Patient Oriented Research in Anticoagulation

描述(由申请人提供)： 斯蒂芬·E·基梅尔，医学博士，医学博士，现任心脏病学部医学助理教授，生物统计和流行病学系流行病学助理教授，宾夕法尼亚大学临床流行病学和生物统计中心(CEB)高级学者(核心教员)。他是一位久负盛名的临床研究人员，拥有广泛的成功研究记录。他的研究记录证明了他致力于以患者为导向的研究事业，该研究一直专注于药物和设备对心血管结果的影响，并渴望成为一名导师。他应用了广泛的流行病学工具和以患者为中心的研究方法来解决研究问题。他的近期和长期职业目标集中在他作为一名以患者为导向的研究人员、教师和导师的愿望和意图上，继续发展和成熟。 宾夕法尼亚大学致力于为临床和以患者为导向的研究创造一个强有力的环境。宾夕法尼亚大学校区为候选人提供的资源包括成功的以患者为导向的研究和指导所需的所有组件，包括生物统计支持、数据管理支持和最先进的研究/临床实验室服务。拟议的以患者为导向、由NHLBI资助的研究项目正处于第一年。 血栓栓塞症(TE)可发生在静脉或动脉系统，并与相当大比例的人群的发病率和死亡率有关。虽然使用华法林钠可以预防大多数血栓形成事件，但使用华法林进行适当水平的抗凝(AC)是非常困难的。患者内和患者间对华法林的反应有显著差异的原因通常仍不清楚。这项前瞻性队列研究的目的是确定最近发现的遗传变异(CYP2C9酶和载脂蛋白E)和黏附对AC控制的影响。通过了解基因多态的影响；以及通过药物遗传学和药物流行病学学科的合并对AC控制的坚持，本研究希望提供关键信息，用于临床(患者预筛查)和科学(根据AC控制不良的原因，针对特定患者群体制定和应用特定策略)。最终目标是改进一种高效但未得到充分利用的药物的使用，并在很大一部分有血栓栓塞症风险的人群中降低发病率和死亡率。

DESCRIPTION (provided by applicant): Stephen E. Kimmel, MD, MSCE is currently an Assistant Professor of Medicine in the Division of Cardiology, and Assistant Professor of Epidemiology in the Department of Biostatistics and Epidemiology, and a Senior Scholar (core faculty member) in the Center for Clinical Epidemiology and Biostatistics (CCEB) at the University of Pennsylvania (Penn). He is an established clinical researcher with an extensive track record of successful research. His research record attests to his commitment to a career in patient-oriented research, which has been focused on the effects of medications and devices on cardiovascular outcomes, and his desire to be a mentor. He has applied a wide variety of epidemiologic tools and patient-oriented research methods to address research issues. His immediate and long-term career goals center on his desire and intent to continue to evolve and mature as a patient-oriented researcher, teacher, and mentor. The University of Pennsylvania has committed itself to the development of a strong environment for clinical and patient-oriented research. The resources available to the candidate on the Penn campus include all of the components necessary for successful patient-oriented research and mentoring, including biostatistical support, data management support, and state of the art research/clinical laboratory services. The proposed patient-oriented, NHLBI-funded research project is in its first year. Thromboembolism (TE) can occur in the venous or arterial system and is associated with substantial morbidity and mortality in a large proportion of the population. Although, most of these thromboembolic events can be prevented using warfarin sodium, proper levels of anticoagulation (AC) with warfarin are very difficult to maintain. The reason for the marked intra-patient and inter-patient variability in response to warfarin often remains unknown. The objective of this prospective cohort study is to determine the effects of recently discovered genetic variants (of the CYP2C9 enzyme and apolipoprotein E) and of adherence on AC control. By understanding the effects of genetic polymorphisms; and adherence on AC control via the merger of the disciplines of pharmacogenetics and pharmacoepidemiology, this study hopes to provide critical information to apply clinically (patient pre-screening) and scientifically (development and application of specific strategies targeted at specific patient groups based on the cause of their poor AC control). The ultimate goal is to improve the use of a highly efficacious, but underused, drug, and reduce morbidity and mortality in the large proportion of the population at risk for TE.