Characterizing Resiliencies to Physical Stressors in Older Adults: A Dynamical Physiological Systems Approach

表征老年人对身体压力源的适应能力：动态生理系统方法

• 批准号: 10247045
• 负责人: Karen J. Bandeen-Roche
• 金额: $ 232.46万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10247045
• 关键词: Address; Aging; Area; Biological; Biology of Aging; Biomedical Engineering; Bone Marrow Transplantation; Clinical; Clinical Research; Collection; Complex; Data; Disease; Elderly; Electronic Health Record; Geriatrics; Health behavior; Hematologic Neoplasms; Hemodialysis; Heterogeneity; Institution; Intervention Studies; Investigation; Knowledge; Measurement; Measures; Medicine; Molecular; Operative Surgical Procedures; Outcome; Phase; Phenotype; Physical Function; Physiological; Physiology; Pilot Projects; Population; Predictive Value; Preparation; Process; Property; Psychosocial Factor; Recovery; Research; Serious Adverse Event; Stress; System; Testing; Time; Validation; age related; base; clinical database; clinically relevant; cognitive function; cohort; design; frailty; functional decline; hip replacement arthroplasty; novel; phase 2 designs; phase 2 study; resilience; response; statistics; stressor

Project Summary When confronted with a major physical stressor, some older adults are able to recover, with minimal decline, their physical and cognitive function, while others suffer precipitous, irreversible declines in function. This is the central notion behind resiliency. Little is known about the intrinsic (e.g., physiologic and molecular processes) and extrinsic (e.g., health behaviors) factors that impact resiliency. A two-phase study is proposed here to address this gap in our understanding. In phase 1, data will be generated to characterize age-related changes in physical resiliencies, their determinants, and their outcomes. Phase 2 will involve construction and validation of measures of resiliency; assessment of their predictive and clinical value; and investigation of age-related biological mechanisms determining specific resiliencies. Phase 1 Specific Aims: 1. To define, develop and refine phenotypic measures of resiliency responses to three pre-defined physical stressors: hip replacement surgery, initiation of hemodialysis, and bone marrow transplantation for hematologic malignancy. 2. To develop and pilot test candidate indicators of physical resiliency to include static and dynamic, as well as global and stressor-specific, measures. 3. To identify pre-stressor determinants of resilience, including measures of disease states, psychosocial factors, and molecular measures, and to characterize their measurement and statistical properties. 4. To synthesize data developed in Aims 1-3 to inform the design of Phase 2 studies. Phase 2 Specific Aims: 1. For each of clinical stressor to be studied: To build and evaluate assessments of resiliency incorporating measures identified in phase 1. Promising candidate measures will be cross-validated and their accuracy in predicting short- and long-term resilient stressor response rigorously characterized. The relative predictive value of global vs. specific, static vs. dynamic, and solely EHR-based versus broader resiliency measures will be assessed. 2. To characterize and assess age-related biological mechanisms that contribute to resilience or lack thereof that are specific to each clinical stressor, as well as mechanisms that are common across three specific physical stressors in older adults. 3. In preparation for the conduct of intervention studies: to cross-validate measures of resiliency at an external institution and to design pilot studies of strategies to bolster resiliencies based on clinical findings and biological mechanisms identified in Phase 1.

项目摘要 当面对主要的身体压力源时，一些老年人能够恢复，而下降最少， 它们的身体和认知功能，而其他人的功能下降幅度下降。这是 弹性背后的中心概念。关于固有的（例如生理和分子过程）知之甚少 以及影响弹性的外部（例如健康行为）因素。这里提出了一项两阶段的研究 在我们的理解中解决这一差距。在第1阶段，将生成数据以表征与年龄相关的变化 在身体的韧性，决定因素及其结果中。第2阶段将涉及施工和验证 弹性措施；评估其预测性和临床价值；和与年龄有关的调查 确定特定弹性的生物学机制。 第1阶段的特定目的： 1。定义，开发和完善对三个预定物理的弹性响应的表型量度 压力源：髋关节置换手术，血液透析的启动和骨髓移植 血液系统恶性肿瘤。 2。要开发和试点测试候选物理弹性指标，以包括静态和动态 作为全球和压力特定的措施。 3。确定弹性的预压决定因素，包括疾病状态的度量，社会心理 因素和分子测量，并表征其测量和统计特性。 4.合成目标1-3中开发的数据，以告知第二阶段研究的设计。 第2阶段的特定目的： 1。对于要研究的每个临床压力源：建立和评估合并弹性评估 在第1阶段确定的措施。有希望的候选措施将进行交叉验证，其准确性 预测短期和长期的弹性应激响应严格表征。相对预测 全球与特定，静态与动态的价值，仅基于EHR与更广泛的弹性度量 将被评估。 2。表征和评估与年龄相关的生物学机制，有助于弹性或缺乏弹性 每个临床压力源是特定的，以及在三个特定的特定方面常见的机制 老年人的身体压力源。 3。为进行干预研究做准备：跨估量的弹性测量 外部机构并设计基于临床发现的策略的试点研究，以增强弹性 和在第1阶段确定的生物学机制。

项目成果

Physical Resilience Phenotype Trajectories in Incident Hemodialysis: Characterization and Mortality Risk Assessment.

• DOI: 10.1016/j.ekir.2022.06.009
• 发表时间: 2022-09
• 期刊: KIDNEY INTERNATIONAL REPORTS
• 影响因子: 6
• 作者: Hladek, Melissa D.;Zhu, Jiafeng;Crews, Deidra C.;McAdams-DeMarco, Mara A.;Buta, Brian;Varadhan, Ravi;Shafi, Tariq;Walston, Jeremy D.;Bandeen-Roche, Karen
• 通讯作者: Bandeen-Roche, Karen

Identifying predictors of resilience to stressors in single-arm studies of pre-post change.

在变革前后的单臂研究中确定压力源恢复力的预测因子。

• DOI: 10.1093/biostatistics/kxad018
• 发表时间: 2023
• 期刊: Biostatistics (Oxford, England)
• 作者: Varadhan,Ravi;Zhu,Jiafeng;Bandeen-Roche,Karen
• 通讯作者: Bandeen-Roche,Karen