Value and limitations of the BAR-score for donor allocation in liver transplantation.

PURPOSE: The MELD-score was shown to be able to predict 90-day mortality in most patients with end-stage liver disease prior to liver transplantation and is used as a widely accepted measure for transplantation urgency. Prognostic ability of the BAR-score to predict 90-day post-transplant mortality by detection of unfavourable pretransplant combinations of donor and recipient factors may help to better balance urgency versus utility. METHODS: Two German cohorts (Hannover, n=453; Kiel, n=234) were retrospectively analyzed using ROC-curve analysis, goodness-of-model-fit tests, summary measures and risk-adjusted multivariate binary regression. Included were all consecutive liver transplants performed in adult recipients (minimum age 18 years). Excluded were all combined transplants and living-related organ donor transplants. RESULTS: Risk-adjusted multivariate regression revealed that the BAR-score is an independent risk factor for 90-day mortality after transplantation in both cohorts from Hannover and Kiel combined (p<0.001, OR=1.017, 95% CI:1.031-1.113). The area under the ROC-curve (AUROC) for the prediction of 90-day mortality using the BAR-score was 0.662 (95% CI 0.624-0.699, power>95%). Measures for association between observed 90-day mortality and the predicted probabilities in the combined cohort were concordant in 63.5% with low summary measures (Somers' D test 0.32, Goodman-Kruskal Gamma test 0.34 and Kendall's Tau a test 0.07). CONCLUSIONS: The BAR-score performed below accepted thresholds for potentially useful clinical prognostic models. Prognostic models with better predictive ability with AUROCs>0.700, concordance>70% and larger summary measures are required for the prediction of 90-day post-transplant mortality to enable donor organ allocation with reliable weighing of urgency versus utility.

Do editorial policies support ethical research? A thematic text analysis of author instructions in psychiatry journals.

INTRODUCTION: According to the Declaration of Helsinki and other guidelines, clinical studies should be approved by a research ethics committee and seek valid informed consent from the participants. Editors of medical journals are encouraged by the ICMJE and COPE to include requirements for these principles in the journal's instructions for authors. This study assessed the editorial policies of psychiatry journals regarding ethics review and informed consent. METHODS AND FINDINGS: The information given on ethics review and informed consent and the mentioning of the ICMJE and COPE recommendations were assessed within author's instructions and online submission procedures of all 123 eligible psychiatry journals. While 54% and 58% of editorial policies required ethics review and informed consent, only 14% and 19% demanded the reporting of these issues in the manuscript. The TOP-10 psychiatry journals (ranked by impact factor) performed similarly in this regard. CONCLUSIONS: Only every second psychiatry journal adheres to the ICMJE's recommendation to inform authors about requirements for informed consent and ethics review. Furthermore, we argue that even the ICMJE's recommendations in this regard are insufficient, at least for ethically challenging clinical trials. At the same time, ideal scientific design sometimes even needs to be compromised for ethical reasons. We suggest that features of clinical studies that make them morally controversial, but not necessarily unethical, are analogous to methodological limitations and should thus be reported explicitly. Editorial policies as well as reporting guidelines such as CONSORT should be extended to support a meaningful reporting of ethical research.

Outcome stagnation of liver transplantation for primary sclerosing cholangitis in the Model for End-Stage Liver Disease era.

PURPOSE: Survival after liver transplantation (LTX) has decreased in Germany since the implementation of Model for end-stage liver disease (MELD)-based liver allocation. Primary sclerosing cholangitis (PSC) is known for its otherwise excellent outcome after LTX. The influence of MELD-based liver allocation and subsequent allocation policy alterations on the outcome of LTX for PSC is analyzed. METHODS: This is a retrospective observational study including 126 consecutive patients treated with LTX for PSC between January 1, 1999 and August 31, 2012. The PSC cohort was further compared to all other indications for LTX in the study period (n=1420) with a mean follow-up of 7.9 years (SD 3.2). Multivariate risk-adjusted analyses were performed. Alterations of allocation policy have been taken into account systematically. RESULTS: Transplant recipients suffering from PSC are significantly younger (p<0.001), can be discharged earlier (p=0.018), and have lower 3-month mortality than patients with other indications (p=0.044). The observed time on the waiting list is significantly longer for patients with PSC (p<0.001), and there is a trend toward lower match MELD points in the PSC cohort (p=0.052). No improvement in means of short-term mortality could be shown in relation to alterations of allocation policy within the MELD era (p=0.375). Survival rates of the pre-MELD era did not differ significantly from those of the MELD era (p=0.097) in multivariate risk-adjusted analysis. Patients in the MELD era suffered pre-transplant significantly more frequently from dominant bile duct stenosis (p=0.071, p=0.059, p=0.048, respectively; chi2). CONCLUSIONS: Progress is stagnating in LTX for PSC. Current liver allocation for PSC patients should be reconsidered.

How psychiatry journals support the unbiased translation of clinical research. A cross-sectional study of editorial policies.

INTRODUCTION: Reporting guidelines (e.g. CONSORT) have been developed as tools to improve quality and reduce bias in reporting research findings. Trial registration has been recommended for countering selective publication. The International Committee of Medical Journal Editors (ICMJE) encourages the implementation of reporting guidelines and trial registration as uniform requirements (URM). For the last two decades, however, biased reporting and insufficient registration of clinical trials has been identified in several literature reviews and other investigations. No study has so far investigated the extent to which author instructions in psychiatry journals encourage following reporting guidelines and trial registration. METHOD: Psychiatry Journals were identified from the 2011 Journal Citation Report. Information given in the author instructions and during the submission procedure of all journals was assessed on whether major reporting guidelines, trial registration and the ICMJE's URM in general were mentioned and adherence recommended. RESULTS: We included 123 psychiatry journals (English and German language) in our analysis. A minority recommend or require 1) following the URM (21%), 2) adherence to reporting guidelines such as CONSORT, PRISMA, STROBE (23%, 7%, 4%), or 3) registration of clinical trials (34%). The subsample of the top-10 psychiatry journals (ranked by impact factor) provided much better but still improvable rates. For example, 70% of the top-10 psychiatry journals do not ask for the specific trial registration number. DISCUSSION: Under the assumption that better reported and better registered clinical research that does not lack substantial information will improve the understanding, credibility, and unbiased translation of clinical research findings, several stakeholders including readers (physicians, patients), authors, reviewers, and editors might benefit from improved author instructions in psychiatry journals. A first step of improvement would consist in requiring adherence to the broadly accepted reporting guidelines and to trial registration.