Abstract 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.

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.

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.

Background: There is conflicting evidence on how HIV influences COVID19 infection. Aim of this study was to compare characteristics at presentation and clinical outcomes of people living with HIV (PLWH) versus HIV negative patients (non-PLWH) hospitalized with COVID-19. Methods: Patients ≥18 years with SARS-CoV-2 infection, defined as positive RT-PCR from nasal/oropharyngeal swab or positive serology, admitted at L. Spallanzani Institute (Italy) were included. Primary endpoint: time to invasive ventilation/death. Secondary endpoints: time to ventilation/death, time to symptoms resolution (resolution of fever or waning from oxygen). In order to control for measured confounders, Cox regression model was used. Results: A total of 905 hospitalized patients were included in the analysis (22 [2.4%] PLWH, 883 non-PLWH): 65% males, 66% with at least one comorbidity, median PaO2/FiO2 at admission 343 mmHg (260-405). PLWH were slightly younger (56 vs 62 years, p=0.057), less likely with pneumonia (59% vs 87%, p<0.001) and with PaO2/FiO2 <300 mmHg at admission (10% vs 31%, p=0.088), with less alterations in lymphocytes (1505 cells/mm vs 1170, p=0.025) and D-dimer (473 ng/mL vs 661, p=0.015) compared with non-PLWH. Symptoms at presentation were similar in the two groups apart from headache and myalgia that were more frequent in PLWH (both p<0.001). Among PLWH, nadir CD4 was 80 (33-284) cells/μl, CD4 at COVID19 diagnosis 350 cells/μl (138-515), all of them were on antiretroviral therapy and 94% had HIV-1 RNA < 50 copies/mL. The cumulative probability of invasive ventilation/death at day 14 was 9.1% (95% CI 2.4-31.7) in PLWH versus 14.7% (12.3-17.6) in non-PLWH (p=0.492). The cumulative probability of non-invasive or invasive ventilation/ death at day 14 was 14.3% (4.8-38.0) in PLWH versus 24.4% (21.4-27.8) in non-PLWH (p=0.372). Following adjustment for age, gender, comorbidities, PaO2/FiO2 and pneumonia at admission, adjusted hazard ratio (aHR) of mechanical ventilation/death of PLWH was 0.95 (95% CI 0.13-6.98, p=0.958) versus non-PLWH;similarly, aHR of non-invasive or invasive ventilation/death of PLWH was 1.05 (95% CI 0.26-4.28, p=0.947). The probability of symptoms resolution at day 14 was similar in the two groups (aHR 1.16;0.65-2.09;p=0.614). Conclusion: A less severe presentation and no difference in clinical outcomes with Covid-19 even in the adjusted models were observed in PLWH compared to non-PLWH, but further investigations are warranted due to the small sample size of HIV+ population. (Figure Presented).

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 similar to 2 doses/week) increase in TFV-DP was associated with decreased hip BMD (-0.021 g/cm(2); 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.

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

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.

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.

Antiretroviral therapy (ART) has been effective in increasing the lifespan of people living with HIV (PLWH), resulting in near normal life expectancy among those with early diagnosis and ART initiation compared with the general population (Nakagawa,May,&Phillips, 2013).With an increasingprevalence of older adults living with HIV, there is an increasing prevalence of many comorbid conditions, including some cancers and cardiovascular, renal, neurocognitive, and osteoporotic disease, many of which occur at a higher rate in this population than in populations without HIV (Wing, 2016). Moreover, those aging with HIV often experience loneliness, social isolation, loss of close friends, and may have estranged relationships with their families (Greene et al., 2018). With these more fractured social networks, many PLWHmay not have a clear proxy to guide health care decisions should they be unable to make decisions. The “next of kin” laws assigning health care delegates can vary from state to state if legal documentation is lacking.Completionof an advanceddirective (AD)or assigning a medical power of attorney (MPOA) ensures that the patient’s wishes regarding health care decision makers and decisions can be followedmost closely in the event that the patient cannot communicate (Detering, Hancock, Reade, &Silvester,2010).BothADandMPOAarecomponentsof advanced care planning (ACP) shown to improve health outcomes, including reduction in hospitalization at the end of life, increase in the use of hospice services, and the use of less intensive treatment at the end of life (Bischoff, Sudore, Miao, Boscardin, & Smith, 2013). Avoiding life support, identifying an individual who will make decisions when they can no longer do so, and making choices easier for family members are reasons cited by patients for AD completion (Douglas & Brown, 2002). In a systematic reviewof studieson the effect ofACPonend-of-life care in the general population, AD were linked to better patient and family satisfaction, quality of life, or quality of death and dying (Brinkman-Stoppelenburg, Rietjens, & Van der Heide, 2014). Prior ACP has also been shown to be associated with lower surrogate decisional conflict (Chiarchiaro, Buddadhumaruk, Arnold, &White, 2015). Rates of completed ADorMPOAassignment are low in the general population but tend to be completed well in advance of death. A systematic review of U.S. studies from 2011 to 2016 found that among nearly 800,000 Americans, 37%had a completedADand33%had ahealth care power of attorney. Individuals with HIV had the lowest completion rates, whereas those ages 65 years and older and those in hospice, palliative care, or nursing homes had the highest completion rates (Yadav et al., 2017). Among adults in the Health Styles Survey, 26% of nearly 8,000 individualshadanadvancedirective; older age ($55years), greater education, higher income, andpresence of a chronic disease were associated with AD completion (Rao, Anderson, Lin, & Laux, 2014). Finally, in the Health and Retirement Study, the majority (71%) of ADwere completed ayearormorebeforedeath (Enguidanos&Ailshire, 2017). ADcompleted in the3monthsbefore thedeathhadahigher prevalence of preference for more invasive and intensive care compared with those that were completed prior to the last 3 months of life (Enguidanos & Ailshire, 2017). Sponsorships or competing interests thatmay be relevant to content are disclosed at the end of this article.

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.

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.

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/mu L; 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.

Abstract Background Mortality for people living with HIV (PLWH) has drastically decreased since the mid-1990s, and the proportion of deaths due to non-HIV-related conditions has increased. Methods Deceased PLWH were identified within a single academic medical center. Cause of death was determined by chart review, clinic providers, and when available autopsy and toxicology data. Chart review of comorbidities, demographics and preventable causes of cancer was conducted for deaths during the period of 2013–2017. Results The proportion of AIDS-related deaths decreased markedly between 1995 and 2017, while the proportion of deaths from non-AIDS cancers has increased (figure). Patients with non-AIDS cancers were older, had a higher CD4 count and greater proportion with undetectable viral load, and were more likely to be male; over 80% were current or prior smokers (table). Among all deaths from 2013 to 2017, 44% of eligible patients received colon cancer screening, 66% received cervical cancer screening, and 29% received breast cancer screening. Of patients who died from HCC, one out of six had imaging for HCC within 1 year and none within 6 months of diagnosis. Conclusion Improvements in cancer screening and preventative health measures including smoking cessation and lifestyle improvement education may help to reduce the increasing proportion of non-AIDS cancer-related deaths among PLWH. Characteristics by Cause of Death (2013–2017) HIV-Related Cancer ‡ P-value N 22 24 Age at death 50 (44, 56) 56 (53, 61) 0.03 Last available CD4 72(15, 249) 207(94, 301.5) 0.02 Last available viral load < 50 copies 5 (23) 16 (67) 0.004 CD4 Nadir 18(7, 110) 77(35, 126) 0.2 Male 14 (64) 23 (96) 0.009 Smoking within 1 year of death 9 (41) 13 (54) 0.8 Smoking, quit 1-15 years prior to death 5 (23) 6 (25) Smoking, quit > 15 years prior to death 1 (5) 1 (4) Never smoked 7 (32) 4 (17) *Median (IQR) or n (%). ‡ Most common: HCC (6), head/neck (4), prostate (3). Disclosures All authors: No reported disclosures.

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, multi-center cohort study of HIV-infected men and women ≥40 years. METHODS Frailty assessment included a 4-meter 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-meter 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% pre-frail, and 55% non-frail. Eighteen percent had ≥1 fall, and 7% had recurrent falls. In multivariable models, recurrent falls were more likely among frail (OR = 17.3; 95% CI = 7.03-42.6) and pre-frail (OR = 3.80; 95% CI = 1.87-7.72) than non-frail 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. CONCLUSIONS Aging HIV-infected pre-frail 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.