Transforming Research And Clinical Knowledge in Geriatric Traumatic Brain Injury (TRACK-GERI)

转变老年创伤性脑损伤的研究和临床知识 (TRACK-GERI)

• 批准号: 10171929
• 负责人: Raquel C. Gardner
• 金额: $ 62.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171929
• 关键词: Accident and Emergency department; Address; Adult; Age; Aging; Alleles; American; Anatomy; Apolipoprotein E; Atrophic; Biological Markers; Blood; Brain; Brain Injuries; Caring; Cause of Death; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Trials; Cognitive; Cohort Studies; Common Data Element; Data; Dementia; Diabetes Mellitus; Diagnostic; Disabled Persons; Elderly; Enrollment; Enzyme-Linked Immunosorbent Assay; Exclusion; FDA approved; Family; Foundations; Functional disorder; Funding; Genotype; Geriatrics; Glial Fibrillary Acidic Protein; Gold; Guidelines; Health; Health Status; Impaired cognition; Incidence; Infrastructure; Injury; Interview; Knowledge; Measures; National Institute of Neurological Disorders and Stroke; Natural History; Outcome; Outcome Assessment; Outcome Measure; Patients; Pilot Projects; Plasma; Polypharmacy; Population; Prognosis; Prognostic Marker; Prospective cohort; Prospective cohort study; Proxy; Public Health; Recovery; Research; Research Design; Research Methodology; Rest; Site; Structure; Testing; Traumatic Brain Injury; Variant; Vascular Diseases; Vulnerable Populations; White Matter Disease; Withdrawal; Work; age group; base; blood-based biomarker; burden of illness; care outcomes; clinical care; cohort; comorbidity; cost; demographics; design; diagnostic biomarker; disability; effective intervention; evidence base; evidence based guidelines; experience; flexibility; frailty; functional status; high risk; improved; improved outcome; injury recovery; innovation; instrument; medical attention; mortality; multidisciplinary; neuropathology; novel strategies; older patient; outcome prediction; primary endpoint; prognostic; prognostic model; prognostic tool; programs; prospective; standard measure; tool; virtual

PROJECT SUMMARY / ABSTRACT Some 2.8 million Americans seek medical attention for traumatic brain injury (TBI) annually, resulting in estimated annual costs of over $75 billion. Older adults have the highest and fastest rising rate of TBI of any other age-group, with 1 in 50 adults age ≥75y seeking medical attention for TBI in 2013. Older adults with TBI experience higher mortality, slower recovery, worse outcomes, and may be at especially high risk for post-TBI dementia. There are few evidence-based guidelines for management, no tools to provide patients and families with reliable estimates of prognosis, and few proven treatments. Progress has been limited by: 1. systematic exclusion of older disabled patients from most prior prospective TBI studies, and 2. lack of age-appropriate TBI research tools. The overall objective is to launch a 2-site prospective geriatric TBI cohort study that will directly address these barriers by applying state-of-the-art geriatric research methods to the field of TBI to improve representation of older patients in TBI research, and to develop a novel approach to measuring age- appropriate TBI predictors, outcomes, blood-based biomarkers, and neuropathology. The approach rests on 2 foundational concepts: 1. Geriatric TBI is different from TBI in younger patients and will require a targeted age- appropriate approach. 2. Baseline health status – including comorbidities/polypharmacy, physical frailty, functional status, and brain structure – is recognized as a key predictor of outcome in the field of geriatrics but is not systematically measured in TBI research. The central hypothesis is that pre-injury health will be extremely heterogeneous in geriatric TBI and will be a key predictor of outcome in this population. An outstanding team of experts in TBI and aging research will achieve these Aims: Aim 1: Assemble a prospective cohort of patients age ≥65y presenting to the Emergency Department ≤72h after TBI who underwent CT. Enroll 270 TBI patient/study-partner dyads and 90 controls; perform baseline assessments and blood draws, and assess longitudinal outcomes at 2wk, 3mo, 6mo (primary endpoint) and 12mo; offer enrollment in a brain donation program. Aim 2: Develop and validate optimized geriatric TBI predictor and outcome assessments: 2a: Systematically measure apolipoprotein E allele and pre-injury comorbidities/polypharmacy, physical frailty, and multi-domain functional status via detailed patient and study partner interviews using validated geriatric instruments and assess association of these predictors with outcome after TBI. 2b: Describe the natural history of geriatric TBI using validated TBI and geriatric outcomes and then use data-driven analytics to identify the most parsimonious set of measures for longitudinal outcome assessment in this population. 2c (exploratory): Measure pre-injury brain structure (atrophy/white matter disease of uninjured brain visualized on baseline CT) and explore association with outcome after TBI. Aim 3: Identify age-appropriate diagnostic and prognostic blood-based biomarkers. This work will directly inform design of large-scale age-appropriate geriatric TBI clinical trials that are urgently needed to improve care and outcomes in this vulnerable population.

项目总结/摘要 每年约有280万美国人因创伤性脑损伤（TBI）寻求医疗护理， 估计每年的成本超过750亿美元。老年人的TBI发病率最高，增长最快， 其他年龄组，2013年，每50名年龄≥ 75岁的成年人中就有1人因TBI寻求医疗护理。老年TBI患者 经历更高的死亡率、更慢的恢复、更差的结果，并且可能处于TBI后的特别高的风险中。 痴呆几乎没有循证管理指南，没有工具提供给患者和家属 对预后的估计是可靠的，但几乎没有经过验证的治疗方法。进展受到以下因素的限制：1。系统 从大多数先前的前瞻性TBI研究中排除老年残疾患者，以及2.缺乏与年龄相适应的TBI 研究工具。总体目标是启动一项2中心前瞻性老年TBI队列研究， 通过将最先进的老年医学研究方法应用于TBI领域来解决这些障碍， 在TBI研究中代表老年患者，并开发一种新的方法来测量年龄- 适当的TBI预测因子、结果、基于血液的生物标志物和神经病理学。该方法基于2 基本概念：1.老年TBI与年轻患者的TBI不同，需要有针对性的年龄- 适当的方法。2.基线健康状况-包括合并症/多种药物治疗、身体虚弱， 功能状态和大脑结构-被认为是老年医学领域结果的关键预测因素， 在TBI研究中没有系统地测量。核心假设是，受伤前的健康状况将是 在老年TBI患者中，TBI具有极高的异质性，并且将是该人群中结果的关键预测因素。一个 一个优秀的TBI和衰老研究专家团队将实现这些目标：目标1： 年龄≥ 65岁的患者队列，在TBI后≤ 72小时内到急诊室接受CT检查。招收 270例TBI患者/研究伴侣配对和90例对照;进行基线评估和抽血，以及 评估2周、3个月、6个月（主要终点）和12个月时的纵向结局;提供脑招募 捐赠计划。目标2：开发和验证优化的老年TBI预测因子和结局评估： 2a：系统测量载脂蛋白E等位基因和损伤前合并症/多种药物、身体虚弱， 和多领域的功能状态，通过详细的患者和研究伙伴的访谈，使用经验证的老年 工具，并评估这些预测因子与TBI后结果的相关性。2b：描述自然历史 使用经验证的TBI和老年结局，然后使用数据驱动的分析来识别 最简约的一套措施，纵向结果评估在这个人口。2c（探索性）： 测量损伤前脑结构（基线CT上可见的未损伤脑的萎缩/白色疾病） 并探索与TBI后结果的相关性。目标3：确定适合年龄的诊断和预后 血液生物标志物这项工作将直接通知设计大规模的年龄适当的老年TBI 临床试验，迫切需要改善护理和结果，在这个脆弱的人群。