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Abstract Background This article corresponds to a literature review and analyze how heterogeneity of treatment (HTE) is reported and addressed in cohort studies and to evaluate the use of the different measures to HTE analysis. Methods prospective cohort studies, in English language, measuring the effect of a treatment (pharmacological, interventional, or other) published among 119 core clinical journals (defined by the National Library of Medicine) in the last 16 years were selected in the following data source: Medline. One reviewer randomly sampled journal articles with 1: 1 stratification by journal type: high impact journals (the New England Journal of Medicine, JAMA, LANCET, Annals of Internal Medicine, BMJ and Plos Medicine) and low impact journal (the remaining journals) to identify 150 eligible studies. Two reviewers independently and in duplicate used standardized piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a cohort study reported HTE analysis. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of heterogeneity of treatment effect. Results One hundred fifty cohort studies were included of which 88 (58%) reported HTE analysis. High impact journals (Odds Ratio: 3.5, 95% CI: 1.78–7.5; P

Abstract Background The common frequentist approach is limited in providing investigators with appropriate measures for conducting a new trial. To answer such important questions and one has to look at Bayesian statistics. Methods As a worked example, we conducted a Bayesian cumulative meta-analysis to summarize the benefit of patient-specific instrumentation on the alignment of total knee replacement from previously published evidence. Data were sourced from Medline, Embase, and Cochrane databases. All randomised controlled comparisons of the effect of patient-specific instrumentation on the coronal alignment of total knee replacement were included. The main outcome was the risk difference measured by the proportion of failures in the control group minus the proportion of failures in the experimental group. Through Bayesian statistics, we estimated cumulatively over publication time of the trial results: the posterior probabilities that the risk difference was more than 5 and 10%; the posterior probabilities that given the results of all previous published trials an additional fictive trial would achieve a risk difference of at least 5%; and the predictive probabilities that observed failure rate differ from 5% across arms. Results Thirteen trials were identified including 1092 patients, 554 in the experimental group and 538 in the control group. The cumulative mean risk difference was 0.5% (95% CrI: −5.7%; +4.5%). The posterior probabilities that the risk difference be superior to 5 and 10% was less than 5% after trial #4 and trial #2 respectively. The predictive probability that the difference in failure rates was at least 5% dropped from 45% after the first trial down to 11% after the 13th. Last, only unrealistic trial design parameters could change the overall evidence accumulated to date. Conclusions Bayesian probabilities are readily understandable when discussing the relevance of performing a new trial. It provides investigators the current probability that an experimental treatment be superior to a reference treatment. In case a trial is designed, it also provides the predictive probability that this new trial will reach the targeted risk difference in failure rates. Trial registration CRD42015024176 .

Introduction. Ewing's sarcomas (EWSs) of bone and soft tissue are neuroectodermal tumors that affect both axial and appendicular locations. We hypothesized that axial location predicted poor outcome in EWS patients. Materials and Methods. Sixty-seven patients (57 with bone EWS and 10 with soft tissue EWS) were identified from our database. Thirty-four (51%) had axial EWS and 33 (49%) had appendicular EWS. Statistical analyses identified predictors of poor outcome. Results and Discussion. Axial location, large size, metastases at presentation, lack of definitive treatment, and positive surgical margins all correlated with poor outcome in univariate analysis. In multivariate analysis, axial location still predicted poor outcome when adjusted for pretreatment variables. Axial location was not statistically predictive of poor outcome when adjusted for treatment variables. Conclusions. Anatomic location has a negative effect on outcome in EWS that cannot be completely explained by pretreatment or treatment factors. Additional studies are required to determine if there is a biologic difference between axial and appendicular EWS.

BackgroundThe learning curve cumulative sum (LC-CUSUM) test is an innovative tool that allows quantitative monitoring of individual medical performance during the learning process by determining when a predefined acceptable level of performance is reached. This study used the LC-CUSUM test to monitor the learning process and failure rate of anesthesia residents training for specific subspecialty anesthesia procedures.MethodsThe study included 490 tracheal punctures (TP) for jet ventilation, 340 thoracic epidural analgesia (TEA) procedures, and 246 fiberoptic nasal intubations (FONI) performed by 18 residents during their single 6-month rotation.ResultsOverall, 27 (14–52), 19 (5–41), and 14 (6–33) TP, TEA, and FONI procedures were performed, respectively, by each resident. In total, 2 of 18 residents achieved an acceptable failure rate for TEA according to the literature and 4 of 18 achieved an acceptable failure rate for FONI, while none of the residents attained an acceptable rate for TP.ConclusionsA single 6-month rotation in a reference teaching center may not be sufficient to train residents to perform specific or sub-specialty procedures as required. A regional learning network may be useful. More patient-based data are necessary to conduct a risk adjustment analysis for such specific procedures.

The aims of this study were to determine if the learning curve cumulative summation test (LC-CUSUM) can differentiate proficiency in placing intravenous catheters by novice learners, and identify the cause of failure when it occurred. In a prospective, observational study design 6 undergraduate students with no previous experience of placing intravenous catheters received standardized training by a board certified veterinary anesthesiologist in intravenous catheter placement technique. Immediately following training, each student attempted 60 intravenous catheterizations in a dog mannequin thoracic limb model. Results were scored as a success or failure based upon completion of four specific criteria, and where catheter placement failure occurred, the cause was recorded according to pre-defined criteria. Initial acceptable and unacceptable failure rates were set by the study team and the LC-CUSUM was used to generate a learning curve for each student. Using 10% and 25% acceptable and unacceptable failure rates, 3 out of 6 students attained proficiency, requiring between 26 to 48 attempts. Applying 25% and 50% acceptable and unacceptable failure rates, 5 of 6 students obtained proficiency, requiring between 18 and 55 attempts. Wide inter-individual variability was observed and the majority of failed catheterisation attempts were limited to two of the four pre-defined criteria. These data indicate that the LC-CUSUM can be used to generate individual learning curves, inter-individual variability in catheter placement ability is wide, and that specific steps in catheter placement are responsible for the majority of failures. These findings may have profound implications for how we teach and assess technical skills.