Objectives-To determine the independent prognostic effect of 7 potential frailty criteria, including 5 from the Fried phenotype, on several adverse outcomes. Design-Prospective cohort study.Setting-Greater New Haven, Connecticut.Participants-Seven hundred fifty-four initially non-disabled, community-living persons aged 70 and older.Measurements-An assessment of 7 potential frailty criteria (slow gait speed, low physical activity, weight loss, exhaustion, weakness, cognitive impairment and depressive symptoms) was completed at baseline and every 18 months for 72 months. Participants were followed with monthly telephone interviews for up to 96 months to determine the occurrence of chronic disability, longterm nursing home (NH) stays, injurious falls, and death.Results-In analyses that were adjusted for age, sex, race, education, number of chronic conditions, and the presence of the other potential frailty criteria, 3 of the 5 Fried criteria (slow gait speed, low physical activity, and weight loss) were independently associated with chronic disability, long-term NH stays, and death. Slow gait speed was the strongest predictor of chronic disability (Hazard ratio [HR] 2.97, 95% confidence interval [CI], 2.32-3.80), and long-term NH stays (HR 3.86, 95% CI, 2.23-6.67), and was the only significant predictor of injurious falls (HR 2.19, 95% CI, 1.33-3.60). Cognitive impairment was also associated with chronic disability (HR 1.82, 95% CI, 1.40-2.38), long-term NH stays (HR 2.64, 95% CI,, and death (HR 1.54, 95% CI, 1.13-2.10), and the magnitude of these associations was comparable to that of weight loss. Conclusions-The results of our study provide strong evidence to support the use of slow gait speed, low physical activity, weight loss and cognitive impairment as key indicators of frailty, while raising concerns about the value of self-reported exhaustion and muscle weakness.

Refusal of medical and surgical interventions other than medications is common among persons with advanced chronic disease, and is associated with a greater desire for, and understanding of, prognostic information.

We have used the polymerase chain reaction to clone and characterize growth factor receptor tyrosine kinases (RTKs) expressed in 3 pathologically distinct pediatric brain tumors, an anaplastic ependymoma, a glioblastoma multiforme and a primitive neuroectodermal tumor (PNET). These neoplasms are presumed to be derived from embryonic neuroepithelial precursor cells of the central nervous system. This cloning demonstrated expression of 24 distinct kinase genes: 16 receptor type kinases and 8 nonreceptor type kinases. The expression of 6 receptors, including Hek2, IRR, Ryk, FGFR3, and 2 members of the newly identified cell adhesion kinase receptor family, DDR and TKT, in such tumors has not been reported previously. Northern analysis of mRNA levels revealed DDR expression in 6 of 7 pediatric brain tumors including an ependymoma, PNET, glioblastoma and astrocytoma, and also in an adult pheochromocytoma. Thus, the DDR cell adhesion kinase may be widely expressed in pediatric brain tumors. Also, PCR cloning may be an effective procedure for characterizing RTKs in clinical tissue samples and revealing the expression of novel RTK species.