Summary Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0.83, 95% CI 0.63–1.09; p=0.18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1.91, 1.06–3.44; p=0.0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0.82; appendix); these events included pulmonary embolism (two patients [<1%] vs four [1%] patients; p=0.41) and sepsis (seven [1%] vs six [1%]; p=0.79). Interpretation In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. Funding National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians’ Services Incorporated.

Background and Purpose-We performed a comprehensive review of all quality-of-life (QOL) estimates for stroke appearing in the peer-reviewed literature between 1985 and 2000. We examine variation in QOL weights and the rigor of methods used to assess QOL and discuss the implications for cost-utility assessment and resource allocation decisions. Methods-Through a systematic search, we identified 67 articles that met our inclusion criteria. A team of trained researchers read each article and followed detailed guidelines to extract QOL weights and other parameters. This effort yielded 161 QOL estimates for stroke-related health states. All estimates were measured on a 0 to 1 scale, with 0 representing the worst outcome and 1 representing the best. Results-QOL estimates range from Ϫ0.02 to 0.71 (nϭ67) for major stroke, from 0.12 to 0.81 (nϭ14) for moderate stroke, from 0.45 to 0.92 (nϭ38) for minor stroke, and from 0.29 to 0.903 (nϭ42) for general stroke. Although QOL should decrease with severity, there were many instances in which the QOL for major stroke as reported by one study exceeded the QOL for moderate stroke as reported by another. The same reversal was found for moderate and minor stroke, and it occurred even when both authors used similar assessment methods and subject populations. Authors of cost-utility and decision analyses rarely base their choice of QOL weights on their own primary data (19%). When obtaining weights from secondary sources, some authors (23%) chose QOL weights for a severity of stroke that did not match the severity for which they sought data. Conclusions-QOL estimates for stroke vary greatly and are not always estimated in sound fashion. This impedes the comparability and quality of the cost-effectiveness studies that use these QOL weights and hampers good resource allocation decisions.

Bulk transcriptome analysis Observations Validations Highlights Liver organoids from patients with BA exhibited aberrant morphology and disturbed apical-basal organization. Transcriptomic analysis of BA organoids revealed a shift from cholangiocyte to hepatocyte transcriptional signatures. Beta-amyloid accumulation was observed around the bile ducts in BA livers. Exposure to beta-amyloid induced aberrant morphology in control organoids. Beta-amyloid accumulation represents a novel finding with pathobiological implications and diagnostic potential for BA.