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Concept: Random effects model

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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

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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

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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

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Background: Suboptimal diet is one of the most important factors in preventing early death and disability worldwide.Objective: The aim of this meta-analysis was to synthesize the knowledge about the relation between intake of 12 major food groups, including whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages, with risk of all-cause mortality.Design: We conducted a systematic search in PubMed, Embase, and Google Scholar for prospective studies investigating the association between these 12 food groups and risk of all-cause mortality. Summary RRs and 95% CIs were estimated with the use of a random effects model for high-intake compared with low-intake categories, as well as for linear and nonlinear relations. Moreover, the risk reduction potential of foods was calculated by multiplying the RR by optimal intake values (serving category with the strongest association) for risk-reducing foods or risk-increasing foods, respectively.Results: With increasing intake (for each daily serving) of whole grains (RR: 0.92; 95% CI: 0.89, 0.95), vegetables (RR: 0.96; 95% CI: 0.95, 0.98), fruits (RR: 0.94; 95% CI: 0.92, 0.97), nuts (RR: 0.76; 95% CI: 0.69, 0.84), and fish (RR: 0.93; 95% CI: 0.88, 0.98), the risk of all-cause mortality decreased; higher intake of red meat (RR: 1.10; 95% CI: 1.04, 1.18) and processed meat (RR: 1.23; 95% CI: 1.12, 1.36) was associated with an increased risk of all-cause mortality in a linear dose-response meta-analysis. A clear indication of nonlinearity was seen for the relations between vegetables, fruits, nuts, and dairy and all-cause mortality. Optimal consumption of risk-decreasing foods results in a 56% reduction of all-cause mortality, whereas consumption of risk-increasing foods is associated with a 2-fold increased risk of all-cause mortality.Conclusion: Selecting specific optimal intakes of the investigated food groups can lead to a considerable change in the risk of premature death.

Concepts: Nutrition, Death, Meat, Fruit, Random effects model, Pork, Whole grain, Refined grains

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Background Replacing sitting with standing is one of several recommendations to decrease sedentary time and increase the daily energy expenditure, but the difference in energy expenditure between standing versus sitting has been controversial. This systematic review and meta-analysis aimed to determine this difference. Designs and methods We searched Ovid MEDLINE, Ovid Embase Scopus, Web of Science and Google Scholar for observational and experimental studies that compared the energy expenditure of standing versus sitting. We calculated mean differences and 95% confidence intervals using a random effects model. We conducted different predefined subgroup analyses based on characteristics of participants and study design. Results We identified 658 studies and included 46 studies with 1184 participants for the final analysis. The mean difference in energy expenditure between sitting and standing was 0.15 kcal/min (95% confidence interval (CI) 0.12-0.17). The difference among women was 0.1 kcal/min (95% CI 0.0-0.21), and was 0.19 kcal/min (95% CI 0.05-0.33) in men. Observational studies had a lower difference in energy expenditure (0.11 kcal/min, 95% CI 0.08-0.14) compared to randomised trials (0.2 kcal/min, 95% CI 0.12-0.28). By substituting sitting with standing for 6 hours/day, a 65 kg person will expend an additional 54 kcal/day. Assuming no increase in energy intake, this difference in energy expenditure would be translated into the energy content of about 2.5 kg of body fat mass in 1 year. Conclusions The substitution of sitting with standing could be a potential solution for a sedentary lifestyle to prevent weight gain in the long term. Future studies should aim to assess the effectiveness and feasibility of this strategy.

Concepts: Statistics, Obesity, Randomized controlled trial, Body fat percentage, Confidence interval, Random effects model

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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

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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

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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

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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

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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