scholarly journals Individual response to antidepressants for depression in adults – a simulation study and meta-analysis

2019 ◽  
Author(s):  
Klaus Munkholm ◽  
Stephanie Winkelbeiner ◽  
Philipp Homan
Keyword(s):  
Individual Differences ◽  
Simulation Study ◽  
Variance Components ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Meta Analysis ◽  
Empirical Support ◽  
Individual Response ◽  
Inverse Variance ◽  
Meta Analyses

Background. The observation that some patients appear to respond better to antidepressants for depression than others encourages the assumption that the effect of antidepressants differs between individuals and that treatment can be personalized. To test this assumption, we compared the outcome variance in the group of patients receiving antidepressants with the outcome variance of the group of patients receiving placebo in randomized controlled trials (RCTs) of adults with major depressive disorder (MDD). An increased variance in the antidepressant group would indicate individual differences in response to antidepressants. In addition, we illustrate in a simulation study why attempts to personalize antidepressant treatment using RCTs might be misguided.Methods. We first illustrated the variance components of trials by simulating RCTs and crossover trials of antidepressants versus placebo. Second, we analyzed data of a large meta-analysis of antidepressants for depression, including a total of 222 placebo-controlled studies from the dataset that reported outcomes on the 17 or 21 item Hamilton Depression Rating Scale or the Montgomery-Åsberg Depression Rating Scale. We performed inverse variance, random-effects meta-analyses of the variability ratio (VR) between the antidepressant and placebo groups. Outcomes. The meta-analyses of the VR comprised 345 comparisons of 19 different antidepressants with placebo in a total of 61144 adults with an MDD diagnosis. Across all comparisons, we found no evidence for a larger variance in the antidepressant group compared with placebo overall (VR = 1.00, 95% CI: 0.98; 1.01, I2 = 0%) or for any individual antidepressant. Interpretation. Our findings did not provide empirical support for individual differences in response to antidepressants.

scholarly journals Individual response to antidepressants for depression in adults – a meta-analysis and simulation study

2019 ◽  
Author(s):  
Klaus Munkholm ◽  
Stephanie Winkelbeiner ◽  
Philipp Homan
Keyword(s):  
Rating Scales ◽  
Rating Scale ◽  
Meta Analysis ◽  
Simulated Data ◽  
Individual Treatment ◽  
Depression Symptom ◽  
Individual Response ◽  
Inverse Variance ◽  
The Individual ◽  
Symptom Rating

Background The observation that some patients appear to respond better to antidepressants for depression than others encourages the assumption that the effect of antidepressants differs between individuals and that treatment can be personalized. Objective To compare the outcome variance in patients receiving antidepressants with the outcome variance in patients receiving placebo in randomized controlled trials (RCTs) of adults with major depressive disorder (MDD) and to illustrate, using simulated data, components of variation of RCTs. Methods From a dataset comprising 522 RCTs of antidepressants for adult MDD, we selected the placebo-controlled RCTs reporting outcomes on the 17 or 21 item Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Rating Scale and extracted the means and SDs of raw endpoint scores or baseline to endpoint changes scores on eligible depression symptom rating scales. We conducted inverse variance random-effects meta-analysis with the variability ratio (VR), the ratio between the outcome variance in the group of patients receiving antidepressants and the outcome variance in the group receiving placebo, as the primary outcome. An increased variance in the antidepressant group would indicate individual differences in response to antidepressants. Results We analysed 222 RCTs that investigated 19 different antidepressants compared with placebo in 345 comparisons, comprising a total of 61144 adults with an MDD diagnosis. Across all comparisons, the VR for raw endpoint scores was 0.98 (95% CI 0.96 to 1.00, I^2^ = 0%) and 1.00 (95% CI 0.99 to 1.02, I^2^ = 0%) for baseline-to-endpoint change scores. Conclusion Based on these data, we cannot reject the null hypothesis of equal variances in the antidepressant group and the placebo group. Given that RCTs cannot provide direct evidence for individual treatment effects, it may be most reasonable to assume that the average effect of antidepressants applies also to the individual patient.

scholarly journals Beta-binomial models for meta-analysis with binary outcomes: Variations, extensions, and additional insights from econometrics

2021 ◽  
pp. 263208432199622
Author(s):  
Tim Mathes ◽  
Oliver Kuss
Keyword(s):  
Simulation Study ◽  
Count Data ◽  
Negative Binomial ◽  
Meta Analysis ◽  
Negative Binomial Regression ◽  
Binary Outcomes ◽  
Small Scale ◽  
Panel Count Data ◽  
Count Data Models ◽  
Meta Analyses

Background Meta-analysis of systematically reviewed studies on interventions is the cornerstone of evidence based medicine. In the following, we will introduce the common-beta beta-binomial (BB) model for meta-analysis with binary outcomes and elucidate its equivalence to panel count data models. Methods We present a variation of the standard “common-rho” BB (BBST model) for meta-analysis, namely a “common-beta” BB model. This model has an interesting connection to fixed-effect negative binomial regression models (FE-NegBin) for panel count data. Using this equivalence, it is possible to estimate an extension of the FE-NegBin with an additional multiplicative overdispersion term (RE-NegBin), while preserving a closed form likelihood. An advantage due to the connection to econometric models is, that the models can be easily implemented because “standard” statistical software for panel count data can be used. We illustrate the methods with two real-world example datasets. Furthermore, we show the results of a small-scale simulation study that compares the new models to the BBST. The input parameters of the simulation were informed by actually performed meta-analysis. Results In both example data sets, the NegBin, in particular the RE-NegBin showed a smaller effect and had narrower 95%-confidence intervals. In our simulation study, median bias was negligible for all methods, but the upper quartile for median bias suggested that BBST is most affected by positive bias. Regarding coverage probability, BBST and the RE-NegBin model outperformed the FE-NegBin model. Conclusion For meta-analyses with binary outcomes, the considered common-beta BB models may be valuable extensions to the family of BB models.

Alternative Tendon Coaptations to the Pulvertaft Weave Technique: A Systematic Review and Meta-Analysis of Biomechanical Studies

Hand ◽  
2021 ◽  
pp. 155894472110432
Author(s):  
Emily M. Graham ◽  
Jeremie D. Oliver ◽  
Russell Hendrycks ◽  
Dino Maglic ◽  
Shaun D. Mendenhall
Keyword(s):  
Systematic Review ◽  
Yield Strength ◽  
Random Effects ◽  
Meta Analysis ◽  
Dichotomous Data ◽  
Inverse Variance ◽  
Significant Difference ◽  
Alternative Techniques ◽  
Meta Analyses

Background The Pulvertaft weave technique (PT) is frequently used during tendon repairs and transfers. However, this technique is associated with limitations. In this systematic review and meta-analysis, quantitative and qualitative analyses were performed on in vitro, biomechanical studies that compared the PT with alternative techniques. Methods Articles included for qualitative and/or qualitative analysis were identified following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies included in the meta-analysis were analyzed either as continuous data with inverse variance and random effects or as dichotomous data using a Mantel-Haenszel analysis assuming random effects to calculate an odds ratio. Results A comprehensive electronic search yielded 8 studies meeting inclusion criteria for meta-analysis. Two studies with a total of 65 tendon coaptations demonstrated no significant difference in strength between the PT and traditional side-to-side (STS) techniques ( P = .92). Two studies with a total of 43 tendon coaptations showed that the STS with 1 weave has a higher yield strength than the PT ( P = .03). Two studies with a total of 62 tendon repairs demonstrated no significant difference in strength between the PT and the step-cut (SC) techniques ( P = .70). The final 2 studies included 46 tendon repairs and demonstrated that the wrap around (WA) technique has a higher yield strength than the PT ( P < .001). Conclusions The STS, SC, and WA techniques are preferred for improving tendon form. The STS and WA techniques have superior yield strengths than the PT, and the SC technique withstands similar stress to failure as the PT.

scholarly journals Interval estimation of the overall treatment effect in random-effects meta-analyses: Recommendations from a simulation study comparing frequentist, Bayesian, and bootstrap methods

2020 ◽  
Author(s):  
Frank Weber ◽  
Guido Knapp ◽  
Anne Glass ◽  
Günther Kundt ◽  
Katja Ickstadt
Keyword(s):  
Literature Review ◽  
Random Effects ◽  
Simulation Study ◽  
Treatment Effect ◽  
Profile Likelihood ◽  
Meta Analysis ◽  
Artery Bypass ◽  
Interval Length ◽  
Interval Estimators ◽  
Meta Analyses

There exists a variety of interval estimators for the overall treatment effect in a random-effects meta-analysis. A recent literature review summarizing existing methods suggested that in most situations, the Hartung-Knapp/Sidik-Jonkman (HKSJ) method was preferable. However, a quantitative comparison of those methods in a common simulation study is still lacking. Thus, we conduct such a simulation study for continuous and binary outcomes, focusing on the medical field for application.Based on the literature review and some new theoretical considerations, a practicable number of interval estimators is selected for this comparison: the classical normal-approximation interval using the DerSimonian-Laird heterogeneity estimator, the HKSJ interval using either the Paule-Mandel or the Sidik-Jonkman heterogeneity estimator, the Skovgaard higher-order profile likelihood interval, a parametric bootstrap interval, and a Bayesian interval using different priors. We evaluate the performance measures (coverage and interval length) at specific points in the parameter space, i.e. not averaging over a prior distribution. In this sense, our study is conducted from a frequentist point of view.We confirm the main finding of the literature review, the general recommendation of the HKSJ method (here with the Sidik-Jonkman heterogeneity estimator). For meta-analyses including only 2 studies, the high length of the HKSJ interval limits its practical usage. In this case, the Bayesian interval using a weakly informative prior for the heterogeneity may help. Our recommendations are illustrated using a real-world meta-analysis dealing with the efficacy of an intramyocardial bone marrow stem cell transplantation during coronary artery bypass grafting.

Effect of metabolites levels on type 2 diabetes mellitus and glycemic traits: a Mendelian randomization study

2021 ◽  
Author(s):  
Yue Sun ◽  
Ya-Ke Lu ◽  
Hao-Yu Gao ◽  
Yu-Xiang Yan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Significance Level ◽  
Inverse Variance ◽  
Meta Analyses

Abstract Objective To assess the causal associations of plasma levels of metabolites with type 2 diabetes mellitus (T2DM) and glycemic traits. Methods Two-sample mendelian randomization (MR) was conducted to assess the causal associations. Genetic variants strongly associated with metabolites at genome-wide significance level (P &lt; 5 × 10 −8) were selected from public GWAS, and SNPs of Outcomes were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium for T2DM and from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for the fasting glucose, insulin and HbA1c. The Wald ratio and inverse-variance weighted methods were used for analyses, and MR-Egger was used for sensitivity analysis. Results The β estimates per 1 SD increasement of arachidonic acid (AA) level was 0.16 (95% CI: 0.078, 0.242; P&lt;0.001). Genetic predisposition to higher plasma AA levels were associated with higher FG levels (β 0.10 [95%CI: 0.064, 0.134], P&lt;0.001), higher HbA1c levels (β 0.04 [95%CI: 0.027, 0.061]) and lower FI levels (β -0.025 [95%CI: -0.047, -0.002], P=0.033). Besides, 2-hydroxybutyric acid (2-HBA) might have positive causal effect on glycemic traits. Conclusions Our findings suggest that AA and 2-HBA may have the causal associations on T2DM and glycemic traits. It is beneficial for clarifying the pathogenesis of T2DM, which would be valuable for early identification and prevention for T2DM.

scholarly journals Association of age and colostrum discarding with breast-feeding practice in Ethiopia: systematic review and meta-analyses

2019 ◽  
Vol 22 (11) ◽  
pp. 2063-2082 ◽  
Author(s):  
Sisay Mulugeta Alemu ◽  
Yihun Mulugeta Alemu ◽  
Tesfa Dejenie Habtewold
Keyword(s):  
Breast Feeding ◽  
Meta Analysis ◽  
Reproductive Age ◽  
Feeding Practice ◽  
Timely Initiation ◽  
Inverse Variance ◽  
Newcastle Ottawa Scale ◽  
Meta Regression Analysis ◽  
Meta Analyses

AbstractObjectiveTo investigate whether maternal/caregiver’s age, infant age (0–6 months) and discarding colostrum affects timely initiation of breast-feeding (TIBF) and exclusive breast-feeding (EBF) in Ethiopia.DesignA systematic search of PubMed, SCOPUS, EMBASE, CINHAL, Web of Science and WHO Global Health Library electronic databases was done for all articles published in English from 2000 to January 2018. Two reviewers independently screened, extracted and graded the quality of studies using Newcastle–Ottawa Scale. A weighted inverse-variance random-effects model meta-analysis, cumulative meta-analysis and mixed-effects meta-regression analysis were done.SettingAll observational studies conducted in Ethiopia.ParticipantsMothers of children aged less than 2 years.ResultA total of forty articles (fourteen studies on TIBF and twenty-six on EBF) were included. TIBF was associated with colostrum discarding (OR=0·38; 95 % CI 0·21, 0·68) but not with maternal/caregiver’s age (OR=0·98; 95 % CI 0·83, 1·15). In addition, colostrum discarding (OR=0·53; 95 % CI 0·36, 0·78) and infant age (OR=1·77; 95 % CI 1·38, 2·27) were significantly associated with EBF but not maternal/caregiver’s age (OR=1·09; 95 % CI 0·84, 1·41).ConclusionsThere was no association between maternal/caregiver’s age and breast-feeding practice (EBF and TIBF). Colostrum discarding was associated with both EBF and TIBF. This evidence could be helpful to counsel all mothers of reproductive age and who discard colostrum.

scholarly journals “Smoking paradox” is not true in patients with ischemic stroke: a systematic review and meta-analysis

2019 ◽  
Author(s):  
Bo Li ◽  
Dan Li ◽  
Jing-Feng Liu ◽  
Lin Wang ◽  
Bao-Zhu Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Protective Factor ◽  
Meta Analysis ◽  
Vascular Diseases ◽  
Cochrane Library ◽  
Inverse Variance ◽  
First Onset ◽  
Prognostic Outcome ◽  
Meta Analyses ◽  
Review Manager

Abstract Background Ischemic stroke (IS) is a common cause of death from vascular diseases. Studies have found that smoking increases the risk of ischemic stroke, but the association of smoking with the outcome of IS remains unclear. This meta-analysis aims to investigate the effect of smoking on the prognosis of IS. Methods We searched four electronic databases including PubMed, EMBASE, Cochrane library and Web of science for papers, published before January 2019. In this meta-analysis, Review Manager 5.3 software was used to calculate for the pooled estimate effect, as well as the inverse-variance method for pooled mean difference (MD) and odds ratio (OR) of incidence in two groups of population. Results A total of 14,789 citations were identified during the literature search, 21 studies were included in the meta-analyses after screening. The full-adjusted OR of poor prognostic outcome in smoking and nonsmoking patients with stroke was pooled as 0.96 (95% CI 0.77–1.21), suggested that smoking or not has no impact on prognosis of IS. The pooled MD of onset age between smoking and nonsmoking IS patients was − 10.05 (− 12.91, − 7.19), indicated that smoking causes first onset of IS to occur 10 years earlier. Conclusions This meta-analysis showed that smoking was not a protective factor for poor prognosis of IS. Smoking patients with IS are 10 years younger than nonsmoking patients at time of the first onset of stroke.

scholarly journals Individual response to antidepressants for depression in adults-a meta-analysis and simulation study

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0237950 ◽  
Author(s):  
Klaus Munkholm ◽  
Stephanie Winkelbeiner ◽  
Philipp Homan
Keyword(s):  
Simulation Study ◽  
Meta Analysis ◽  
Individual Response

Abstract 54: Genome-Wide Association Analysis of Gene-Sodium Interactions on Blood Pressure Phenotypes: The GenSalt Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Changwei Li ◽  
Jiang He ◽  
James Hixson ◽  
Dongfeng Gu ◽  
Dabeeru Rao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sodium Intake ◽  
Meta Analysis ◽  
Snp Array ◽  
Urinary Sodium Excretion ◽  
Dietary Sodium ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Inverse Variance ◽  
Meta Analyses

Background: Elevated blood pressure (BP) is a major public health challenge. Although the heritability of BP has been long established, current findings can explain only a small proportion of the BP variability attributed to genetic factors. Recent studies indicate that gene-environmental interactions may help to identify novel BP loci. Hence, the current study aimed to identify genetic variants influencing BP regulation by conducting genome-wide gene-sodium interaction analyses among 1,906 participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Methods: GenSalt recruited 1,906 Chinese participants from 633 families. At baseline, one 24-hour and two 8-hour urine specimens were collected to measure urinary sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 868,158 autosomal single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genomewide Human SNP array 6.0 (Affymetrix, Inc, Santa Clara, CA). Mixed effects models were used to test genome-wide SNP-sodium interactions on BP, adjusting for age, gender, and body mass index. Promising findings (interaction term P <1.00х10 -6 ) from GenSalt were further evaluated for replication among Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA) with available data from the database of genotypes and phenotypes (dbGaP). SNP effects in GenSalt and MESA were meta-analyzed using inverse-variance weighted fixed effect models. Results: The meta-analyses identified 3 novel loci that significantly interacted with sodium to influence BP phenotypes. SNP-sodium interactions on systolic BP were identified for NEK2 variant rs10494938 at 1q32.3 (GenSalt P =2.19х10 -6 , MESA P =4.35х10 -4 , and Meta-analysis P = 3.93х10 -8 ). In addition, CASP4 variant rs1944900 at 11q22.3 interacted with sodium to influence both systolic BP (GenSalt P =1.24х10 -9 , MESA P =4.22х10 -2 , and Meta-analysis P = 1.14х10 -10 ) and mean arterial pressure (GenSalt P =1.68х10 -9 , MESA P =4.27х10 -2 , and Meta-analysis P = 1.91х10 -10 ). Furthermore, C9orf3 variant rs17679141 at 9q22.32 interacted with sodium to influence diastolic BP (GenSalt P =2.85х10 -8 , MESA P =4.55х10 -2 , and Meta-analysis P =4.61х10 -9 ). The 3 variants all physically mapped to the intronic regions of their corresponding genes. Conclusion: The current study identified 3 novel loci which may interact with dietary sodium intake to influence BP phenotypes.

Reviewing disease activity indices in spondyloarthritis from the gender perspective: A systematic review and meta-analysis

2021 ◽  
pp. jrheum.200967
Author(s):  
Mar Blasco-Blasco ◽  
Isabel Castrejón ◽  
Vega Jovaní ◽  
Eliseo Pascual ◽  
María Teresa Ruiz-Cantero
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Activity Index ◽  
Meta Analysis ◽  
Disease Activity Index ◽  
Mean Difference ◽  
Inverse Variance ◽  
Peripheral Spondyloarthritis ◽  
Meta Analyses ◽  
Activity Indices

Objective To determine whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) exhibited differences between women and men. Methods We systematically searched MEDLINE, Embase, Web of Science and other sources in English or Spanish from 01 January 1995 to 31 July 2020, to assess the differences according to sex in BASDAI and ASDAS. We performed a comparative analysis by sex using t-student test and mean difference by sex meta-analyses for BASDAI and ASDAS, using a random-effects model via the inverse-variance method. Results Forty-one studies included BASDAI (6,785 women/12,929 men) and 16 of them included ASDAS (2,046 women/4,403 men). Disease activity detected through BASDAI was significantly higher in women than in men (mean: 4.9 vs. 4.2, p=0.02), whereas ASDAS did not detect differences between sexes (mean: 2.8 women vs. 2.8 men). In the meta-analyses, BASDAI detected significant differences between women and men [mean difference= 0.55 (95% confidence intervals (95%CI): 0.46, 0.65), p<0.00001], but ASDAS did not identify significant mean difference between sexes [0.04 (95%CI: -0.05, 0.12), p=0.38]. Conclusion The two most widely used indexes of disease activity in spondyloarthritis discriminate differently according to sex by their different evaluation of peripheral disease. Their different components and weights influence BASDAI and ASDAS values. BASDAI may be influenced by fatigue, but in predominantly peripheral manifestations like enthesitis, ASDAS may not be sensitive enough to detect activity. This may represent a gender bias unfavourable to women, because peripheral spondyloarthritis is more common in women than in men.

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