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.

Long-Term Testosterone Supplementation in Older Men Attenuates Age-Related Decline in Aerobic Capacity.

Context: Testosterone increases skeletal muscle mass and strength, but long-term effects of testosterone supplementation on aerobic capacity, or peak oxygen uptake (V̇O2peak), in healthy older men with low testosterone have not been evaluated. Objective: To determine the effects of testosterone supplementation on V̇O2peak during incremental cycle ergometry. Design: A double-blind, randomized, placebo-controlled, parallel-group trial (Testosterone's Effects on Atherosclerosis Progression in Aging Men). Setting: Exercise physiology laboratory. Participants: Healthy men aged ≥ 60 years with total testosterone levels of 100 to 400 ng/dL (3.5 to 13.9 nmol/L) or free testosterone levels < 50 pg/mL (174 pmol/L). Interventions: Randomization to 1% transdermal testosterone gel adjusted to achieve serum levels of 500 to 950 ng/dL or placebo applied daily for 3 years. Main Outcome Measures: Change in V̇O2peak. Results: Mean (±SD) baseline V̇O2peak was 24.2 ± 5.2 and 23.6 ± 5.6 mL/kg/min for testosterone and placebo, respectively. V̇O2peak did not change in men treated with testosterone but fell significantly in men receiving placebo (average 3-year decrease, 0.88 mL/kg/min; 95% CI, -1.39 to 0.38 mL/kg/min; P = 0.035); the difference in change in V̇O2peak between groups was significant (average 3-year difference, 0.91 mL/kg/min; 95% CI, 0.010 to 0.122 mL/kg/min; P = 0.008). The 1-g/dL mean increase in hemoglobin (P < 0.001) was significantly associated with changes in V̇O2peak in testosterone-treated men. Conclusion: The mean 3-year change in V̇O2peak was significantly smaller in men treated with testosterone than in men receiving placebo and was associated with increases in hemoglobin. The difference in V̇O2peak change between groups may indicate attenuation of its expected age-related decline; the clinical meaningfulness of the modest treatment effect remains to be determined.

Effect of Protein Intake on Lean Body Mass in Functionally Limited Older Men: A Randomized Clinical Trial.

Importance: The Institute of Medicine set the recommended dietary allowance (RDA) for protein at 0.8 g/kg/d for the entire adult population. It remains controversial whether protein intake greater than the RDA is needed to maintain protein anabolism in older adults. Objective: To investigate whether increasing protein intake to 1.3 g/kg/d in older adults with physical function limitations and usual protein intake within the RDA improves lean body mass (LBM), muscle performance, physical function, fatigue, and well-being and augments LBM response to a muscle anabolic drug. Design, Setting, and Participants: This randomized clinical trial with a 2 × 2 factorial design was conducted in a research center. A modified intent-to-treat analytic strategy was used. Participants were 92 functionally limited men 65 years or older with usual protein intake less thanor equal to 0.83 g/kg/d within the RDA. The first participant was randomized on September 21, 2011, and the last participant completed the study on January 19, 2017. Interventions: Participants were randomized for 6 months to controlled diets with 0.8 g/kg/d of protein plus placebo, 1.3 g/kg/d of protein plus placebo, 0.8 g/kg/d of protein plus testosterone enanthate (100 mg weekly), or 1.3 g/kg/d of protein plus testosterone. Prespecified energy and protein contents were provided through custom-prepared meals and supplements. Main Outcomes and Measures: The primary outcome was change in LBM. Secondary outcomes were muscle strength, power, physical function, health-related quality of life, fatigue, affect balance, and well-being. Results: Among 92 men (mean [SD] age, 73.0 [5.8] years), the 4 study groups did not differ in baseline characteristics. Changes from baseline in LBM (0.31 kg; 95% CI, -0.46 to 1.08 kg; P = .43) and appendicular (0.04 kg; 95% CI, -0.48 to 0.55 kg; P = .89) and trunk (0.24 kg; 95% CI, -0.17 to 0.66 kg; P = .24) lean mass, as well as muscle strength and power, walking speed and stair-climbing power, health-related quality of life, fatigue, and well-being, did not differ between men assigned to 0.8 vs 1.3 g/kg/d of protein regardless of whether they received testosterone or placebo. Fat mass decreased in participants given higher protein but did not change in those given the RDA: between-group differences were significant (difference, -1.12 kg; 95% CI, -2.04 to -0.21; P = .02). Conclusions and Relevance: Protein intake exceeding the RDA did not increase LBM, muscle performance, physical function, or well-being measures or augment anabolic response to testosterone in older men with physical function limitations whose usual protein intakes were within the RDA. The RDA for protein is sufficient to maintain LBM, and protein intake exceeding the RDA does not promote LBM accretion or augment anabolic response to testosterone. Trial Registration: clinicaltrials.gov Identifier: NCT01275365.

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.

Design of a randomized trial to determine the optimum protein intake to preserve lean body mass and to optimize response to a promyogenic anabolic agent in older men with physical functional limitation.

The dietary protein allowance for older men to maintain lean body mass and muscle strength and to accrue optimal anabolic responses to promyogenic stimuli is poorly characterized. The OPTIMEN trial was designed to assess in older men with moderate physical dysfunction and insufficient habitual protein intake (

Effects of an Ambulation Orderly Program Among Cardiac Surgery Patients.

BACKGROUND: Despite the known benefits of ambulation, most hospitalized patients remain physically inactive. One possible approach to this problem is to employ "ambulation orderlies" (AOs) - employees whose main responsibility is to ambulate patients throughout the day. For this study, we examined an AO program implemented among postcardiac surgery patients and its effect on patient outcomes. METHODS: We evaluated postoperative length of stay, hospital complications, discharge disposition, and 30-day readmission for all patients who underwent coronary artery bypass or cardiac valve surgery in the 9 months prior to and after the introduction of the AO program. In addition to pre-post comparisons, we performed an interrupted time series analysis to adjust for temporal trends and differences in baseline characteristics. RESULTS: We included 447 and 478 patients in the pre- and post-AO intervention groups, respectively. Postoperative length of stay was lower in the post-AO group, with median (interquartile range) of 10 (7, 14) days vs 9 (7, 13) days (P <.001), and also had significantly less variability in mean monthly length of stay (Levene's test P = .03). Using adjusted interrupted time series analysis, the program was associated with a decreased mean monthly postoperative length of stay (-1.57 days, P = .04), as well as a significant decrease in the trend of mean monthly postoperative length of stay (P = .01). Other outcomes were unaffected. CONCLUSION: The implementation of an AO program was associated with a significant reduction in postoperative length and variability of hospital stay. These results suggest that an AO program is a reasonable and practical approach towards improving hospital outcomes.

Ambulation Orderlies and Recovery After Cardiac Surgery: A Pilot Randomized Controlled Trial.

BACKGROUND: One potential strategy to increasing physical activity after surgery is to utilize an ambulation orderly (AO), a dedicated employee whose assures frequent patient walking. However, the impact of an AO on physical and functional recovery from surgery is unknown. METHODS: We randomized post-operative cardiac surgical patients to receive either the AO or usual care. We measured average daily step count, changes in 6-minute walk test (6MWT) distance, and changes in functional independence (Barthel Index.) Our primary goal was to test protocols, measure variability in activity, and establish effect sizes. RESULTS: Thirty-six patients were randomized (18 per group, 45% bypass surgery). Overall, patients exhibited significant recovery of physical function from baseline to discharge in the 6MWT (from 83 to 172 meters, p < 0.001) and showed improvement in independent function (Barthel Index, 67 to 87, p <0.001). Moreover, each additional barrier to ambulation (supplemental oxygen, intravenous poles/fluid, walkers, urinary catheters, and chest tubes) reduced average daily step count by 330 steps/barrier, p = 0.04. However, the AO intervention resulted in only a small difference in average daily step counts (2718 vs. 2541 steps/day, Cohen's d = 0.16, 608 patients needed for larger trial), which we attributed to several trial factors that likely weakened the AO intervention. CONCLUSIONS: In this pilot study, we observed significant in-hospital physical and functional recovery from surgery, but the addition of an AO made only marginal differences in daily step counts. Future studies should consider stepped-wedge or cluster trial designs to increase intervention effectiveness. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov unique identifier: NCT02375282.