A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries.

BACKGROUND: Injuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined. METHODS: We conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group. RESULTS: The demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups. CONCLUSIONS: A multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.).

Middle-Aged Men With HIV Have Diminished Accelerometry-Based Activity Profiles Despite Similar Lab-Measured Gait Speed: Pilot Study.

BACKGROUND: People aging with HIV are living with increased risk for functional decline compared with uninfected adults of the same age. Early preclinical changes in biomarkers in middle-aged individuals at risk for mobility and functional decline are needed. OBJECTIVE: This pilot study aims to compare measures of free-living activity with lab-based measures. In addition, we aim to examine differences in the activity level and patterns by HIV status. METHODS: Forty-six men (23 HIV+, 23 HIV-) currently in the MATCH (Muscle and Aging Treated Chronic HIV) cohort study wore a consumer-grade wristband accelerometer continuously for 3 weeks. We used free-living activity to calculate the gait speed and time spent at different activity intensities. Accelerometer data were compared with lab-based gait speed using the 6-minute walk test (6-MWT). Plasma biomarkers were measured and biobehavioral questionnaires were administered. RESULTS: HIV+ men more often lived alone (P=.02), reported more pain (P=.02), and fatigue (P=.048). In addition, HIV+ men had lower blood CD4/CD8 ratios (P<.001) and higher Veterans Aging Cohort Study Index scores (P=.04) and T-cell activation (P<.001) but did not differ in levels of inflammation (P=.30) or testosterone (P=.83). For all participants, accelerometer-based gait speed was significantly lower than the lab-based 6-MWT gait speed (P<.001). Moreover, accelerometer-based gait speed was significantly lower in HIV+ participants (P=.04) despite the absence of differences in the lab-based 6-MWT (P=.39). HIV+ participants spent more time in the lowest quartile of activity compared with uninfected (P=.01), who spent more time in the middle quartiles of activity (P=.02). CONCLUSIONS: Accelerometer-based assessment of gait speed and activity patterns are lower for asymptomatic men living with HIV compared with uninfected controls and may be useful as preclinical digital biomarkers that precede differences captured in lab-based measures.

Atypical Skeletal Muscle Profiles in Human Immunodeficiency Virus-Infected Asymptomatic Middle-Aged Adults.

Background: Human immunodeficiency virus (HIV)-infected individuals are at increased risk of age-associated functional impairment, even with effective antiretroviral therapy (ART). A concurrent characterization of skeletal muscle, physical function, and immune phenotype in aviremic middle-aged HIV-infected adults represents a knowledge gap in prognostic biomarker discovery. Methods: We undertook a prospective observational study of 170 middle-aged, HIV-infected ambulatory men and women with CD4+ T-cell counts of at least 350/µL and undetectable plasma viremia while on effective ART, and uninfected control participants. We measured biomarkers for inflammation and immune activation, fatigue, the Veterans Aging Cohort Study mortality index, and physical function. A subset also received a skeletal muscle biopsy and computed tomography scan. Results: Compared to the uninfected participants, HIV-infected participants displayed increased immune activation (P < .001), inflammation (P = .001), and fatigue (P = .010), and in a regression model adjusting for age and sex displayed deficits in stair-climb power (P < .001), gait speed (P = .036), and predicted metabolic equivalents (P = .019). Skeletal muscle displayed reduced nuclear peroxisome proliferator-activated receptor-γ coactivator 1α-positive myonuclei (P = .006), and increased internalized myonuclei (P < .001) that correlated with immune activation (P = .003) and leukocyte infiltration (P < .001). Internalized myonuclei improved a model for HIV discrimination, increasing the C-statistic from 0.84 to 0.90. Conclusions: Asymptomatic HIV-infected middle-aged adults display atypical skeletal muscle profiles, subclinical deficits in physical function, and persistent inflammation and immune activation. Identifying biomarker profiles for muscle dysregulation and risk for future functional decline in the HIV-infected population will be key to developing and monitoring preventive interventions. Clinical Trials Registration: NCT03011957.