A randomized, double-blind clinical trial using fixed daily doses of 100 or 200 IU of recombinant FSH in ICSI cycles

The effect of 100 and 200 IU per day recombinant FSH (rFSH) on numbers of oocytes retrieved and the total dose used in ovarian stimulation before intracytoplasmic sperm injection was investigated in a double-blind, randomized multicentre trial. A total of 91 women was treated with a low-dose protocol and 88 with a high-dose regimen at five centres. For each started cycle, significantly more oocytes were retrieved in the 200 IU group than in 100 IU group (12.0 versus 5.7, P < 0.001); total rFSH consumption was 1121 and 1875 IU in the low- and high-dose groups respectively. Significant variations were noted between centres with regard to numbers of oocytes collected per started cycle, ranging from 2.8 to 7.2 in the 100 IU group and from 9.0 to 19.1 in the high-dose group. Exploratory analyses of secondary outcomes suggested there were no differences in vital pregnancy rates per started cycle (19.2 versus 16.9%) and per embryo transfer (26.2 versus 19.3%) in the low- and high dose groups respectively. There were four hospitalizations due to ovarian hyperstimulation syndrome, all in the 200 IU group.     

Economic,clinical, and quality-of-life outcomes associated with olanzapine treatment in mania. Results from a randomized controlled trial

INTRODUCTION: The objectives of this study were to determine the economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in patients diagnosed with mania. METHODS: Patients with a diagnosis of bipolar I disorder with manic or mixed episodes were enrolled in a randomized controlled trial. The study design comprised a 3-week acute phase followed by a 49-week open label extension. In the open label extension, the use of lithium and fluoxetine was permitted for patients who experienced breakthrough symptoms. Clinical, economic, and quality-of-life outcomes of treatment were assessed. RESULTS: During the acute phase, olanzapine patients experienced a statistically significant greater mean improvement from baseline on the Y-MRS total score compared to the placebo patients. In the open label extension, patients experienced a statistically significant mean change of 11.8 units on the Y-MRS from the end of the acute phase. When compared to costs incurred in the previous 12 months of therapy, patients experienced savings of almost $900 per month during the 49 weeks of olanzapine therapy. These cost savings were largely driven by reductions in in-patient costs during the open label extension. Health-related quality of life improvements measured by the SF-36 were seen on several dimensions both in the 3-week acute phase as well as in the 49-week open label extension. CONCLUSION: From a clinical, economic, and quality-of-life outcomes standpoint, olanzapine had a significant impact in the treatment of mania, and could be considered a cost-effective treatment option for use in this population if these findings are extrapolated to non-clinical trial populations.     

Comparison of the efficacy of an education program for people with diabetes and insulin pump treatment (INPUT) in a randomized controlled trial setting and the effectiveness in a routine care setting: Results of a comparative effectiveness study

ObjectiveTo compare the efficacy of an education program for people with diabetes and insulin pump treatment (INPUT) in a randomized controlled trial (RCT) to the effectiveness in an implementation trial (IT).Methods135 people with diabetes on insulin pump treatment (CSII) underwent structured education with INPUT under RCT-conditions, 191 people with diabetes on CSII underwent structured education with INPUT under IT-conditions. Baseline characteristics and treatment outcomes at the 6-month follow-up were compared.ResultsAt baseline, RCT-participants were younger (42.7 ± 14.2 vs. 47.2 ± 14.1 years, p = 0.005), had higher HbA1c-values (8.3 ± 0.8% vs. 7.8 ± 1.2%, p = 0.001) and had more diabetes-related distress (27.8 ± 16.4 vs 22.4 ± 14.4, p = 0.002). At follow-up, INPUT results were comparable under the RCT and IT settings. After adjustment for baseline HbA1c, reduction of HbA1c in the IT was significantly greater than in the RCT (Δ0.17%; 95% CI 0.023–0.319%, p = 0.024). Participants with higher HbA1c-levels, more diabetes-related distress and more hypoglycemia problems were most likely to benefit from INPUT regardless of the trial setting.ConclusionsEfficacy of the INPUT program for people with CSII was demonstrated under RCT- and routine care conditions.Practice implicationsEducation with the INPUT program is effective not only under standardized RCT conditions but also under conditions of routine care.     

Hydrosalpinx and IVF outcome: cumulative results after salpingectomy in a randomized controlled trial.

BACKGROUND: A randomized controlled trial of salpingectomy prior to IVF in patients with hydrosalpinges has been conducted in Scandinavia. The results from the first transfer cycle have been published and clearly demonstrated an improved pregnancy outcome after salpingectomy had been performed in patients with hydrosalpinges large enough to be visible on ultrasound. The present article is aimed at analysing the effect of salpingectomy on cumulative birth rate, including all individual transfer cycles. METHODS AND RESULTS: A total of 186 women underwent 452 cycles. Among the 77 women randomized to no surgical intervention, 24 underwent salpingectomy after one or two failed cycles. Cumulative results were analysed by Cox regression, taking into account the number of cycles per patient and the presence of a salpingectomy after a previous transfer. Salpingectomy implied a significant increase in birth rate (hazard ratio 2.1, 95% CI 1.6-3.6, P = 0.014). Within the subgroup of patients with ultrasound-visible hydrosalpinges, the birth rate was even higher (hazard ratio 3.8, 95% CI 1.5-9.2, P = 0.004). Implantation rate was significantly higher in patients who had undergone salpingectomy (27.2% versus 20.2, P = 0.03) and, in the subgroup of patients with ultrasound-visible hydrosalpinges, the difference was even larger (30.3% versus 17.1%, P = 0.003). CONCLUSIONS: The results of the cumulative cycles strengthen the recommendation for a laparoscopic salpingectomy prior to IVF in patients with ultrasound-visible hydrosalpinges.     

九味镇心颗粒治疗广泛性焦虑障碍多中心随机双盲对照试验

目的:评估九味镇心颗粒治疗广泛性焦虑障碍的临床疗效和安全性.方法:采用随机双盲双模拟多中心对照研究设计,对符合中国精神障碍分类与诊断标准第3版(CCMD-3)广泛性焦虑障碍诊断的448例患者,按3:1比例随机分成九味镇心颗粒组337例与盐酸丁螺环酮组111例,治疗4周.用汉密顿焦虑量表(HAMA)进行疗效评估,减分率≥30％为有效.用治疗中出现的症状量表(TESS)、心电图、血、尿常规、生化及生命体征评估安全性.结果:经4周治疗,九味镇心颗粒组与盐酸丁螺环酮组有效率差异无统计学意义(62.3％ vs.66.7％,P＞0.05).九味镇心颗粒组HAMA减分分数与盐酸丁螺环酮组相当[(12.7±5.8)vs.(13.2±6.5),P＞0.05].九味镇心颗粒组和盐酸丁螺环酮组的不良事件发生率分别为23.8％和30.6％ (P ＞0.05),与药物相关的不良事件发生率分别为13.4％和18.0％ (P ＞0.05),其中九味镇心颗粒常见口干(8.0％)、头晕(4.5％)、恶心(3.6％)、便秘(3.3％)等,盐酸丁螺环酮口干(12.6％)、便秘(6.3％)、恶心(5.4％)、头晕(5.4％)等.结论:九味镇心颗粒是治疗广泛性焦虑障碍一种安全有效的药物.     

Results of a controlled trial of the acaricide Paragerm on Dermatophagoides spp. in dwelling houses

The effect of Paragerm spray from either a hand pressurized can or from a general room mist device (MCR device) on mattress mite populations was compared with the effect of a control spray. After 1 month a reduction in mite population due to the cleaning procedures was evident in the control treated mattresses; Paragerm treated mattresses had significantly fewer mites, notably those treated with the aerosol can spray, nine out of fifteen of which were mite free. Dissection of the mattresses showed that some mites survive and they could form the nucleus from which reinfestation could occur.     

Treatment of chlordecone (Kepone) toxicity with cholestyramine. Results of a controlled clinical trial.

Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165 +/- 27 days--mean +/- S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the "ntestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal excretion by seven times. In a five-month trial, cholestyramine significantly accelerated elimination of chlordecone from blood, with a half life of 80 +/- 4 days (S.E.M.) (P less than 0.005) and fat (half life of 64 days, with a range of 52 to 85) (P less than 0.05). Cholestyramine offers a practical means for detoxification of persons exposed to chlordecone and possibly to other lipophilic toxins.     

Predictors of outcome in a fatigued population in primary care following a randomized controlled trial

BACKGROUND: The objective of this study was to examine factors that predicted outcome in a chronically fatigued group of patients who were randomized to cognitive behaviour therapy or counselling in primary care. METHOD: Illness perceptions, attributions, fatigue, disability and demographic variables were recorded at assessment and levels of fatigue and disability were measured at 6 months post randomization. Logistic regression was used to examine associations. RESULTS: Factors that predicted a poor outcome (four or more on the fatigue questionnaire) were: poor social adjustment at assessment; the patients self-report that they had never seen the GP for an emotional reason; a physical illness attribution; and, a long perceived future illness duration. CONCLUSIONS: Patients who are more psychologically minded are more likely to improve with psychological treatments in primary care. General practitioners need to assess this before referring to an appropriate therapist.     

What influences participants' treatment preference and can it influence outcome? Results from a primary care-based randomised trial for shoulder pain.

BACKGROUND: In randomised clinical trials (RCTs), outcome may be influenced by the opinions of the participants about the efficacy of treatments. AIM: To examine how initial treatment preferences of participants in a shoulder pain trial affected functional outcome and future treatment preferences. DESIGN OF STUDY: Observational cohort study nested within a multicentre, pragmatic RCT of steroid injection versus physiotherapy for unilateral shoulder pain. SETTING: Nine general practices in north Staffordshire. METHOD: Two hundred and seven adults were randomised in the trial. Disability scores and preferences of the participants for the trial treatments were elicited at two points: prior to randomisation and 6 months post-randomisation. A good functional outcome was defined as at least a halving in the disability score at the 6 months follow-up point. RESULTS: Pre-randomisation preferences were: 40% for injection and 20% for physiotherapy, and 40% gave no preference. A good outcome was achieved in a higher percentage of participants who gave a pre-randomisation treatment preference compared with those who did not (62% compared with 48% percentage difference = 14%; 95% confidence interval [CI] = -1 to 27%) with similar percentages in each preferred treatment group. However, receiving the preferred treatment did not confer any additional benefit in those who expressed a preference (receiving preferred treatment = 56%; not receiving preferred treatment = 69%). At 6 months post-randomisation, participants with a good, as opposed to poor, outcome were more likely to report as their preferred treatment the one to which they had been randomised, irrespective of pre-randomisation preference and whether the preferred treatment was received. CONCLUSION: This analysis suggests that preferences prior to treatment can affect outcome, but that treatment outcome is a stronger influence on post-treatment preferences. We present some empirical evidence to support the statement that treatment preferences can have important effects on the results of RCTs.     

Long‐term treatment with allergoid immunotherapy with Parietaria. Clinical and immunologic effects in a randomized, controlled trial

BACKGROUND: Specific immunotherapy (SIT) is a valuable treatment for respiratory allergy, and the use of chemically modified allergens (allergoids) has improved its safety, as testified by several studies. We evaluated the effects of a SIT course with an allergoid extract of Parietaria pollen in a double-blind, placebo-controlled trial. METHODS: The study was double-blind in the first year; then it was prolonged up to 3 years with all patients on active treatment. Clinical effectiveness, safety, skin reactivity, systemic immunologic parameters, and subjective assessment were evaluated. We also had available a self-evaluation recorded in a follow-up visit 4 years after the discontinuation of SIT. RESULTS: A significant reduction of the symptoms plus drug intake scores during the pollen seasons was observed in the patients receiving active SIT. The placebo patients, after switching to active SIT, also showed significant clinical improvement. The clinical efficacy persisted during years 2 and 3 of treatment. After year 1, the actively treated patients reported a significant subjective improvement (frequency of symptoms, P = 0.001; duration of symptoms, P = 0.024; physical performance, P = 0.043) compared with the placebo group. The self-evaluation by visual analog scale showed that all patients maintained a significant clinical improvement up to 4 years after discontinuing SIT (year 1: active=+31.6%, placebo=-15.7%; year 7: active=+35.8%, placebo=+31.3%). The systemic immunologic changes after active SIT paralleled those described elsewhere (IgE decreased from 22 to 9 and from 21 to 8 IU/ml; IgG4 increased from 43 to 87 and from 18 to 60 IU/ml). A significant decrease in skin reactivity to three different allergen concentrations was observed at year 3 compared with pretreatment values (P<0.05). CONCLUSIONS: The investigational SIT with Parietaria appeared to be effective and safe; a 3-year course of treatment achieved a long-lasting efficacy.     

Insulin desensitization with insulin lispro and an insulin pump in a 5-year-old child.

BACKGROUND AND OBJECTIVE: Allergic reactions to insulin, though rare, can have serious consequences in children with type I diabetes mellitus. We report a case of insulin allergy in a 5-year-old child in whom insulin desensitization was accomplished using an insulin pump. METHODS AND RESULTS: A 5-year-old girl with insulin-dependent diabetes mellitus (IDDM) developed progressive reactions to insulin and was found to have positive intradermal skin tests to regular and NPH insulin. Addition of oral antihistamine and co-administration of subcutaneous dexamethasone along with the insulin failed to control her symptoms. The patient was therefore hospitalized and desensitized to insulin using an insulin pump and insulin lispro. CONCLUSION: An insulin pump can be used for insulin desensitization in selected children. The slow constant infusion rate provided by the pump may be an ideal means of achieving insulin desensitization. In addition, insulin lispro, a synthetic insulin analog, should be considered for use in insulin-allergic individuals.     

Prediction of successful outcome in a randomised controlled trial of the long-term efficacy of interferon alpha treatment for chronic hepatitis C

To evaluate the efficacy of a 12-month course of recombinant interferon alpha (IFN-alpha2b), and to assess predictive factors of successful response to IFN therapy in chronic active hepatitis C (HCV CAH), 242 patients with histologically proven HCV CAH were assigned randomly to two groups, one treated with IFN-alpha2b (3 MU three times weekly, intramuscularly), the other untreated. To determine the efficacy of IFN-alpha2b 12 months after therapy, a second liver biopsy was carried out on 100 treated patients and 27 untreated patients. The biochemical, virological, and serological response of patients followed up for at least 50 months after treatment was also evaluated to confirm the efficacy of IFN-alpha2b. The genotypes of infecting HCV, anti-HCV core IgM, and HCV-RNA concentrations were also analysed and the predictors of response determined by univariate and multivariate analyses. Response was defined in terms of the normalisation of aminotransferase activities and the disappearance of HCV-RNA. The overall long-term response was 39.4%. Anti-HCV core IgM levels were significantly lower in long-term responders. Patients with increased levels of IgM anti HCV core (>3.8 sample/cut-off), infected with genotype 1b were nonresponders. Liver histology improved significantly in patients with long-term response. Multivariate analysis identified three independent predictors of the likelihood of long-term response to IFN therapy: age younger than 40 years, basal anti-HCV core IgM levels < or = 3.8, and genotypes other than 1b. These data indicate that the treatment with IFN-alpha2b used in this randomised controlled trial is effective in HCV CAH. Anti-HCV core IgM was the strongest predictor of long-term response in the present study.     

Clinical outcomes of extended versus intermittent administration of piperacillin/tazobactam for the treatment of hospital-acquired pneumonia: a randomized controlled trial

The purpose of this study was to assess the pharmacokinetic (PK) characteristics, clinical efficiency, and pharmacoeconomic parameters of piperacillin/tazobactam administered by extended infusion (EI) or intermittent infusion (II) in the treatment of hospital-acquired pneumonia (HAP) in critically ill patients with low illness severity in China. Fifty patients completed the study, with 25 patients receiving 4/0.5 g piperacillin/tazobactam over 30 min as the II group and 25 patients receiving 4/0.5 g piperacillin/tazobactam over 3 h every 6 h as the EI group. Drug assay was performed using high-performance liquid chromatography (HPLC). The percentage of the dosing interval for which the free piperacillin concentration (%fT) exceeds the minimum inhibitory concentration (MIC) was calculated. The patients’ therapy cost, clinical efficiency, and adverse effects were also recorded. %fT>MIC was about 100, 98.73, and 93.04 % in the EI arm versus 81.48, 53.29, and 42.15 % in the II arm, respectively, when the microorganism responsible for HAP had an MIC of 4, 8, and 16 mg/L. The therapy cost in the EI group was lower than that of the II group ($1351.72?±?120.39 vs. $1782.04?±?164.51, p?=?0.001). However, the clinical success rate, clinical failure rate, and drug-related adverse events did not significantly differ between groups. EI treatment with piperacillin/tazobactam was a cost-effective approach to the management of HAP, being equally clinically effective to conventional II.     

Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial

BACKGROUND: LH activity may influence treatment response and outcome in IVF cycles. METHODS: A randomized, assessor-blind, multinational trial compared ongoing pregnancy rates (primary end-point) in 731 women undergoing IVF after stimulation with highly purified menotrophin (HP-hMG) (n = 363) or recombinant FSH (rFSH) (n = 368) following a long GnRH agonist protocol. Patients received identical pre- and post-randomization interventions. One or two embryos were transferred on day 3. RESULTS: More oocytes were retrieved (P < 0.001) after rFSH treatment (11.8) compared with HP-hMG treatment (10.0), but a higher proportion developed into top-quality embryos (P = 0.044) with HP-hMG (11.3%) than with rFSH (9.0%). At the end of stimulation, lower estradiol (E(2)) (P = 0.031) and higher progesterone (P < 0.001) levels were found with rFSH, even after adjusting for follicular response. The distribution of hypo-, iso- and hyper-echogenic endometrium showed a significant (P = 0.023) shift towards the hyperechogenic pattern after rFSH treatment. The ongoing pregnancy rate per cycle was 27% with HP-hMG and 22% with rFSH [odds ratio (95% confidence interval): 1.25 (0.89-1.75)]. CONCLUSION: Superiority of HP-hMG over rFSH in ongoing pregnancy rate could not be concluded from this study, but non-inferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality, endocrine response and endometrial echogenicity exist between HP-hMG and rFSH preparations, which may be relevant for treatment outcome.     

Clinical and cost-effectiveness of a new nurse-led continence service: a randomised controlled trial

BACKGROUND: Continence services in the UK have developed at different rates within differing care models, resulting in scattered and inconsistent services. Consequently, questions remain about the most cost-effective method of delivering these services. AIM: To evaluate the impact of a new service led by a continence nurse practitioner compared with existing primary/secondary care provision for people with urinary incontinence and storage symptoms. DESIGN OF STUDY: Randomised controlled trial with a 3- and 6-month follow-up in men and women (n = 3746) aged 40 years and over living in private households (intervention [n = 2958]; control [n = 788]). SETTING: Leicestershire and Rutland, UK. METHOD: The continence nurse practitioner intervention comprised a continence service provided by specially trained nurses delivering evidence-based interventions using predetermined care pathways. They delivered an 8-week primary intervention package that included advice on diet and fluids; bladder training; pelvic floor awareness and lifestyle advice. The standard care arm comprised access to existing primary care including GP and continence advisory services in the area. Outcome measures were recorded at 3 and 6 months post-randomisation. RESULTS: The percentage of individuals who improved (with at least one symptom alleviated) at 3 months was 59% in the intervention group compared with 48% in the standard care group (difference of 11%, 95% CI = 7 to 16; P<0.001) The percentage of people reporting no symptoms or 'cured' was 25% in the intervention group and 15% in the standard care group (difference of 10%, 95% CI = 6 to 13, P = 0.001). At 6 months the difference was maintained. There was a significant difference in impact scores between the two groups at 3 and 6 months. CONCLUSIONS: The continence nurse practitioner-led intervention reduced the symptoms of incontinence, frequency, urgency and nocturia at 3 and 6 months; impact was reduced; and satisfaction with the new service was high.     

Antacid titration in the prevention of acute gastrointestinal bleeding: a controlled, randomized trial in 100 critically ill patients.

We randomized 100 critically ill patients at risk of developing acute gastrointestinal ulceration and bleeding into two groups. One (51 patients) received antacid prophylaxis, and the other (49 patients) received no specific form of prophylaxis. Hourly antacid titration kept the pH of the gastric contents above 3.5. Two of the 51 patients who received antacid prophylaxis and gastrointestinal bleeding. Twelve of the 49 control patients bled (P less than 0.005). Of the 12 patients in the control group who bled, seven were placed on antacid medication, and all seven apparently stopped bleeding. Analysis of all the patients showed that an increasing prevalence of respiratory, failure, sepsis, peritonitis, jaundice, renal failure and hypotension was correlated with a greater frequency of bleeding. No patients required operative treatment to control bleeding. These data indicate that the occurrence of acute gastrointestinal bleeding in critically ill patients can be reduced by antacid titration.     

Selective and total shunts in the treatment of bleeding varices. A randomized controlled trial.

Two types of surgical therapy of bleeding esophageal varices were evaluated in 48 patients by a randomized controlled trial: 24 were randomized for a total shunt and 24 for the selective shunt. In two of the latter, a total shunt had to be performed for technical reasons. The fatality rates (six in the 24 total, and six in 22 selective [performed], and seven in 24 selective [randomized]), the frequency of shunt occlusion (two in each group), and of recurrent gastronintestinal bleeding (three in each group) were similar. Encephalopathy developed more often after a total shunt -- 10 of 24, or one per 58 patient-months -- than after selective (performed) -- one of 22, or one per 593 patient-months (P less than 0.005). Total shunts consistently diverted the hepatopetal mesenteric-portal flow from the liver. Deterioration of hepatic function (maximum rate of urea synthesis) was greater after total than selective shunt (P less than 0.05).     

A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study.

BACKGROUND. Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. METHODS. We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. RESULTS. During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. CONCLUSIONS. In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.