Pulmonary Function and Quality of Life in Aging Men With and Without HIV from the Multicenter AIDS Cohort Study.

People living with HIV have greater pulmonary function impairments and decreased health-related quality of life (HRQoL) compared to uninfected peers. We examined whether pulmonary impairment was associated with HRQoL or respiratory health status. Using Multicenter AIDS Cohort Study data (2017-2019), associations between outcomes [HRQoL (36-Item Short Form Survey) and respiratory health status (St. George's Respiratory Questionnaire)] with pulmonary impairment [diffusing capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1), defined as <80% predicted for both] were examined. Adjusted analyses utilized linear and zero-inflated beta regression, the latter summarized by odds ratio (OR) and quotient ratios (QRs). We also considered whether the subset of adjustment variables age, HIV serostatus, or smoking modified the relationships examined. Of 1048 men, 55% had HIV, with median age 57 [interquartile range (IQR) = 48, 64] years and 1.2 (IQR = 0, 18.1) smoking pack-years. Impaired DLCO, but not impaired FEV1, was significantly associated with lower physical HRQoL [-2.71 (-4.09, -1.33); -1.46 (-3.45, 0.54), respectively]. Pulmonary impairment was associated with higher odds of any St. George's Respiratory Questionnaire (SGRQ) (total score) limitation [DLCO OR = 1.53 (1.15, 2.04); FEV1 OR = 2.48 (1.16, 5.30)] and was elevated in individuals with more severe SGRQ limitations [DLCO QR = 1.13 (0.94, 1.36); FEV1 QR = 1.27 (0.98, 1.64)]. HIV did not modify any associations examined. Age modified the DLCO and any respiratory limitation (SGRQ symptom score) association for every 10 mL CO/min/mmHg decrease in DLCO [age 30 OR = 1.03 (0.51, 2.08); age 50 OR = 1.85 (1.27, 3.85); and age 70 OR = 3.45 (2.00, 5.88)]. Similarly, age modified the DLCO and any respiratory limitation (SGRQ total score) association. FEV1 associations with SGRQ and HRQoL scores were similar across all ages. Impaired pulmonary function was associated with lower HRQoL and greater respiratory impairments. Future studies can determine if interventions aimed at preserving pulmonary function are effective in improving HRQoL and respiratory health among aging men with and without HIV.

Pulmonary and physical function limitations in aging men with and without HIV from the Multicenter AIDS Cohort Study (MACS).

PURPOSE: We examined the associations between pulmonary impairments and physical function and whether age, HIV serostatus, or smoking modified these relationships. METHODS: Using Multicenter AIDS Cohort Study data, we examined associations between pulmonary function (diffusing capacity for carbon monoxide [DLCO], one-second forced expiratory volume [FEV1]) and subsequent physical outcomes (gait speed, grip strength, frailty [non-frail, pre-frail, frail]) using mixed models. RESULTS: Of 1,048 men, 55% were living with HIV, median age was 57(IQR=48,64) and median cumulative pack-years was 1.2(IQR = 0,18.1); 33% and 13% had impaired DLCO and FEV1(<80% predicted), respectively. Participants with impaired DLCO had 3.5 kg (95%CI: -4.6, -2.4) weaker grip strength, 0.04 m/sec (95%CI: -0.06, -0.02) slower gait speed and 4.44-fold (95%CI: 1.81, 10.93) greater odds of frailty compared to participants with normal DLCO. Participants with impaired FEV1 had 3.1 kg (95%CI: -4.8, -1.4) weaker grip strength, similar gait speed (-0.001 m/sec [95%CI: -0.04, 0.03]) and 5.72-fold (95%CI: 1.90, 17.19) greater odds of frailty compared to participants with normal FEV1. Age, but not smoking or HIV, significantly modified the DLCO effect on gait speed and grip strength. CONCLUSIONS: Pulmonary impairment and decreased physical function were associated. Preserving pulmonary function may help preserve physical function in aging men with and without HIV.

Impact of a pilot multimodal intervention to decrease antibiotic use for respiratory infections in a geriatric clinic.

Background: More than 80% of antibiotics are prescribed in the outpatient setting, of which 30% are inappropriate. The National Action Plan for Combating Antimicrobial Resistance called for a 50% decrease in outpatient antibiotic use by 2020. Inappropriate antibiotics are associated with adverse reactions and Clostridioides difficile infection, especially among older adults. Study design: Before and after study. Methods: We performed a quality improvement initiative at the University of Colorado Seniors Clinic. Providers received education on antibiotic guidelines, electronic antibiotic order sets were introduced with standardized stop dates. Antibiotic use data were collected for 6 months before and 6 months after the intervention, from December to May to avoid seasonal variation. Descriptive statistics and linear mixed-effects regression models were used for this comparison. Results: Total antibiotic prescriptions for acute respiratory conditions decreased from 137 prescriptions before the intervention (December 1, 2017, to May 31, 2018) to 112 prescriptions after the intervention (December 1, 2018, to May 31, 2019), driven primarily by decreases in antibiotic prescriptions for pneumonia, sinusitis, and bronchitis. Prescriptions for broad-spectrum antibiotics declined following the intervention including decreases in levofloxacin from 12 (9%) to 3 (3%) and amoxicillin-clavulanate from 15 (12%) to 7 (7%). We detected significant reductions in prescribed antibiotic durations (days) after the intervention for sinusitis (estimate, -2.0; 95% CI, -3.1 to -1.0; P = .0003), pharyngitis (estimate, -2.5; 95% CI, -4.6 to -0.5; P = .018), and otitis (-3.2; 95% CI, -5.2 to -1.3; P = .008). Conclusions: Low-cost interventions were initially successful in changing patterns of antibiotic use and decreasing overall antibiotic prescribing among older patients in the outpatient setting. Long-term follow-up studies are needed to determine the sustainability and clinical impact of these interventions.

Regional Differences in Risk of Recurrent Falls Among Older U.S. Women and Men with HIV in the HIV Infection, Aging, and Immune Function Long-Term Observational Study.

Geographic location was a strong predictor of falls among women with and without HIV in the Women's Interagency HIV Study. We examined regional variation in falls in a more geographically diverse cohort of older people with HIV (PWH) and explored whether physical activity, sex, or body-mass index modified these associations. PWH enrolled in the A5322 HAILO (HIV Infection, Aging, and Immune Function Long-Term Observational Study). Participants who reported falls in the 6 months before each semiannual visit and had ≥1 consecutive pair of fall assessments were included. We examined associations of geographic region [Northeast, Midwest, South, and West] with recurrent falls (≥2) over each 12-month period using repeated measures multinomial logistic regression models and assessed effect modification by adding an interaction term between geographic region and each potential effect modifier. A total of 788 men and 192 women with median age of 51 years at study entry contributed up to 240 weeks of data. U.S. regions included Northeast (22%), Midwest (29%), South (20%), and West (28%). In multivariable analyses, compared with the Western region, greater risk was seen among Midwestern (odds ratio [OR] = 2.35 [95% confidence interval (CI) = 1.29-4.28]) and Southern regions (OR = 2.09 [95% CI = 1.09-4.01]). Among those with higher physical activity, the Midwestern region had higher odds of recurrent falls than the Western region. Among obese individuals, the Southern region had higher odds of recurrent falls than the Western region. Sex did not modify the association between region and recurrent falls. Among older PWH, fall risk varied by geographic region. Associations between geographic region and recurrent falls appeared to be modified by physical activity and obesity. This may help identify subgroups of older PWH for targeted fall screening/interventions.

Health impacts of a randomized biomass cookstove intervention in northern Ghana.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has adverse health effects. REACCTING (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana) was a randomized cookstove intervention study that aimed to determine the effects of two types of "improved" biomass cookstoves on health using self-reported health symptoms and biomarkers of systemic inflammation from dried blood spots for female adult cooks and children, and anthropometric growth measures for children only. METHODS: Two hundred rural households were randomized into four different cookstove groups. Surveys and health measurements were conducted at four time points over a two-year period. Chi-square tests were conducted to determine differences in self-reported health outcomes. Linear mixed models were used to assess the effect of the stoves on inflammation biomarkers in adults and children, and to assess the z-score deviance for the anthropometric data for children. RESULTS: We find some evidence that two biomarkers of oxidative stress and inflammation, serum amyloid A and C-reactive protein, decreased among adult primary cooks in the intervention groups relative to the control group. We do not find detectable impacts for any of the anthropometry variables or self-reported health. CONCLUSIONS: Overall, we conclude that the REACCTING intervention did not substantially improve the health outcomes examined here, likely due to continued use of traditional stoves, lack of evidence of particulate matter emissions reductions from "improved" stoves, and mixed results for HAP exposure reductions. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov (National Institutes of Health); Trial Registration Number: NCT04633135 ; Date of Registration: 11 November 2020 - Retrospectively registered. URL: https://clinicaltrials.gov/ct2/show/NCT04633135?term=NCT04633135&draw=2&rank=1.

A Unique Gut Microbiome-Physical Function Axis Exists in Older People with HIV: An Exploratory Study.

Impairments in physical function and increased systemic levels of inflammation have been observed in middle-aged and older persons with HIV (PWH). We previously demonstrated that in older persons, associations between gut microbiota and inflammation differed by HIV serostatus. To determine whether relationships between the gut microbiome and physical function measurements would also be distinct between older persons with and without HIV, we reanalyzed existing gut microbiome and short chain fatty acid (SCFA) data in conjunction with previously collected measurements of physical function and body composition from the same cohorts of older (51-74 years), nonfrail PWH receiving effective antiretroviral therapy (N = 14) and age-balanced uninfected controls (N = 22). Associations between relative abundance (RA) of the most abundant bacterial taxa or stool SCFA levels with physical function and body composition were tested using HIV-adjusted linear regression models. In older PWH, but not in controls, greater RA of Alistipes, Escherichia, Prevotella, Megasphaera, and Subdoligranulum were associated with reduced lower extremity muscle function, decreased lean mass, or lower Short Physical Performance Battery (SPPB) scores. Conversely, greater RA of Dorea, Coprococcus, and Phascolarctobacterium in older PWH were associated with better muscle function, lean mass, and SPPB scores. Higher levels of the SCFA butyrate associated with increased grip strength in both PWH and controls. Our findings indicate that in older PWH, both negative and positive associations exist between stool microbiota abundance and physical function. Different relationships were observed in older uninfected persons, suggesting features of a unique gut-physical function axis in PWH.

Associations Between Tenofovir Diphosphate in Dried Blood Spots, Impaired Physical Function, and Fracture Risk.

BACKGROUND: In this study, we evaluate associations between cumulative antiretroviral adherence/exposure, quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), and human immunodeficiency virus (HIV)-related aging factors. METHODS: This is a cross-sectional analysis of younger (ages 18-35) and older (ages ≥60) persons with HIV (PWH) taking TFV disoproxil fumarate. Tenofovir diphosphate concentrations were quantified in DBS. Linear and logistic regression models were used to evaluate associations between TFV-DP and bone mineral density (BMD), physical function, frailty, and falls. RESULTS: Forty-five PWH were enrolled (23 younger, 22 older). Every 500 fmol/punch (equivalent to an increase in ~2 doses/week) increase in TFV-DP was associated with decreased hip BMD (-0.021 g/cm2; 95% confidence interval [CI], -0.040 to -0.002; P = .03). Adjusting for total fat mass, every 500 fmol/punch increase in TFV-DP was associated with higher odds of Short Physical Performance Battery impairment (score ≤10; adjusted odds ratio [OR], 1.6; 95% CI, 1.0-2.5; P = .04). Every 500 fmol/punch increase in TFV-DP was associated with slower 400-meter walk time (14.8 seconds; 95% CI, 3.8-25.8; P = .01) and remained significant after adjusting for age, lean body mass, body mass index (BMI), and fat mass (all P ≤ .01). Every 500 fmol/punch increase in TFV-DP was associated with higher odds of reporting a fall in the prior 6 months (OR, 1.8; 95% CI, 1.1-2.8; P = .02); this remained significant after adjusting for age, lean body mass, BMI, and total fat mass (all P < .05). CONCLUSIONS: Higher TFV-DP levels were associated with lower hip BMD, poorer physical function, and greater risk for falls, a concerning combination for increased fracture risk.

Effect of Statin Therapy on Age-Associated Changes in Physical Function Among Men With and Without HIV in the Multicenter AIDS Cohort Study.

BACKGROUND: The longer-term risks of statins on physical function among people with HIV are unclear. METHODS: Longitudinal analysis of Multicenter AIDS Cohort Study men between 40 and 75 years of age with ≥2 measures of gait speed or grip strength. Generalized estimating equations with interaction terms between (1) statin use and age and (2) HIV serostatus, age, and statin use were considered to evaluate associations between statin use and physical function. Models were adjusted for demographics and cardiovascular risk factors. RESULTS: Among 2021 men (1048 with HIV), baseline median age was 52 (interquartile range 46-58) years; 636 were consistent, 398 intermittent, and 987 never statin users. There was a significant interaction between age, statin, and HIV serostatus for gait speed. Among people with HIV, for every 5-year age increase, gait speed (m/s) decline was marginally greater among consistent versus never statin users {-0.008 [95% confidence interval (CI) -0.017 to -0.00007]; P = 0.048}, with more notable differences between intermittent and never users [-0.017 (95% CI -0.027 to -0.008); P < 0.001]. Similar results were observed among men without HIV. Significant differences in grip strength (kg) decline were seen between intermittent and never users [-0.53 (95% CI -0.98 to -0.07); P = 0.024] and differences between consistent and never users [-0.28 (95% CI -0.63 to 0.06); P = 0.11] were not statistically significant. CONCLUSIONS: Among men with and without HIV, intermittent statin users had more pronounced declines in physical function compared with consistent and never users. Consistent statin use does not seem to have a major impact on physical function in men with or without HIV.

Physical Function and Frailty Tools in Mortality Prediction of Middle-Aged Adults With HIV.

BACKGROUND: Frailty and physical function impairments occur at an earlier than expected age in people with HIV (PWH). The goal of this study was to determine which tools or combination of tools assessing frailty/physical function were most predictive of mortality in a middle-aged population of PWH. METHODS: Using electronic health records, we determined survival, death, or loss to follow-up for 359 PWH, aged 45-65 years originally enrolled in a 2009-2010 cross-sectional cohort study. The predictive accuracy of various physical function measures [frailty score, Veterans Aging Cohort Study (VACS) index, 400-m walk, Short Physical Performance Battery (SPPB), grip strength, and falls] were compared using integrated time-dependent receiver operating characteristic area under the curve (AUC) in single variable models. Two-variable models were compared with the best single-variable model to determine if AUC improved with additional physical function variables. RESULTS: At 8-year follow-up, frailty, 400-m walk pace, SPPB, chair rise pace, VACS score, and falls were associated with increased hazard of mortality; grip strength was only predictive in sex-adjusted models. The VACS index and 400-m walk pace were the best individual predictors of mortality with time-dependent receiver operating characteristic AUC scores of 0.82, followed by SPPB (0.73), chair-rise pace (0.68), falls (0.65), frailty (0.63), and grip strength (0.55). Addition of the 400-m walk to VACS index yielded the only significant improvement in the prediction of survival compared with the VACS index alone (P = 0.04). CONCLUSION: Our study highlights several clinically applicable physical function measures predictive of mortality in middle-aged PWH that can be tailored to specific patient subpopulations and clinical or research encounters.

Impact of Wildfire Smoke on Adverse Pregnancy Outcomes in Colorado, 2007-2015.

Colorado is regularly impacted by long-range transport of wildfire smoke from upwind regions. This smoke is a major source of ambient PM2.5. Maternal exposure to total PM2.5 during pregnancy has been linked to decreased birth weight and other adverse outcomes, although the impact of wildfire smoke contribution has only recently been investigated. The objective of this study was to estimate associations between adverse pregnancy outcomes and ambient wildfire smoke PM2.5. Wildfire smoke PM2.5 exposures were estimated using a previously published method incorporating ground-based monitors and remote sensing data. Logistic regression models stratified by ZIP code and mixed models with random intercept by ZIP code were used to test for associations. The primary outcomes of interest were preterm birth and birth weight. Secondary outcomes included gestational hypertension, gestational diabetes, neonatal intensive care unit admission, assisted ventilation, small for gestational age, and low birth weight. Exposure to wildfire smoke PM2.5 over the full gestation and during the second trimester were positively associated with pre-term birth (OR = 1.076 (µg/m3)-1 [95% CI = 1.016, 1.139; p = 0.013] and 1.132 (µg/m3)-1 [95% CI = 1.088, 1.178]; p < 0.0001, respectively), while exposure during the first trimester was associated with decreased birth weight (-5.7 g/(µg/m3) [95% CI: -11.1, -0.4; p = 0.036]). Secondary outcomes were mixed.

Examining Mortality to Identify Opportunities for Improved Care Among Adults with HIV in a Single Academic Medical Center.

Mortality for people living with HIV (PLWH) has dramatically decreased since the mid-1990s and the proportion of deaths attributable to non-AIDS-related conditions has increased. Deceased PLWH were identified from a single academic medical center through provider survey and electronic medical record query. Cause of death was determined using the Coding Causes of Death in HIV tool following review of available medical records. Chart review of comorbidities, demographics, laboratory values, and previous completion of screening tests for malignancies was conducted for deaths during the period of 2013-2017. The proportion of AIDS-related deaths decreased markedly between 1995 and 2017, while the proportion of deaths from non-AIDS malignancies increased. From 2013 to 2017, 30 of 121 deaths were attributed to AIDS-related conditions, 32 to non-AIDS malignancies, 14 to suicide/homicide or sudden death, 10 to cardiac causes, 28 to other non-HIV causes, and 7 to unknown causes. Those who died of non-AIDS-related malignancies were older than AIDS-related deaths [mean age 55.8 (7.6) vs. 47.3 (13.5), p value = .003]. Less than half of potentially eligible patients had documented colon cancer screening. The number of individuals dying from AIDS-related conditions has decreased significantly and non-AIDS-related causes, particularly non-AIDS-related malignancies, have become more prominent causes of death. As our patients age, a greater focus needs to be placed on management of comorbid illnesses and screening and prevention of malignancy.

Frailty, Neurocognitive Impairment, or Both in Predicting Poor Health Outcomes Among Adults Living With Human Immunodeficiency Virus.

Background: Neurocognitive impairment (NCI) is strongly associated with frailty in people living with human immunodeficiency virus (PLWH); the overlap of frailty and NCI and the impact on health outcomes in PLWH are unknown. Methods: PLWH in a longitudinal, observational study of aging completed entry evaluations for frailty and NCI. Outcomes of falls (recurrent) increased limitations in independent activities of daily living (IADL), or mortality were combined. Poisson regression models estimated prevalence ratios (PR) for ≥1 outcome over 2 years. Results: Among 987 participants, the median age at entry was 51 years; 19% were female; the median CD4 count was 616 cells/µL; and HIV-1 RNA was <200 copies/mL in 94%. Most (79%) participants had neither frailty nor NCI; 2% had both; 4% frailty only; and 15% NCI only. Over 2 years of observation, 100 (10%) participants experienced recurrent falls; 175 (18%) had worsening IADL limitations; 17 (2%) died; and 254 (26%) experienced ≥1 poor health outcome. In adjusted models, frailty with NCI was associated with more than double the risk of a poor health outcome (PR 2.65; 95% CI 1.98, 3.54); a significant association was also seen with frailty alone (PR 2.26; 95%CI 1.71, 2.99) and NCI alone (PR 1.73; 95% CI 1.36, 2.20). Conclusions: The presence of frailty with NCI was associated with a greater risk of falls, disability, or death in PLWH than NCI alone. Interventions that target prevention or reversal of both frailty and NCI (such as increased physical activity) may significantly limit poor health outcomes among PLWH.

Frailty is strongly associated with increased risk of recurrent falls among older HIV-infected adults.

OBJECTIVE: Both frailty and falls occur at earlier-than-expected ages among HIV-infected individuals, but the contribution of frailty-to-fall risk in this population is not well understood. We examined this association among participants enrolled in AIDS Clinical Trials Group (ACTG) A5322. DESIGN: A prospective, multicenter cohort study of HIV-infected men and women aged at least 40 years. METHODS: Frailty assessment included a 4-m walk, grip strength, and self-reported weight loss, exhaustion, and low physical activity. Multinomial logistic regression assessed the association between baseline frailty, grip, and 4-m walk, and single and recurrent (2+) falls over the next 12 months; logistic regression assessed effect modification by several factors on association between frailty and any (1+) falls. RESULTS: Of 967 individuals, 6% were frail, 39% prefrail, and 55% nonfrail. Eighteen percent had at least one fall, and 7% had recurrent falls. In multivariable models, recurrent falls were more likely among frail (odds ratio 17.3, 95% confidence interval 7.03-42.6) and prefrail (odds ratio 3.80, 95% CI 1.87-7.72) than nonfrail individuals. Significant associations were also seen with recurrent falls and slow walk and weak grip. The association between frailty and any falls was substantially stronger among individuals with peripheral neuropathy. CONCLUSION: Aging HIV-infected prefrail and frail individuals are at significantly increased risk of falls. Incorporation of frailty assessments or simple evaluations of walk speed or grip strength in clinical care may help identify individuals at greatest risk for falls. Peripheral neuropathy further increases fall risk among frail persons, defining a potential target population for closer fall surveillance, prevention, and treatment.