In the development cohort, the physical frailty phenotype was defined using 5 criteria proposed and validated in the Cardiovascular Health Study (CHS)2: unintentional shrinking, slowness, weakness, exhaustion, and low activity. The measurements used in this study to define the frailty construct were similar but not identical to those

used in the original CHS study. A participant without any of the 5 components was defined as nonfrail, 1 to 2 components as prefrail, and 3 and more components as frail. 1. Unintentional shrinking: Gemcitabine body mass index (BMI) of less than 18.5 kg/m2 and/or unintentional weight loss of 10 pounds (4.5 kg) or more in the past 6 months. In the validation cohort, the CHS criteria for phenotypic frailty were modified based on the available data. Weakness was defined by the lowest quintile of performance on rising from chair test; slowness was defined by Performance-Oriented Mobility Assessment gait performance score of 8 or lower; exhaustion was defined by their response (“not at all”) to “Did you have a lot of energy?”; low activity was defined by “none” self-report of participation in any physical activity (walking or recreational or sports activity). Another frailty scale, the FRAIL scale,7 is a simple rapid screening test that has been developed and validated to allow physicians to identify persons with the physical

frailty syndrome for more in-depth assessment. Accordingly we used data of the SLAS-1 participants to score their responses (0 or 1) to Fatigue: energy Quizartinib concentration (none of the time); Resistance: climb

stairs (limited a lot), Aerobic: activity or work (limited a lot); Illnesses: 5 or more illnesses; Loss of weight: unintended loss of 10 lb/4 kg in past 6 months, and classified them as follows: frail, 3 or more; prefrail: 1 or 2. The FRAIL scale was used in addition to the CHS Frailty scale as comparators in evaluating the ability of the FRI scale to predict adverse health outcomes. The candidate variables selected as potential predictors of the FRI are well established or putative risk factors for physical frailty, and were not congruent characteristics of frailty. Difficulties in performing IADL-ADL activities, history of hospitalization, falls, and symptoms Protein kinase N1 congruent with physical frailty (such as climbing stairs, physical work limitations, breathlessness) were excluded. Available biomarkers of nutrition and inflammation, such as CRP, IL-6, folate, B12, homocysteine, and others, were not used because they are not routinely used in primary care settings, but biomarkers such as low hemoglobin, white cell counts (WCCs), and lymphocyte counts were used instead. Low hemoglobin is reportedly associated with frailty and with elevated levels of circulating IL-6 levels in frail older adults.