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.
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.
|Vajravelu, Ravy K; Mamtani, Ronac; Scott, Frank I et al. (2018) Incidence, Risk Factors, and Clinical Effects of Recurrent Diverticular Hemorrhage: A Large Cohort Study. Gastroenterology 155:1416-1427|
|Vajravelu, Ravy K; Scott, Frank I; Mamtani, Ronac et al. (2018) Medication class enrichment analysis: a novel algorithm to analyze multiple pharmacologic exposures simultaneously using electronic health record data. J Am Med Inform Assoc 25:780-789|
|Osterman, Chelsea K; Alanzi, Jaber; Lewis, James D et al. (2018) Association Between Symptomatic Versus Asymptomatic Recurrence and Survival in Bladder Cancer. Clin Genitourin Cancer 16:235-239|
|Vajravelu, Ravy K; Osterman, Mark T; Aberra, Faten N et al. (2017) Indeterminate QuantiFERON-TB Gold Increases Likelihood of Inflammatory Bowel Disease Treatment Delay and Hospitalization. Inflamm Bowel Dis 24:217-226|
|Shelton, Edward; Laharie, David; Scott, Frank I et al. (2016) Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis. Gastroenterology 151:97-109.e4|
|Mamtani, Ronac; Lewis, James D; Scott, Frank I et al. (2016) Disentangling the Association between Statins, Cholesterol, and Colorectal Cancer: A Nested Case-Control Study. PLoS Med 13:e1002007|
|Goldberg, David S; French, Benjamin; Lewis, James D et al. (2016) Liver transplant center variability in accepting organ offers and its impact on patient survival. J Hepatol 64:843-51|
|Mamtani, Ronac; Yang, Yu-Xiao; Scott, Frank I et al. (2016) Association of Itraconazole, a Hedgehog Inhibitor, and Bladder Cancer. J Urol 196:343-8|
|Scott, Frank I; Mamtani, Ronac; Brensinger, Colleen M et al. (2016) Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer. JAMA Dermatol 152:164-72|
|Mamtani, Ronac; Clark, Amy S; Scott, Frank I et al. (2016) Association Between Breast Cancer Recurrence and Immunosuppression in Rheumatoid Arthritis and Inflammatory Bowel Disease: A Cohort Study. Arthritis Rheumatol 68:2403-11|
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