Comparison of results from different imputation techniques for missing data from an anti-obesity drug trial

BackgroundIn randomised trials of medical interventions, the most reliable analysis follows the intention-to-treat (ITT) principle. However, the ITT analysis requires that missing outcome data have to be imputed. Different imputation techniques may give different results and some may lead to bias. In anti-obesity drug trials, many data are usually missing, and the most used imputation method is last observation carried forward (LOCF). LOCF is generally considered conservative, but there are more reliable methods such as multiple imputation (MI).ObjectivesTo compare four different methods of handling missing data in a 60-week placebo controlled anti-obesity drug trial on topiramate.MethodsWe compared an analysis of complete cases with datasets where missing body weight measurements had been replaced using three different imputation methods: LOCF, baseline carried forward (BOCF) and MI.Results561 participants were randomised. Compared to placebo, there was a significantly greater weight loss with topiramate in all analyses: 9.5 kg (SE 1.17) in the complete case analysis (N = 86), 6.8 kg (SE 0.66) using LOCF (N = 561), 6.4 kg (SE 0.90) using MI (N = 561) and 1.5 kg (SE 0.28) using BOCF (N = 561).ConclusionsThe different imputation methods gave very different results. Contrary to widely stated claims, LOCF did not produce a conservative (i.e., lower) efficacy estimate compared to MI. Also, LOCF had a lower SE than MI

A novel suture method to place and adjust peripheral nerve catheters

We have developed a peripheral nerve catheter, attached to a needle, which works like an adjustable suture. We used in‐plane ultrasound guidance to place 45 catheters close to the femoral, saphenous, sciatic and distal tibial nerves in cadaver legs. We displaced catheters after their initial placement and then attempted to return them to their original positions. We used ultrasound to evaluate the initial and secondary catheter placements and the spread of injectate around the nerves. In 10 cases, we confirmed catheter position by magnetic resonance imaging. We judged 43/45 initial placements successful and 42/43 secondary placements successful by ultrasound, confirmed in 10/10 cases by magnetic resonance imaging

A new tool to assess Clinical Diversity In Meta‐analyses (CDIM) of interventions

OBJECTIVE: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions.STUDY DESIGN AND SETTING: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups.RESULTS: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters.CONCLUSION: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.</p

Organizational Factors and Long-Term Mortality after Hip Fracture Surgery. A Cohort Study of 6143 Consecutive Patients Undergoing Hip Fracture Surgery

In hospital and health care organizational factors may be changed to reduce postoperative mortality. The aim of this study is to evaluate a possible association between mortality and 'length of hospital stay', 'priority of surgery', 'time of surgery', or 'surgical delay' in hip fracture surgery.Observational cohort study.Prospectively and consecutively reported data from the Danish Anaesthesia Database were linked to The Danish National Registry of Patients and The Civil Registration System. Records on vital status, admittance, discharges, codes of diagnosis, anaesthetic and surgical procedures were retrieved.6143 patients aged more than 65 years undergoing hip fracture surgery.All-cause mortality.The one year mortality was 30% (28-31%, 95% Confidence interval (CI)). In a multivariate model 'length of hospital stay' less than 10 days and more than 20 days are associated with mortality with hazard ratios of 1.34 (1.20-1.53 CI, p<0.001) and 1.27 (1.06-1.51 CI, p<0.001), respectively. 'Priority of surgery' categorized as 'non-scheduled' is associated with mortality with a hazard ratio of 1.31 (1.13-1.50 CI, p<0.001). Surgical delay and time of surgery are not significantly associated with mortality.Non-scheduled surgery and length of hospital stay were associated with increased mortality. Confounding by indication may bias observational studies evaluating early and late discharge as well as priority; therefore cluster randomized clinical trials comparing different clinical set ups may be warranted evaluating health care organizational factors