Pitfalls of using the risk ratio in meta‐analysis

For meta-analysis of studies that report outcomes as binomial proportions, the most popular measure of effect is the odds ratio (OR), usually analyzed as log(OR). Many meta-analyses use the risk ratio (RR) and its logarithm, because of its simpler interpretation. Although log(OR) and log(RR) are both unbounded, use of log(RR) must ensure that estimates are compatible with study-level event rates in the interval (0, 1). These complications pose a particular challenge for random-effects models, both in applications and in generating data for simulations. As background we review the conventional random-effects model and then binomial generalized linear mixed models (GLMMs) with the logit link function, which do not have these complications. We then focus on log-binomial models and explore implications of using them; theoretical calculations and simulation show evidence of biases. The main competitors to the binomial GLMMs use the beta-binomial (BB) distribution, either in BB regression or by maximizing a BB likelihood; a simulation produces mixed results. Two examples and an examination of Cochrane meta-analyses that used RR suggest bias in the results from the conventional inverse-variance-weighted approach. Finally, we comment on other measures of effect that have range restrictions, including risk difference, and outline further research

Jumping to Conclusions About the Beads Task? A Meta-analysis of Delusional Ideation and Data-Gathering

It has been claimed that delusional and delusion-prone individuals have a tendency to gather less data before forming beliefs. Most of the evidence for this "jumping to conclusions" (JTC) bias comes from studies using the "beads task" data-gathering paradigm. However, the evidence for the JTC bias is mixed. We conducted a random-effects meta-analysis of individual participant data from 38 clinical and nonclinical samples (n = 2,237) to investigate the relationship between data gathering in the beads task (using the "draws to decision" measure) and delusional ideation (as indexed by the "Peters et al Delusions Inventory"; PDI). We found that delusional ideation is negatively associated with data gathering (r(s) = -0.10, 95% CI [-0.17, -0.03]) and that there is heterogeneity in the estimated effect sizes (Q-stat P = .03, I² = 33). Subgroup analysis revealed that the negative association is present when considering the 23 samples (n = 1,754) from the large general population subgroup alone (r(s) = -0.10, 95% CI [-0.18, -0.02]) but not when considering the 8 samples (n = 262) from the small current delusions subgroup alone (r(s) = -0.12, 95% CI [-0.31, 0.07]). These results provide some provisional support for continuum theories of psychosis and cognitive models that implicate the JTC bias in the formation and maintenance of delusions.9 page(s

Seatbelt use and risk of major injuries sustained by vehicle occupants during motor-vehicle crashes: A systematic review and meta-analysis of cohort studies

BackgroundIn 2004, a World Health Report on road safety called for enforcement of measures such as seatbelt use, effective at minimizing morbidity and mortality caused by road traffic accidents. However, injuries caused by seatbelt use have also been described. Over a decade after publication of the World Health Report on road safety, this study sought to investigate the relationship between seatbelt use and major injuries in belted compared to unbelted passengers.MethodsCohort studies published in English language from 2005 to 2018 were retrieved from seven databases. Critical appraisal of studies was carried out using the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Pooled risk of major injuries was assessed using the random effects meta-analytic model. Heterogeneity was quantified using I-squared and Tau-squared statistics. Funnel plots and Egger's test were used to investigate publication bias. This review is registered in PROSPERO (CRD42015020309).ResultsEleven studies, all carried out in developed countries were included. Overall, the risk of any major injury was significantly lower in belted passengers compared to unbelted passengers (RR 0.47; 95%CI, 0.29 to 0.80; I-2=99.7; P=0.000). When analysed by crash types, belt use significantly reduced the risk of any injury (RR 0.35; 95%CI, 0.24 to 0.52). Seatbelt use reduces the risk of facial injuries (RR=0.56, 95% CI=0.37 to 0.84), abdominal injuries (RR=0.87; 95% CI=0.78 to 0.98) and, spinal injuries (RR=0.56, 95% CI=0.37 to 0.84). However, we found no statistically significant difference in risk of head injuries (RR=0.49; 95% CI=0.22 to 1.08), neck injuries (RR=0.69: 95%CI 0.07 to 6.44), thoracic injuries (RR 0.96, 95%CI, 0.74 to 1.24), upper limb injuries (RR=1.05, 95%CI 0.83 to 1.34) and lower limb injuries (RR=0.77, 95%CI 0.58 to 1.04) between belted and non-belted passengers.ConclusionIn sum, the risk of most major road traffic injuries is lower in seatbelt users. Findings were inconclusive regarding seatbelt use and susceptibility to thoracic, head and neck injuries during road traffic accidents. Awareness should be raised about the dangers of inadequate seatbelt use. Future research should aim to assess the effects of seatbelt use on major injuries by crash type

Evidence in support of the call to ban the tackle and harmful contact in school rugby: a response to World Rugby

In a paper published in BJSM (June 2016), World Rugby employees Ross Tucker and Martin Raftery and a third coauthor Evert Verhagen took issue with the recent call to ban tackling in school rugby in the UK and Ireland. That call (to ban tackling) was supported by a systematic review published in BJSM. Tucker et al claim that: (1) the mechanisms and risk factors for injury along with the incidence and severity of injury in youth rugby union have not been thoroughly identified or understood; (2) rugby players are at no greater risk of injury than other sports people, (3) this is particularly the case for children under 15 years and (4) removing the opportunity to learn the tackle from school pupils might increase rates of injuries. They conclude that a ban ‘may be unnecessary and may also lead to unintended consequences such as an increase in the risk of injury later in participation.’ Here we aim to rebut the case by Tucker et al. We share new research that extends the findings of our original systematic review and meta-analysis. A cautionary approach requires the removal of the tackle from school rugby as the quickest and most effective method of reducing high injury rates in youth rugby, a public health priority

The earth is flat (p < 0.05): significance thresholds and the crisis of unreplicable research

The widespread use of ‘statistical significance’ as a license for making a claim of a scientific finding leads to considerable distortion of the scientific process (according to the American Statistical Association). We review why degrading p -values into ‘significant’ and ‘nonsignificant’ contributes to making studies irreproducible, or to making them seem irreproducible. A major problem is that we tend to take small p -values at face value, but mistrust results with larger p -values. In either case, p -values tell little about reliability of research, because they are hardly replicable even if an alternative hypothesis is true. Also significance ( p ≤ 0.05) is hardly replicable: at a good statistical power of 80%, two studies will be ‘conflicting’, meaning that one is significant and the other is not, in one third of the cases if there is a true effect. A replication can therefore not be interpreted as having failed only because it is nonsignificant. Many apparent replication failures may thus reflect faulty judgment based on significance thresholds rather than a crisis of unreplicable research. Reliable conclusions on replicability and practical importance of a finding can only be drawn using cumulative evidence from multiple independent studies. However, applying significance thresholds makes cumulative knowledge unreliable. One reason is that with anything but ideal statistical power, significant effect sizes will be biased upwards. Interpreting inflated significant results while ignoring nonsignificant results will thus lead to wrong conclusions. But current incentives to hunt for significance lead to selective reporting and to publication bias against nonsignificant findings. Data dredging, p -hacking, and publication bias should be addressed by removing fixed significance thresholds. Consistent with the recommendations of the late Ronald Fisher, p -values should be interpreted as graded measures of the strength of evidence against the null hypothesis. Also larger p -values offer some evidence against the null hypothesis, and they cannot be interpreted as supporting the null hypothesis, falsely concluding that ‘there is no effect’. Information on possible true effect sizes that are compatible with the data must be obtained from the point estimate, e.g., from a sample average, and from the interval estimate, such as a confidence interval. We review how confusion about interpretation of larger p -values can be traced back to historical disputes among the founders of modern statistics. We further discuss potential arguments against removing significance thresholds, for example that decision rules should rather be more stringent, that sample sizes could decrease, or that p -values should better be completely abandoned. We conclude that whatever method of statistical inference we use, dichotomous threshold thinking must give way to non-automated informed judgment

Physical activity and exercise for chronic pain in adults:an overview of Cochrane Reviews

Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure

Reduced morbidity by using LigaSure compared to conventional inguinofemoral lymphadenectomy in vulvar cancer patients:A randomized controlled trial

Background: Inguinofemoral lymphadenectomy (IFL) is part of the surgical treatment of different malignancies of the genital tract and/or the lower limb including vulvar carcinoma, penile carcinoma and melanoma. IFL is associated with morbidity in up to 85% of the patients. The aims of this MAMBO-IC study (Morbidity And Measurement of the Body) are to study the feasibility of using LigaSure for IFL and to assess the differences in the incidence of short-term complications using LigaSure versus conventional IFL randomized within each individual patient. Methods: In this multicenter randomized controlled trial (RCT), women diagnosed with squamous cell carcinoma of the vulva with an indication for bilateral IFL were included. It was randomly assigned for which groin the LigaSure was used; the other groin was treated with conventional IFL (sharp/diathermia). We estimated the incidence of >= 1 complication(s) per groin using logistic regression and compared this between the two surgical methods, adjusting for possible confounders. Results: We included 40 groins of 20 patients. The estimated incidence of >= 1 complication(s) was 29% after LigaSure versus 70% after conventional IFL (risk difference 41% (95% CI 19-62), p <0.001). Patients' reported restriction of daily living activities and maximum pain score were equal for both treatment methods. There were no differences in the surgeon reported workload scores. Conclusions: This RCT shows that LigaSure for IFL is feasible and associated with significantly less short-term surgical complications compared to conventional IFL. Further studies with a larger sample size are needed to validate our findings. ISRCTN15057626

External validation of prediction models for early relapse in advanced epithelial ovarian cancer using Australian and Dutch population-based data

Objective: To externally validate the published postoperative and BRCA models predictive of early relapse in patients with advanced-stage epithelial ovarian cancer (EOC) using independent Australian and Dutch cohorts. Methods: Advanced-stage EOC patients diagnosed between January 1, 2002, and June 1, 2006, in Australia, and between January 1, 2016, and December 31, 2017, in the Netherlands were included. Data from patients who underwent cytoreductive surgery and platinum-based chemotherapy were used to validate both models. Missing data were addressed through multiple imputation. Model updates included recalibration-in-the-large, recalibration, and model revision, with a closed testing procedure to identify the most suitable approach. Model performance was assessed for calibration, discrimination, and the Brier score. Results: The Australian cohort (N = 1334) included 457 early relapsers and 859 late or non-relapsers, showing baseline differences compared to the development cohort. Discrimination was adequate for both the postoperative and BRCA models (c-statistics: 0.69 and 0.70, respectively). The postoperative model required full revision, while recalibration-in-the-large was sufficient for the BRCA model in the Australian cohort. The Dutch cohort (N = 1212) included 283 early relapsers and 929 late or non-relapsers, with baseline characteristics similar to those of the development cohort. Both models demonstrated adequate discrimination (c-statistics: 0.71 and 0.70, respectively). Recalibration-in-the-large corrected miscalibration in the Dutch cohort. Conclusion: The postoperative and BRCA model were successfully validated for predicting early relapse in advanced-stage EOC patients, confirming their robustness. However, local data updates are advised to enhance accuracy across clinical settings. Online calculators were built for clinical use (Link 1; Link 2).</p

The prevalence of intrusive memories in adult depression: A meta-analysis

Background Intrusive memories have typically been associated with post-traumatic stress disorder (PTSD) but some studies have suggested they can also occur in depression-alone. Objective This meta-analysis aimed to estimate the prevalence of intrusive memories in adult depression and to explore methodological and other factors that may moderate this prevalence. Method The databases PsycINFO, PsycARTICLES, MedLine, PubMed, CINAHL and Embase were searched for relevant articles, published up to and including July 2016. Studies measuring point prevalence of intrusive memories in adults aged 18 years or above with depression were included and assessed for quality. Meta-analysis was completed under a random effects model. Results Seven studies measuring point prevalence of intrusive memories in adult depression were included. The overall pooled prevalence estimate calculated was 76.0% (95% CI 59.4 – 89.4%), reducing to 66.0% (95% CI 51.0 – 79.5%) when restricted to intrusive memories experienced within the week prior to assessment. Heterogeneity was high. Between-groups analyses indicated that adults with depression are as likely to experience intrusive memories as adults with PTSD, and more likely to experience intrusive memories than healthy controls (risk ratio of 2.94, 95% CI 1.53 – 5.67). Limitations The strength of conclusions is limited by the small number of studies included. Consideration of the relationship between depression, intrusive memories and trauma exposure is required. Conclusions Intrusive memories are experienced by a large majority of adults with depression and may therefore be an important target for cognitive intervention. Larger scale measurement of clinical outcome is needed with identification of individual factors predicting treatment response

Inter-individual differences in the responses to pain neuroscience education in adults with chronic musculoskeletal pain: A systematic review and meta-analysis of randomised controlled trials.

Pain neuroscience education (PNE) is an approach used in the management of chronic musculoskeletal pain. Previous reviews on PNE and other pain interventions, have focused on mean treatment effects, but in the context of “precision medicine,” any inter-individual differences in treatment response are also important to quantify. If inter-individual differences are present, and predictors identified, PNE could be tailored to certain people for optimizing effectiveness. Such heterogeneity can be quantified using recently formulated approaches for comparing the response variance between the treatment and control groups. Therefore, we conducted a systematic review and meta-analysis on the extracted standard deviations of baseline-to-follow up change to quantify the inter-individual variation in pain, disability and psychosocial outcomes in response to PNE. Electronic databases were searched between January 1, 2002 and June 14, 2018. The review included 5 randomized controlled trials (n = 428) in which disability outcomes were reported. Using a random effects meta-analysis, the pooled SD (95% confidence interval) for control group-adjusted response heterogeneity to PNE was 7.36 units /100 (95% confidence interval = −3.93 to 11.12). The 95% prediction interval for this response heterogeneity SD was wide (−10.20 to 14.57 units /100). The control group-adjusted proportion of “responders” in the population who would be estimated to exceed a clinically important change of 10/100 ranged from 18 to 45%. Therefore, when baseline-to-follow up random variability in disability is taken into account (informed by the control arm), there is currently insufficient evidence for the notion of clinically important inter-individual differences in disability responses to PNE in people with chronic musculoskeletal pain. The protocol was published on PROSPERO (CRD42017068436). Perspective: We bring a novel method to pain science for calculating inter-individual differences in response to a treatment. This is conductedwithin the context of a systematic review and meta-analysis on PNE. We highlight how using erroneous methods for calculating inter-individual differences can drastically change conclusions when compared to appropriate methods.</p