Abstract 3789: Nessun Dorma : Have the Risks of Rosiglitazone been Exaggerated?

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
George A Diamond ◽  
Sanjay Kaul
Keyword(s):  
Confidence Intervals ◽  
Effect Size ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Sensitivity Analyses ◽  
Odds Ratios ◽  
True Effect Size ◽  
Index Study ◽  
The Stability

Background A highly publicized meta-analysis of 42 clinical trials comprising 27,844 diabetics ignited a firestorm of controversy by charging that treatment with rosiglitazone was associated with a “…worrisome…” 43% greater risk of myocardial infarction ( p =0.03) and a 64% greater risk of cardiovascular death ( p =0.06). Objective The investigators excluded 4 trials from the infarction analysis and 19 trials from the mortality analysis in which no events were observed. We sought to determine if these exclusions biased the results. Methods We compared the index study to a Bayesian meta-analysis of the entire 42 trials (using odds ratio as the measure of effect size) and to fixed-effects and random-effects analyses with and without a continuity correction that adjusts for values of zero. Results The odds ratios and confidence intervals for the analyses are summarized in the Table . Odds ratios for infarction ranged from 1.43 to 1.22 and for death from 1.64 to 1.13. Corrected models resulted in substantially smaller odds ratios and narrower confidence intervals than did uncorrected models. Although corrected risks remain elevated, none are statistically significant (*p<0.05). Conclusions Given the fragility of the effect sizes and confidence intervals, the charge that roziglitazone increases the risk of adverse events is not supported by these additional analyses. The exaggerated values observed in the index study are likely the result of excluding the zero-event trials from analysis. Continuity adjustments mitigate this error and provide more consistent and reliable assessments of true effect size. Transparent sensitivity analyses should therefore be performed over a realistic range of the operative assumptions to verify the stability of such assessments especially when outcome events are rare. Given the relatively wide confidence intervals, additional data will be required to adjudicate these inconclusive results.

scholarly journals Association of bisphenol A with puberty timing: a meta-analysis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Hui Meng ◽  
Yunping Zhou ◽  
Yunxia Jiang
Keyword(s):  
Bisphenol A ◽  
Confidence Intervals ◽  
Random Effects ◽  
Strong Correlation ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Random Effects Models ◽  
Study Heterogeneity ◽  
The Relationship ◽  
Prevalence Ratios

AbstractObjectivesThe results of existing studies on bisphenol A (BPA) and puberty timing did not reach a consensus. Thereby we performed this meta-analytic study to explore the association between BPA exposure in urine and puberty timing.MethodsMeta-analysis of the pooled odds ratios (OR), prevalence ratios (PR) or hazards ratios (HR) with 95% confidence intervals (CI) were calculated and estimated using fixed-effects or random-effects models based on between-study heterogeneity.ResultsA total of 10 studies involving 5621 subjects were finally included. The meta-analysis showed that BPA exposure was weakly associated with thelarche (PR: 0.96, 95% CI: 0.93–0.99), while no association was found between BPA exposure and menarche (HR: 0.99, 95% CI: 0.89–1.12; OR: 1.02, 95% CI: 0.73–1.43), and pubarche (OR: 1.00, 95% CI: 0.79–1.26; PR: 1.00, 95% CI: 0.95–1.05).ConclusionsThere was no strong correlation between BPA exposure and puberty timing. Further studies with large sample sizes are needed to verify the relationship between BPA and puberty timing.

scholarly journals Association of UCP1 and UCP2 variants with diabetic retinopathy susceptibility in type-2 diabetes mellitus patients: a meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xujia Liu ◽  
Zehua Jiang ◽  
Guihua Zhang ◽  
Tsz Kin Ng ◽  
Zhenggen Wu
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Fixed Effects ◽  
Literature Search ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Fixed Effects Models ◽  
Type 2 Dm ◽  
Subgroup Analyses

Abstract Background Genetic association of uncoupling proteins (UCPs) variants with the susceptibility of diabetic retinopathy (DR) in diabetes mellitus (DM) patients has been reported but with controversy. Here we aimed to conduct a meta-analysis to confirm the association of different UCPs variants with DR. Methods Three databases (Medline Ovid, Embase Ovid and CENTRAL) were applied in the literature search. Five genetic models, including allelic, homozygous, heterozygous, dominant and recessive models, were evaluated. Odds ratios (OR) were estimated under the random or fixed-effects models. Subgroup analyses, publication bias and sensitivity analyses were also conducted. Results Eleven studies on 2 UCPs variants (UCP1 rs1800592 and UCP2 rs659366) were included. Our meta-analysis showed that UCP1 rs1800592 was not associated with DR in type-2 DM patients, and UCP2 rs659366 also showed no association with DR. In the subgroup analyses on the stage of DR, allele G of UCP1 rs1800592 significantly increased the susceptibility of proliferative diabetic retinopathy (PDR) in type-2 DM patients in the allelic (OR = 1.26, P = 0.03) and homozygous models (OR = 1.60, P = 0.04). Subgroup analysis on ethnicity did not found any significant association of rs1800592 and rs659366 with DR. Conclusion Our meta-analysis confirmed the association of UCP1 rs1800592 variant with PDR in patients with type-2 DM, suggesting its potential as a genetic marker for PDR prediction in population screening.

Use of Statins and Breast Cancer: A Meta-Analysis of Seven Randomized Clinical Trials and Nine Observational Studies

2005 ◽  
Vol 23 (34) ◽  
pp. 8606-8612 ◽  
Author(s):  
Stefanos Bonovas ◽  
Kalitsa Filioussi ◽  
Nikolaos Tsavaris ◽  
Nikolaos M. Sitaras
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Publication Bias ◽  
Observational Studies ◽  
Fixed Effects ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Fixed Effects Model

Purpose A growing body of evidence suggests that statins may have chemopreventive potential against breast cancer. Laboratory studies demonstrate that statins induce apoptosis and reduce cell invasiveness in various cell lines, including breast carcinoma cells. However, the clinical relevance of these data remains unclear. The nonconclusive nature of the epidemiologic data prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Patients and Methods A comprehensive search for articles published up until 2005 was performed; reviews of each study were conducted; and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed. Results Seven large randomized trials and nine observational studies (five case-control and four cohort studies) contributed to the analysis. We found no evidence of publication bias or heterogeneity among the studies. Statin use did not significantly affect breast cancer risk (fixed effects model: RR = 1.03; 95% CI, 0.93 to 1.14; random effects model: RR = 1.02; 95% CI, 0.89 to 1.18). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, the sensitivity analysis confirmed the stability of our results. Conclusion Our meta-analysis findings do not support a protective effect of statins against breast cancer. However, this conclusion is limited by the relatively short follow-up times of the studies analyzed. Further studies are required to investigate the potential decrease in breast cancer risk among long-term statin users.

scholarly journals Association between BRCA1 polymorphisms rs799917 and rs1799966 and breast cancer risk: a meta-analysis

2019 ◽  
Vol 47 (4) ◽  
pp. 1409-1416
Author(s):  
Meiming Yang ◽  
Xiaoli Du ◽  
Feng Zhang ◽  
Shifang Yuan
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Confidence Intervals ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Recessive Model ◽  
Dominant Model ◽  
Odds Ratios

Background Several studies have reported correlations between BRCA1 polymorphisms rs799917 and rs1799966 with the risk of breast cancer (BC). However, this relationship remains controversial. Methods We conducted a meta-analysis of seven studies to assess the associations between BRCA1 rs799917 and rs1799966 and BC risk, with the aim of more accurately determining the potential correlation. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the correlation of rs799917 and rs1799966 with BC risk. Results There was no overall correlation between BRCA1 rs799917 and BC risk (TT vs CC: OR = 0.87, 95% CI = 0.66–1.16; CT vs CC: OR = 1.02, 95% CI = 0.89–1.15; dominant model: OR = 0.99, 95% CI = 0.88–1.11; recessive model: OR = 0.87, 95% CI = 0.65–1.16). Subgroup analysis by ethnicity also revealed no significant correlation between rs799917 and BC risk in either Asians or Caucasians. There was also no significant association between BRCA1 rs1799966 and BC risk (GG vs AA: OR = 0.70, 95% CI = 0.33–1.47; AG vs AA: OR = 0.68, 95% CI = 0.35–1.30; dominant model: OR = 0.76, 95% CI = 0.49–1.06; recessive model: OR = 0.82, 95% CI = 0.49–1.36). Conclusion BRCA1polymorphisms rs799917 and rs1799966 were not significantly associated with BC risk in this meta-analysis.

A Meta-Analysis Study of the Effect of Chilling on Prevalence of Salmonella on Pig Carcasses

2008 ◽  
Vol 71 (7) ◽  
pp. 1330-1337 ◽  
Author(s):  
U. GONZALES BARRON ◽  
D. BERGIN ◽  
F. BUTLER
Keyword(s):  
Relative Risk ◽  
Effect Size ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Risk Difference ◽  
Detection Methods ◽  
Binary Outcomes ◽  
Production Chain ◽  
Prevalence Studies ◽  
Pig Carcasses

In the field of food safety, meta-analysis can be used to combine results of prevalence studies of pathogens at critical stages within the food processing chain so that policy makers can access reliable and concise information on the effectiveness of interventions for controlling and preventing foodborne illnesses in humans. The objective of this work was to demonstrate the applicability of a parametric approach of meta-analysis to the specific case of determining the overall effect of chilling on Salmonella prevalence on pig carcasses. A meta-analysis was performed on each of two parameters measuring effect size for binary outcomes (relative risk and risk difference). Both meta-analyses confirmed that the chilling operation has a significant beneficial effect (P &lt; 0.001) on the reduction of Salmonella prevalence on pig carcasses. Because risk difference is a parameter sensitive to the differences across studies in carcass swab areas and Salmonella detection methods, its meta-analysis highly reflected this heterogeneity (P &lt; 0.001). However, parameterization of relative risk, not being biased by the above sources of variability, did not give rise to heterogeneity among studies and produced a fixed-effects meta-analysis solution, which is deemed more suitable for compilations based on a small number of individual studies (n = 9). Because of the systematic approach of meta-analysis (i.e., individual studies are weighed according to precision) and its reliance for actual data, the output distribution of the relative risk effect size (~eN(−0.868,0.166)) merits consideration for inclusion in the chilling stage of quantitative risk assessments modeling the prevalence of this pathogen along the pork production chain.

scholarly journals The efficacy of n-3 fatty acids DHA and EPA (fish oil) for perinatal depression

2010 ◽  
Vol 104 (11) ◽  
pp. 1577-1585 ◽  
Author(s):  
Linda A. W. Jans ◽  
Erik J. Giltay ◽  
A. J. Willem Van der Does
Keyword(s):  
Effect Size ◽  
Fixed Effects ◽  
Perinatal Depression ◽  
Post Partum ◽  
Meta Analysis ◽  
Placebo Treatment ◽  
Small Sample ◽  
Future Research ◽  
Fixed Effects Model ◽  
Beneficial Effects

Depressive symptoms are common during pregnancy and the post-partum period. Although essential n-3 PUFA may have beneficial effects on depression, it remains unclear whether they are also effective for perinatal depression. The purpose of the present study was to assess the efficacy of n-3 supplementation for perinatal depression, by performing a meta-analysis on currently available data. After a thorough literature search, we included seven randomised controlled trials in the meta-analysis, all with EPA and/or DHA supplementation. Most studies were judged to be of low-to-moderate quality, mainly due to small sample sizes and failure to adhere to Consolidated Standards of Reporting Trials guidelines. Some studies were not primarily designed to address perinatal depression. A total of 309 women on n-3 fatty acid supplementation were compared with 303 women on placebo treatment. n-3 Supplementation was not found to be significantly more effective than placebo at post-treatment with a pooled effect size (Hedges's g) of − 0·03 (95 % CI − 0·18, 0·13; P = 0·76) using a fixed-effects model. Heterogeneity was low-to-moderate (I2 = 30 %). In a subgroup analysis of three small studies of pregnant women with major depression, there was some indication of effectiveness (effect size 0·17; 95 % CI − 0·21, 0·55). In conclusion, the question of whether EPA and DHA administration is effective in the prevention or treatment of perinatal depression cannot be answered yet. Future research should focus on women who are clinically depressed (or at risk). The quality of research in this area needs to improve.

Effects on suicidal risk: Comparison of clozapine to other newer medicines indicated to treat schizophrenia or bipolar disorder

2021 ◽  
pp. 026988112110297
Author(s):  
Alberto Forte ◽  
Maurizio Pompili ◽  
Benedetta Imbastaro ◽  
Gabriele Pasquale De Luca ◽  
Martina Mastrangelo ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Confidence Intervals ◽  
Suicidal Behavior ◽  
Meta Analysis ◽  
Random Effect ◽  
Paired Comparisons ◽  
Suicidal Risk ◽  
Odds Ratios ◽  
Unique Effect ◽  
Reduce Risk

Background: Clozapine is the only treatment with regulatory-recognition of lowering suicidal risk, at least in schizophrenia patients. It remains uncertain whether such effects extend to other drugs for psychosis. Methods: We searched for reports on rates of suicidal behavior during treatment with clozapine and other modern drugs for psychosis (aripiprazole, olanzapine, risperidone, quetiapine, and ziprasidone) versus comparison or control treatments and analyzed the contrasts by random-effect meta-analysis to obtain pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: We identified 35 paired comparisons of modern drugs for psychosis versus comparison or control treatments in 18 reports. There was moderate overall superiority of all agents tested over alternatives (OR = 0.522, p = 0.004). With clozapine, this effect was large (OR = 0.229, p < 0.0001) and consistent (7/7 trials), but significant antisuicidal effects were not found with other drugs for psychosis in 28 other trials (OR = 0.941, p = 0.497). Apparent efficacy of specific agents ranked: risperidone ⩾ olanzapine ⩾ aripiprazole ⩾ ziprasidone ⩾ mixed drugs for psychosis ⩾ quetiapine, but none of these differences was significant. Conclusions: An ability of clozapine to reduce risk of suicides and attempts in schizophrenia patients appears to be a unique effect not shared with other modern medicines indicated for schizophrenia or bipolar disorder.

Comparative Effectiveness of Lenalidomide Plus Dexamethasone for the Treatment of Refractory/Relapsed Multiple Myeloma: A Systematic Review and Mixed Treatment Comparison

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4076-4076
Author(s):  
Sallie Stradwick ◽  
Nick Freemantle ◽  
John Snowden ◽  
Felipe Rodrigues ◽  
Nic Brereton
Keyword(s):  
Multiple Myeloma ◽  
Combination Therapy ◽  
Confidence Intervals ◽  
Random Effects ◽  
Comparative Effectiveness ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Treatment Comparison ◽  
Mixed Treatment ◽  
Secondary Outcomes

Abstract Abstract 4076 OBJECTIVES: To evaluate the comparative effectiveness of lenalidomide (25 mg) plus dexamethasone (40 mg) (LEN/dex) for the treatment of relapsed/refractory multiple myeloma (RRMM) compared to thalidomide and bendamustine. Primary outcome of interest was time to progression (TTP). Secondary outcomes of interest were overall response rates (ORR) and overall survival (OS). METHODS: A comprehensive systematic literature review was conducted to identify any randomised controlled trials (RCTs) investigating the clinical efficacy of specified therapies for the treatment of RRMM. Specified therapies included lenalidomide, thalidomide and bendamustine. Of these therapies, only LEN/dex combination therapy is approved in RRMM but bendamustine and thalidomide (monotherapy or in combination with dexamethasone) have also shown activity in the treatment of myeloma. Electronic databases were searched from March 2002 to 2012 (language unrestricted. Randomized clinical trials were independently evaluated against predetermined criteria for inclusion and determined to be eligible for the meta-analysis prior to any outcome assessment. Fixed effects and random effects mixed-treatment comparisons (MTC) were carried out, adopting the methods described by Lu and Ades1. MTCs estimate the comparative effectiveness of multiple treatments using an evidence base of trials that individually do not compare all treatment options. Results for TTP were reported as hazard ratios (HR) and 95% confidence intervals and an associated probability of best treatment. Results for binary variables (ORR, OS) were reported as odds ratios (OR) and 95% confidence intervals. RESULTS: Sixteen original RCTs met the initial inclusion criteria; twelve (N = 3,590), nine (N = 3,350) and six (N = 2,295) of which were able to be connected to form a network of evidence which provided the heterogeneous trial base for MTC analysis of ORR, OS, and TTP comparison, respectively. Two trials directly investigated the efficacy of LEN/dex (N = 353) and three trials assessed the efficacy of thalidomide monotherapy (N = 785). No RCTs were identified that investigated the efficacy of bendamustine or thalidomide/dexamethasone combination therapy in RRMM. There were too few studies (investigating treatment arms of interest) relative to the number of trials in the network to formally estimate or test for heterogeneity. Therefore a fixed effects network meta-analysis was used instead of a random effects network meta-analysis. Comparability of trial populations was assessed and discussed in detail since these could not be adjusted for in the statistical model. Age, sex, baseline disease characteristics, time since diagnosis and medical history were similar between study populations. TTP analysis was statistically significant and favoured LEN/dex over thalidomide monotherapy: HR = 2.34 [1.31, 4.17]. The associated probability of LEN/dex being the best treatment within the evidence network is 97.9%. Secondary outcomes analysis were also statistically significant in favour of LEN/dex over thalidomide monotherapy (ORR: OR = 10.48 [4.75, 22.81]; OS: OR = 1.43 [1.12, 1.84]). CONCLUSIONS: Results demonstrated statistically significant superiority of lenalidomide plus dexamethasone therapy versus thalidomide monotherapy for the treatment of RRMM. No analyses were possible versus bendamustine or thalidomide/dexamethasone combination therapy due to the lack of RCTs investigating the efficacy of these therapeutic regimens in RRMM. Disclosures: Stradwick: Celgene International: Consultancy. Freemantle:BresMed: Consultancy. Off Label Use: Thalidomide monotherapy activity in the treatment of myeloma. Brereton:Celgene International: Consultancy.

scholarly journals Angiotensin-converting enzyme I/D polymorphism is not associated with type 2 diabetes in a Chinese population

2012 ◽  
Vol 13 (3) ◽  
pp. 372-378 ◽  
Author(s):  
Donghao Zhou ◽  
Rikje Ruiter ◽  
Jingling Zhang ◽  
Ming’ai Zhou ◽  
Hongjun Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Angiotensin Converting Enzyme ◽  
Chinese Population ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Dominant Model ◽  
Converting Enzyme ◽  
Fixed Effects Model

Objective: A role for the angiotensin-converting enzyme ( ACE) gene has been suggested in the aetiology of type 2 diabetes (T2DM). However, results have been inconsistent. In this study, we performed a meta-analysis to further clarify the association between ACE I/D polymorphism and T2DM risk in a Chinese population. Methods: PubMed, EMBASE, CNKI and Wan Fang Data were searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a fixed-effects model or random-effects model. Results:: A total of 41 studies (4708 cases and 5368 controls) for the association between ACE I/D polymorphism and T2DM in a Chinese population were identified. The pooled ORs for the association between ACE I/D polymorphism and T2DM risk were not statistically significant under all genetic models (co-dominant model: DD vs. II: OR = 1.17, 95% CI 0.97–1.42 and ID vs. II: OR = 1.01, 95% CI 0.93–1.10; dominant model: OR = 1.06, 95% CI 0.94–1.19; multiplicative model: OR = 1.08, 95% CI 0.98–1.18). Although a marginally significant association was observed under a recessive model (OR = 1.17, 95% CI 1.00–1.36), robustness of this estimate could not be established under additional sensitivity analyses. Conclusions:: The meta-analysis presented in this study indicated that ACE I/D polymorphism may not be associated with the risk of T2DM in the Chinese population.

Meta-analysis of the impacts of water management on aquatic communities

2008 ◽  
Vol 65 (3) ◽  
pp. 437-447 ◽  
Author(s):  
Tim J Haxton ◽  
C Scott Findlay
Keyword(s):  
Water Management ◽  
Confidence Intervals ◽  
Effect Size ◽  
Meta Analysis ◽  
Ecological Impacts ◽  
Aquatic Communities ◽  
Flow Modification ◽  
Meta Analyses ◽  
Fail Safe ◽  
Habitat Generalists

Systematic meta-analyses were conducted on the ecological impacts of water management, including effects of (i) dewatering on macroinvertebrates, (ii) a hypolimnetic release on downstream aquatic fish and macro invertebrate communities, and (iii) flow modification on fluvial and habitat generalists. Our meta-analysis indicates, in general, that (i) macroinvertebrate abundance is lower in zones or areas that have been dewatered as a result of water fluctuations or low flows (overall effect size, –1.64; 95% confidence intervals (CIs), –2.51, –0.77), (ii) hypolimnetic draws are associated with reduced abundance of aquatic (fish and macroinvertebrates) communities (overall effect size, –0.84; 95% CIs, –1.38, –0.33) and macroinvertebrates (overall effect size, –0.73; 95% CIs, –1.24, –0.22) downstream of a dam, and (iii) altered flows are associated with reduced abundance of fluvial specialists (–0.42; 95% CIs, –0.81, –0.02) but not habitat generalists (overall effect size, –0.14; 95% CIs, –0.61, 0.32). Publication bias is evident in several of the meta-analyses; however, multiple experiments from a single study may be contributing to this bias. Fail-safe Ns suggest that many (>100) studies showing positive or no effects of water management on the selected endpoints would be required to qualitatively change the results of the meta-analysis, which in turn suggests that the conclusions are reasonably robust.

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