A Framework to Support the Sharing and Reuse of Computable Phenotype Definitions Across Health Care Delivery and Clinical Research Applications.

INTRODUCTION: The ability to reproducibly identify clinically equivalent patient populations is critical to the vision of learning health care systems that implement and evaluate evidence-based treatments. The use of common or semantically equivalent phenotype definitions across research and health care use cases will support this aim. Currently, there is no single consolidated repository for computable phenotype definitions, making it difficult to find all definitions that already exist, and also hindering the sharing of definitions between user groups. METHOD: Drawing from our experience in an academic medical center that supports a number of multisite research projects and quality improvement studies, we articulate a framework that will support the sharing of phenotype definitions across research and health care use cases, and highlight gaps and areas that need attention and collaborative solutions. FRAMEWORK: An infrastructure for re-using computable phenotype definitions and sharing experience across health care delivery and clinical research applications includes: access to a collection of existing phenotype definitions, information to evaluate their appropriateness for particular applications, a knowledge base of implementation guidance, supporting tools that are user-friendly and intuitive, and a willingness to use them. NEXT STEPS: We encourage prospective researchers and health administrators to re-use existing EHR-based condition definitions where appropriate and share their results with others to support a national culture of learning health care. There are a number of federally funded resources to support these activities, and research sponsors should encourage their use.

Strategies for treating chronic HCV infection in patients with cirrhosis: latest evidence and clinical outcomes.

The burden of chronic hepatitis C virus (HCV) infection is significant and growing. HCV is considered one of the leading causes of liver disease worldwide and the leading cause of liver transplantation globally. While those infected is estimated in the hundreds of millions, this is likely an underestimation because of the indolent nature of this disease when first contracted. Approximately 20% of patients with HCV infection will progress to advanced fibrosis and cirrhosis. Those that do are at risk of decompensated liver disease including GI bleeding, encephalopathy, severe lab abnormalities, and hepatocellular carcinoma. Those individuals with advanced fibrosis and cirrhosis have historically been difficult to treat. The backbone of previous HCV regimens was interferon (IFN). The outcomes for IFN based regimens were poor and resulted in increased adverse events among those with advanced fibrosis and cirrhosis. Now, in the era of new direct acting antiviral (DAA's) medications, there is hope for curing chronic HCV in everyone, including those with advanced fibrosis and cirrhosis. This article provides a review on the most up to date data on the use of DAA's in patients with advanced fibrosis and cirrhosis. We are at a point where HCV could be truly eradicated, but to do so will require ensuring there are effective and safe treatments for those with advanced fibrosis and cirrhosis.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.