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PloS One 2018Proposals to increase research reproducibility frequently call for focusing on effect sizes instead of p values, as well as for increasing the statistical power of... (Review)
Review
Proposals to increase research reproducibility frequently call for focusing on effect sizes instead of p values, as well as for increasing the statistical power of experiments. However, it is unclear to what extent these two concepts are indeed taken into account in basic biomedical science. To study this in a real-case scenario, we performed a systematic review of effect sizes and statistical power in studies on learning of rodent fear conditioning, a widely used behavioral task to evaluate memory. Our search criteria yielded 410 experiments comparing control and treated groups in 122 articles. Interventions had a mean effect size of 29.5%, and amnesia caused by memory-impairing interventions was nearly always partial. Mean statistical power to detect the average effect size observed in well-powered experiments with significant differences (37.2%) was 65%, and was lower among studies with non-significant results. Only one article reported a sample size calculation, and our estimated sample size to achieve 80% power considering typical effect sizes and variances (15 animals per group) was reached in only 12.2% of experiments. Actual effect sizes correlated with effect size inferences made by readers on the basis of textual descriptions of results only when findings were non-significant, and neither effect size nor power correlated with study quality indicators, number of citations or impact factor of the publishing journal. In summary, effect sizes and statistical power have a wide distribution in the rodent fear conditioning literature, but do not seem to have a large influence on how results are described or cited. Failure to take these concepts into consideration might limit attempts to improve reproducibility in this field of science.
Topics: Animals; Conditioning, Psychological; False Positive Reactions; Fear; Journal Impact Factor; Mice; Models, Statistical; Rats; Reproducibility of Results; Research Design; Rodentia; Sample Size; Statistics as Topic
PubMed: 29698451
DOI: 10.1371/journal.pone.0196258 -
Journal of Vascular Surgery Apr 2017Direct revascularization (DR), according to the angiosome concept, provides direct blood flow to the site of tissue loss in patients with critical limb ischemia (CLI).... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Direct revascularization (DR), according to the angiosome concept, provides direct blood flow to the site of tissue loss in patients with critical limb ischemia (CLI). DR may lead to improved outcomes; however, evidence for this is controversial. This systematic review and meta-analysis investigated the outcomes of surgical and endovascular DR compared with indirect revascularization (IR) in patients with CLI.
METHODS
A systematic review was undertaken using the Cochrane Collaboration specified tool, and a meta-analysis was done according to the MOOSE (Meta-analysis of Observational Studies in Epidemiology) criteria. The electronic databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched for studies of DR compared with IR in patients with CLI with tissue loss. All articles were critically assessed for relevance, validity, and availability of data regarding patient and lesion characteristics and outcomes. When possible, data were systematically pooled, and a meta-analysis was performed for wound healing, major amputation, amputation-free survival, and overall survival.
RESULTS
Of 306 screened abstracts, 19 cohort studies with 3932 patients were included. Nine scored 7 or higher on the Newcastle-Ottawa score. DR significantly improved wound healing (risk ratio [RR], 0.60; 95% confidence interval [CI], 0.51-0.71), major amputation (RR, 0.56; 95% CI, 0.47-0.67), and amputation-free survival rates (RR, 0.83; 95% CI, 0.69-1.00) compared with IR. This significance was lost in major amputation on sensitivity analysis for bypass studies. No significant difference was found in overall survival. In studies stratifying for collaterals, no differences between DR and IR were found in wound healing or major amputations in the presence of collaterals.
CONCLUSIONS
DR significantly improves wound healing and major amputation rates after endovascular treatment in patients with CLI, supporting the angiosome theory. In the presence of collaterals, outcomes after IR are similar to outcomes after DR. Alternatively, patients without collaterals may benefit even more from DR as a primary treatment strategy. The angiosome theory is less applicable in bypass surgery, because bypasses are generally anastomosed to the least affected artery, with runoff passing the ankle to maintain bypass patency.
Topics: Amputation, Surgical; Chi-Square Distribution; Collateral Circulation; Critical Illness; Disease-Free Survival; Endovascular Procedures; Humans; Ischemia; Limb Salvage; Models, Cardiovascular; Odds Ratio; Postoperative Complications; Regional Blood Flow; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures; Wound Healing
PubMed: 28342514
DOI: 10.1016/j.jvs.2016.10.100 -
Vascular Aug 2017Introduction Acute mesenteric ischaemia is associated with a significant morbidity and mortality. Endovascular techniques have emerged as a viable alternative treatment... (Meta-Analysis)
Meta-Analysis Review
Introduction Acute mesenteric ischaemia is associated with a significant morbidity and mortality. Endovascular techniques have emerged as a viable alternative treatment option to conventional surgery. Our objective was to conduct a systematic review of the literature and perform a meta-analysis of reported outcomes. Methods Our review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards and the protocol was registered in PROSPERO (CRD42016035667). We searched electronic information sources (MEDLINE, EMBASE, CINAHL, CENTRAL) and bibliographic lists of relevant articles to identify studies reporting outcomes of endovascular treatment for acute mesenteric ischaemia of embolic or thrombotic aetiology. We defined 30-day or in-hospital mortality and bowel resection as the primary outcome measures. We used the Newcastle-Ottawa scale to assess the methodological quality of observational studies. We calculated combined overall effect sizes using random effects models; results are reported as the odds ratio and 95% confidence interval. Results We identified 19 observational studies reporting on a total of 3362 patients undergoing endovascular treatment for acute mesenteric ischaemia. The pooled estimate of peri-interventional mortality was 0.245 (95% confidence interval 0.197-0.299), that of the requirement for bowel resection 0.326 (95% confidence interval 0.229-0.439), and the pooled estimate for acute kidney injury was 0.132 (95% confidence interval 0.082-0.204). Eight studies reported comparative outcomes of endovascular versus surgical treatment for acute mesenteric ischaemia (endovascular group, 3187 patients; surgical group, 4998 patients). Endovascular therapy was associated with a significantly lower risk of 30-day mortality (odds ratio 0.45, 95% confidence interval 0.30-0.67, P = 0.0001), bowel resection (odds ratio 0.45, 95% confidence interval 0.34-0.59, P < 0.00001) and acute renal failure (odds ratio 0.58, 95% confidence interval 0.49-0.68, P < 0.00001). No differences were identified in septic complications or the development of short bowel syndrome. Conclusion Endovascular treatment for acute mesenteric ischaemia is associated with a considerable mortality and requirement of bowel resection. However, endovascular therapy confers improved outcomes compared to conventional surgery, as indicated be reduced mortality, risk of bowel resection and acute renal failure. An endovascular-first approach should be considered in patients presenting with acute mesenteric ischaemia.
Topics: Chi-Square Distribution; Endovascular Procedures; Humans; Mesenteric Ischemia; Mesenteric Vascular Occlusion; Odds Ratio; Risk Assessment; Risk Factors; Splanchnic Circulation; Stents; Treatment Outcome
PubMed: 28121281
DOI: 10.1177/1708538116689353 -
Nutrition, Metabolism, and... Mar 2017The generation of reactive oxygen species (ROS) plays an important role in the etiology of several pathological conditions. High levels of 8-hydroxy-2-deoxyguanosine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The generation of reactive oxygen species (ROS) plays an important role in the etiology of several pathological conditions. High levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of oxidative damage of DNA, have been found in patients with heart failure (HF). We performed a meta-analysis of the literature to investigate the association between 8-OHdG levels and HF.
METHODS AND RESULTS
A systematic search was performed in the PubMed, Web of Science, Scopus, EMBASE databases and studies evaluating 8-OHdG levels in HF patients and controls were included. Differences between cases and controls were expressed as standard mean difference (SMD) or mean difference (MD) with pertinent 95% confidence intervals (95%CI). Impact of clinical and demographic features on effect size was assessed by meta-regression. Six studies (446 HF patients and 140 controls) were included in the analysis. We found that HF patients showed higher 8-OHdG levels than controls (SMD:0.89, 95%CI: 0.68, 1.10). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD:6.28 ng/mg creatinine, 95%CI: 4.01, 8.56) and in blood samples (MD:0.36 ng/ml, 95%CI: 0.04, 0.69). Interestingly, 8-OHdG levels progressively increased for increasing New York Heart Association (NYHA) class. Meta-regression models showed that none of clinical and demographic variables impacted on the difference in 8-OHdG levels among HF patients and controls.
CONCLUSIONS
8-OHdG levels are higher in HF patients HF than in controls, with a progressive increase for increasing NYHA class. However, larger prospective studies are needed to test 8-OHdG as a biomarker of HF severity and progression.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Chi-Square Distribution; DNA Damage; Deoxyguanosine; Heart Failure; Humans; Myocardium; Oxidative Stress; Predictive Value of Tests; Prognosis; Risk Factors; Severity of Illness Index; Stroke Volume; Up-Regulation; Ventricular Function, Left
PubMed: 28065503
DOI: 10.1016/j.numecd.2016.10.009 -
Sarcoidosis, Vasculitis, and Diffuse... Sep 2015Several chronic inflammatory disorders, such as rheumatoid arthritis, inflammatory myositis and systemic lupus erythematosus, have been linked to an increased risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several chronic inflammatory disorders, such as rheumatoid arthritis, inflammatory myositis and systemic lupus erythematosus, have been linked to an increased risk of venous thromboembolism (VTE). However, the data on sarcoidosis is unclear.
OBJECTIVES
To evaluate the risk of VTE among patients with sarcoidosis.
METHODS
We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing risk of VTE in patients with sarcoidosis versus non-sarcoidosis participants. Estimated effects were extracted from each study and were pooled together using the random-effect, generic inverse variance method of DerSimonian and Laird.
RESULT
Out of 772 potentially relevant articles, three eligible studies were identified and included in the data analysis. The pooled risk ratio of VTE in patients with sarcoidosis was 1.42 (95% CI, 1.12-1.79). The statistical heterogeneity of this study was moderate with an I2 of 72%.
CONCLUSION
Our study demonstrated a statistically significant increased VTE risk among patients with sarcoidosis.
Topics: Chi-Square Distribution; Humans; Incidence; Odds Ratio; Prognosis; Risk Assessment; Risk Factors; Sarcoidosis; Venous Thromboembolism
PubMed: 26422561
DOI: No ID Found -
International Journal of Rheumatic... Aug 2016To investigate the association between giant cell arteritis (GCA) and risk of peripheral arterial disease (PAD). (Meta-Analysis)
Meta-Analysis Review
AIM
To investigate the association between giant cell arteritis (GCA) and risk of peripheral arterial disease (PAD).
METHODS
We conducted a systematic review and meta-analysis of observational cohort studies that reported relative risks, hazard ratios or standardized incidence ratios with 95% confidence comparing PAD risk in patients with GCA versus non-GCA subjects. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, generic inverse variance of DerSimonian and Laird.
RESULTS
Four studies with 9789 patients with GCA and 236 728 controls were identified and included in our data analysis. The pooled risk ratio of PAD among patients with GCA compared with controls was 1.88 (95% CI 1.04-3.41). The statistical heterogeneity was high with an I(2) of 89%.
CONCLUSION
Our study demonstrated a statistically significant increased risk of PAD among patients with GCA.
Topics: Case-Control Studies; Chi-Square Distribution; Giant Cell Arteritis; Humans; Observational Studies as Topic; Odds Ratio; Peripheral Arterial Disease; Risk Factors
PubMed: 26218931
DOI: 10.1111/1756-185X.12631 -
Age and Ageing Jan 2018light-to-moderate alcohol consumption is protective against all-cause mortality and cardiovascular diseases. There is limited evidence in the literature on how alcohol... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
light-to-moderate alcohol consumption is protective against all-cause mortality and cardiovascular diseases. There is limited evidence in the literature on how alcohol consumption is related to frailty.
METHODS
five databases (Embase, Scopus, MEDLINE, CINAHL, PsycINFO) were systematically searched in July 2016 for prospective studies published between 2000 and 2016 examining baseline alcohol consumption and subsequent frailty risk among middle-aged or older community-dwelling population. Odds ratios (ORs) for incident frailty were pooled using a random-effects model. Heterogeneity, methodological quality and publication bias were assessed.
RESULTS
of 926 studies identified by the systematic search, four studies were included (total n = 44,051, ≥55 years, 66.2% alcohol users). OR of incident frailty for the highest (at least 24 g of alcohol/day for men, 12g of alcohol/day for women) or the most frequent (≥5 days of drinking/week) alcohol consumption compared with no drinking were used for a meta-analysis. Pooled OR among three studies measuring alcohol consumption quantitatively showed that the highest alcohol consumption was associated with lower frailty risk (3 studies:pooled OR = 0.44, 95%CI = 0.19-1.00, P = 0.05). Adding the other study measuring frequency of alcohol consumption made little change (4 studies:pooled OR = 0.61, 95%CI = 0.44-0.77, P < 0.001). Two of the included studies suggested a possible U-shaped association with lowest risks for moderate drinkers. Heterogeneity was moderate in both analyses (I2 = 52-67%). There was no evidence of publication bias.
CONCLUSIONS
this systematic review and meta-analysis study provides the first pooled evidence suggesting that heavier alcohol consumption is associated with lower incident frailty compared with no alcohol consumption among community-dwelling middle-aged and older people. However, this association may be due to unadjusted effect measures, residual confounding, 'sick quitter' effect or survival bias.
Topics: Age Factors; Aged; Aged, 80 and over; Alcohol Drinking; Chi-Square Distribution; Female; Frail Elderly; Frailty; Geriatric Assessment; Humans; Incidence; Logistic Models; Male; Middle Aged; Odds Ratio; Prognosis; Prospective Studies; Protective Factors; Risk Assessment; Risk Factors; Time Factors
PubMed: 28541395
DOI: 10.1093/ageing/afx086 -
Briefings in Bioinformatics Jan 2018Genome-wide association studies are moving to genome-wide interaction studies, as the genetic background of many diseases appears to be more complex than previously... (Review)
Review
Genome-wide association studies are moving to genome-wide interaction studies, as the genetic background of many diseases appears to be more complex than previously supposed. Thus, many statistical approaches have been proposed to detect gene-gene (GxG) interactions, among them numerous information theory-based methods, inspired by the concept of entropy. These are suggested as particularly powerful and, because of their nonlinearity, as better able to capture nonlinear relationships between genetic variants and/or variables. However, the introduced entropy-based estimators differ to a surprising extent in their construction and even with respect to the basic definition of interactions. Also, not every entropy-based measure for interaction is accompanied by a proper statistical test. To shed light on this, a systematic review of the literature is presented answering the following questions: (1) How are GxG interactions defined within the framework of information theory? (2) Which entropy-based test statistics are available? (3) Which underlying distribution do the test statistics follow? (4) What are the given strengths and limitations of these test statistics?
Topics: Entropy; Epistasis, Genetic; Genetic Variation; Genome-Wide Association Study; Genomics; Humans; Information Theory; Models, Genetic; Models, Statistical
PubMed: 27769993
DOI: 10.1093/bib/bbw086 -
European Urology Oct 2017Retropubic (RP-TVT) and transobturator miurethral (TO-TVT) midurethral sling (MUS) are popular surgical treatments for female stress urinary incontinence. The long-term... (Meta-Analysis)
Meta-Analysis Review
Updated Systematic Review and Meta-analysis of the Comparative Data on Colposuspensions, Pubovaginal Slings, and Midurethral Tapes in the Surgical Treatment of Female Stress Urinary Incontinence.
CONTEXT
Retropubic (RP-TVT) and transobturator miurethral (TO-TVT) midurethral sling (MUS) are popular surgical treatments for female stress urinary incontinence. The long-term efficacy and safety of the procedures is still a topic of intense clinical research and several randomised controlled trials (RCTs) have been published in the last years OBJECTIVE: To evaluate the efficacy and safety of MUS compared with other surgical treatments for female stress urinary incontinence.
EVIDENCE ACQUISITION
A systematic review and meta-analysis of the literature was performed using the Medline, Scopus, and Web of Science databases to update our previously published analyses.
EVIDENCE SYNTHESIS
Twenty-eight RCTs were identified. In total, the meta-analyses included 15 855 patients. Patients receiving MUS had significantly higher overall (odds ratio [OR]: 0.59, p=0.0003) and objective (OR: 0.51, p=0.001) cure rates than those receiving Burch colposuspension. Patients undergoing MUS and pubovaginal slings had similar cure rates. Patients treated with RT-TVT had higher subjective (OR: 0.83, p=0.03) and objective (OR: 0.82, p=0.01) cure rates than those receiving TO-TVT. However, the latter had a lower risk of intraoperative bladder or vaginal perforation (OR: 2.4, p=0.0002), pelvic haematoma (OR: 2.61, p=0.002), urinary tract infections (OR: 1.31, p=0.04) and voiding lower urinary tract symptoms (OR: 1.66, p=0.002). Sensitivity analyses limited to RCTs with follow-up durations >60 mo demonstrated similar outcomes for RP-TVT and TO-TVT. No significant differences in efficacy were identified comparing inside-to-out and outside-to-in TO-TVT but vaginal perforations were less common with the former (OR: 0.21, p=0.0002).
CONCLUSIONS
The present analysis confirms the superiority of MUS over Burch colposuspension. The studies comparing insertion of RT-TVT and TO-TVT showed higher subjective and objective cure rates for the RP-TVT but at the cost of higher risks of some complications and voiding lower urinary tract symptoms. Efficacy of inside-out and outside-in techniques of TO-TVT insertion was similar, although the risk of vaginal perforation was lower in the inside-to-out TO-TVT.
PATIENT SUMMARY
Retropubic and transobturator midurethral slings are a popular treatment for female stress urinary incontinence. The available literature suggest that those slings are either more effective or safer than other older surgical procedures. Retropubic tapes are followed with slightly higher continence rates as compared with the transobturator tapes but are associated with higher risk of intra- and postoperative complications.
Topics: Chi-Square Distribution; Female; Humans; Odds Ratio; Postoperative Complications; Prosthesis Design; Risk Factors; Suburethral Slings; Time Factors; Treatment Outcome; Urinary Incontinence, Stress; Urologic Surgical Procedures
PubMed: 28479203
DOI: 10.1016/j.eururo.2017.04.026 -
Clinical Obesity Feb 2018Survivors of childhood brain tumours (SCBT) have increased cardiometabolic risks, but the determinants of these risks are unclear. This systematic review aims to compare... (Meta-Analysis)
Meta-Analysis Review
Survivors of childhood brain tumours (SCBT) have increased cardiometabolic risks, but the determinants of these risks are unclear. This systematic review aims to compare the prevalence of overweight and obesity as well as adiposity measures between SCBT and non-cancer controls. The PubMed, EMBASE, MEDLINE, CINAHL and the Cochrane Library databases were searched. The primary outcomes were the prevalence of overweight and obesity based on body mass index. The secondary outcomes were adiposity measures including percent fat mass, waist-to-hip and waist-to-height ratios. Forty-one studies were included in the meta-analysis. The prevalence of overweight and obesity combined was similar between overall SCBT, SCBT excluding craniopharyngioma and non-cancer controls (42.6%, 95% CI 30.1-55.1 vs. 31.7%, 95% CI 20.4-43.0 vs. 40.4%, 95% CI 34.0-46.8). We also found that SCBT have higher percent fat mass (mean difference 4.1%, 95% CI 2.0-6.1), waist-to-hip ratio (mean difference 0.07, 95% CI 0.02-0.13) and waist-to-height ratio (mean difference 0.06, 95% CI 0.01-0.10) than non-cancer controls. We conclude that SCBT have similar overweight and obesity distribution but higher adiposity than non-cancer controls. More studies were needed to explore the determinants of adiposity and its contribution to cardiometabolic outcomes in SCBT.
Topics: Adiposity; Adolescent; Brain Neoplasms; Cancer Survivors; Chi-Square Distribution; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Odds Ratio; Overweight; Pediatric Obesity; Prevalence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Young Adult
PubMed: 29024558
DOI: 10.1111/cob.12224