General pathways and personalized risk of morbidity after sepsis

 描述（由申请人提供）：此K 08提案将完成Hallie Prescott，MD; MSc的培训，以实现她的长期职业目标，即改善危重病幸存者的长期生存和生活质量。Prescott博士是密歇根大学的一名肺病和重症监护医生和科学家，拥有临床研究设计和生物统计学硕士学位。该提案基于Prescott博士先前的经验，利用先进的统计方法，精细的临床数据和密歇根大学丰富的培训环境，以提高我们对脓毒症后发病率的理解和管理。该研究将在主要导师西奥多J. Iwashyna，MD，PhD，共同导师Kenneth朗加，MD，PhD和共同导师Richard Gonzalez，PhD的指导下完成，计划导师策略和来自医生科学家顾问委员会的额外投入。这个为期5年的计划包括正式的课程，专业发展和指导研究，具有明确的里程碑，以确保生产力和成功过渡到独立。这项指导性研究有2个具体的科学目的：目的1：测试脓毒症后发病的一般途径的3个竞争假设的相对重要性。* 目标2：开发一种诊断特异性再入院风险评估工具，以个性化严重脓毒症幸存者在出院后立即（90天）的治疗。为了完成这些高水平的目标，Prescott博士还将（1）描述严重脓毒症幸存者的多发病率和住院的流行病学特征，（2）确定严重脓毒症后增加最多的健康状况。 严重脓毒症，（3）确定特定临床数据在改善风险预测方面的增量效益，（4）比较互补的最新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R 01提案上：（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）或检查脓毒症后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）实施和评估目标2中开发的诊断特异性风险特征工具。除了为改善严重脓毒症幸存者护理的计划性研究奠定基础外，该提案还将为普雷斯科特博士提供易于适用于其他危重疾病研究领域的研究技能。这个K 08奖将支持和加速普雷斯科特博士的职业发展活动，使她能够成功地进入她作为一个独立的职业生涯的下一阶段。调查员

 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.