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Concept: Random effects model


Endurance exercise training studies frequently show modest changes in VO2max with training and very limited responses in some subjects. By contrast, studies using interval training (IT) or combined IT and continuous training (CT) have reported mean increases in VO2max of up to ∼1.0 L · min(-1). This raises questions about the role of exercise intensity and the trainability of VO2max. To address this topic we analyzed IT and IT/CT studies published in English from 1965-2012. Inclusion criteria were: 1)≥3 healthy sedentary/recreationally active humans <45 yrs old, 2) training duration 6-13 weeks, 3) ≥3 days/week, 4) ≥10 minutes of high intensity work, 5) ≥1∶1 work/rest ratio, and 6) results reported as mean ± SD or SE, ranges of change, or individual data. Due to heterogeneity (I(2) value of 70), statistical synthesis of the data used a random effects model. The summary statistic of interest was the change in VO2max. A total of 334 subjects (120 women) from 37 studies were identified. Participants were grouped into 40 distinct training groups, so the unit of analysis was 40 rather than 37. An increase in VO2max of 0.51 L ·min(-1) (95% CI: 0.43 to 0.60 L · min(-1)) was observed. A subset of 9 studies, with 72 subjects, that featured longer intervals showed even larger (∼0.8-0.9 L · min(-1)) changes in VO2max with evidence of a marked response in all subjects. These results suggest that ideas about trainability and VO2max should be further evaluated with standardized IT or IT/CT training programs.

Concepts: Statistics, Exercise, Change, Analysis of variance, High-intensity interval training, Random effects model, Endurance, Interval training


BACKGROUND: Cholesterol-lowering medications such as statins have anti-inflammatory and antioxidant properties, which may be beneficial for treating depression and improving mood. However, evidence regarding their effects remains inconsistent, with some studies reporting links to mood disturbances. We aimed to conduct a meta-analysis to determine the impact of statins on psychological wellbeing of individuals with or without hypercholesterolemia. METHODS: Articles were identified using medical, health, psychiatric and social science databases, evaluated for quality, and data were synthesized and analyzed in RevMan-5 software using a random effects model. RESULTS: The 7 randomized controlled trials included in the analysis represented 2,105 participants. A test for overall effect demonstrated no statistically significant differences in psychological wellbeing between participants receiving statins or a placebo (standardized mean difference (SMD) = -0.08, 95% CI -0.29 to 0.12; P = 0.42). Sensitivity analyses were conducted to separately analyze depression (n = 5) and mood (n = 2) outcomes; statins were associated with statistically significant improvements in mood scores (SMD = -0.43, 95% CI -0.61 to -0.24). CONCLUSIONS: Our findings refute evidence of negative effects of statins on psychological outcomes, providing some support for mood-related benefits. Future studies could examine the effects of statins in depressed populations.

Concepts: Epidemiology, Evidence-based medicine, Systematic review, Randomized controlled trial, Statistical significance, Effect size, Psychiatry, Random effects model


Objective To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat.Design Systematic review and meta-analysis of randomised control trials.Data sources Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews.Study selection Randomised controlled trials of the addition of corticosteroids to standard clinical care for patients aged 5 or older in emergency department and primary care settings with clinical signs of acute tonsillitis, pharyngitis, or the clinical syndrome of sore throat. Trials were included irrespective of language or publication status.Review methods Reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. Random effects model was used for meta-analyses. Quality of evidence was assessed with the GRADE approach.Results 10 eligible trials enrolled 1426 individuals. Patients who received single low dose corticosteroids (the most common intervention was oral dexamethasone with a maximum dose of 10 mg) were twice as likely to experience pain relief after 24 hours (relative risk 2.2, 95% confidence interval 1.2 to 4.3; risk difference 12.4%; moderate quality evidence) and 1.5 times more likely to have no pain at 48 hours (1.5, 1.3 to 1.8; risk difference 18.3%; high quality). The mean time to onset of pain relief in patients treated with corticosteroids was 4.8 hours earlier (95% confidence interval -1.9 to -7.8; moderate quality) and the mean time to complete resolution of pain was 11.1 hours earlier (-0.4 to -21.8; low quality) than in those treated with placebo. The absolute pain reduction at 24 hours (visual analogue scale 0-10) was greater in patients treated with corticosteroids (mean difference 1.3, 95% confidence interval 0.7 to 1.9; moderate quality). Nine of the 10 trials sought information regarding adverse events. Six studies reported no adverse effects, and three studies reported few adverse events, which were mostly complications related to disease, with a similar incidence in both groups.Conclusion Single low dose corticosteroids can provide pain relief in patients with sore throat, with no increase in serious adverse effects. Included trials did not assess the potential risks of larger cumulative doses in patients with recurrent episodes of acute sore throat.Systematic review registration PROSPERO CRD42017067808.

Concepts: Epidemiology, Clinical trial, Medical statistics, Systematic review, Randomized controlled trial, Relative risk, Meta-analysis, Random effects model


OBJECTIVES:Constipation is common in the community, and may affect survival adversely. An association between constipation and development of colorectal cancer (CRC) could be one possible explanation. We performed a systematic review and meta-analysis examining this issue.METHODS:We searched MEDLINE, EMBASE, and EMBASE Classic (through July 2012). Eligible studies were cross-sectional surveys, cohort studies, or case-control studies reporting the association between constipation and CRC. For cross-sectional surveys and cohort studies, we recorded number of subjects with CRC according to the constipation status, and for case-control studies, number of subjects with constipation according to CRC status were recorded. Study quality was assessed according to published criteria. Data were pooled using a random effects model, and the association between CRC and constipation was summarized using an odds ratio (OR) with a 95% confidence interval (CI).RESULTS:The search strategy identified 2,282 citations, of which 28 were eligible. In eight cross-sectional surveys, presence of constipation as the primary indication for colonoscopy was associated with a lower prevalence of CRC (OR=0.56; 95% CI 0.36-0.89). There was a trend toward a reduction in odds of CRC in constipation in three cohort studies (OR=0.80; 95% CI 0.61-1.04). The prevalence of constipation in CRC was significantly higher than in controls without CRC in 17 case-control studies (OR=1.68; 95% CI 1.29-2.18), but with significant heterogeneity, and possible publication bias.CONCLUSIONS:Prospective cross-sectional surveys and cohort studies demonstrate no increase in prevalence of CRC in patients or individuals with constipation. The significant association observed in case-control studies may relate to recall bias.Am J Gastroenterol advance online publication, 12 March 2013; doi:10.1038/ajg.2013.52.

Concepts: Scientific method, Experimental design, Epidemiology, Colorectal cancer, Constipation, Study design, Random effects model, Panel data


BACKGROUND: Studies demonstrate the potential for statins to prevent dementia and Alzheimer’s disease (AD), but the evidence is inconclusive. OBJECTIVE: Conduct a meta-analysis to estimate any benefit of statins in preventing dementia and examine the potential effect of study design and confounding on the benefit of statins in dementia. A secondary goal is to explore factors that may elucidate the mechanisms by which statins exert their potentially beneficial effect. METHODS: Performed systematic literature review to identify relevant publications. Relative risk (RR) estimates were pooled using both fixed and random effect models. Studies were stratified by study design and potential confounding factors. RESULTS: The pooled results for all-type dementia suggest that use of statins is associated with a lower RR of dementia when compared to non-statin users (random effects model: RR 0.82 (95%CI [0.69, 0.97]). The pooled results for AD also suggested a lower RR with statin user compared to non-statin users in random effects models (RR: 0.70, 95% CI [0.60, 0.83]). Study design and methods used to address biases may influence the results. CONCLUSION: These pooled results suggest that statins may provide a slight benefit in the prevention of AD and all-type dementia. This benefit observed in both disease states should be interpreted with caution as observational studies are subject to bias, and it is possible that the slight benefit observed may disappear when these biases are addressed in a well-designed randomized controlled trial. Copyright © 2012 John Wiley & Sons, Ltd.

Concepts: Alzheimer's disease, Scientific method, Experimental design, Epidemiology, Medical statistics, Systematic review, Analysis of variance, Random effects model


Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which were thought to have a positive impact on dementia. We carried out the present meta-analysis to investigate whether statins might be associated with a reduction on risk of dementia. We carried out a meta-analysis of prospective cohort studies to examine the risk of dementia associated with statins. Ovid-Medline database, PubMed database, Springer Link database and Google Scholar in English search were carried out for relevant studies. Selected studies had to describe an original study defined by strict screening and diagnostic criteria. We included eight prospective cohort studies that reported relative risks with 95% confidence intervals for the association of statins and dementia risk. A random effects model was used to calculate the summary risk estimates. The studies eligible for analysis involved 2851 cases and 57020 participants. The summary relative risk of dementia for the use of statins was 0.62 (95% confidence interval 0.43-0.81), with evidence of heterogeneity (P = 0.001, I2  = 70.8%). Findings of the present meta-analysis show that statin use was associated with a reduced risk of dementia. Geriatr Gerontol Int 2013; ●●: ●●-●●.

Concepts: Cohort study, Epidemiology, Estimator, Statin, Relative risk, Confidence interval, Biostatistics, Random effects model


BACKGROUND: Flail chest is a life-threatening injury typically treated with supportive ventilation and analgesia. Several small studies have suggested large improvements in critical care outcomes after surgical fixation of multiple rib fractures. The purpose of this study was to compare the results of surgical fixation and nonoperative management for flail chest injuries. STUDY DESIGN: A systematic review of previously published comparative studies using operative and nonoperative management of flail chest was performed. Medline, Embase, and the Cochrane databases were searched for relevant studies with no language or date restrictions. Quantitative pooling was performed using a random effects model for relevant critical care outcomes. Sensitivity analysis was performed for all outcomes. RESULTS: Eleven manuscripts with 753 patients met inclusion criteria. Only 2 studies were randomized controlled designs. Surgical fixation resulted in better outcomes for all pooled analyses including substantial decreases in ventilator days (mean 8 days, 95% CI 5 to 10 days) and the odds of developing pneumonia (odds ratio [OR] 0.2, 95% CI 0.11 to 0.32). Additional benefits included decreased ICU days (mean 5 days, 95% CI 2 to 8 days), mortality (OR 0.31, 95% CI 0.20 to 0.48), septicemia (OR 0.36, 95% CI 0.19 to 0.71), tracheostomy (OR 0.06, 95% CI 0.02 to 0.20), and chest deformity (OR 0.11, 95% CI 0.02 to 0.60). All results were stable to basic sensitivity analysis. CONCLUSIONS: The results of this meta-analysis suggest surgical fixation of flail chest injuries may have substantial critical care benefits; however, the analyses are based on the pooling of primarily small retrospective studies. Additional prospective randomized trials are still necessary.

Concepts: Comparison, Critical thinking, Medical statistics, Randomized controlled trial, Cultural studies, Analysis, Random effects model, Flail chest


Background and Objective: Enteral feeding is vital in the critical care setting; however, the optimal route of enteral feeding (postpyloric vs gastric feeding) remains debated. We aimed to systematically review the current evidence to see whether postpyloric feeding could provide additional benefits to intensive care unit (ICU) patients. Method: Randomized controlled trials (RCTs) comparing the efficacy and safety of postpyloric feeding vs gastric feeding were included in our systematic review. Odds ratio (OR) was used for binary outcome data and weighted mean difference (WMD) was used for continuous outcome data. Summary effects were pooled using a fixed or random effects model as appropriate. Results: Seventeen RCTs were included in our meta-analysis. Postpyloric tube feeding could deliver higher proportions of estimated energy requirement (WMD, 12%; 95% confidence interval [CI], 5%-18%) and reduce the gastric residual volume (GRV) (WMD, -169.1 mL; 95% CI, -291.995 to -46.196 mL). However, the meta-analysis failed to demonstrate any benefits to critically ill patients with postpyloric tube feeding in terms of mortality (OR, 1.05; 95% CI, 0.77-1.44), new-onset pneumonia (OR, 0.77; 95% CI, 0.53-1.13), and aspiration (OR, 1.20; 95% CI, 0.64-2.25). There was no significant publication bias as represented by an Egger’s bias coefficient of 0.21 (95% CI, -1.01 to 1.43; P = .7). Conclusion: As compared with gastric feeding, postpyloric feeding is able to deliver higher proportions of the estimated energy requirement and can help reduce the GRV.

Concepts: Epidemiology, Evidence-based medicine, Systematic review, Randomized controlled trial, Intensive care medicine, Feeding tube, Meta-analysis, Random effects model


Healthcare-associated infections (HCAIs) cause significant morbidity and mortality in neonatal intensive care units (NICUs). Meticulous hand hygiene is the most effective strategy to prevent HCAI. However, hand hygiene compliance (HHC) is low, especially in ICUs. Hence, we aimed to evaluate the efficacy of strategies for improving HHC in NICUs. A systematic review of the literature and meta-analysis were carried out. PubMed, EMBASE, Cochrane CENTRAL and CINAHL were searched in October 2013. PRISMA guidelines were followed. The quality of included studies was assessed by the Newcastle-Ottawa scale (NOS). Sixteen eligible non-randomised studies were included. A total of 27,155 hand hygiene moments were observed. Meta-analysis using a random effects model indicated that a range of strategies, such as educational campaigns, musical parodies, reminders, easy access to hand hygiene sanitisers, UV sensors and performance feedback, improved HHC [odds ratio (OR) 2.04; 95 % confidence interval (CI) 1.40, 2.97]. Significant statistical heterogeneity was noted. Studies which specifically provided performance feedback at either the individual or group levels reported a more significant improvement in HHC compared to those that did not (OR 2.81; 95 % CI 1.32, 5.96 vs. OR 1.55; 95 % CI 1.13-2.11). Strategies to improve HHC in NICUs seem to be more effective when they include performance feedback at the personal or group levels. Randomised controlled trials (RCTs) specifically assessing the benefits of performance feedback in improving HHC are needed.

Concepts: Better, Improve, Nosocomial infection, Randomized controlled trial, Random effects model, Hygiene, Hand washing, Neonatal intensive care unit


Olfactory ensheathing cell (OEC) transplantation is a candidate cellular treatment approach for human spinal cord injury (SCI) due to their unique regenerative potential and autologous origin. The objective of this study was, through a meta-epidemiologic approach, (i) to assess the efficacy of OEC transplantation on locomotor recovery after traumatic experimental SCI and (ii) to estimate the likelihood of reporting bias and/or missing data. A study protocol was finalized before data collection. Embedded into a systematic review and meta-analysis, we conducted a literature research of databases including PubMed, EMBASE, and ISI Web of Science from 1949/01 to 2014/10 with no language restrictions, screened by two independent investigators. Studies were included if they assessed neurobehavioral improvement after traumatic experimental SCI, administrated no combined interventions, and reported the number of animals in the treatment and control group. Individual effect sizes were pooled using a random effects model. Details regarding the study design were extracted and impact of these on locomotor outcome was assessed by meta-regression. Missing data (reporting bias) was determined by Egger regression and Funnel-plotting. The primary study outcome assessed was improvement in locomotor function at the final time point of measurement. We included 49 studies (62 experiments, 1,164 animals) in the final analysis. The overall improvement in locomotor function after OEC transplantation, measured using the Basso, Beattie, and Bresnahan (BBB) score, was 20.3% (95% CI 17.8-29.5). One missing study was imputed by trim and fill analysis, suggesting only slight publication bias and reducing the overall effect to a 19.2% improvement of locomotor activity. Dose-response ratio supports neurobiological plausibility. Studies were assessed using a 9-point item quality score, resulting in a median score of 5 (interquartile range [IQR] 3-5). In conclusion, OEC transplantation exerts considerable beneficial effects on neurobehavioral recovery after traumatic experimental SCI. Publication bias was minimal and affirms the translational potential of efficacy, but safety cannot be adequately assessed. The data justify OECs as a cellular substrate to develop and optimize minimally invasive and safe cellular transplantation paradigms for the lesioned spinal cord embedded into state-of-the-art Phase I/II clinical trial design studies for human SCI.

Concepts: Spinal cord, Clinical trial, Medical statistics, Evidence-based medicine, Effectiveness, Effect size, Meta-analysis, Random effects model