RISK FACTORS FOR PHENYTOIN TOXICITY

这一职业发展奖是由一位即将完成流行病学博士学位的博士级别的临床药剂师寻求的，他完全致力于作为一名独立的、联邦资助的衰老药物流行病学学术研究员的职业生涯。应聘者将使用经过验证的“80%研究/20%临床”的职业模式，这将提供临床研究问题的来源以及进行以患者为中心的研究的基础设施。已经制定了一个分三个阶段的职业发展计划，专门解决候选人背景中的差距。除了将作为“核心课程”的研究项目外，职业发展计划还将进一步发展他对衰老的关注，并提供分子和遗传流行病学的课堂和实验室培训，目的是使他能够与实验室科学家进行知识和有效的合作。在奖项的后一阶段，候选人将发展更多的研究想法，进行试点研究，并申请联邦研究(例如，R01)资助。正式的职业咨询程序是职业发展计划的一个组成部分。这项建议的研究部分是对严重神经系统苯妥英中毒的风险因素的研究，多个数据来源表明，这是导致严重药物不良反应的主要原因之一，特别是在老年人中。这项研究将检查治疗和患者特定的因素，包括年龄和表达细胞色素P450酶同工酶CYP2C19和CYP2C9的基因的多态性，这两种酶负责苯妥英的代谢。这项研究设计是一项病例对照研究，嵌套在我们卫生系统内被视为癫痫障碍的患者群体中。我们将在卫生系统的三家主要医院同时进行监测，以确定潜在的病例，并从卫生系统内因癫痫发作而服用苯妥英钠的患者中随机选择控制组。这一职业发展奖将使候选人能够完成他所需的技能和经验的发展，这些技能和经验将使他成为老龄化药物流行病学的独立学术调查员。

This career development award is being sought by a doctoral-level clinical pharmacist nearing the completion of his PhD in Epidemiology who is fully committed to a career as an independent, federally-funded academic investigator in the pharmacoepidemiology of aging. The Candidate will use the proven "80% research / 20% clinical" career model, which will provide a source of clinical research questions as well as the infrastructure to conduct patient-oriented research. A three-phase career development plan has been formulated specifically to address gaps in the Candidate's background. In addition to the research project that will serve as the "core curriculum," the career development plan will further develop his focus on aging, and provide classroom and laboratory training in molecular and genetic epidemiology with the objective of enabling him to collaborative knowledgeably and effectively with laboratory scientists. In the latter phase of the award, the Candidate will develop additional research ideas, perform pilot studies, and apply for federal research (e.g., R01) funding. A formal career advisory process is an integral component of the career development plan. The research component of this proposal is a study of risk factors for severe neurologic phenytoin toxicity, which has been shown in multiple data sources to be one of the leading causes of serious adverse drug reactions, particularly in the elderly. The study will examine therapy- and patient-specific factors, including age and polymorphisms in the genes that express cytochrome P450 enzyme isoforms CYP2C19 and CYP2C9, which are responsible for phenytoin metabolism. The study design is a case-control study that is nested within the population of patients seen for seizure disorders within our health system. Concurrent surveillance in the three major hospitals in our health system will be used to identify potential cases, with controls being randomly selected from patients prescribed phenytoin for seizure disorders within our health system. This career development award will enable the Candidate to complete the development of the skills and experience that he will need to evolve into an independent academic investigator in the pharmacoepidemiology of aging.