Microvascular disease, statins, ACE-inhibitors and post-operative SBO

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DESCRIPTION (provided by applicant): This is an application for a K08 award for Dr. Frank I. Scott, who will be an Instructor at the University of Pennsylvania starting July 1, 2011. This K08 will provide the candidate with the necessary support to launch a successful career in epidemiologic research in post-operative adhesion-related complications. To achieve his goals, Dr. Scott has proposed a comprehensive career development plan: (1) to implement advanced epidemiologic and biostatistical methods to conduct observational research~ (2) to develop a new research tool for the study of complications of abdominal surgery and post-surgical small bowel obstruction (SBO)~ (3) to conduct research on host-related risk factors and modifiers of adhesion-related SBO~ and (4) to develop an independent research career in epidemiologic and clinical research. Dr. Scott has assembled a mentoring team to assist him in achieving these goals. Dr. James D. Lewis, MD, MSCE, Professor of Medicine and Epidemiology in the Division of Gastroenterology at the University of Pennsylvania, will serve as the candidate's primary mentor. Dr. Lewis is a world-renowned expert in pharmacoepidemiology and gastrointestinal disease epidemiology. Dr. Gary D. Wu, MD, Professor of Medicine and Associate Chief of Research in the Gastroenterology Division will serve as an advisor. Dr. Najjia N. Mahmoud, MD, Associate Professor of Surgery, who has collaborated with Dr. Scott and Dr. Lewis on prior adhesion-related research, will continue to provide invaluable input as an advisor. Dr. Wensheng Guo, PhD, in the department of Biostatistics and Epidemiology, will share his expertise in longitudinal analyses. Post-operative adhesions are responsible for a significant amount of morbidity and mortality, and are the leading cause of SBO in adults. Little is currently known about which host-related factors may impact the risk of post-operative SBO, although hypoxia appears to play a role in animal models. Dr. Scott's research will examine the impact of co-morbid medical conditions associated with microvascular disease on the incidence of post-operative SBO utilizing data from The Health Improvement Network (THIN). Prior research efforts have been limited by the lack of valid medical data from a large population undergoing abdominal surgery. The proposed research will validate diagnostic codes for abdominal surgery and SBO within THIN, thereby generating a novel dataset for such research (AIM 1). The candidate will then conduct a case-control study to assess the association between several common medical conditions, such as hypertension, hyperlipidemia, and diabetes, with the risk of SBO after an intra-abdominal surgery using THIN (AIM 2). Finally, he will assess the effects of statins and ACE-inhibitors, which have known pleiotropic anti-fibrotic effects, on the incidence of post-operative SBO (AIM 3). This research will serve as the foundation for future prospective evaluation of the effect of risk factor modification and medication use to prevent adhesion-related SBO. PUBLIC HEALTH RELEVANCE: Adhesion-related small bowel obstruction is responsible for a significant amount of morbidity and mortality. Because hypoxia is believed to contribute to adhesion formation, we will examine whether conditions associated with microvascular disease are risk factors for post-operative small bowel obstruction. Furthermore, we will study several medications commonly used to treat these conditions, statins and ACE- inhibitors that have anti-fibrotic properties that may reduce the risk of SBO after surgery.