General pathways and personalized risk of morbidity after sepsis

 描述(由申请人提供)：这份K08提案将完成医学硕士哈莉·普雷斯科特的培训，朝着她的长期职业目标--提高危重疾病幸存者的长期生存和生活质量--迈进。普雷斯科特博士是密歇根大学的肺部和重症监护内科医生和科学家，拥有临床研究设计和生物统计学硕士学位。这项建议建立在普雷斯科特博士以前的经验基础上，利用先进的统计方法、细粒度的临床数据和密歇根大学丰富的培训环境来提高我们对脓毒症后发病率的理解和管理。这项研究将在主要导师西奥多·J·伊瓦希纳医学博士、共同导师肯尼斯·兰加医学博士和共同导师理查德·冈萨雷斯博士的指导下完成，并有计划的导师-导师战略和来自医生-科学家顾问委员会的额外意见。这一5年计划包括正式课程、专业发展和有指导的研究，并有明确的里程碑，以确保生产率和成功过渡到独立。这项有指导的研究有两个具体的科学目标：目标1：检验败血症后发病率一般途径的3个相互竞争的假说的相对重要性。*目标2：开发一种特定于诊断的再入院风险描述工具，以便在医院后立即(90天)对严重脓毒症幸存者进行个性化治疗。除了完成这些高水平的目标，普雷斯科特博士还将(1)描述严重败血症幸存者的多种发病率和住院的流行病学特征，(2)确定在以下情况下增加最多的健康状况 (3)确定特定临床数据在改善风险预测方面的增量效益；(4)比较互补的尖端个性化预测方法的准确性和可用性。这项工作将建立在至少两个R01建议的基础上：(1)检查严重脓毒症后特定慢性健康状况增加的机制(如目标1中所确定的)，或检查败血症后的发病率与不太严重的感染和无菌炎症的发病率有何不同，以及(2)实施和评估在目标2中开发的特定诊断风险描述工具。除了为改善严重脓毒症幸存者的护理的程序性研究路线奠定基础之外，该建议还将为普雷斯科特博士提供易于应用于其他危重疾病研究领域的研究技能。简言之，这一K08奖项将支持和加速普雷斯科特博士的职业发展活动，并使她能够成功地进入她作为独立调查员的职业生涯的下一个阶段。

 DESCRIPTION (provided by applicant): This K08 proposal will complete Hallie Prescott, MD; MSc's training towards her long-term career goal of improving the long-term survival and quality of life of critical illness survivors. Dr. Prescott is a pulmonary & critical care physician and scientist at the University of Michigan, with Master's training in clinical study design and biostatistics. This proposal builds on Dr. Prescott's prior experience, leveraging advanced statistical methods, granular clinical data, and the rich training environment at University of Michigan to improve our understanding and management of post-sepsis morbidity. The research will be completed under the guidance of primary mentor Theodore J. Iwashyna, MD, PhD, co-mentor Kenneth Langa, MD, PhD, and co-mentor Richard Gonzalez, PhD, with a planned mentor-the-mentor strategy and additional input from an advisory board of physician-scientists. This 5-year plan includes formal coursework, professional development, and mentored research, with defined milestones to ensure productivity and a successful transition to independence. This mentored research has 2 specific Scientific Aims: AIM 1: Test the relative importance 3 competing hypotheses for the general pathway of post- sepsis morbidity. * AIM 2: Develop a diagnosis-specific readmission risk profile tool to personalize treatment for severe sepsis survivors in the immediate (90-day) post-hospital setting. Inherent to completing these high-level Aims, Dr. Prescott will also (1) characterize the epidemiology of multi- morbidity and hospitalization in severe sepsis survivors, (2) identify the health conditions most increased after severe sepsis, (3) define the incremental benefits of specific clinical data in improving risk prediction, (4) compare the accuracy and usability of complementary cutting edge personalized prediction methodologies. This work will build to at least two R01 proposals: (1) to examine the mechanism by which a specific chronic health condition is increased after severe sepsis (as identified in Aim 1) or to examine how post-sepsis morbidity differs from that of less-severe infections and sterile inflammation, and (2) to implement and evaluate the diagnosis-specific risk profile tool developed in Aim 2. Beyond establishing the foundation for a programmatic line of research to improve the care of severe sepsis survivors, this proposal will provide Dr. Prescott with research skills that are readily applicable to additional domains of critical illness research In short, this K08 award will support and accelerate the career development activities of Dr. Prescott and allow her to successfully launch into the next phase of her career as an independent investigator.