Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

BACKGROUND: People with HIV (PWH) have lower exercise capacity compared to peers without HIV, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. METHODS: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models. RESULTS: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p = 0.067). AHRR was lower among PWH (91 vs 101%; difference 10%, 95% CI 1.9-18.9; p = 0.02). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p < 0.001) and was sustained at week 24 (+5, 95%CI 1-9; p = 0.008) compared to no change among controls (95%CI -4 to 4; p = 0.95; pinteraction = 0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p = 0.70). CONCLUSIONS: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

Prospective telehealth analysis of functional performance, frailty, quality of life, and mental health after COVID-19 hospitalization.

BACKGROUND: COVID-19 is a global pandemic with poorly understood long-term consequences. Determining the trajectory of recovery following COVID-19 hospitalization is critical for prioritizing care, allocating resources, facilitating prognosis, and informing rehabilitation. The purpose of this study was to prospectively evaluate recovery following COVID-19 hospitalization. METHODS: Participants age 18 years or older who were hospitalized for ≥24 h due to COVID-19 completed phone/video call virtual assessments (including the 10-time chair rise test) and survey forms at three time points (2-6, 12, and 18 weeks) after hospital discharge. Univariate logistic and linear regression models assessed the associations of the outcomes with primary predictors (categorical age, sex, race/ethnicity group, and categorical pre-hospitalization frailty) at baseline; the same were used to assess differences in change from week 2-6 (continuous outcomes) or outcome persistence/worsening (categorical) at last contact. RESULTS: One hundred nine adults (age 53.0 [standard deviation 13.1]; 53% female) participated including 43 (39%) age 60 or greater; 59% identified as an ethnic and/or racial minority. Over 18 weeks, the mean time to complete the 10-time chair rise test decreased (i.e., improved) by 6.0 s (95% CI: 4.1, 7.9 s; p < 0.001); this change did not differ by pre-hospital frailty, race/ethnicity group, or sex, but those age ≥ 60 had greater improvement. At weeks 2-6, 67% of participants reported a worse Clinical Frailty Scale category compared to their pre-hospitalization level, whereas 42% reported a worse frailty score at 18 weeks. Participants who did not return to pre-hospitalization levels were more likely to be female, younger, and report a pre-hospitalization category of 'very fit' or 'well'. CONCLUSIONS: We found that functional performance improved from weeks 2-6 to 18 weeks of follow-up; that incident clinical frailty developed in some individuals following COVID-19; and that age, sex, race/ethnicity, and pre-hospitalization frailty status may impact recovery from COVID-19. Notably, individuals age 60 and older were more likely than those under age 45 years to return to their pre-hospitalization status and to make greater improvements in functional performance. The results of the present study provide insight into the trajectory of recovery among a representative cohort of individuals hospitalized due to COVID-19.

Blunted Muscle Mitochondrial Responses to Exercise Training in Older Adults With HIV.

BACKGROUND: Muscle mitochondrial dysfunction associated with HIV and antiretroviral therapy (ART) may improve with exercise. METHODS: Muscle specimens obtained before and after 24 weeks of exercise in older people with HIV (PWH; n = 18; ART >2 years) and uninfected controls (n = 21) were analyzed for citrate synthase (CS) activity and complexes (C) I-V, manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor-γ coactivator-1 (PGC1α), and voltage-dependent anion channel 1 (VDAC1) content. RESULTS: Only controls had increased CS, MnSOD, PGC1α, and CIV (P ≤ .01; P < .01 vs PWH) after training. CONCLUSIONS: The blunted mitochondrial adaptations to training in PWH suggests the need for different types of exercise-induced stimulation. CLINICAL TRIALS REGISTRATION: NCT02404792.

The Impact of Moderate or High-Intensity Combined Exercise on Systemic Inflammation Among Older Persons With and Without HIV.

BACKGROUND: We investigated whether higher-intensity exercise provided greater decrease in markers of inflammation, and whether responses differed by HIV serostatus. METHODS: People with HIV (PWH; n = 32) and controls (n = 37) aged 50-75 years completed 12 weeks moderate-intensity exercise, then were randomized to moderate- or high-intensity exercise for 12 additional weeks (n = 27 and 29, respectively). Inflammation biomarkers were measured at 0, 12, 24 weeks. Mixed and multiple regression models were adjusted for baseline inflammation, age, and body mass index. RESULTS: Baseline tumor necrosis factor-α (TNF-α), soluble TNF receptor 2 (sTNFR2), and soluble CD14 (sCD14) were significantly higher among PWH than controls (P < .04). From week 0-12, changes in interleukin-6 (IL-6), TNF-α, and sTNFR1 were not significantly different by HIV serostatus. We found no significant interaction between HIV serostatus/exercise intensity on week 12-24 changes in IL-6, TNF-α, and sTNFR1. Among high-intensity exercisers, PWH and controls had significant increases in sCD14 (P ≤ .003), controls significant increases in IL-10 (P = .01), and PWH nonsignificant decrease in highly sensitive C-reactive protein (P = .07). Other markers were not significantly different by serostatus or intensity. CONCLUSIONS: Moderate and high-intensity exercise elicited similar effects on inflammation among PWH and controls, with additional beneficial effects seen among high-intensity exercisers. Increase in sCD14 and attenuated IL-10 increase (PWH only) merit further study. CLINICAL TRIALS REGISTRATION: NCT02404792.

A supervised exercise intervention fails to improve depressive symptoms and quality of life among sedentary older adults with HIV infection.

Older people living with HIV (PLWH) experience multimorbidity that can negatively impact quality of life (QoL). Exercise can improve physical function, but effects on QoL are not well understood. 32 PLWH and 37 controls aged 50-75 completed 12-weeks of moderate-intensity exercise, then were randomized to moderate or high-intensity for 12 additional weeks. Depressive symptoms (CES-D scores) were significantly greater and QOL (SF-36 mental and physical summary scores) significantly lower among PLWH at baseline (all p < 0.05). PLWH had significantly greater worsening in CES-D scores compared to controls (3.4 [0.7, 6.0]; p = 0.01) between 13and 24 weeks. Mental QoL changed minimally, with no significant difference in changes by serostatus between weeks 0 and 12 or weeks 13 and 24 (p ≤ 0.22). Changes in physical function summary scores were similar by serostatus between 0 and 12 weeks (1.5 [-1.6, 4.6], p = 0.35), but declined significantly more among PLWH between 13 and 24 weeks (-4.1 [-7.2,-1], p = 0.01). Exercise intensity had no significant effect on changes in CES-D or SF-36 summary scores; high-intensity exercise was associated with greater improvements in vitality/fatigue (4.1 [0.8, 7.3], p = 0.02), compared to moderate-intensity. Exercise initiation failed to improve depressive symptoms or QoL among PLWH. Additional interventions may be needed to maximize these patient-reported outcomes among older PLWH initiating an exercise program.

Skeletal muscle DNA methylation: Effects of exercise and HIV.

Aging, human immunodeficiency virus (HIV) infection, and antiretroviral therapy modify the epigenetic profile and function of cells and tissues, including skeletal muscle (SkM). In some cells, accelerated epigenetic aging begins very soon after the initial HIV infection, potentially setting the stage for the early onset of frailty. Exercise imparts epigenetic modifications in SkM that may underpin some health benefits, including delayed frailty, in people living with HIV (PWH). In this first report of exercise-related changes in SkM DNA methylation among PWH, we investigated the impact of 24 weeks of aerobic and resistance exercise training on SkM (vastus lateralis) DNA methylation profiles and epigenetic age acceleration (EAA) in older, virally suppressed PWH (n = 12) and uninfected controls (n = 18), and associations of EAA with physical function at baseline. We identified 983 differentially methylated positions (DMPs) in PWH and controls at baseline and 237 DMPs after training. The influence of HIV serostatus on SkM methylation was more pronounced than that of exercise training. There was little overlap in the genes associated with the probes most significantly differentiated by exercise training within each group. Baseline EAA (mean ± SD) was similar between PWH (-0.4 ± 2.5 years) and controls (0.2 ± 2.6 years), and the exercise effect was not significant (p = 0.79). EAA and physical function at baseline were not significantly correlated (all p ≥ 0.10). This preliminary investigation suggests HIV-specific epigenetic adaptations in SkM with exercise training but confirmation in a larger study that includes transcriptomic analysis is warranted.

Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV.

BACKGROUND: Weight gain has been well-described with integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Doravirine (DOR) has been identified as a relatively "weight-neutral" drug; however, there is little data describing its effect on weight change in routine clinical practice. METHODS: We conducted a retrospective chart review of weight change among people with HIV changing from an INSTI- to a non-INSTI regimen with DOR. RESULTS: At the time of ART switch, among 49 people with HIV, the mean age was 47 years, 24% were female, and 75% had HIV-1 viral load <200 copies/mL. Most (55%) people with HIV were taking bictegravir/TAF/emtricitabine prior to the switch. Although 84% switched due to concerns about weight gain, only 16% had a weight gain of ≥10% in the year preceding, and 49% had no substantial change in weight. 86% switched to DOR/lamivudine/tenofovir disoproxil fumarate. A weight decrease (-2.6% [95% CI: -5.1, -0.1%, p = .041] was seen over the year following the ART switch. Weight change prior to switch was greatest in the year 2021 compared to 2019, 2020, and 2022. CONCLUSIONS: Overall, modest changes in weight were seen following ART switch from INSTI-based regimen to a DOR-based, non-INSTI regimen. Further investigations with larger people with HIV cohorts will be helpful to guide clinical practice, while the impact of the COVID-19 pandemic on weight change should also be considered.

Retrospective analysis of the management of pelvic decubitus ulcers and their outcomes.

Background: Many patients with decubitus-related osteomyelitis are ineligible for myocutaneous flapping, and optimal management in this population is unknown. We describe treatments and outcomes of hospitalized patients with decubitus ulcer-related osteomyelitis who did not undergo surgical reconstruction or coverage. Methods: We systematically identified hospitalized patients with diagnoses of pelvic, sacral, or femoral osteomyelitis due to decubitus ulceration between 1 January 2018 and 31 December 2018. Demographics, comorbidities, laboratory data, and outcomes were collected by manual chart review. T-tests or Chi-square tests were used for descriptive statistical comparisons; logistic regressions were used to explore the odds of readmission, osteomyelitis-related readmission, and death. Results: Of 89 patients meeting inclusion criteria, 34 (38%) received surgical debridement and ⩾6 weeks of antibiotics; 55 (62%) received either antibiotics alone or debridement and <6 weeks of antibiotics. Mean age was 55 (standard deviation 18) years, 55% of patients were male, and 69% had spinal cord injury or other form of paralysis. Within 1 year, 56 (63%) patients were readmitted, 38 (44%) patients were readmitted due to complications from osteomyelitis, and 15 (17%) died. We found no significant differences in readmission (OR = 1.33, 95% CI: 0.54-3.21, p = 0.53), readmission related to osteomyelitis (OR = 1.64, 95% CI: 0.69-4.04, p = 0.27), subsequent sepsis (OR = 2.27, 95% CI: 0.83-6.93, p = 0.13), or death (OR = 2.88, 95% CI: 0.83-13.4, p = 0.12) by treatment group. Conclusions: Among patients with decubitus-related osteomyelitis who did not undergo myocutaneous flapping, outcomes were generally poor regardless of treatment, and not significantly improved with prolonged antibiotics. Prospective studies are needed to assess best practice strategies for this challenging patient population.

Impact of Alcohol Misuse on Requirements for Critical Care Services and Development of Hospital Delirium in Patients With COVID-19 pneumonia.

Alcohol misuse has been associated with increased morbidity in the setting of pulmonary infections, including the need for critical care resource utilization and development of delirium. How alcohol misuse impacts morbidity and outcomes among patients admitted with COVID-19 pneumonia is not well described. We sought to determine if alcohol misuse was associated with an increased need for critical care resources and development of delirium among patients hospitalized with COVID-19 pneumonia. DESIGN: Retrospective cohort study. SETTING: Twelve University of Colorado hospitals between March 2020 and April 2021. PATIENTS: Adults with a COVID-19 diagnosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was admission to the ICU. Secondary outcomes included need for mechanical ventilation, development of delirium, and in-hospital mortality. Alcohol misuse was defined by International Classification of Diseases, 10th Revision codes. Of 5,979 patients hospitalized with COVID-19, 26% required ICU admission and 15.4% required mechanical ventilation. Delirium developed in 4.5% and 10.5% died during hospitalization. Alcohol misuse was identified in 4%. In analyses adjusted for age, sex, body mass index, diabetes, and liver disease, alcohol misuse was associated with increased odds of ICU admission (adjusted odds ratio [aOR], 1.46; p < 0.01), mechanical ventilation (aOR, 1.43; p = 0.03), and delirium (aOR, 5.55; p < 0.01) compared with patients without misuse. Mortality rates were not associated with alcohol misuse alone, although the presence of both alcohol misuse and in-hospital delirium significantly increased odds of in-hospital death (aOR, 2.60; p = 0.04). CONCLUSIONS: Among patients hospitalized with COVID-19, alcohol misuse was associated with increased utilization of critical care resources including ICU admission and mechanical ventilation. Delirium was an important modifiable risk factor associated with worse outcomes in hospitalized patients with alcohol misuse, including increased odds of death.

Rehabilitation Therapy Allocation and Changes in Physical Function Among Patients Hospitalized Due to COVID-19: A Retrospective Cohort Analysis.

OBJECTIVE: Limited staffing and initial transmission concerns have limited rehabilitation services during the COVID-19 pandemic. The purpose of this analysis was to determine the associations between Activity Measure for Post-Acute Care (AM-PAC) mobility categories and allocation of rehabilitation, and in-hospital AM-PAC score change and receipt of rehabilitation services for patients with COVID-19. METHODS: This was a retrospective cohort study of electronic health record data from 1 urban hospital, including adults with a COVID-19 diagnosis, admitted August 2020 to April 2021. Patients were stratified by level of medical care (intensive care unit [ICU] and floor). Therapy allocation (referral for rehabilitation, receipt of rehabilitation, and visit frequency) was the primary outcome; change in AM-PAC score was secondary. AM-PAC Basic Mobility categories (None [21-24], Minimum [18-21], Moderate [10-17], and Maximum [6-9]) were the main predictor variable. Primary analysis included logistic and linear regression, adjusted for covariates. RESULTS: A total of 1397 patients (ICU: n = 360; floor: n = 1037) were included. AM-PAC mobility category was associated with therapy allocation outcomes for floor but not patients in the ICU: the Moderate category had greater adjusted odds of referral (adjusted odds ratio [aOR] = 10.88; 95% CI = 5.71-21.91), receipt of at least 1 visit (aOR = 3.45; 95% CI = 1.51-8.55), and visit frequency (percentage mean difference) (aOR = 42.14; 95% CI = 12.45-79.67). The secondary outcome of AM-PAC score improvement was highest for patients in the ICU who were given at least 1 rehabilitation therapy visit (aOR = 5.31; 95% CI = 1.90-15.52). CONCLUSION: AM-PAC mobility categories were associated with rehabilitation allocation outcomes for floor patients. AM-PAC score improvement was highest among patients requiring ICU-level care with at least 1 rehabilitation therapy visit. IMPACT: Use of AM-PAC Basic Mobility categories may help improve decisions for rehabilitation therapy allocation among patients who do not require critical care, particularly during times of limited resources.

Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

Background: People with HIV (PWH) have lower exercise capacity compared to HIV-uninfected peers, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. Methods: The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus, and change from baseline to 12 and 24 weeks using mixed effects models. Results: Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p=0.067). AHRR was lower among PWH (91 vs 102%; difference 11%, 95% CI 2.5-19.7; p=0.01). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p<0.001) and was sustained at week 24 (+5, 95%CI 1-9; p=0.008) compared to no change among controls (95%CI -4 to 4; p=0.95; pinteraction=0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p=0.70). Conclusions: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

Disparities in the allocation of inpatient physical and occupational therapy services for patients with COVID-19.

BACKGROUND: Survivors of the novel coronavirus (COVID-19) experience significant morbidity with reduced physical function and impairments in activities of daily living. The use of in-hospital rehabilitation therapy may reduce long-term impairments. OBJECTIVE: To determine the frequency of therapy referral and treatment amongst hospitalized COVID-19 patients, assess for disparities in referral and receipt of therapy, and identify potentially modifiable factors contributing to disparities in therapy allocation. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study using data collected from the University of Colorado Health Data Compass data warehouse assessing therapy referral rates and estimated delivery based on available administrative billing. MEASUREMENTS: Multivariable logistic regression was used to determine the association between sex and/or underrepresented minority race with therapy referral or delivery. RESULTS: Amongst 6239 COVID-19-related hospitalization, a therapy referral was present in 3952 patients (51.9%). Hispanic ethnicity was independently associated with lower odds of receipt of therapy referral (adjusted OR [aOR]: 0.78, 95% confidence interval [CI]: 0.67-0.93, p = .001). Advanced age (aOR: 1.53, 95% CI: 1.46-1.62, p < .001), greater COVID illness severity (aOR for intensive care unit admission: 1.63, 95% CI: 1.37-1.94, p < .01) and hospital stay (aOR: 1.14, 95% CI: 1.12-1.15, p < .01) were positively associated with referral. CONCLUSIONS AND RELEVANCE: In a cohort of patients hospitalized for COVID-19 across a multicenter healthcare system, we found that referral rates and delivery of physical therapy and/or occupational therapy sessions were significantly reduced for patients of Hispanic identity compared with patients of non-Hispanic, Caucasian identity after adjustment for potential confounding by available demographic and illness severity variables.

Developing and Deploying a Scalable Computing Platform to Support MOOC Education in Clinical Data Science.

One of the challenges of teaching applied data science courses is managing individual students' local computing environment. This is especially challenging when teaching massively open online courses (MOOCs) where students come from across the globe and have a variety of access to and types of computing systems. There are additional challenges with using sensitive health information for clinical data science education. Here we describe the development and performance of a computing platform developed to support a series of MOOCs in clinical data science. This platform was designed to restrict and log all access to health datasets while also being scalable, accessible, secure, privacy preserving, and easy to access. Over the 19 months the platform has been live it has supported the computation of more than 2300 students from 101 countries.

Assessing the utility and accuracy of ICD10-CM non-traumatic subarachnoid hemorrhage codes for intracranial aneurysm research.

BACKGROUND: The 10th revision of International Classification of Disease, Clinical Modification (ICD10-CM) increased the number of codes to identify non-traumatic subarachnoid hemorrhage from 1 to 22. ICD10-CM codes are able to specify the location of aneurysms causing subarachnoid hemorrhage (aSAH); however, it is not clear how frequently or accurately these codes are being used in practice. OBJECTIVE: To systematically evaluate the usage and accuracy of location-specific ICD10-CM codes for aSAH. METHODS: We extracted all uses of ICD10-CM codes for non-traumatic subarachnoid hemorrhage (I60.x) during the first 3 years following the implementation of ICD10-CM from the billing module of the electronic health record (EHR) for UCHealth. For those codes that specified aSAH location (I60.0-I60.6), EHR documentation was reviewed to determine whether there was an active aSAH, any patient history of aSAH, or unruptured intracranial aneurysm/s and the locations of those outcomes. RESULTS: Between 1 October 2015 and 30 September 2018, there were 3119 instances of non-traumatic subarachnoid hemorrhage ICD10-CM codes (I60.00-I60.9), of which 297 (9.5%) code instances identified aSAH location (I60.0-I60.6). The usage of location-specific codes increased from 5.7% in 2015 to 11.2% in 2018. These codes accurately identified current aSAH (64%), any patient history of aSAH (84%), and any patient history of intracranial aneurysm (87%). The accuracy of identified outcome location was 53% in current aSAH, 72% for any history of aSAH, and 76% for any history of an intracranial aneurysm. CONCLUSIONS: Researchers should use ICD10-CM codes with caution when attempting to detect active aSAH and/or aneurysm location.

Elevated glycohemoglobin is linked to critical illness in CoVID-19: a retrospective analysis.

BACKGROUND: Several studies have explored hospitalization risk factors with the novel coronavirus disease 2019 (COVID-19) infection. Our goal was to identify clinical characteristics outside of laboratory or radiologic data associated with intubation or death within 7 days of admission. METHODS: The first 436 patients admitted to the University of Colorado Hospital (Denver metropolitan area) with confirmed COVID-19 were included. Demographics, comorbidities, and select medications were collected by chart abstraction. Missing height for calculating body mass index (BMI) was imputed using the median height for patients' sex and race/ethnicity. Adjusted odds ratios (aOR) were estimated using multivariable logistic regression and a minimax concave penalty (MCP) regularized logistic regression explored prediction. RESULTS: Participants had a mean [standard deviation (SD)] age 55 (17), BMI 30.9 (8.2), 55% were male and 80% were ethnic/racial minorities. Increasing age [aOR: 1.24 (1.07, 1.45) per 10 years], higher BMI (aOR 1.03 (1.00, 1.06), and poorly controlled diabetes [hemoglobin A1C (HbA1c) ⩾ 8] (aOR 2.26 (1.24, 4.12) were significantly (p < 0.05) associated with greater odds of intubation or death. Female sex [aOR: 0.63, 95% CI (0.40, 0.98); p value = 0.043] was associated with lesser odds of intubation or death. The odds of death and/or intubation increased 19% for every 1 unit increase in HbA1c value [OR: 1.19 (1.01, 1.43); p = 0.04]. Our final MCP model included indicators of A1C ⩾ 8, age > 65, sex, and minority status, but predicted intubation/death only slightly better than random chance [area under the receiver operating characteristic curve (AUC) = 0.61 (0.56, 0.67)]. CONCLUSION: In a hospitalized patient cohort with COVID-19, worsening control of diabetes as evidenced by higher HbA1c was associated with increased risk of intubation or death within 7 days of admission. These results complement and help clarify previous associations found between diabetes and acute disease in COVID-19. Importantly, our analysis is missing some known predictors of severity in COVID-19. Our predictive model had limited success, suggesting unmeasured factors contribute to disease severity differences.

Predicting prognosis in COVID-19 patients using machine learning and readily available clinical data.

RATIONALE: Prognostic tools for aiding in the treatment of hospitalized COVID-19 patients could help improve outcome by identifying patients at higher or lower risk of severe disease. The study objective was to develop models to stratify patients by risk of severe outcomes during COVID-19 hospitalization using readily available information at hospital admission. METHODS: Hierarchical ensemble classification models were trained on a set of 229 patients hospitalized with COVID-19 to predict severe outcomes, including ICU admission, development of acute respiratory distress syndrome, or intubation, using easily attainable attributes including basic patient characteristics, vital signs at admission, and basic lab results collected at time of presentation. Each test stratifies patients into groups of increasing risk. An additional cohort of 330 patients was used for blinded, independent validation. Shapley value analysis evaluated which attributes contributed most to the models' predictions of risk. MAIN RESULTS: Test performance was assessed using precision (positive predictive value) and recall (sensitivity) of the final risk groups. All test cut-offs were fixed prior to blinded validation. In development and validation, the tests achieved precision in the lowest risk groups near or above 0.9. The proportion of patients with severe outcomes significantly increased across increasing risk groups. While the importance of attributes varied by test and patient, C-reactive protein, lactate dehydrogenase, and D-dimer were often found to be important in the assignment of risk. CONCLUSIONS: Risk of severe outcomes for patients hospitalized with COVID-19 infection can be assessed using machine learning-based models based on attributes routinely collected at hospital admission.

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.

A supervised exercise intervention fails to improve subjective and objective sleep measures among older adults with and without HIV.

BACKGROUND: Chronic sleep disruption can have significant negative health effects and prior studies suggest that people with HIV (PWH) have disproportionately higher rates of sleep problems. METHODS: We evaluated baseline sleep of sedentary, older adults (50-75 years) with (n = 28) and without HIV (n = 29) recruited into a 24-week exercise study. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI); objective sleep parameters were assessed using wrist-worn actigraphy. Regression models were used to investigate changes in outcomes. RESULTS: Fifty-seven participants completed the intervention. At baseline, PWH had significantly lower sleep efficiency (88.7 [95% CI 86, 91]%) compared to controls (91.8 [95% CI 91, 93]%; p = 0.02); other sleep measures indicated poorer sleep among PWH but did not reach statistical significance (p ≥ 0.12). Overall, sleep outcomes did not significantly change with the exercise intervention (all p > 0.05). In adjusted analyses, PWH demonstrated a decrease in total sleep time (-22.1 [-43.7, -0.05] p = 0.045) and sleep efficiency (-1.3 [-2.5, -.01], p = 0.03) during the 24 weeks of exercise; these differences were attenuated and no longer significant after adjusting for exercise intensity. At the completion of the intervention, compared to controls, PWH had significantly poorer sleep by PSQI score (2.2 [0.6, 3.8]; p = 0.006) and sleep efficiency (-2.8 [-5.4,-0.2]%; p = 0.04). CONCLUSIONS: In this study, sleep disturbance was more prevalent in sedentary older PWH compared to uninfected controls. An exercise intervention had minimal effect on sleep impairments among PWH nor controls. Among older adults, interventions beyond cardiovascular and resistance exercise may be needed to significantly alter subjective and objective sleep outcomes.

Body Composition Changes in Response to Moderate- or High-Intensity Exercise Among Older Adults With or Without HIV Infection.

BACKGROUND: People with HIV (PWH) are at an increased risk for adiposity and sarcopenia, despite effective antiretroviral therapy. Our objective was to compare the effects of prescribed exercise on body composition in older PWH and uninfected controls. SETTING: Academic medical center. METHODS: Sedentary PWH (n = 27) and uninfected controls (n = 28) aged 50-75 years completed 24 weeks of cardiovascular and resistance exercise. Participants completed 12 weeks of moderate-intensity exercise and then were randomized to moderate- or high-intensity exercise for 12 additional weeks. Total lean (LEAN) and fat mass (FAT), and visceral adipose tissue area (VAT) were measured using dual-energy x-ray absorptiometry at baseline and 24 weeks; baseline and intervention differences were compared by HIV serostatus using multivariable regression analyses adjusted for baseline values, age, and exercise adherence. RESULTS: At baseline, PWH had significantly lower FAT (P = 0.003), but no significant differences in LEAN or VAT compared with controls (P > 0.20). Changes over 24 weeks were not significantly different by HIV serostatus, although controls tended to gain more LEAN (0.8 kg; range, 0-1.6 kg; P = 0.04] than PWH (0.6 kg; range, -0.2 to 1.4 kg; P = 0.12) and lose less FAT and VAT (controls: (-0.9 kg; range, -1.8 to 0.0 kg and -10.3 cm; range, -19.6, 1.0) cm; both P = 0.03 vs PWH: -2.0 kg; range, -2.9 to -1.1 kg and -17.7 cm; range, -27.1 to -8.2 cm; both P < 0.001). Exercise intensity differences were not apparent for LEAN, FAT, or VAT. CONCLUSIONS: Exercise reduced total and visceral fat in older PWH and controls. Minimal gains in lean mass suggest that greater emphasis on resistance exercise may be needed to more effectively increase muscle in PWH.