Identification of the Components of Frailty Using Administrative Data and Metabolite Profiling

使用管理数据和代谢物分析识别虚弱的组成部分

• 批准号: 10657394
• 负责人: Jordan Blair Strom
• 金额: $ 17.28万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10657394
• 关键词: Adult; Adverse event; Age; Aortic Valve Stenosis; Area; Biochemical; Biological; Biological Markers; Bioprosthesis device; Cardiology; Cardiovascular Diseases; Cardiovascular system; Chronology; Citric Acid Cycle; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Code; Collection; Consensus; Data; Data Sources; Decision Making; Energy Metabolism; Environment; Epidemiology; Etiology; Faculty; Funding; Goals; Health; Healthcare; Heterogeneity; Human; Impairment; Individual; Internal Medicine; International; Israel; K-Series Research Career Programs; Knowledge; Lead; Link; Longevity; Machine Learning; Measures; Mediating; Medical; Medical center; Medicare; Medicine; Mentors; Mentorship; Methodology; Operative Surgical Procedures; Outcome; Outcomes Research; Patient Care; Patients; Persons; Phenotype; Physician Executives; Physicians; Physiological; Population; Procedures; Prospective cohort; Proteomics; Provider; Public Health Schools; Quality of life; Recovery; Registries; Research; Research Personnel; Risk; Risk Factors; Scientist; Selection for Treatments; Stroke; Subgroup; Syndrome; Techniques; Time; Training; Treatment outcome; United States National Institutes of Health; Vulnerable Populations; Work; administrative database; adverse event risk; adverse outcome; aortic valve replacement; biomarker identification; clinical training; comorbidity; end of life; frailty; health data; health service use; heart imaging; high risk; human old age (65+); improved; individual variation; insight; medical schools; member; metabolomics; mid-career faculty; minimally invasive; molecular phenotype; mortality; new technology; novel; novel marker; optimal treatments; participant enrollment; patient oriented research; personalized medicine; predictive modeling; professor; programs; prospective; randomized, clinical trials; surgical risk; treatment effect; treatment response; trial enrollment

PROJECT SUMMARY Candidate: Dr. Strom received an MD from Harvard Medical School (HMS), and has completed clinical training in internal medicine (MGH), cardiology (BIDMC), and non-invasive cardiac imaging (BIDMC). Additionally, he completed an MSc in Epidemiology program at the Harvard T.H. Chan School of Public Health, in May, 2018. He is now a junior faculty member at BIDMC with 75% protected time to conduct clinical research. Through this proposed 5-year program, Dr. Strom will pursue additional training in advanced prediction modeling, machine learning, patient-oriented research, and metabolomics. The candidate’s long- term goal is to become an R01-funded investigator in the area of applied outcomes research. Environment: The candidate will be mentored by Robert W. Yeh (Primary Mentor), Associate Professor of Medicine at HMS and Director of the Smith Center for Outcomes Research in Cardiology, Robert E. Gerszten (Co-Mentor), Professor of Medicine at HMS and Chief of Cardiovascular Medicine at BIDMC, and Changyu Shen (Co-Mentor), upcoming Associate Professor of Medicine at HMS and Lead Biostatistician for the Smith Center. Dr. Yeh has a track record of leading practice-changing studies and successful mentorship of clinician investigators. Dr. Gerszten is an internationally recognized expert in molecular phenotyping of cardiovascular diseases using metabolomics and proteomics and has mentored several K-award and R01 funded clinical investigators. Dr. Shen has a long track record of NIH funding, expertise in evaluating heterogeneity of treatment effect in cardiovascular diseases, and has mentored multiple prior trainees. Research: The optimal therapy for a given individual with aortic stenosis remains uncertain. This proposal seeks to define the clinical and biologic components of frailty that modify risk after aortic valve replacement (AVR) and alter treatment benefit. For Aims 1-2, we will leverage the unique linkage of Medicare data to the US CoreValve Pivotal trials, a collection of clinical trials that randomized individuals with severe aortic stenosis to transcatheter AVR (TAVR) with a self-expanding bioprosthesis vs. surgical AVR (SAVR). In Aim 1, we will we will identify which variables, related to in-person assessments of frailty and candidate frailty codes, best predict adverse outcomes after AVR. In Aim 2, we will identify if novel variables identified in Aim 1, identify a heterogeneous treatment response in individuals undergoing AVR. In Aim 3, we will prospectively enroll patients undergoing TAVR at BIDMC with concurrent frailty phenotyping to identify whether metabolites associated with longevity correlate with frailty and predict adverse outcomes, independent of age and comorbidities. The research will identify the mechanisms by which frailty confers adverse risk and differential treatment benefit in AVR, providing insights that may personalize treatment selection and improve patient care.

项目摘要 候选人：Strom博士从哈佛医学院（HMS）获得了医学博士学位，并拥有Comp Clinical 内科培训（MGH），心脏病学（BIDMC）和非侵入性心脏成像（BIDMC）。 此外，他在哈佛T.H。 2018年5月。他现在是BIDMC的初级教职员工，有75％的保护时间进行临床 研究。 预测建模，机器学习，以患者为导向的研究和代谢组学。 术语目标是成为应用结果研究领域的R01资助的研究者。 环境：候选人将由协会教授罗伯特·W·耶（Robert W. Yeh）（主要导师）指导 HMS的医学和史密斯史密斯成果研究中心心脏病学中心主任，罗伯特·E·格斯茨 （Co-Encortor），HMS医学教授，BIDMC的心血管医学主任和Changyu Shen（Co-​​Centor），即将在HMS的医学副教授，史密斯的Biostician副教授 中央 研究人员。 使用代谢组学和蛋白质组学的疾病，并指导了严重程度K-宣布和R01资助的临床 调查人员。 心血管疾病的治疗效果，并指导了多个先前的学员。 研究：为特定个体患有主动脉狭窄缓解的最佳疗法，不属于特征。 旨在定义脆弱的临床和生物学成分，以修改主动脉瓣置换后风险 （AVR）和AIM益处1-2，我们将利用Medicare数据的联系 美国Corevalve Pivotal试验，这是一个随机患有严重主动脉狭窄的个体的Clials的集合 与AIM 1中的自膨胀生物植被（Safr）的经导管AVR（TAVR）。 我们将确定哪些变量，与脆弱和候选脆弱法规的面对面评估有关的变量，最佳 在AIM 2中预测AVR后的不良结果，我们将确定在AM 1中确定的新变量 在AIM 3中接受AVR的个体的异质治疗反应。 在BIDMC接受TAVR的患者并发脆弱的表型，以确定代谢物是否是代谢物 与寿命相关的与脆弱相关并预测不良后果，独立于年龄和 合并症。 AVR的治疗益处，提供可以个性化治疗选择并改善患者护理的见解。