Muscle Mass and Strength Cutpoints in Persons at Risk of Mobility Disability

 描述（由申请人提供）：与年龄相关的肌肉质量和力量损失是导致行动不便、健康状况不佳和死亡的重要因素。重要的是要确定老年人中的移动性限制是由于低肌肉质量和力量，因为他们可能是潜在的服从治疗与新的疗法，增加肌肉质量和肌肉力量。因此，为了响应RFA-AG-15-013，我们组建了一个由专家和关键意见领袖组成的大型跨学科团队，以开发和评估低肌肉质量和肌肉力量的诊断临界点，这些临界点预测老年人中移动性残疾的风险增加，操作上定义为步态速度< 0.8米/秒。我们将分析来自两种类型的研究，包括大量的个人与行动不便，以实现以下列出的目标的汇总数据：1。社区居住的老年人的研究，仅限于参与者与流动投诉; 2。对心力衰竭、髋骨骨折、骨关节炎或人类免疫缺陷病毒（HIV）感染的有活动能力残疾风险的患者的临床人群进行仔细表征，并对低肌肉质量、肌肉力量或活动能力受限的老年人进行随机试验。目的1是制定和评估低肌肉质量和力量的诊断临界点-分别针对男性和女性-关于其敏感性，特异性和阳性预测值（PPV），以确定在流行病学研究中存在普遍和偶发移动性残疾风险的人群， 社区居住老年人的行动能力残疾发生率高于一般人口。我们将权衡灵敏度和特异性之间的权衡，建立瘦体重和力量的临界点。我们将评估各种方法来异速生长规模的肌肉质量，力量和体能指标，预测风险的流动性残疾。我们将评估包括肌肉质量和力量的复合多成分模型是否比每个单独的分界点更能预测移动性残疾。我们将评估共病对肌肉质量、力量和活动性之间关系的影响。我们还将建立肌肉质量和力量变化的分界点，以最好地区分那些发展为行动障碍的人。目标2将目标1中确定的临界点应用于仔细表征的临床人群和随机试验的受试者，以评价其在这些人群中的灵敏度、特异性和PPV。目的3将比较新的临界点的灵敏度，特异性和阳性预测值与以前提出的其他人。我们在1中增加了两个探索性目标。确定肌肉质量的考虑是否提高了临界点的灵敏度、特异性和PPV，以及2.评估各种方法，以异速生长标度肥胖， 切割点。我们将召开一次利益攸关方共识会议，审查结果，以实现就这些循证分界点达成共识的目标。该项目的研究结果对临床实践，公共卫生和政策以及药物开发具有重要意义。

 DESCRIPTION (provided by applicant): The age-related loss of muscle mass and strength is an important contributor to mobility disability, poor health outcomes, and death. It is important t identify older adults in whom mobility limitation is due to low muscle mass and strength because they may be potentially amenable to treatment with novel therapies that increase muscle mass and muscle strength. Accordingly, in response to RFA-AG-15-013, we have assembled a large interdisciplinary team of experts and key opinion leaders to develop and evaluate diagnostic cut-points for low muscle mass and muscle strength that predict an increased risk of mobility-disability among older adults, defined operationally as gait speed < 0.8 meters/ sec. We will analyze pooled data from two types of studies that include large number of individuals with mobility-disability to accomplish the aims listed below: 1. Studies of community-dwelling older adults, limited to participants with mobility complaints; 2. Carefully characterized clinical populations of patients with heart failure, hip fracture, osteoarthritis, or human immune-deficiency virus (HIV)-infection at risk for mobility-disability, and participants of randomized trals of older adults with low muscle mass, muscle strength or mobility limitation. Aim 1 is to develop and assess diagnostic cut-points for low muscle mass and strength - separately for men and women - with regard to their sensitivity, specificity and positive predictive value (PPV) in identifying those at risk of prevalent and incident mobility disability in epidemiologic studies of community-dwelling older adults with higher prevalence of mobility disability than the general population. We will weigh the trade-off between sensitivity and specificity in establishing cut-points for lean mass and strength. We will evaluate various approaches to allometrically scale muscle mass, strength and physical performance measures in predicting risk of mobility disability. We will evaluate whether composite, multi-component models that include both muscle mass and strength may be more predictive of mobility-disability than separate cut-points for each. We will assess the effects of comorbid conditions on the relation between muscle mass, strength, and mobility. We will also establish cut-points for change in muscle mass and strength that best discriminate those who develop mobility disability from those who do not. Aim 2 will apply the cut-points established in aim 1 to carefully characterized clinical populations an to participants of randomized trials to evaluate their sensitivity, specificity, and PPV in these populations. Aim 3 will compare the sensitivity, specificity, and positive predictive value of new cut-points with those proposed previously by others. We have added two exploratory aims to 1. determine whether consideration of muscle quality improves the sensitivity, specificity, and PPV of cut-points, and 2. evaluate various approaches to allometrically scale adiposity in establishing the cut-points. We will convene a consensus conference of stakeholders to review the results towards the goal of securing a consensus on these evidence-based cut points. The findings of this project have important implications for clinical practice, public health and policy, and drug development.