the isosorbide mononitrate group and six women (11%) of the misoprostol group (P < 0.001). The cesarean rate was not significantly different between the groups, but the major indications were different: dystocia (45%) in the IMN group vs. persistent non-reassuring fetal heart rate pattern (56%) in the misoprostol group.                 Cervical ripening with IMN resulted in fewer adverse effects, but was less effective than misoprostol.\nStudy3: The \"PRIM\" study: a randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term. The purpose of this study was to compare the efficacy and safety profile of prostaglandin E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term.                 Primigravid women were assigned randomly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostaglandin E2. Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery. Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening.                 Prostaglandin E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score. Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostaglandin E2. There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment. However, in the prostaglandin E2 group, 7% of the pregnancies had abnormal fetal heart rate patterns (P = .0002). Maternal satisfaction was significantly higher in the isosorbide mononitrate group.                 Although isosorbide mononitrate was less effective, maternal satisfaction was significantly greater. The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate, but not prostaglandin E2, on an outpatient basis.\nStudy4: Randomized comparison of glyceryl trinitrate and prostaglandin E2 for cervical ripening at term. To estimate the adverse effects of glyceryl trinitrate compared with prostaglandin (PG) E2 vaginal tablet for cervical ripening in term pregnancy.                 One hundred ten women with term pregnancies referred for induction of labor with Bishop scores of 6 or less were randomly assigned to receive a 500-microg glyceryl trinitrate tablet vaginally (n = 54) or a 3-mg PGE2 tablet vaginally (n = 56), every 6 hours for maximum of two doses. Subjects were sent to the labor ward for amniotomy or oxytocin if their Bishop scores were more than 6 or their cervices were not ripe 24 hours after treatment. Adverse effects, changes in the Bishop scores, progress, and outcomes of labor were assessed.                 Glyceryl trinitrate was associated with fewer episodes of uterine tachysystole (0% versus 9%; P =.02). The median Bishop score after 12 hours was lower in women given glyceryl trinitrate compared with those given PGE2. Adverse effects, including headache and palpitations, were more frequent with glyceryl trinitrate than with PGE2. The cesarean rate was not significantly different between groups.                 Cervical ripening with glyceryl trinitrate resulted in fewer episodes of tachysystole, but there were significantly more minor side effects. It can be used for cervical ripening at term, but it was not as effective as PGE2.\nStudy5: Nitric oxide donor isosorbide mononitrate for pre-induction cervical ripening at 41 weeks' gestation: A randomized controlled trial. Nitric oxide donors have been shown to cause cervical ripening. The aim of this study was to determine whether sustained release isosorbide mononitrate (ISMN-SR) 60 mg administered vaginally is effective for pre induction cervical ripening at 41 weeks' gestation.                 A double-blind randomised controlled trial was carried out at the University Obstetric Unit, Galle, Sri Lanka for a period of 9 months, commencing 1st August 2003. One hundred and fifty-six consecutive women with uncomplicated singleton pregnancies at 41 weeks' gestation with a modified Bishop Score <5 were allocated by stratified (primip/multip) block randomization to receive either ISMN-SR 60 mg (n = 78) or vitamin C 100 mg (n = 78) vaginally. Modified Bishop Score at 41 weeks + 2 days' gestation and the proportions establishing spontaneous labor or becoming favorable for induction of labor (IOL) by 41 weeks + 2 days' gestation were evaluated in each group.                 At the commencement of the study there were no differences between the mean age, parity or modified Bishop Score of the two groups. In the ISMN-SR group, there was a marked increase in the proportion establishing spontaneous labor (28% vs 7.5%, P < 0.01) and being favorable for IOL (40% vs 9% P < 0.001), 2 days after therapy. In the ISMN-SR group, there was a significantly higher increase in the mean modified Bishop Score (3.8, 95% CI 2.3-5.3 vs 1.3, 95% CI 0.3-2.2, P < 0.01) and a marked decrease in the proportion of subjects requiring further ripening of the cervix with a Foley catheter. (32% vs 79%, P < 0.001). The cesarean section rates were similar in both groups.                 Sustained release ISMN administered vaginally is effective for preinduction cervical ripening.\nStudy6: Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: a randomized controlled trial to determine effects on maternal and fetal hemodynamics. Our aim was to assess the effects of vaginally administered isosorbide mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant women at term.                 We conducted a randomized controlled trial. Women were randomly selected to receive vaginally administered isosorbide mononitrate, 20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n = 12). Maternal pulse, blood pressure, and fetal heart rate were recorded at baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were performed at 0, 180, and 330 minutes.                 Maternal pulse rate was greater after the administration of isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal examination-only group (greatest difference in means, 21 beats/min; P <.01). Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40-mg isosorbide mononitrate groups than in the vaginal examination-only group (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide mononitrate group or the vaginal examination-only group (difference in mean, 15 beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia or maternal hypotension. Neither dose of isosorbide mononitrate had a significant effect on umbilical artery resistance or pulsatility index.                 Vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term has an effect on both maternal and fetal hemodynamics, but this effect is not clinically significant.\n",
            "output": "Conclusions: NO donors do not appear currently to be a useful tool in the process of induction of labour. More studies are required to examine how NO donors may work alongside established induction of labour protocols, especially those based in outpatient settings."
        },
        {
            "input": "Study: Comparison of glucose polymer and glucose for screening and tolerance tests in pregnancy. Forty-eight of 100 pregnant women received a 100-g (nonfasting) glucose screening test at about 28 weeks' gestation, followed by a 100-g glucose tolerance test. Another 52 received a 100-g (nonfasting) glucose polymer screening test followed by a 100-g glucose polymer tolerance test. Mean plasma glucose one hour after the glucose screening test was significantly lower than after the glucose polymer screening test. A further 178 women received a glucose polymer screening test and a glucose polymer tolerance test (230 in total). These women and the infants they delivered were studied to derive diagnostic criteria for the 100-g glucose polymer tolerance test by correlating maternal carbohydrate tolerance with indexes of neonatal metabolic performance, and to determine an adequate method of screening for carbohydrate intolerance of pregnancy (gestational diabetes). Diagnostic criteria similar to those of O'Sullivan and Mahan were also developed for the glucose polymer tolerance test. These values are up to 5% lower than those recommended by the National Diabetes Data Group (1979) for the 100-g glucose tolerance test.\n",
            "output": "Conclusions: There is insufficient evidence to assess which is the best strategy for diagnosing GDM."
        },
        {
            "input": "Study1: The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients. In a randomized prospective coconut oil (daily 6g[63% C8:0 and 36% C10:0] [EPA-] [n = 48])-controlled trial, we investigated the effect of a one-month dietary supplementation with daily 6 g fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3 as their methyl esthers [EPA+] [n = 40]) on the incidence and course of early postoperative rejection in 88 first cadaveric, cyclosporine-treated renal transplant recipients. At one month there were no differences in renal function and incidence of rejection episodes. When analyzed separately for rejection (re+) or nonrejection (re-), the rejecting and fish oil-treated patients showed a significant better recovery of renal function after a histologically confirmed rejection episode, creatinine clearance being 43 ml/min/1.73m2 in the EPA+re+group versus 27 ml/min/1.73 m2 in the EPA-re+group (P less than 0.05), and serum creatinine being 183 and 283 mumol/l (P less than 0.05), respectively. The prerejection renal function and the decline of renal function during the rejection episode did not differ significantly between the EPA+re+ and the EPA-re+ groups. The nonrejecting fish oil-treated patients showed no better renal function than the nonrejecting coconut oil-treated patients. However, cyclosporine trough levels were significantly higher in the fish oil-treated group (EPA+re- 251 versus EPA-re- 200 ng/ml [P less than 0.05]). From these results we conclude that dietary supplements with fish oil favorably influence renal function in the recovery phase following a rejection episode in cyclosporine-treated renal transplant recipients. We further conclude that one month after grafting there is no difference in the incidence of rejection episodes between the fish- and coconut oil-treated patients. The same holds true for renal function in the absence of rejection, and for the decline in renal function during a rejection episode.\nStudy2: One-year randomized controlled trial with omega-3 fatty acid-fish oil in clinical renal transplantation. nan\nStudy3: Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants. Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection episodes in cyclosporine-treated recipients of renal transplants.                 In a randomized, double-blind trial, 33 recipients of first cadaveric kidney transplants who were treated with cyclosporine and prednisolone ingested 6 g of fish oil daily during the first postoperative year (the fish-oil group), whereas another 33 renal-graft recipients treated with cyclosporine and prednisolone ingested 6 g of coconut oil daily for three months after which time it was stopped (the control group).                 One year after transplantation, the fish-oil group had higher median values than the controls for glomerular filtration rate (53 vs. 40 ml per minute per 1.73 m2, P = 0.038) and effective renal plasma flow (214 vs. 178 ml per minute per 1.73 m2, P = 0.023) and lower mean arterial pressure (103 vs. 118 mm Hg, P = 0.0011). The cyclosporine doses in the two groups were similar. The cumulative number of rejection episodes was 20 in the controls, as compared with 8 in the fish-oil group (P = 0.029). One-year graft survival also tended to be better in the fish-oil group, (97 vs. 84 percent, P = 0.097).                 The daily administration of 6 g of fish oil during the first postoperative year has a beneficial effect on renal hemodynamics and blood pressure in renal-transplant recipients treated with cyclosporine. Although the fish-oil group had significantly fewer rejection episodes than the control group, graft survival at one year was not significantly better in the fish-oil group.\nStudy4: Effect of n-3 polyunsaturated fatty acids on cyclosporine pharmacokinetics in kidney graft recipients: a randomized placebo-controlled study. Highly concentrated marine polyunsaturated fatty acids (n-3 PUFA), affecting the lipids and lipophilic drugs metabolism, can interfere with cyclosporine (CyA) pharmacokinetics. This prospective, randomized and placebo-controlled, double-blind study involved 42 kidney graft recipients. From day +1, 21 pts (E) received 6 g n-3 PUFA (85% EPA + DHA, Esapent, Pharmacia) and 21 pts (P) received placebo (olive oil), both reduced to 3 g from day +30 on. A quadruple immunosuppressive regimen was employed. Plasma creatinine, lipids and CyA pharmacokinetics were investigated 1, 3, 6, 9 and 12 months after graft. The two groups were comparable for age, weight, M/F ratio, hypertension prevalence and baseline lipids. Active treatment did not affect total and HDL-cholesterol, but significantly lowered triglycerides (E:120 +/- 12 vs P:166 +/- 21 mg/dl, p < 0.0001). At one year, E pts had lower creatinine than P (1.26 +/- 0.06 vs. 1.88 +/- 0.2 mg/dl, p < 0.05), comparable CyA dosage, and a larger CyA area under the curve (AUC) (n.s.), with a higher blood peak level (Cmax) (p < 0.04) and less variance in time to peak (n.s.). The larger AUC in the E group at all intervals and the better pattern of plasma creatinine, with no rise in blood pressure, provided evidence of better CyA absorption and metabolism in n-3 PUFA supplemented kidney graft recipients.\nStudy5: Dietary supplementation with fish oil modifies renal reserve filtration capacity in postoperative, cyclosporin A-treated renal transplant recipients. The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 = EPA and 20% C22:6 omega-3 = DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA+). Renal function tests were performed using the simultaneous determination of 125I-iothalamate and 131I-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA- and EPA+ groups. Filtration fraction (FF) differed significantly, being 0.21 in the EPA- group versus 0.26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA + re - and EPA - re -. These two groups were comparable in age, donor age, and GFR. The EPA + re-group had a significantly lower ERPF (164 ml/min per 1.73 m2) than the EPA-re- group (262 ml/min per 1.73 m2). FF was significantly higher in the EPA+ re-group (0.26) than in the EPA-re-group (0.21).(ABSTRACT TRUNCATED AT 250 WORDS)\nStudy6: Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study. An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits.\nStudy7: Results of a 1-year randomized controlled trial with omega-3 fatty acid fish oil in renal transplantation under triple immunosuppressive therapy. nan\nStudy8: Dietary fish oil in renal transplant recipients treated with cyclosporin-A: no beneficial effects shown. This study aimed to determine whether dietary supplementation with fish oil has a beneficial effect on graft function and the incidence of rejection in renal allograft recipients treated with cyclosporin A (CsA). Renal function, blood pressure, the incidence of acute rejection episodes, graft survival, and renal histology and immunochemistry were investigated. In a randomized, placebo-controlled, double-blind trial, groups of 25 recipients of primary cadaveric renal allografts who had been treated with CsA took fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3) or coconut oil (63% C8:0 and 36% C10:0) at 6 g/day for 3 months. There were no differences between the two patient groups with regard to HLA matching, panel-reactive antibody titers, or the demographic characteristics of donors or recipients. The GFR and effective RPF were determined at 1, 3, and 12 months after transplantation by simultaneous measurement of (125I-)iothalamate and (131I-)hippuran clearances. At 1 yr after transplantation, patients treated with fish oil showed better renal function than did the control patients, but this difference was not statistically significant. Blood pressure and antihypertensive drug use were similar in both groups. The number of rejection episodes was also similar, and renal histopathological and immunohistochemical studies showed no significant differences between the fish-oil group and the control patients. It is concluded that fish oil, at a dose of 6 g/day, has no beneficial effect after renal transplantation within the time scale of the study.\nStudy9: Decrease of erythrocyte deformability in cyclosporine-treated renal transplant patients: correction with fish oil as well as corn oil. Twenty-nine renal transplant recipients with good, stable transplant function were included in a double-blind cross-over study to investigate the effects of different immunosuppressive treatment modalities and also the effects of fish oil and corn oil supplementation on erythrocyte deformability. Ten patients were treated with cyclosporine (CyA) only, 10 patients with CyA and prednisolone, and 9 patients with azathioprine and prednisolone. Erythrocyte deformability, as measured by an ektacytometric technique, was significantly decreased in both CyA-treated groups compared with the azathioprine-prednisolone-treated group, and this decrease was corrected with fish oil and with corn oil. The cause and the clinical significance of less deformable erythrocytes due to CyA are not yet clear. However, less deformable erythrocytes could play a role in the genesis of the complications of CyA.\nStudy10: Effects of fish oil in cyclosporine-treated renal transplant recipients. nan\n",
            "output": "Conclusions: There is insufficient evidence from currently available RCTs to recommend fish oil therapy to improve renal function, rejection rates, patient survival or graft survival. The improvements in HDL cholesterol and diastolic blood pressure were too modest to recommend routine use. To determine a benefit in clinical outcomes, future RCTs will need to be adequately powered with these outcomes in mind."
        },
        {
            "input": "Study: Prospective, controlled study of a polyvalent pseudomonas vaccine in cystic fibrosis--three year results. Thirty four children with cystic fibrosis allocated to pseudomonas vaccine and control groups were studied for three years. No significant differences were observed in the numbers colonised by Pseudomonas aeruginosa or in the overall disease progress of the two groups.\n",
            "output": "Conclusions: Vaccines against Pseudomonas aeruginosa cannot be recommended."
        },
        {
            "input": "Study1: Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants. To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants.                 A prospective, controlled, randomized, unmasked trial lasting 21 days was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions during the study period. Mean (+/- standard error of the mean) age at study entry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex (IPC), participants were randomized to receive 18 days of treatment with: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO + oral iron group); 3) 2 mg/kg/day of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron + EPO group). To assess efficacy of the 3 treatments, serial blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red blood cell indices and plasma levels of transferrin, transferrin receptor (TfR), ferritin, and iron. Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine.                 At the end of treatment, Hb, Hct, reticulocyte count, and plasma TfR were markedly higher in both of the EPO-treated groups, compared with the oral iron group. At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group, compared with the EPO + oral iron group. During treatment, plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups. By the end of treatment, ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups. Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sampled at the end of the 2-hour parenteral iron infusion, compared with values observed immediately before and after parenteral iron-dosing.                 In stable VLBW infants receiving EPO treatment, parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small, but significant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone. However, to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury, we suggest that the parenteral iron dose used should be reduced and/or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity.\nStudy2: Erythropoietin (rHuEPO) administration to premature infants for the treatment of their anemia. In an attempt to stimulate erythrocyte production and thereby decrease the requirement for red blood transfusions, recombinant human erythropoietin (rHuEPO) was administered to 16 premature infants with birth weights less than 1000 g and to 18 with birth weights of 1000-1300 g; two corresponding groups, who did not receive rHuEPO, were used as control groups. The rHuEPO was administered subcutaneously in a dose of 300 IU/kg three times a week for 6-8 weeks. The erythropoietin decreased the red blood requirement in both groups of infants, and the increment of hemoglobin following rHuEPO administration was not statistically significant. No correlation was observed between gestational age, number of transfusions, and reticulocyte percentage. The effect of rHuEPO was higher in the group of infants with birth weights of 1000-1300 g than in those of less than 1000 g. No significant side effects were observed during rHuEPO administration.\nStudy3: Enhancement of erythropoiesis by erythropoietin, bovine protein and energy fortified mother's milk during anaemia of prematurity. Twenty-four premature infants, < 32 weeks gestational age, were randomly assigned in a double-blind, placebo-controlled trial to 6 weeks of treatment with either recombinant human erythropoietin (rHuEpo) 150 U/kg three times per week given sc (n = 12) or placebo (n = 12). The infants were fed a diet rich in protein (3.2 g/kg/day) and energy (130 kcal/kg/day) based on their own mother's milk fortified with bovine protein together with moderate iron supplementation (4 mg/kg/day). During the treatment (rHuEpo versus placebo) significant differences in mean (+/- SD) reticulocyte count (4.8 +/- 1.2 versus 2.7 +/- 1.4%; p < 0.01), mean packed red cell volume (PCV) (0.38 +/- 0.03 versus 0.34 +/- 0.04, p < 0.05) and mean haemoglobin concentration (12.6 +/- 1.1 versus 11.5 +/- 1.2 g/100 ml; p < 0.05) were found. Within the rHuEpo group, PCV and haemoglobin concentration remained unaltered from entry to 1 week after cessation of treatment whereas a significant decline was observed in the placebo group. No indications of iron deficiency were seen. We conclude that moderate doses of rHuEpo given to infants fed a diet rich in protein and energy are effective in ameliorating anaemia of prematurity. High iron supplementation does not seem to be essential for a significant erythropoietic response. No adverse effect attributable to rHuEpo was observed.\nStudy4: Effect of recombinant human erythropoietin administration on lipid peroxidation and antioxidant enzyme(s) activities in preterm infants. In the present investigation, we studied the effect of recombinant human erythropoietin (r-HuEPO) on serum malondialdehyde (MDA) as an index of lipid peroxidation, related to iron-catalyzed free radical reaction and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities in very-low-birth weight (VLBW) infants. Forty premature infants, at gestational ages were less than 33 weeks and birthweights were less than 1,500 g, were enrolled in the study. The study population was randomly divided into 2 groups. Twenty infants in Group 1 (treatment group) were given r-HuEPO, and 20 infants in Group 2 served as the control. r-HuEPO treatment (750 U/kg a week) was initiated on the 10th day of life and continued for 6 weeks. Preterm infants given erythrocyte transfusions during the study were excluded from the results. Serum ferritin and MDA levels, and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were analyzed at the end of the first week of life (at the beginning of the study). Subsequently, serum ferritin, and MDA levels were measured at the end of the 3rd and the 6th week. SOD, CAT, and GPX activities in the hemolysate were analyzed at the end of the 4th week. Six infants in the control group and 1 infant in the r-HuEPO group received transfusions through the end of the study, and these infants were excluded from the results. Significantly decreased serum ferritin concentrations were found in the r-HuEPO group compared to those in the control group both at the end of the 3rd and the 6th week (P < 0.05, and P < 0.01, respectively). In addition, serum MDA levels were also significantly reduced in Group 1 compared to control both at the end of the 3rd and the 6th week (P < 0.01 and P < 0.05, respectively). A good correlation was found between serum MDA and ferritin levels in Group 1. When the 2 groups were compared with respect to activities of SOD, CAT, and GPX at the end of the 4th week, no differences were observed. Our findings in this study show that administration of r-HuEPO significantly decreases lipid peroxidation, but does not affect erythrocyte antioxidant enzyme(s) activities in preterm infants. The mechanism responsible for the r-HuEPO-induced decrease in lipid peroxidation may concern inhibition to iron-catalyzed free radical reactions.\nStudy5: Does early erythropoietin therapy decrease transfusions in anemia of prematurity? To investigate the effect of early erythropoietin treatment on induction of erythropoiesis and the need for transfusion in Very Low Birth Weight (VLBW) infants with acute neonatal problems.                 The study group consisted of 14 VLBW prematures with gestational ages less than 32 weeks who were given subcutaneous erythropoietin (600 U/kg per week) and oral iron (3 mg/kg per day) during the first 7-8 weeks of their life, while 13 other VLBW prematures that were given placebo constituted the control group. Weekly hematocrit, (Hct) reticulocyte (Ret) values and the volume of blood drawn and transfused were recorded in the both groups.                 The groups were comparable regarding with birth weights and gestational ages. The volume of the blood drawn (76.8 +/- 42.5 and 37.0 +/- 15.2) was higher and the volume of the transfusions (51.84 +/- 49.30 and 68.84 +/- 41.2) was lower in the study group but the differences between the groups were not significant (p>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."
        }
    ]
}