Effects of Zinc Supplementation on Cardiometabolic Risk Factors: a Systematic Review and Meta-analysis of Randomized Controlled Trials

Biological Trace Element Research - The prevalence of cardiometabolic risk factors has been increasing worldwide. The results of reported studies on the effects of zinc supplementation on...     

Use of Fibrates and Cancer Risk: A Systematic Review and Meta-Analysis of 17 Long-Term Randomized Placebo-Controlled Trials

Background

Fibrates comprise a class of well-established antilipidemic agents that significantly reduce cardiovascular events. Given the concerns of cancer with fibrate therapy, we undertook a systematic review and meta-analysis to investigate the effects of fibrates on cancer outcomes.

Methods

We systematically searched Medline, Scopus, SCI Expanded, and the Cochrane Library for studies published up to 2012. We included randomized controlled trials (RCTs) that evaluated a fibrate therapy compared with placebo, had a minimum duration of two years, and reported data on the incidence of and/or deaths from cancer during the trial. Reviews of each study were performed and the relative data were abstracted. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the inverse variance weighted approach. Subgroup, sensitivity and meta-regression analyses were also conducted.

Results

Seventeen RCTs, involving 44,929 participants with an average follow-up of 5.2 years, contributed to the analysis. The degree of variability between trials was consistent with what would be expected to occur by chance alone. The quantitative synthesis of data retrieved from the RCTs was not indicative of a fibrate effect on cancer incidence (780 [fibrate] vs 814 [control]; RR = 1.02, 95% CI 0.92–1.12) or cancer death (385 [fibrate] vs 377 [control]; RR = 1.06, 95% CI: 0.92–1.22). When the analysis was restricted to major RCTs, the results did not substantially change. Similarly, we found no evidence of differential effects by length of follow-up or type of fibrate. Insignificant results were also obtained for the role of fibrates in cancers of the respiratory tract, breast, colon, gastrointestinal tract, prostate, genitourinary tract, or in melanoma.

Conclusion

Our findings demonstrate that fibrates have a neutral effect on cancer outcomes. However, it is important to continue monitoring their long-term safety profiles.     

Associated Factors and Consequences of Risk of Bias in Randomized Controlled Trials of Yoga: A Systematic Review

Background

Bias in randomized controlled trials (RCTs) of complementary therapy interventions seems to be associated with specific factors and to potentially distort the studies’ conclusions. This systematic review assessed associated factors of risk of bias and consequences for the studies’ conclusions in RCTs of yoga as one of the most commonly used complementary therapies.

Methods

Medline/PubMed, Scopus, IndMED and the Cochrane Library were searched through February 2014 for yoga RCTs. Risk of selection bias was assessed using the Cochrane tool and regressed to a) publication year; b) country of origin; c) journal type; and d) impact factor using multiple logistic regression analysis. Likewise, the authors’ conclusions were regressed to risk of bias.

Results

A total of 312 RCTs were included. Impact factor ranged from 0.0 to 39.2 (median = 1.3); 60 RCT (19.2%) had a low risk of selection bias, and 252 (80.8%) had a high or unclear risk of selection bias. Only publication year and impact factor significantly predicted low risk of bias; RCTs published after 2001 (adjusted odds ratio (OR) = 12.6; 95% confidence interval (CI) = 1.7, 94.0; p<0.001) and those published in journals with impact factor (adjusted OR = 2.6; 95%CI = 1.4, 4.9; p = 0.004) were more likely to have low risk of bias. The authors’ conclusions were not associated with risk of bias.

Conclusions

Risk of selection bias was generally high in RCTs of yoga; although the situation has improved since the publication of the revised CONSORT statement 2001. Pre-CONSORT RCTs and those published in journals without impact factor should be handled with increased care; although risk of bias is unlikely to distort the RCTs’ conclusions.     

Characteristics of Randomized Controlled Trials Designed for Elderly: A Systematic Review

ObjectivesTo quantify the proportion of randomized controlled trials (RCTs) specifically designed for elderly, and to assess their characteristics, as compared to RCTs not specifically designed for elderly.DesignReview and synthesis of published literature.MeasurementsWe searched PubMed for articles published in the year 2012. We included RCTs. Articles were excluded if not conducted with human subjects or if findings of secondary analyses were reported. A random sample of 10% was drawn and of this selection the following trial characteristics were extracted: sample size, disease category, age of sample, and age-related inclusion criteria. Clinical trials were defined to be specifically designed for elderly if a lower age cut-off of ≥ 55 years was used, or when participants had an average age of ≥ 70 years.ResultsThe search strategy yielded 26,740 articles, from which a random sample was drawn, resulting in 2375 articles. After exclusion, data was extracted from 1369 publications. Of these 1369 RCTs, 96 (7%) were specifically designed for elderly. In comparison with trials not designed for older adults, trials designed for elderly contained a significantly larger median number of participants (125 vs. 80, p = 0.008) significantly more trials designed for elderly fell into the disease categories eye (6% vs. 2%, p = 0.005), musculoskeletal (13% vs. 7%, p = 0.023) and circulatory system (16% vs. 9%, p = 0.039). No significant difference was observed with regard to the other disease categories.ConclusionThere is a low proportion of RCTs specifically designed for elderly. As older patients will increasingly form the majority in medical practice, there is an urgent need for stronger evidence for the formulation of treatment guidelines specifically for older adults.     

Primary Prevention of Cannabis Use: A Systematic Review of Randomized Controlled Trials

A systematic review of primary prevention was conducted for cannabis use outcomes in youth and young adults. The aim of the review was to develop a comprehensive understanding of prevention programming by assessing universal, targeted, uni-modal, and multi-modal approaches as well as individual program characteristics. Twenty-eight articles, representing 25 unique studies, identified from eight electronic databases (EMBASE, MEDLINE, CINAHL, ERIC, PsycINFO, DRUG, EBM Reviews, and Project CORK), were eligible for inclusion. Results indicated that primary prevention programs can be effective in reducing cannabis use in youth populations, with statistically significant effect sizes ranging from trivial (0.07) to extremely large (5.26), with the majority of significant effect sizes being trivial to small. Given that the preponderance of significant effect sizes were trivial to small and that percentages of statistically significant and non-statistically significant findings were often equivalent across program type and individual components, the effectiveness of primary prevention for cannabis use should be interpreted with caution. Universal multi-modal programs appeared to outperform other program types (i.e, universal uni-modal, targeted multi-modal, targeted unimodal). Specifically, universal multi-modal programs that targeted early adolescents (10–13 year olds), utilised non-teacher or multiple facilitators, were short in duration (10 sessions or less), and implemented boosters sessions were associated with large median effect sizes. While there were studies in these areas that contradicted these results, the results highlight the importance of assessing the interdependent relationship of program components and program types. Finally, results indicated that the overall quality of included studies was poor, with an average quality rating of 4.64 out of 9. Thus, further quality research and reporting and the development of new innovative programs are required.     

Suvorexant for Primary Insomnia: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Objective

We performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials evaluating suvorexant for primary insomnia.

Methods

Relevant studies were identified through searches of PubMed, databases of the Cochrane Library, and PsycINFO citations through June 27, 2015. We performed a systematic review and meta-analysis of suvorexant trial efficacy and safety outcomes. The primary efficacy outcomes were either subjective total sleep time (sTST) or subjective time-to-sleep onset (sTSO) at 1 month. The secondary outcomes were other efficacy outcomes, discontinuation rate, and individual adverse events. The risk ratio, number-needed-to-treat/harm, and weighted mean difference (WMD) and 95% confidence intervals (CI) based on a random effects model were calculated.

Results

The computerized literature database search initially yielded 48 results, from which 37 articles were excluded following a review of titles and abstracts and another eight review articles after full-text review. Thus, we identified 4 trials that included a total of 3,076 patients. Suvorexant was superior to placebo with regard to the two primary efficacy outcomes (sTST: WMD = −20.16, 95% CI = −25.01 to −15.30, 1889 patients, 3 trials, sTSO: WMD = −7.62, 95% CI = −11.03 to −4.21, 1889 patients, 3 trials) and was not different from placebo in trial discontinuations. Suvorexant caused a higher incidence than placebo of at least one side effects, abnormal dreams, somnolence, excessive daytime sleepiness/sedation, fatigue, dry mouth, and rebound insomnia.

Conclusions

Our analysis of published trial results suggests that suvorexant is effective in treating primary insomnia and is well-tolerated.     

Comparative Efficacy of Lamivudine and Emtricitabine: A Systematic Review and Meta-Analysis of Randomized Trials

Introduction

Lamivudine and emtricitabine are considered equivalent by several guidelines, but evidence of comparable efficacy is conflicting.

Methods

We searched two databases up to June 30 2013 to identify randomized and quasi-randomized trials in which lamivudine and emtricitabine were used as part of combination antiretroviral therapy for treatment-naïve or experienced HIV-positive adult patients. We only included trials where partner drugs in the regimen were identical or could be considered to be comparable. We allowed for comparisons between tenofovir and abacavir provided the study population did not begin treatment with a viral load >100,000 copies/ml.

Results

12 trials contributed 15 different randomized comparisons providing data on 2251 patients receiving lamivudine and 2662 patients receiving emtricitabine. Treatment success was not significantly different in any of the 12 trials. In the three trials that directly compared lamivudine and emtricitabine, the relative risk for achieving treatment success was non-significant (RR 1.03 95%CI 0.96-1.10). For all trials combined, the pooled relative risk for treatment success was not significantly different (RR 1.00, 95%CI 0.97–1.02). No heterogeneity was observed (I ² = 0). Similarly, there was no difference in the pooled relative risk for treatment failure (RR 1.08, 95%CI 0.94–1.22, I ² = 3.4%).

Conclusions

The findings of this systematic review suggest that lamivudine and emtricitabine are clinically equivalent.     

The Efficacy of Resiliency Training Programs: A Systematic Review and Meta-Analysis of Randomized Trials

Importance

Poor mental health places a burden on individuals and populations. Resilient persons are able to adapt to life’s challenges and maintain high quality of life and function. Finding effective strategies to bolster resilience in individuals and populations is of interest to many stakeholders.

Objectives

To synthesize the evidence for resiliency training programs in improving mental health and capacity in 1) diverse adult populations and 2) persons with chronic diseases.

Data Sources

Electronic databases, clinical trial registries, and bibliographies. We also contacted study authors and field experts.

Study Selection

Randomized trials assessing the efficacy of any program intended to enhance resilience in adults and published after 1990. No restrictions were made based on outcome measured or comparator used.

Data Extraction and Synthesis

Reviewers worked independently and in duplicate to extract study characteristics and data. These were confirmed with authors. We conducted a random effects meta-analysis on available data and tested for interaction in planned subgroups.

Main Outcomes

The standardized mean difference (SMD) effect of resiliency training programs on 1) resilience/hardiness, 2) quality of life/well-being, 3) self-efficacy/activation, 4) depression, 5) stress, and 6) anxiety.

Results

We found 25 small trials at moderate to high risk of bias. Interventions varied in format and theoretical approach. Random effects meta-analysis showed a moderate effect of generalized stress-directed programs on enhancing resilience [pooled SMD 0.37 (95% CI 0.18, 0.57) p = .0002; I² = 41%] within 3 months of follow up. Improvement in other outcomes was favorable to the interventions and reached statistical significance after removing two studies at high risk of bias. Trauma-induced stress-directed programs significantly improved stress [−0.53 (−1.04, −0.03) p = .03; I² = 73%] and depression [−0.51 (−0.92, −0.10) p = .04; I² = 61%].

Conclusions

We found evidence warranting low confidence that resiliency training programs have a small to moderate effect at improving resilience and other mental health outcomes. Further study is needed to better define the resilience construct and to design interventions specific to it.

Registration Number

PROSPERO #CRD42014007185     

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials

Objective

To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI).

Methods

PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI.

Results

A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66).

Conclusions

Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI.     

Shensongyangxin Capsules for Paroxysmal Atrial Fibrillation: A Systematic Review of Randomized Clinical Trials

Objective

To evaluate the evidence for the effectiveness and safety of Shensongyangxin Capsules (SSYX) for treating paroxysmal atrial fibrillation (PAF).

Methods

We searched for randomized clinical trials for SSYX in PAF up to June 2015. The Cochrane risk of bias tool was used to assess the methodological quality. RevMan 5.3 was used to synthesize the results.

Results

We included 22 trials involving 2,347 PAF patients. The quality of the included studies was generally poor. The results of the meta-analysis showed that SSYX plus routine treatment was more effective at improving P-wave dispersion (Pwd) and the frequency of PAF attacks compared with routine treatment alone. The results from the included trials that compared SSYX plus routine treatment and arrhythmic drugs plus routine treatment were inconsistent. Trials reported on Pwd, quality of life, frequency of PAF attacks or maintenance rate of sinus rhythm and found that SSYX combined with anti-arrhythmic drugs plus routine treatment was more effective than anti-arrhythmic drugs plus routine treatment. Four of the trials reported adverse events, indicating that SSYX was potentially safer than anti-arrhythmic drugs.

Conclusions

There appears to be some benefit from the use of SSYX. However, due to poor methodological quality, we could not draw confirmative conclusions regarding the beneficial effect of using SSYX.     

Aerobic Exercise for Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Although some trials assessed the effectiveness of aerobic exercise for Parkinson''s disease (PD), the role of aerobic exercise in the management of PD remained controversial.

Objective

The purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD.

Methods

Seven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I² statistic.

Results

18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, −0.57; 95% CI −0.94 to −0.19; p = 0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p = 0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p<0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI −0.23 to 0.46; p = 0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD.

Conclusion

Aerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings.