How effective are Z-drug hypnotics for treatment of adult insomnia? Meta-analysis of data submitted to the Food and Drug Administration

The Problem: Z-drugs are the most commonly prescribed hypnotics worldwide. They are widely prescribed because general practitioners and patients believe that they are effective and superior to older hypnotics. Previous meta-analyses of Z-drugs suffer from publication or reporting bias and did not adequately examine study heterogeneity. We wanted to investigate the effectiveness of Z-drugs in adults using a data source that was less likely to be affected by publication bias. The approach: We examined clinical trials of currently approved Z-drugs submitted to the Food and Drug Administration (FDA) since pharmaceutical companies are required to provide information on all sponsored trials, whether published or not, when applying for new drug approvals. We included randomized double blind placebo controlled trials and excluded studies with a crossover design, those including healthy patients with normal sleep or single night studies with induced insomnia. We analysed drug efficacy as change score from baseline to posttest for drug and placebo groups, and the difference of both change scores for available outcomes. Weighted raw and standardized mean differences with their confidence intervals (CIs) under random-effects assumptions were calculated for polysomnographic (PSG) and subjective outcomes: wake after sleep onset, sleep latency, number of awakenings, total sleep time, sleep efficiency, subjective sleep quality, and morning sleepiness score. We performed weighted regression moderator analysis to explain heterogeneity of drug effects. Findings: We included 16 studies comprising 4973 subjects from different countries, varying drug dosages, treatment lengths and study years. Z-drugs showed significant but small improvements (reductions) only in PSG (d+ = -0.36, 95% CI = -0.57 to -0.16) and subjective sleep latency (d+ = -0.33, 95% CI = -0.62 to -0.041) compared with placebo. Analyses of weighted mean raw differences indicated that drugs decreased sleep latency by only 22 minutes (95% CI = -33 TO -11) with no evidence of change in other measures. Moderator analyses indicated that sleep latency was more likely to be reduced with larger drug doses, studies published earlier, including higher proportions of younger or women patients, and of longer treatment duration. Consequences: This study of FDA data shows that, despite being commonly prescribed, Z-drugs have limited benefit with small reductions in subjective and PSG sleep latency especially with larger dosages, but no improvement in other sleep measures compared to placebo. Placebo effects were moderate for sleep latency. Doctors and patients need to be aware of the relative benefits as well as harms of hypnotic drugs when deciding to use them in preference to psychological treatments

Prevalence, impact and treatment of generalised anxiety disorder in bipolar disorder : A systematic review and meta-analysis

Publisher Copyright: © 2016, BMJ Publishing Group. All rights reserved.Question Recent data suggest that anxiety disorders are as often comorbid with bipolar disorder (BD) as with unipolar depression; however, less attention has been paid to comorbidity of anxiety disorders with BD. Generalised anxiety disorder (GAD) is one of the most prevalent anxiety disorders that is highly comorbid with other mental disorders. We carried out a systematic review and meta-analysis to assess the degree of comorbidity between GAD and BD. Study selection and analysis We searched for all studies, which included primary data concerning the existence of GAD in patients with BD. The literature search strategy, selection of publications and the reporting of results have been conducted with PRISMA guidelines. The meta-analysis calculated prevalence estimates using the variance-stabilising Freeman-Tukey double arcsine transformation. We applied the inverse variance method using both fixed-effects and random-effects models to estimate summary effects for all combined studies. Heterogeneity was assessed and measured with Cochran’s Q and I2 statistics, respectively. Findings The current meta-analysis analysed data from 28 independent studies and a total of 2975 patients from point prevalence studies and 4919 patients from lifetime studies. The overall random-effects point prevalence of GAD in patients with BD was 12.2% (95% CI 10.9% to 13.5%) and the overall random-effects lifetime estimate was 15.1% (95% CI 9.7% to 21.5%). Both estimates reported significant heterogeneity (94.0% and 94.7%, respectively). Conclusions Published studies report prevalence rates with high heterogeneity and consistently higher than those typically reported in the general population. It is believed that comorbid GAD might be associated with a more severe BD course and increased suicidality, and it is unknown how best to treat such conditions. The current meta-analysis confirms that GAD is highly prevalent in BD and the rate is higher in comparison to those in the general population.publishersversionPeer reviewe

Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration

Kirsch and colleagues show that, in antidepressant trials, there is a greater difference in efficacy between drug and placebo amongst more severely depressed patients. However, this difference seems to result from a poorer response to placebo amongst more depressed patients

Is Social Media a New Type of Social Support? Social Media Use in Spain during the COVID-19 Pandemic: A Mixed Methods Study

This study examines Spanish adults’ social media use during the COVID-19 pandemic using mixed-methods to assess and understand frequency, context, and changes in social media use during two critical time points in Spain. We conducted semi-structured interviews in April 2020, and two waves of surveys (April 2020, April 2021) among Spanish adults. We coded and analyzed qualitative data related to social media use during the first lockdown period in Spain using Dedoose software; and ran descriptive statistics and chi-square tests to assess changes in social media use over the two survey waves related to perceived social support and loneliness. Participants ranged in age from 18–92 and were representative of the Spanish population’s sociodemographics. Interview data show that WhatsApp was most commonly used, and that social media allowed for social support and engaging in healthy behaviors. Survey data show that women and individuals aged 18–34 had the greatest increases in social media use. Statistically significant associations were found between social support and loneliness with social media use. Our results show that promoting social media use as an emotional resource for social support in times of crisis or isolation can minimize loneliness and can be a beneficial tool for general worldwide crises.This research was supported by pilot grant funding from the Institute for Collaboration on Health, Intervention, and Policy (InCHIP) at University of Connecticut

536Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs) Comparing Initial Non-Nucleoside Reverse-Transcriptase Inhibitor (NNRTI)- versus Ritonavir Boosted Protease Inhibitor (PI/r)-based Anti-Retroviral Therapy (ART)

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Manipulating the alpha level cannot cure significance testing

We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable

The Efficacy of Exercise in Reducing Depressive Symptoms among Cancer Survivors: A Meta-Analysis

INTRODUCTION: The purpose of this meta-analysis was to examine the efficacy of exercise to reduce depressive symptoms among cancer survivors. In addition, we examined the extent to which exercise dose and clinical characteristics of cancer survivors influence the relationship between exercise and reductions in depressive symptoms. METHODS: We conducted a systematic search identifying randomized controlled trials of exercise interventions among adult cancer survivors, examining depressive symptoms as an outcome. We calculated effect sizes for each study and performed weighted multiple regression moderator analysis. RESULTS: We identified 40 exercise interventions including 2,929 cancer survivors. Diverse groups of cancer survivors were examined in seven exercise interventions; breast cancer survivors were examined in 26; prostate cancer, leukemia, and lymphoma were examined in two; and colorectal cancer in one. Cancer survivors who completed an exercise intervention reduced depression more than controls, d(+) = -0.13 (95% CI: -0.26, -0.01). Increases in weekly volume of aerobic exercise reduced depressive symptoms in dose-response fashion (β = -0.24, p = 0.03), a pattern evident only in higher quality trials. Exercise reduced depressive symptoms most when exercise sessions were supervised (β = -0.26, p = 0.01) and when cancer survivors were between 47-62 yr (β = 0.27, p = 0.01). CONCLUSION: Exercise training provides a small overall reduction in depressive symptoms among cancer survivors but one that increased in dose-response fashion with weekly volume of aerobic exercise in high quality trials. Depressive symptoms were reduced to the greatest degree among breast cancer survivors, among cancer survivors aged between 47-62 yr, or when exercise sessions were supervised

Sex-Related Differences in Self-Reported Neurocognitive Impairment among High-Risk Cocaine Users in Methadone Maintenance Treatment Program

Background Previous research has suggested possible sex-related differences in executive functioning among cocaine users; however, no studies specifically explain sex-related differences in neurocognitive impairment (NCI) among cocaine users receiving clinical care. Knowledge about this association can aid in the development of targeted prevention strategies to reduce adverse health outcomes. This study was designed to examine the sex-related differences in NCI among high-risk cocaine users receiving substance-abuse treatment. Methods The Neuropsychological Impairment Scale (NIS) was administered to 199 cocaine users (98 men; 101 women), receiving methadone maintainance treatment, to assess self-reported NCI by identifying the patients’ awareness of neuropsychological symptoms. We used T-test comparison to find differences in NCI between men and women and multiple regression analysis to explore the relative contribution of sex to NCI. Results Consistent with prior work, high NCI was evident within this sample, as indicated by high scores on most of the NIS subscales. Women reported greater impairment than men, as evidenced by significantly higher scores on several NIS subscales, after controlling for demographic and other confounding variables. Interestingly, cocaine craving significantly predicted NCI among men but not among women, as suggested by the significant association between cocaine craving and all except one of the NIS subscales. Conclusions These findings suggest that cocaine users enter into treatment with a range of NCI – with women having significantly more neurocognitive deficits than men – that may contribute to differential treatment outcomes. This highlights the need to include additional services such as neuropsychological screening and sex-specific treatment programs to optimally reduce adverse health outcomes in these high-risk, cognitively impaired patients

Depicting estimates using the intercept in meta-regression models: The moving constant technique

In any scientific discipline, the ability to portray research patterns graphically often aids greatly in interpreting a phenomenon. In part to depict phenomena, the statistics and capabilities of meta-analytic models have grown increasingly sophisticated. Accordingly, this article details how to move the constant in weighted meta-analysis regression models (viz. “meta-regression”) to illuminate the patterns in such models across a range of complexities. Although it is commonly ignored in practice, the constant (or intercept) in such models can be indispensible when it is not relegated to its usual static role. The moving constant technique makes possible estimates and confidence intervals at moderator levels of interest as well as continuous confidence bands around the meta-regression line itself. Such estimates, in turn, can be highly informative to interpret the nature of the phenomenon being studied in the meta-analysis, especially when a comparison with an absolute or a practical criterion is the goal. Knowing the point at which effect size estimates reach statistical significance or other practical criteria of effect size magnitude can be quite important. Examples ranging from simple to complex models illustrate these principles. Limitations and extensions of the strategy are discussed