Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.

BackgroundBefore considering whether to use a multivariable (diagnostic or prognostic) prediction model, it is essential that its performance be evaluated in data that were not used to develop the model (referred to as external validation). We critically appraised the methodological conduct and reporting of external validation studies of multivariable prediction models.MethodsWe conducted a systematic review of articles describing some form of external validation of one or more multivariable prediction models indexed in PubMed core clinical journals published in 2010. Study data were extracted in duplicate on design, sample size, handling of missing data, reference to the original study developing the prediction models and predictive performance measures.Results11,826 articles were identified and 78 were included for full review, which described the evaluation of 120 prediction models. in participant data that were not used to develop the model. Thirty-three articles described both the development of a prediction model and an evaluation of its performance on a separate dataset, and 45 articles described only the evaluation of an existing published prediction model on another dataset. Fifty-seven percent of the prediction models were presented and evaluated as simplified scoring systems. Sixteen percent of articles failed to report the number of outcome events in the validation datasets. Fifty-four percent of studies made no explicit mention of missing data. Sixty-seven percent did not report evaluating model calibration whilst most studies evaluated model discrimination. It was often unclear whether the reported performance measures were for the full regression model or for the simplified models.ConclusionsThe vast majority of studies describing some form of external validation of a multivariable prediction model were poorly reported with key details frequently not presented. The validation studies were characterised by poor design, inappropriate handling and acknowledgement of missing data and one of the most key performance measures of prediction models i.e. calibration often omitted from the publication. It may therefore not be surprising that an overwhelming majority of developed prediction models are not used in practice, when there is a dearth of well-conducted and clearly reported (external validation) studies describing their performance on independent participant data.

Objectives To examine the reporting characteristics and methodological details of randomised trials indexed in PubMed in 2000 and 2006 and assess whether the quality of reporting has improved after publication of the Consolidated Standards of Reporting Trials (CONSORT) Statement in 2001.Design Comparison of two cross sectional investigations.Study sample All primary reports of randomised trials indexed in PubMed in December 2000 (n=519) and December 2006 (n=616), including parallel group, crossover, cluster, factorial, and split body study designs.Main outcome measures The proportion of general and methodological items reported, stratified by year and study design. Risk ratios with 95% confidence intervals were calculated to represent changes in reporting between 2000 and 2006.Results The majority of trials were two arm (379/519 (73%) in 2000 v 468/616 (76%) in 2006) parallel group studies (383/519 (74%) v 477/616 (78%)) published in specialty journals (482/519 (93%) v 555/616 (90%)). In both 2000 and 2006, a median of 80 participants were recruited per trial for parallel group trials. The proportion of articles that reported drug trials decreased between 2000 and 2006 (from 393/519 (76%) to 356/616 (58%)), whereas the proportion of surgery trials increased (51/519 (10%) v 128/616 (21%)). There was an increase between 2000 and 2006 in the proportion of trial reports that included details of the primary outcome (risk ratio (RR) 1.18, 95% CI 1.04 to 1.33), sample size calculation (RR 1.66, 95% CI 1.40 to 1.95), and the methods of random sequence generation (RR 1.62, 95% CI 1.32 to 1.97) and allocation concealment (RR 1.40, 95% CI 1.11 to 1.76). There was no difference in the proportion of trials that provided specific details on who was blinded (RR 0.91, 95% CI 0.75 to 1.10). Conclusions Reporting of several important aspects of trial methods improved between 2000 and 2006; however, the quality of reporting remains well below an acceptable level. Without complete and transparent reporting of how a trial was designed and conducted, it is difficult for readers to assess its conduct and validity.

Objective To compare arthroscopic hip surgery with physiotherapy and activity modification for improving patient reported outcome measures in patients with symptomatic femoroacetabular impingement (FAI). Design Two group parallel, assessor blinded, pragmatic randomised controlled trial. Setting Secondary and tertiary care centres across seven NHS England sites. Participants 222 participants aged 18 to 60 years with symptomatic FAI confirmed clinically and with imaging (radiography or magnetic resonance imaging) were randomised (1:1) to receive arthroscopic hip surgery (n=112) or a programme of physiotherapy and activity modification (n=110). Exclusion criteria included previous surgery, completion of a physiotherapy programme targeting FAI within the preceding 12 months, established osteoarthritis (Kellgren-Lawrence grade ≥2), and hip dysplasia (centre-edge angle <20 degrees). Interventions Participants in the physiotherapy group received a goal based programme tailored to individual patient needs, with emphasis on improving core stability and movement control. A maximum of eight physiotherapy sessions were delivered over five months. Participants in the arthroscopic surgery group received surgery to excise the bone that impinged during hip movements, followed by routine postoperative care. Main outcome measures The primary outcome measure was the hip outcome score activities of daily living subscale (HOS ADL) at eight months post-randomisation, with a minimum clinically important difference between groups of 9 points. Secondary outcome measures included additional patient reported outcome measures and clinical assessment. Results At eight months post-randomisation, data were available for 100 patients in the arthroscopic hip surgery group (89%) and 88 patients in the physiotherapy programme group (80%). Mean HOS ADL was 78.4 (95% confidence interval 74.4 to 82.3) for patients randomised to arthroscopic hip surgery and 69.2 (65.2 to 73.3) for patients randomised to the physiotherapy programme. After adjusting for baseline HOS ADL, age, sex, and study site, the mean HOS ADL was 10.0 points higher (6.4 to 13.6) in the arthroscopic hip surgery group compared with the physiotherapy programme group (P<0.001)). No serious adverse events were reported in either group. Conclusions Patients with symptomatic FAI referred to secondary or tertiary care achieve superior outcomes with arthroscopic hip surgery than with physiotherapy and activity modification. Trial registration ClinicalTrials.gov NCT01893034 .