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

描述（由申请人提供）：这是一个K 08奖博士申请。斯科特，谁将在宾夕法尼亚大学讲师开始2011年7月1日。 K08 将为候选人提供必要的支持，以成功开展术后粘连相关并发症的流行病学研究。 为了实现自己的目标，斯科特博士提出了一个全面的职业发展计划：（1）采用先进的流行病学和生物统计学方法进行观察性研究~（2）为腹部手术并发症和术后小肠梗阻（SBO）的研究开发新的研究工具~（3）进行粘连相关SBO的宿主相关危险因素和修饰物的研究~（4）在流行病学和临床研究方面发展独立的研究事业。 斯科特博士组建了一个指导小组，以帮助他实现这些目标。 James D.刘易斯，医学博士，医学和流行病学教授在胃肠病学在宾夕法尼亚大学，将作为候选人的主要导师。 刘易斯博士是世界著名的药物流行病学和胃肠道疾病流行病学专家。 加里博士D.吴，医学博士，医学教授和副主任研究胃肠科将担任顾问。 Dr. Najjia N.外科副教授Mahmoud，医学博士，曾与Scott博士和刘易斯博士合作进行先前的粘连相关研究，他将继续作为顾问提供宝贵的意见。 生物统计学和流行病学系的郭文胜博士将分享他在纵向分析方面的专业知识。 术后粘连是导致 严重的发病率和死亡率，是成年人SBO的主要原因。目前尚不清楚哪些宿主相关因素可能影响术后SBO的风险，尽管缺氧似乎在动物模型中起作用。 Scott博士的研究将利用健康改善网络（THIN）的数据，研究与微血管疾病相关的共病医疗条件对术后SBO发生率的影响。 由于缺乏来自接受腹部手术的大量人群的有效医学数据，以前的研究工作受到限制。拟议的研究将验证THIN中腹部手术和SBO的诊断代码，从而为此类研究生成新的数据集（AIM 1）。 然后，候选人将进行一项病例对照研究，以评估几种常见的医学疾病（如高血压、高脂血症和糖尿病）与使用THIN（AIM 2）进行腹腔内手术后SBO风险之间的关联。 最后，他将评估他汀类药物和ACE抑制剂对术后SBO发生率的影响（AIM 3），这些药物具有已知的多效性抗纤维化作用。这项研究将作为未来前瞻性评价风险因素修改和药物使用预防粘连相关SBO的影响的基础。

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.