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

微血管疾病、他汀类药物、ACE 抑制剂和术后 SBO

• 批准号: 8353125
• 负责人: Frank Irving Scott
• 金额: $ 15.51万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8353125
• 关键词: Abdomen; Abscess; Address; Adhesions; Admission activity; Adult; Affect; American; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Animals; Award; Barrier Contraception; Biometry; Biostatistical Methods; Case-Control Studies; Clinical; Clinical Research; Code; Cohort Studies; Colon; Comorbidity; Data; Data Set; Databases; Development; Development Plans; Diabetes Mellitus; Diabetic Angiopathies; Diagnosis; Diagnostic; Disease; Disease Association; Doctor of Philosophy; Epidemiologic Methods; Epidemiologic Studies; Epidemiology; Evaluation; Exposure to; Foreign Bodies; Foundations; Future; Gastroenterology; Gastrointestinal Diseases; General Practitioners; Goals; Gold; Health; Health Care Costs; Hospitals; Human; Hyperlipidemia; Hypertension; Hypoxia; In Vitro; Incidence; Infertility; Inflammation; Integration Host Factors; Intestinal Obstruction; Intra-abdominal; Knowledge; Laboratories; Laparoscopy; Measures; Medical; Medical History; Medical Records; Medicine; Mentors; Meta-Analysis; Modeling; Modification; Morbid Obesity; Morbidity - disease rate; Mus; Nicotine; Operative Surgical Procedures; Outcome; Pathogenesis; Patients; Pennsylvania; Peripheral Vascular Diseases; Peritoneum; Pharmaceutical Preparations; Pharmacoepidemiology; Play; Population; Postoperative Period; Powder dose form; Predictive Value; Procedures; Property; Prospective Studies; Questionnaires; Recommendation; Research; Resources; Risk; Risk Factors; Role; Small Intestines; Surgical Mesh; Surveys; Techniques; Testing; Thiazide Diuretics; Time; Tissues; Tobacco use; Translating; Trauma; Universities; Validation; Woman; base; career; career development; case control; cohort; cytokine; design; disorder risk; epidemiology study; experience; follow-up; instructor; mortality; novel; population based; prevent; professor; prospective; response; skills; tool

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.

描述(申请人提供)：这是2011年7月1日起在宾夕法尼亚大学担任讲师的Frank I.Scott博士的K08奖项申请表。这个K08 将为候选人提供必要的支持，以便在术后粘连相关并发症的流行病学研究中开始成功的职业生涯。为了实现他的目标，Scott博士提出了一个全面的职业发展计划：(1)应用先进的流行病学和生物统计学方法进行观察性研究~(2)开发研究腹部手术并发症和术后肠梗阻(SBO)的新研究工具~(3)开展宿主相关危险因素和粘连相关SBO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生涯。斯科特博士已经组建了一个指导团队来帮助他实现这些目标。宾夕法尼亚大学消化系医学和流行病学教授、医学博士詹姆斯·D·刘易斯博士将担任候选人的主要导师。刘易斯博士是世界知名的药物流行病学和胃肠道疾病流行病学专家。消化内科医学教授兼副主任加里·D·吴博士将担任顾问。纳贾亚·N·马哈茂德博士是外科副教授，曾与斯科特博士和刘易斯博士合作进行与粘连相关的研究，他将继续作为顾问提供宝贵的意见。生物统计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。手术后粘连是导致 大量的发病率和死亡率，是成人SBO的主要原因。目前对哪些宿主相关因素可能影响术后SBO的风险知之甚少，尽管低氧似乎在动物模型中发挥了作用。斯科特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。之前的研究工作由于缺乏大量接受腹部手术的人群的有效医学数据而受到限制。拟议的研究将验证腹部手术和Thin Thin内SBO的诊断代码，从而为此类研究生成一个新的数据集(AIM 1)。然后，候选人将进行一项病例对照研究，以评估几种常见疾病之间的联系，如高血压、高脂血症和糖尿病，以及使用Thin进行腹部手术后发生SBO的风险(AIM 2)。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)，这两种药物已知具有多效性抗纤维化作用。这项研究将作为未来对危险因素修改和药物使用预防粘连相关SBO的效果进行前瞻性评估的基础。 公共卫生相关性：粘连相关的小肠梗阻是导致大量发病率和死亡率的原因。由于缺氧被认为有助于粘连的形成，我们将检查与微血管疾病相关的条件是否为术后小肠梗阻的危险因素。此外，我们将研究几种治疗这些疾病的常用药物，他汀类药物和血管紧张素转换酶抑制剂，这些药物具有抗纤维化特性，可以降低手术后SBO的风险。