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PubMed2004

A non-parametric procedure for evaluating treatment effect in the meta-analysis of survival data.

This paper addresses the problem of combining information from independent clinical trials which compare survival distributions of two treatment groups. Current meta-analytic methods which take censoring into account are often not feasible for meta-analyses which synthesize summarized results in published (or unpublished) references, as these methods require information usually not reported. The paper presents methodology which uses the log(-log) survival function difference, (i.e. log(-logS2(t))-log(-logS1(t)), as the contrast index to represent the multiplicative treatment effect on survival in independent trials. This article shows by the second mean value theorem for integrals that this contrast index, denoted as theta, is interpretable as a weighted average on a natural logarithmic scale of hazard ratios within the interval [0,t] in a trial. When the within-trial proportional hazards assumption is true, theta is the logarithm of the proportionality constant for the common hazard ratio for the interval considered within the trial. In this situation, an important advantage of using theta as a contrast index in the proposed methodology is that the estimation of theta is not affected by length of follow-up time. Other commonly used indices such as the odds ratio, risk ratio and risk differences do not have this invariance property under the proportional hazard model, since their estimation may be affected by length of follow-up time as a technical artefact. Thus, the proposed methodology obviates problems which often occur in survival meta-analysis because trials do not report survival at the same length of follow-up time. Even when the within-trial proportional hazards assumption is not realistic, the proposed methodology has the capability of testing a global null hypothesis of no multiplicative treatment effect on the survival distributions of two groups for all studies. A discussion of weighting schemes for meta-analysis is provided, in particular, a weighting scheme based on effective sample sizes is suggested for the meta-analysis of time-to-event data which involves censoring. A medical example illustrating the methodology is given. A simulation investigation suggested that the methodology performs well in the presence of moderate censoring.

Clinical Trials as Topic↗

PubMed2005

A meta-analysis of transjugular intrahepatic portosystemic shunt versus paracentesis for refractory ascites.

BACKGROUND/AIMS: Meta-analysis designed to provide evidence-based guidance on the effect of TIPS and paracentesis on mortality and encephalopathy in cirrhotic patients with refractory ascites. METHODS: Five randomized trials published between 1989 and 2005 were identified. RESULTS: The five trials involved 330 patients, and none included patients >76 years, with bilirubin >5-10 mg/dl or creatinine >3 mg/dl. Ascites recurrence was lower in the TIPS arm (RR 0.56; 95% CI 0.47-0.66). TIPS was associated with a greater risk of encephalopathy (RR 1.36; 95% CI 1.1-1.68) and severe encephalopathy (RR 1.72; 95% CI 1.14-2.58). TIPS did not affect mortality, as estimated by the RR (0.93; 95% CI 0.67-1.28, random effect model) and pooled hazard ratio (RR 1.09; 95% CI 0.84-1.88). Analysis of this outcome measure was limited by significant heterogeneity among trials. Liver-related mortality was homogenous and similar in both arms. Results were unaffected by excluding trials of lower quality or with a greater number of alcoholics. Meta-analysis of trials including patients with recidivant ascites revealed a lower mortality in the TIPS arm (RR 0.68; 95% CI 0.49-0.93). CONCLUSIONS: In patients with refractory ascites, a better control of ascites by TIPS does not translate into improved survival and worsens encephalopathy.

Ascites↗

PubMed2006

Role of preoperative chemotherapy for non-small-cell lung cancer: a meta-analysis.

The efficacy of preoperative chemotherapy for improving postoperative survival in patients with non-small-cell lung cancer (NSCLC) is controversial. We therefore conducted a meta-analysis of the published phase III randomized clinical trials (RCTs) to quantitatively evaluate the survival benefit of preoperative chemotherapy. After searching the MEDLINE database from 1980 to 2005, five studies were selected for the present meta-analysis. DerSimonian-Laird random effects analysis was used to estimate the hazard ratio (HR) of patients who underwent preoperative chemotherapy at the time points of 1, 3, and 5 years after surgery. A total of 564 patients in stages IB-IIIA served as the data sources. Preoperative chemotherapy was assigned to a total of 281 patients, while surgery alone was assigned to 283 patients. The combined HRs at 1, 3, and 5 years after resection were 0.65 (95% CI, 0.45-0.94), 0.83 (95% CI, 0.74-0.93), and 0.85 (95% CI, 0.70-1.04), respectively, for preoperative chemotherapy compared to surgery alone. The combined survival differences at 1 and 3 years time point were significant, while the difference at 5 years after resection was not significant. When only the 122 stage IIIA patients were analyzed, none of the HR at any time point was significant. In conclusion, the present meta-analysis suggests that the benefit of preoperative chemotherapy for patients with NSCLC is unclear, especially for stage IIIA patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Dietary cured meat and the risk of adult glioma: a meta-analysis of nine observational studies.

OBJECTIVE: N-nitroso compounds (NOCs) are recognized neural carcinogens in animal models and are suspected human carcinogens. A meta-analysis was performed examining the possible association of dietary N-nitroso intake from cured meats and the risk of gliomas in adults. METHODS: A prospective protocol was developed outlining the intent, methods, and statistical analysis of the meta-analysis. Data from nine epidemiological studies were pooled using a general variance-based meta-analytic method employing confidence intervals as described by Greenland. The outcome of interest was a summary relative risk (SRR) reflecting the risk of brain tumor (glioma) development associated with high dietary intake of cured meats (as defined by individual study investigators). Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity. RESULTS: Nine observational studies met protocol-specified inclusion criteria. Analysis for heterogeneity demonstrated a lack of statistical heterogeneity (p = 0.58). Pooling the data on dietary cured meat intake of all types yielded an RR of 1.48 (1.20-1.83), suggesting a 48% increased risk of glioma development among adults ingesting high levels of cured meat. Analyzing brain tumor risk by meat type yielded an RR of 0.90 (0.63-1.25) for hotdogs (a nonstatistically significant result), 1.31 (1.00-1.71) for bacon, and 1.64 (1.27-2.14) for ham. Sensitivity analyses showed that the failure of most studies to adjust for total energy intake might lead to a spurious positive association between cured meat intake and brain tumor risk. Insufficient data were available for analyzing dose-response relationships, although a few individual studies showed evidence of increasing risk with increasing cured meat intake. CONCLUSION: The available data do not provide clear support for the suspected causal association between ingestion of NOCs from cured meat in adults and subsequent brain tumor risk. Uncontrolled confounding may account for the previously noted positive association seen in some epidemiological studies.

Adult↗

PubMed2001

Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis: meta-analysis based on original patient data.

A meta-analysis (MA) based on original patient data has been performed comparing low molecular weight heparins (LMWH) with unfractionated heparin (UFH) in thrombosis prophylaxis after major surgical interventions. The analyses have been done for the following prespecified groups of studies: all studies, studies in orthopaedic surgery (OS) and studies in general surgery (GS, with further separation into low-dose studies [GS-LD] and high-dose studies [GS-HD]). Deep vein thrombosis (DVT, all locations) and wound haematoma were used as primary endpoints for efficacy and safety, respectively. The analysis confirms the results of previous publication-based meta-analyses. In GS there is no relevant difference between LMWH and UFH regarding efficacy; the safety results strongly depend on the dosage: under low-dose LMWH the risk of wound haematoma is significantly lower, under high-dose LMWH it is significantly higher than under UFH. However, most of the studies in the last group used regimens of LMWH that are not considered appropriate any more. In OS there is a trend towards a better efficacy and safety of LMWH. In addition, LMWHs are superior to UFH, in OS, with respect to the secondary endpoints proximal DVT and pulmonary embolism. The rates of proximal DVT and pulmonary embolism, respectively, are consistently lower under LMWH than under UFH, whereas slightly smaller rates of distal DVT are observed under UFH.

Double-Blind Method↗

PubMedDate not supplied

Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis.

OBJECTIVE: There is a rapidly evolving debate on the indications and appropriate duration of therapy for postmenopausal hormone therapy. The objective of this meta-analysis was to examine the specific relationships of postmenopausal estrogen therapy (ET), postmenopausal combined (estrogen-progestogen) hormone therapy (CHT), and the incidence of breast cancer. DESIGN: We performed computerized searches of MEDLINE and CancerLit through September 2003 and reviewed reference lists of retrieved studies and meta-analyses. We included English-language studies that identified noncontraceptive postmenopausal hormone use; reported on the risks of "current use" of ET and/or CHT and breast cancer incidence; were case-control, cohort, or experimental; and reported either an odds ratio (OR), relative risk (RR), or HR with CIs. Two investigators were involved during all stages of study selection and independently extracted all data selected for inclusion in meta-analyses. RESULTS: Meta-analysis of 13 studies of ET and breast cancer (700,000 women) resulted in an OR of 1.16 (95% confidence limits [CL] 1.06, 1.28), with estimates for less than 5 years use 1.16 (1.02, 1.32) and more than 5 years use 1.20 (1.06, 1.37). Meta-analysis of eight studies of CHT and breast cancer (650,000 women) resulted in an OR of 1.39 (95% CL 1.12, 1.72), with estimates for less than 5 years use 1.35 (1.16, 1.57) and more than 5 years use 1.63 (1.22, 2.18). CONCLUSIONS: Data from observational studies support the association of increased but considerably different risks for breast cancer incidence among current users of ET and CHT. These represent the first pooled estimates for ET. CHT estimates correspond to those from randomized trials.

Breast Neoplasms↗

PubMed2002

Surgery for pediatric vocal cord paralysis: a meta-analysis.

OBJECTIVE: The study goal was to determine the impact of various surgical procedures for bilateral vocal cord paralysis in children by using established principles of meta-analysis. STUDY DESIGN AND SETTING: We conducted a retrospective review of the literature in which a predetermined protocol was used to identify articles for meta-analysis. Six articles met inclusion criteria, and pertinent data were extracted. RESULTS: Pooled data analysis demonstrated primary procedure-specific decannulation rates for external arytenoidopexy for 19 of 24 (79%), external arytenoidectomy for 14 of 19 (74%), CO2 laser arytenoidectomy for 4 of 10 (40%), and costal cartilage graft procedures for 2 of 2 (100%). External arytenoid procedures are more efficacious than CO2 laser procedures in terms of primary decannulation (P = 0.02). CONCLUSION: Meta-analysis of the existing literature reveals that external arytenoidopexy and external arytenoidectomy are equivalently effective procedures and that the two combined are significantly more effective than CO2 ablative procedures. SIGNIFICANCE: External procedures appear to be more effective as a first-line treatment in pediatric vocal cord paralysis, with arytenoidopexy with or without partial arytenoidectomy offering an attractive first-line surgical option.

Adolescent↗

PubMed1991

A meta-analysis of prophylactic antibiotics in head and neck surgery.

Although it is generally agreed that prophylactic antibiotics are necessary for the prevention of postoperative wound infection, the choice of antibiotic regimen is controversial. In an attempt to determine the most effective antibiotic regimen, a meta-analysis of published clinical trials of prophylactic antibiotics for head and neck surgery was undertaken. The meta-analysis revealed a relative difference in infection rates of 43.7 percent in favor of the use of antibiotics versus placebo, of 8.3 percent in favor of multiple antibiotics versus a single antibiotic, of 13.7 percent in favor of multiple antibiotics versus cefazolin, and of 4.1 percent in favor of multiple-day prophylaxis versus single-day prophylaxis. This meta-analysis suggests that a 1-day course of clindamycin may be the most effective prophylactic antibiotic regimen for head and neck surgery.

Anti-Bacterial Agents↗

PubMed2006

The PTPN22 C1858T functional polymorphism and autoimmune diseases--a meta-analysis.

OBJECTIVE: To assess whether combined evidence shows the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) C1858T polymorphism and autoimmune diseases, and to summarize the effect size of the polymorphism associated with susceptibility of autoimmune diseases. METHODS: We surveyed studies on the PTPN22 C1858T polymorphism and autoimmune diseases using comprehensive Medline search and review of the references. Meta-analysis was performed for genotypes T/T (recessive effect), T/T + C/T (dominant effect) and T-allele in random effects models. RESULTS: Twenty-nine studies with 43 comparisons including 13 rheumatoid arthritis (RA), six systemic lupus erythematosus (SLE), six type-1 DM (T1D), three Grave's disease (GD), four inflammatory bowel diseases (IBD), three juvenile idiopathic arthritis (JIA), two psoriasis, two multiple sclerosis, two Addison's disease and two Celiac disease were available for the meta-analysis. The overall odds ratios (ORS) for T-allele, T/T and T/T + C/T genotypes were significantly increased in RA, SLE, GD and T1D (OR for T-allele = 1.58, 1.49, 1.85, 1.61, respectively, P < 0.00001). This meta-analysis showed the association between the T-allele and the T/T genotype and JIA (OR = 1.34, P = 0.03; OR = 1.97, P = 0.02) but did not reveal the association between the PTPN22 C1858T polymorphism and IBD, psoriasis, multiple sclerosis, Addison's disease and Celiac disease. CONCLUSION: This meta-analysis demonstrates that the PTPN22 1858T allele confers susceptibility to RA, SLE, GD, T1D and JIA, supporting evidence of association of the PTPN22 gene with subgroup of autoimmune diseases.

Autoimmune Diseases↗

PubMed2006

Efficacy of different intraocular lens materials and optic edge designs in preventing posterior capsular opacification: a meta-analysis.

PURPOSE: To evaluate the efficacy of different intraocular lens (IOL) materials and optic edge designs in preventing posterior capsular opacification (PCO). DESIGN: Systematic review and meta-analysis. METHODS: Pertinent studies were selected through an electronic search of the Cochrane Library, MEDLINE, and Embase. The randomized controlled trials meeting the predefined criteria were reviewed systematically by meta-analysis. The treatment effects were measured as risk difference, and the pooled estimates were computed according to a random effect model. RESULTS: In total, 23 randomized controlled trials were included in the present meta-analysis. The pooled risk differences of Nd:YAG laser capsulotomy rates were -24% (95% confidence interval [CI], -29% to -20%) comparing acrylic with polymethylmethacrylate (PMMA) lenses; -9% (95% CI, -17% to -1%) comparing silicone with PMMA lenses; 14% (95% CI, -8% to 36%) comparing hydrogel with PMMA lenses; 4% (95% CI, -2% to 10%) comparing silicone with acrylic lenses; 19% (95% CI, 8% to 30%) comparing hydrogel with acrylic lenses; and 28% (95% CI, 10% to 46%) comparing hydrogel with silicone lenses. The pooled risk differences of PCO rates were -39% (95% CI, -47% to -31%) comparing acrylic with PMMA lenses; -14% (95% CI, -29% to 0%) comparing silicone with acrylic lenses; 56% (95% CI, 36% to 75%) comparing hydrogel with acrylic lenses; and 48% (95% CI, 31% to 64%) comparing hydrogel with silicone lenses. When comparing sharp with rounded-edge designs, pooled risk differences of capsulotomy rates were -47% (95% CI, -77% to -17%) in PMMA lenses, -22% (95% CI, -47% to 2%) in acrylic lenses, and -9% (95% CI, -17% to 0%) in silicone lenses; pooled risk differences of PCO rates were -28% (95% CI, -50% to -7%) in acrylic lenses and -37% (95% CI, -46% to -27%) in silicone lenses. CONCLUSIONS: The rates of PCO and Nd:YAG laser capsulotomy may be influenced by different IOL biomaterials and optic edge designs. The lenses made by acrylic and silicone and those with sharp optic edges are superior in lowering the rates of PCO and laser capsulotomy.

Acrylic Resins↗

PubMedDate not supplied

Incidence of cancer among female flight attendants: a meta-analysis.

BACKGROUND: Airline flight personnel work in a unique environment with exposure to known or suspected carcinogens and mutagens including ionizing cosmic radiation. A meta-analysis was conducted to study whether the occupational exposure of female flight attendants (FA) increased their relative risk of cancer incidence. METHODS: A bibliographical computer search from 1966 to 2005 of cancer incidence cohort studies of female FA was performed. Combined relative risks (RRc) in cancer incidence were calculated by means of meta-analysis. RESULTS: RRc and 95% confidence interval (CI) for malignant melanoma and breast cancer in female FA were 2.13 (95% CI: 1.58-2.88) and 1.41 (1.22-1.62) (p < 0.0001). Excess risk was not significant for all-site cancer with RRc of 1.10 (0.99-1.21). CONCLUSIONS: The meta-analysis confirmed the significantly increased risks for malignant melanoma and breast cancer in female FA. Increased exposure to cosmic radiation during flight has been suggested as a potential occupational risk factor. Ultraviolet radiation exposure on board seems an unlikely occupational risk, but nonoccupational leisure time sun exposure is a possible risk factor. The etiology of the observed increase in incidence of some cancers remains controversial because assessment of possible confounders, especially nonoccupational exposure factors, has thus far been limited.

Air Pollutants, Radioactive↗

PubMed2005

Meta-analysis: pharmacologic treatment of obesity.

BACKGROUND: In response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used. PURPOSE: To assess the efficacy and safety of weight loss medications approved by the U.S. Food and Drug Administration and other medications that have been used for weight loss. DATA SOURCES: Electronic databases, experts in the field, and unpublished information. STUDY SELECTION: Up-to-date meta-analyses of sibutramine, phentermine, and diethylpropion were identified. The authors assessed in detail 50 studies of orlistat, 13 studies of fluoxetine, 5 studies of bupropion, 9 studies of topiramate, and 1 study each of sertraline and zonisamide. Meta-analysis was performed for all medications except sertraline, zonisamide, and fluoxetine, which are summarized narratively. DATA EXTRACTION: The authors abstracted information about study design, intervention, co-interventions, population, outcomes, and methodologic quality, as well as weight loss and adverse events from controlled trials of medication. DATA SYNTHESIS: All pooled weight loss values are reported relative to placebo. A meta-analysis of sibutramine reported a mean difference in weight loss of 4.45 kg (95% CI, 3.62 to 5.29 kg) at 12 months. In the meta-analysis of orlistat, the estimate of the mean weight loss for orlistat-treated patients was 2.89 kg (CI, 2.27 to 3.51 kg) at 12 months. A recent meta-analysis of phentermine and diethylpropion reported pooled mean differences in weight loss at 6 months of 3.6 kg (CI, 0.6 to 6.0 kg) for phentermine-treated patients and 3.0 kg (CI, -1.6 to 11.5 kg) for diethylpropion-treated patients. Weight loss in fluoxetine studies ranged from 14.5 kg of weight lost to 0.4 kg of weight gained at 12 or more months. For bupropion, 2.77 kg (CI, 1.1 to 4.5 kg) of weight was lost at 6 to 12 months. Weight loss due to topiramate at 6 months was 6.5% (CI, 4.8% to 8.3%) of pretreatment weight. With one exception, long-term studies of health outcomes were lacking. Significant side effects that varied by drug were reported. LIMITATIONS: Publication bias may exist despite a comprehensive search and despite the lack of statistical evidence for the existence of bias. Evidence of heterogeneity was observed for all meta-analyses. CONCLUSIONS: Sibutramine, orlistat, phentermine, probably diethylpropion, bupropion, probably fluoxetine, and topiramate promote modest weight loss when given along with recommendations for diet. Sibutramine and orlistat are the 2 most-studied drugs.

Adult↗

PubMed2006

Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis.

BACKGROUND: Non-invasive positive pressure ventilation (NIPPV), using continuous positive airway pressure (CPAP) or bilevel ventilation, has been shown to reduce the need for invasive mechanical ventilation in patients with acute cardiogenic pulmonary oedema. We assessed additional benefits of NIPPV in a meta-analysis. METHODS: Meta-analysis comparison in acute cardiogenic pulmonary oedema was undertaken to compare (1) CPAP with standard therapy (oxygen by face-mask, diuretics, nitrates, and other supportive care), (2) bilevel ventilation with standard therapy, and (3) bilevel ventilation with CPAP, incorporating randomised controlled trials identified by electronic and hand search (1966-May, 2005). In 23 trials that fulfilled inclusion criteria, we assessed the effect of NIPPV on hospital mortality and mechanical ventilation, estimated as relative risks. FINDINGS: CPAP was associated with a significantly lower mortality rate than standard therapy (relative risk 0.59, 95% CI 0.38-0.90, p=0.015). A non-significant trend towards reduced mortality was seen in the comparison between bilevel ventilation and standard therapy (0.63, 0.37-1.10, p=0.11). We recorded no substantial difference in mortality risk between bilevel ventilation and CPAP (p=0.38). The need for mechanical ventilation was reduced with CPAP (0.44, 0.29-0.66, p=0.0003) and with bilevel ventilation (0.50, 0.27-0.90, p=0.02), compared with standard therapy; but no significant difference was seen between CPAP and bilevel ventilation (p=0.86). Weak evidence of an increase in the incidence of new myocardial infarction with bilevel ventilation versus CPAP was recorded (1.49, 0.92-2.42, p=0.11). Heterogeneity of treatment effects was not evident for mortality or mechanical ventilation across patients' groups. INTERPRETATION: In patients with acute cardiogenic pulmonary oedema, CPAP and bilevel ventilation reduces the need for subsequent mechanical ventilation. Compared with standard therapy, CPAP reduces mortality; our results also suggest a trend towards reduced mortality after bilevel NIPPV.

Continuous Positive Airway Pressure↗

PubMed1992

Chlorination, chlorination by-products, and cancer: a meta-analysis.

OBJECTIVES: Individual epidemiological investigations into the association between chlorination by-products in drinking water and cancer have been suggestive but inconclusive. Enough studies exist to provide the basis for a meaningful meta-analysis. METHODS: An extensive literature search was performed to identify pertinent case-control studies and cohort studies. Consumption of chlorinated water, surface water, or water with high levels of chloroform was used as a surrogate for exposure to chlorination by-products. Relative risk estimates were abstracted from the individual studies and pooled. RESULTS: A simple meta-analysis of all cancer sites yielded a relative risk estimate for exposure to chlorination by-products of 1.15 (95% CI: 1.09, 1.20). Pooled relative risk estimates for organ-specific neoplasms were 1.21 (95% CI: 1.09, 1.34) for bladder cancer and 1.38 (95% CI: 1.01, 1.87) for rectal cancer. When studies that adjusted for potential confounders were pooled separately, estimates of relative risks did not change substantially. CONCLUSIONS: The results of this meta-analysis suggest a positive association between consumption of chlorination by-products in drinking water and bladder and rectal cancer in humans.

Case-Control Studies↗

PubMed1992

Quality assessment and meta-analysis of systemic tetracycline use in chronic adult periodontitis.

The use of systemic tetracycline in the treatment of periodontal disease has been controversial. To investigate this controversy, we performed a quality assessment and attempted to perform a meta-analysis of 13 published studies. We evaluated the quality of the study protocol and data analysis and presentation for each study. We were unable to combine data from the majority of studies due to heterogeneity of the outcomes evaluated and limitations in data reported in the individual studies. Therefore, only 2 studies were included in the quantitative meta-analysis. On a scale of 0-1, the mean score for this group of studies was 0.27 (+/- 0.19) for study protocol and 0.31 (+/- 0.11) for data analysis and presentation. Mean reduction in probing depth for the group treated with tetracycline plus scaling was 2.45 mm; for the group which received only scaling, 2.02 mm; for the group that received only tetracycline, 1.98 mm; and for the control group, 0.65 mm. We conclude that analysis of data from the published literature does not demonstrate that the use of systemic tetracycline is more beneficial than conventional treatment in the management of adult periodontal disease. More information is needed in order to perform an extensive meta-analysis of this subject.

Adult↗

PubMed2004

Updated meta-analysis of clinical trials of Serenoa repens extract in the treatment of symptomatic benign prostatic hyperplasia.

OBJECTIVES: To determine, by analysing all available clinical trial data, the clinical efficacy against placebo of an extract from the fruit of the American dwarf palm tree, Serenoa repens (Permixon, Pierre Fabre Médicament, Castres, France), as there is controversy about the use of phytotherapeutic agents in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). METHODS: All clinical trial data published on Permixon, comprising 14 randomized clinical trials and three open-label trials, involving 4280 patients, were analysed. These trials were of different size (22-1100 patients) and duration (21-720 days). The peak urinary flow rate and nocturia were the two common endpoints. The statistical analysis was based on a random-effects meta-analysis. RESULTS: Permixon was associated with a mean (sem) reduction in the International Prostate Symptom Score (IPSS) of 4.78 (0.41). The mean placebo effect on peak urinary flow rate was an increase of 1.20 (0.49) mL/s. The estimated effect of Permixon was a further increase of 1.02 (0.50) mL/s (P = 0.042). Placebo was associated with a reduction in the mean number of nocturnal voids of 0.63 (0.14); there was a further reduction attributable to Permixon of 0.38 (0.07) (P < 0.001). There was some heterogeneity among the studies for nocturia; one over 2 years involving 396 patients and showing no difference between placebo and Permixon had a large effect on the results. CONCLUSIONS: This meta-analysis of all available published trials of Permixon for treating men with BPH showed a significant improvement in peak flow rate and reduction in nocturia above placebo, and a 5-point reduction in the IPSS.

Androgen Antagonists↗

PubMed1998

Comparison of intrauterine insemination with timed intercourse in superovulated cycles with gonadotropins: a meta-analysis.

OBJECTIVE: To compare timed intercourse and IUI with the husband's sperm in patients with unexplained infertility who are undergoing superovulation with gonadotropins. DESIGN: Meta-analysis. All published reports of randomized, prospective studies with an English-language abstract extracted from MEDLINE were analyzed. A crossover search was done from the papers obtained. SETTING: Academic center. PATIENT(S): Couples with unexplained infertility. INTERVENTION(S): Meta-analysis of studies evaluating patients superovulated with gonadotropins and randomized for timed intercourse or IUI. MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs) were obtained. The common odds ratio (OR) and 95% confidence intervals (95% CI) were calculated. RESULT(S): There were 49 pregnancies in 431 cycles of timed intercourse (11.37%), whereas there were 110 pregnancies in 549 cycles of IUI (20.04%). The PRs for IUI were significantly increased compared with those for timed intercourse in superovulation cycles (common OR = 1.84; 95% CI = 1.30-2.62). CONCLUSION(S): On the basis of the meta-analysis of 980 cycles in randomized and prospective studies, a patient's chances of becoming pregnant are greater with IUI with her husband's sperm than with timed intercourse in cycles superovulated with gonadotropins.

Adult↗

PubMed2026

Pharmacological Interventions for Weight Reduction in Patients With Schizophrenia Treated With Antipsychotics: A Systematic Review and Network Meta-Analysis.

IMPORTANCE: Significant weight gain is a concerning adverse effect of antipsychotic medications experienced by patients with schizophrenia spectrum disorders (SSDs). Its high prevalence and significant contribution to cardiometabolic morbidity in this population warrant better consensus on the management of antipsychotic-induced weight gain and related comorbidity. OBJECTIVES: To evaluate the association between pharmacological interventions and changes in body weight among antipsychotic-treated patients with SSDs. DATA SOURCES: Ovid MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) Search Portal were searched up to December 5, 2025. STUDY SELECTION: Randomized clinical trials examining any pharmacological intervention for weight reduction in antipsychotic-treated patients with SSDs were included. No restrictions to study duration were applied. DATA EXTRACTION AND SYNTHESIS: A systematic review and frequentist random-effects network meta-analysis was conducted. Certainty in the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. The first round of data analysis took place between May 2025 to November 2025 and was updated in December 2025. MAIN OUTCOMES AND MEASURES: The primary outcome was change in body weight following treatment with pharmacological agent vs placebo or standard care. Secondary outcomes included other anthropometric and metabolic parameters. RESULTS: A total of 95 studies examining 39 individual pharmacological interventions were included in this review (pooled N = 5898). The network meta-analysis found that semaglutide (mean difference [MD], -10.98 kg; 95% CI, -13.33 to -8.62; k = 3; moderate certainty), liraglutide (MD, -5.43 kg; 95% CI, -8.54 to -2.33; k = 2; moderate certainty), topiramate (MD, -3.95 kg; 95% CI, -5.89 to -2.02; k = 5; moderate certainty), metformin (MD, -3.86 kg; 95% CI, -5.02 to -2.70; k = 16; moderate certainty), and exenatide (MD, -2.97 kg; 95% CI, -5.83 to -0.11; k = 3; moderate certainty) were associated with the most significant reductions in body weight compared to placebo. Other interventions including ramelteon, nizatidine, and aripiprazole were also found to be associated with weight-reducing effects but with very low certainty of evidence. Clinically meaningful weight change of 5% or greater was observed with semaglutide and metformin. Beneficial effects on other metabolic outcomes were also noted with several of the medications, and there were no major concerns with gastrointestinal adverse effects or leaving the study early (ie, dropouts) between interventions. CONCLUSIONS AND RELEVANCE: This systematic review and network meta-analysis found substantial variability in weight-related outcomes across pharmacological interventions for antipsychotic-treated individuals with SSDs. Semaglutide, liraglutide, topiramate, metformin, and exenatide were associated with the greatest reductions in body weight and were supported by the highest-certainty evidence, providing guidance for clinicians managing antipsychotic-associated weight gain.

Humans↗