Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

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BackgroundThis study assesses the impact that a resident oversight and credentialing policy for central venous catheter (CVC) placement had on institution-wide central line associated bloodstream infections (CLABSI). We therefore investigated the rate of CLABSI per 1,000 line days during the 12 months before and after implementation of the policy.MethodsThis is a retrospective analysis of prospectively collected data at an academic medical center with four adult ICUs and a pediatric ICU. All patients undergoing non-tunneled CVC placement were included in the study. Data was collected on CLABSI, line days, and serious adverse events in the year prior to and following policy implementation on 9/01/08.ResultsA total of 813 supervised central lines were self-reported by residents in four departments. Statistical analysis was performed using paired Wilcoxon signed rank tests. There were reductions in median CLABSI rate (3.52 vs. 2.26; p = 0.015), number of CLBSI per month (16.0 to 10.0; p = 0.012), and line days (4495 vs. 4193; p = 0.019). No serious adverse events reported to the Pennsylvania Patient Safety Authority.ConclusionsImplementation of a new CVC resident oversight and credentialing policy has been significantly associated with an institution-wide reduction in the rate of CLABSI per 1,000 central line days and total central line days. No serious adverse events were reported. Similar resident oversight policies may benefit other teaching institutions, and support concurrent organizational efforts to reduce hospital acquired infections.