Brown Joshua D, Alipour-Haris Golnoosh, Pahor Marco, Manini Todd M
Center for Drug Evaluation & Safety, Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.
Institute on Aging, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.
J Clin Med. 2020 Nov 22;9(11):3757. doi: 10.3390/jcm9113757.
Frailty is a geriatric syndrome represented by susceptibility to precipitating health events and reduced functional reserve. Frailty can be difficult to measure in clinical practice and research. One approach to approximate frailty is based on a deficit accumulation approach, which assesses a larger number of less specific measures such as the presence of comorbidities, physical or cognitive assessments, and lab tests, and summarizes these as a frailty index. The objective of this study was to develop such an index using the Lifestyle Interventions and Independence for Elders (LIFE) Study and evaluate the validity of the frailty measure derived based on baseline information via its association with the primary outcomes of the trial, namely major mobility disability (MMD) and persistent MMD (pMMD). Further, this study aimed to evaluate the effectiveness of the physical activity intervention among participants based on their baseline frailty score. Subjects in the LIFE Study were evaluated at baseline for demographics, clinical history, and a battery of physical and cognitive functioning assessments. In total, 75 possible deficits were scored either as present (yes/no) or based on each score's quintiles for score-based assessments. The frailty index was measured as the total sum of deficits divided by the total number of possible deficits on a continuous scale between 0 and 100 (i.e., percent of deficits present). The frailty index was further divided into quintiles for comparison. A proportional hazards model was estimated for the MMD outcome controlling for other baseline information. A data driven approach was also used to determine relevant cut-offs in the frailty index where the trial intervention appeared to be modified. Among 1635 trial participants, the mean frailty index was 30.4 ± 6.6 and normally distributed. Over 2.5 years of average follow-up, 14.6%, 16.5%, 18.6%, 22.6%, and 27.6% of participants experienced MMD in quintiles 1-5, respectively. Each 1-unit increase in the frailty index increased the hazard of MMD by 4% (2-5%), and there was a nearly 2-fold increase in MMD between the highest and lowest frailty quintiles. Using log-rank criteria, a cut-point at the median was identified. Further, iterations tested for a frailty cut-off and indicated a subgroup beyond the 85th percentile wherein the physical activity intervention appeared to be no longer be effective. This internally derived deficit accumulation frailty index was uniquely able to identify individuals at higher risk of MMD and pMMD and showed that along the spectrum of frailty, the physical activity intervention remained effective for the majority of participants.
衰弱是一种老年综合征,表现为易发生健康事件和功能储备降低。在临床实践和研究中,衰弱可能难以测量。一种近似衰弱的方法是基于缺陷累积法,该方法评估大量不太具体的指标,如合并症的存在、身体或认知评估以及实验室检查,并将这些指标汇总为一个衰弱指数。本研究的目的是利用老年人生活方式干预与独立性(LIFE)研究开发这样一个指数,并通过其与试验的主要结局(即严重行动障碍(MMD)和持续性MMD(pMMD))的关联来评估基于基线信息得出的衰弱测量指标的有效性。此外,本研究旨在根据参与者的基线衰弱评分评估体育活动干预对他们的有效性。LIFE研究中的受试者在基线时接受了人口统计学、临床病史以及一系列身体和认知功能评估。总共75个可能的缺陷被评定为存在(是/否),或者对于基于评分的评估,根据每个评分的五分位数进行评定。衰弱指数的测量方法是将缺陷总数除以0到100连续范围内可能缺陷的总数(即存在缺陷的百分比)。衰弱指数进一步分为五分位数进行比较。针对MMD结局估计了一个控制其他基线信息的比例风险模型。还采用了一种数据驱动方法来确定衰弱指数中的相关临界值(在该临界值处试验干预似乎发生了改变)。在1635名试验参与者中,平均衰弱指数为30.4±6.6,呈正态分布。在平均2.5年的随访中,第1至5五分位数的参与者分别有14.6%、16.5%、18.6%、22.6%和27.6%经历了MMD。衰弱指数每增加1个单位,MMD的风险增加4%(2% - 5%),并且在最高和最低衰弱五分位数之间,MMD的发生率几乎增加了1倍。使用对数秩检验标准,确定了中位数处的一个切点。此外,对衰弱临界值进行了反复测试,结果表明在第85百分位数以上存在一个亚组,在该亚组中体育活动干预似乎不再有效。这种内部推导的缺陷累积衰弱指数能够独特地识别出发生MMD和pMMD风险较高的个体,并表明在整个衰弱范围内,体育活动干预对大多数参与者仍然有效。