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Background: Concerns about serious adverse gastrointestinal (GI) events with sodium polystyrene sulfonate (SPS) led to development of two new potassium binders, patiromer and sodium zirconium cyclosilicate (SZC), for treatment of hyperkalemia., Objective: To compare risk of intestinal ischemia/thrombosis or other serious GI events associated with SPS, patiromer, or SZC in hospitalized patients., Design: Retrospective cohort study., Participants: National sample of 3,144,960 veterans hospitalized 2016-2022 in the U.S. Department of Veterans Affairs Healthcare System., Main Measures: Demographics, comorbidities, medications and outcomes were ascertained from the VA Corporate Data Warehouse. Exposures were SPS, patiromer, SZC. Outcomes were 30-day intestinal ischemia/thrombosis, and a composite of intestinal ischemia/thrombosis, peptic ulcer/perforation or bowel resection/ostomy., Key Results: Potassium binders were used during 39,270 (1.3%) hospitalizations: SPS = 30,040 (1.0%), patiromer = 3,750 (0.1%), and SZC = 5,520 (0.2%). Intestinal ischemia/thrombosis occurred with 106/30,040 (0.4%) SPS, 12/3750 (0.3%) patiromer and 24/5520 (0.4%) SZC, vs. 6998/3,105,650 (0.2%) without potassium binder. Adjusted odds ratios (aOR) were 1.40 [95% CI, 1.16 to 1.69] with SPS, 1.36 [CI, 0.79 to 2.36] with patiromer, and 1.78 [CI, 1.21 to 2.63] with SZC exposures. Composite GI adverse events occurred with 754/30,040 (2.5%) SPS, 96/3750 (2.6%) patiromer, 2.6% SZC, vs. 144/5520 (2.4%) without binder; aOR were 1.00 [CI, 0.94 to 1.08] with SPS, 1.08 [CI, 0.89 to 1.32] with patiromer, and 1.08 [CI, 0.93 to 1.27] with SZC exposures. No statistical difference in intestinal ischemia/thrombosis between each new agent and SPS was seen (p = 0.274 for SPS vs. SZC; p = 0.916 for SPS vs. patiromer)., Conclusion: Risk of intestinal ischemia/thrombosis or other serious adverse GI events was low and did not differ across three potassium-binding drugs., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Intensive care unit (ICU) admissions are often accompanied by many physical and existential pressure points that can be extraordinarily wearing on patients and their families and surrogate decision makers (SDMs). Multidisciplinary palliative support, including physicians, advanced practice nurses, nutritionists, chaplains and other team members, may alleviate many of these sources of potential suffering. However, the palliative needs of ICU patients undoubtedly exceed the bandwidth of current consultative specialty palliative medicine teams. Informed by standard-of-care palliative medicine domains, we review common ICU symptoms (pain, dyspnea and thirst) and their prevalence, sources and their treatment. We then identify palliative needs and impacts in the domains of communication, SDM support and transitions of care for patients and their families through their journey in the ICU, from discharge and recovery at home to chronic critical illness, post-ICU disability or death. Finally, we examine the evidence for strategies to incorporate specialty palliative medicine and palliative principles into ICU care for the improvement of patient- and family-centered care. While randomized controlled studies have failed to demonstrate measurable improvement in pre-determined outcomes for patient- and family-relevant outcomes, embracing the principles of palliative medicine and assuring their delivery in the ICU is likely to translate to overall improvement in humanistic, person-centered care that supports patients and their SDMs during and following critical illness., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: Clinical practice guidelines recommend palliative care for people with advanced heart failure (aHF), yet it remains underutilized., Objectives: We examined medical center variation in specialist palliative care (SPC) and identified factors associated with variation among people with aHF., Methods: We conducted a retrospective cohort study of 21,654 people with aHF who received healthcare in 83 Veterans Affairs Medical Centers (VAMCs) from 2018-2020. We defined aHF with ICD-9/10 codes and hospitalizations. We used random intercept multilevel logistic regression to derive SPC reach (i.e., predicted probability) for each VAMC adjusting for demographic and clinical characteristics. We then examined VAMC-level SPC delivery characteristics associated with predicted SPC reach including the availability of outpatient SPC (proportion of outpatient consultations), cardiology involvement (number of outpatient cardiology-initiated referrals), and earlier SPC (days from aHF identification to consultation)., Results: Of the sample the mean age = 72.9+/-10.9 years, 97.9% were male, 61.6% were White, and 32.2% were Black. The predicted SPC reach varied substantially across VAMCs from 9% to 57% (mean: 28% [95% Confidence Interval: 25%-30%]). Only the availability of outpatient SPC was independently associated with higher SPC reach. VAMCs, in which outpatient delivery made up the greatest share of SPC consultations (9% or higher) had 11% higher rates of SPC reach relative to VAMCs with a lower proportion of outpatient SPC., Conclusion: SPC reach varies widely across VAMCs for people with aHF. Outpatient palliative is common among high-reach VAMCs but its role in reach warrants further investigation. Strategies used by high-reach VAMCs may be potential targets to test for implementation and dissemination., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Importance: Despite the frequency of total knee arthroplasty (TKA) and clinical implications of prosthetic joint infections (PJIs), knowledge gaps remain concerning the incidence, microbiological study results, and factors associated with these infections., Objectives: To identify the incidence rates, organisms isolated from microbiological studies, and patient and surgical factors of PJI occurring early, delayed, and late after primary TKA., Design, Setting, and Participants: This cohort study obtained data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse on patients who underwent elective primary TKA in the VA system between October 1, 1999, and September 30, 2019, and had at least 1 year of care in the VA prior to TKA. Patients who met these criteria were included in the overall cohort, and patients with linked Veterans Affairs Surgical Quality Improvement Program (VASQIP) data composed the VASQIP cohort. Data were analyzed between December 9, 2021, and September 18, 2023., Exposures: Primary TKA as well as demographic, clinical, and perioperative factors., Main Outcomes and Measures: Incident hospitalization with early, delayed, or late PJI. Incidence rate (events per 10 000 person-months) was measured in 3 postoperative periods: early (≤3 months), delayed (between >3 and ≤12 months), and late (>12 months). Unadjusted Poisson regression was used to estimate incidence rate ratios (IRRs) with 95% CIs of early and delayed PJI compared with late PJI. The frequency of organisms isolated from synovial or operative tissue culture results of PJIs during each postoperative period was identified. A piecewise exponential parametric survival model was used to estimate IRRs with 95% CIs associated with demographic and clinical factors in each postoperative period., Results: The 79 367 patients (median (IQR) age of 65 (60-71) years) in the overall cohort who underwent primary TKA included 75 274 males (94.8%). A total of 1599 PJIs (2.0%) were identified. The incidence rate of PJI was higher in the early (26.8 [95% CI, 24.8-29.0] events per 10 000 person-months; IRR, 20.7 [95% CI, 18.5-23.1]) and delayed periods (5.4 [95% CI, 4.9-6.0] events per 10 000 person-months; IRR, 4.2 [95% CI, 3.7-4.8]) vs the late postoperative period (1.3 events per 10 000 person-months). Staphylococcus aureus was the most common organism isolated overall (489 [33.2%]); however, gram-negative infections were isolated in 15.4% (86) of early PJIs. In multivariable analyses, hepatitis C virus infection, peripheral artery disease, and autoimmune inflammatory arthritis were associated with PJI across all postoperative periods. Diabetes, chronic kidney disease, and obesity (body mass index of ≥30) were not associated factors. Other period-specific factors were identified., Conclusions and Relevance: This cohort study found that incidence rates of PJIs were higher in the early and delayed vs late post-TKA period; there were differences in microbiological cultures and factors associated with each postoperative period. These findings have implications for postoperative antibiotic use, stratification of PJI risk according to postoperative time, and PJI risk factor modification.

Background: The measurement of specialist palliative care (SPC) across Department of Veterans Affairs (VA) facilities relies on algorithms applied to administrative databases. However, the validity of these algorithms has not been systematically assessed., Measures: In a cohort of people with heart failure identified by ICD 9/10 codes, we validated the performance of algorithms to identify SPC consultation in administrative data and differentiate outpatient from inpatient encounters., Intervention: We derived separate samples of people by receipt of SPC using combinations of stop codes signifying specific clinics, current procedural terminology (CPT), a variable representing encounter location, and ICD-9/ICD-10 codes for SPC. We calculated sensitivity, specificity, and positive and negative predictive values (PPV, NPV) for each algorithm using chart review as the reference standard., Outcomes: Among 200 people who did and did not receive SPC (mean age = 73.9 years (standard deviation [SD] = 11.5), 98% male, 73% White), the validity of the stop code plus CPT algorithm to identify any SPC consultation was: Sensitivity = 0.89 (95% Confidence Interval [CI] 0.82-0.94), Specificity = 1.0 [0.96-1.0], PPV = 1.0 [0.96-1.0], NPV = 0.93 [0.86-0.97]. The addition of ICD codes increased sensitivity but decreased specificity. Among 200 people who received SPC (mean age = 74.2 years [SD = 11.8], 99% male, 71% White), algorithm performance in differentiating outpatient from inpatient encounters was: Sensitivity = 0.95 (0.88-0.99), Specificity = 0.81 (0.72-0.87), PPV = 0.38 (0.29-0.49), and NPV = 0.99 (0.95-1.0). Adding encounter location improved the sensitivity and specificity of this algorithm., Conclusions: VA algorithms are highly sensitive and specific in identifying SPC and in differentiating outpatient from inpatient encounters. These algorithms can be used with confidence to measure SPC in quality improvement and research across the VA., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Background: Heart failure (HF) is common among people aging with HIV (PWH) and without HIV (PWoH). Despite the poor prognosis for HF, advance directives (AD) completion is low but has not been compared among PWH and PWoH., Objectives: Determine the prevalence and predictors of AD screening among PWH and PWoH with incident HF., Methods: We included Veterans with an incident HF diagnosis code from 2013-2018 in the Veterans Aging Cohort Study (VACS) without prior AD screening. Health records were reviewed for AD screening note titles within -30 days to 1-year post-HF diagnosis. Analyses were stratified by HIV status. Trends in annual AD screening were evaluated with the Cochran-Mantel-Haenszel test. The associations of AD screening with demographics, disease severity (Charlson Comorbidity Index, VACS 2.0 Index), and healthcare encounters (cardiology, palliative care, hospitalization) were evaluated with Cox proportional hazards regression., Results: HF was diagnosed in 4516 Veterans (28.2% PWH, 71.8% PWoH). Annual AD screening rates increased in both groups (P trend <0.0001) and aggregate rates were higher among PWH than PWoH (53.5% vs. 48.2%, p=.001). In both groups, the likelihood of AD screening increased with greater disease severity, palliative care contact, and hospitalization (HR range=1.04-3.32, all p≤.02) but not with cardiology contact (p≥.53)., Conclusions: AD screening rates after incident HF remain suboptimal but increased over time and were higher in PWH. Future quality improvement and implementation efforts should aim for universal AD screening with incident HF diagnosis, initiated by providers skilled in discussing AD, including in the cardiology subspecialty setting., Competing Interests: Declaration of Competing Interest All authors report no conflicts of interest., (Published by Elsevier Inc.)

Chronic obstructive pulmonary disease (COPD) is one of the most common comorbid diseases among aging people with HIV (PWH) and is often mismanaged. To address this gap, we are conducting the study, "Advancing care for COPD in people living with HIV by Implementing Evidence-based management through proactive E-consults (ACHIEVE)." This intervention optimizes COPD management by promoting effective, evidence-based care and de-implementing inappropriate therapies for COPD in PWH receiving care at Veteran Affairs (VA) medical centers. Study pulmonologists are proactively supporting ID providers managing a population of PWH who have COPD, offering real-time evidence-based recommendations tailored to each patient. We are leveraging VA clinical and informatics infrastructures to communicate recommendations between the study team and clinical providers through the electronic health record (EHR) as an E-consult. If effective, ACHIEVE could serve as a model of effective, efficient COPD management among PWH receiving care in VA. This paper outlines the rationale and methodology of the ACHIEVE trial, one of a series of studies funded by the National Heart, Lung, and Blood Institute (NHLBI) within the ImPlementation REsearCh to DEvelop Interventions for People Living with HIV (PRECluDE) consortium to study chronic disease comorbidities in HIV populations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: People aging with and without HIV (PWH and PWoH) want to avoid neurocognitive dysfunction, especially delirium. Continued use of alcohol in conjunction with neurocognitively active medications (NCAMs) may be a largely underappreciated cause, especially for PWH who experience polypharmacy a decade earlier than PWoH. We compare absolute and relative risk of delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs., Methods: Using the VACS cohort, we compare absolute and relative risk of inpatient delirium among PWH and PWoH by age, level of alcohol use, and exposure to NCAMs between 2007 and 2019. We matched each case based on age, race/ethnicity, sex, HIV, baseline year, and observation time with up to 5 controls. The case/control date was defined as date of admission for cases and the date corresponding to the same length of time on study for controls. Level of alcohol use was defined using Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Medication exposure was measured from 45 to 3 days prior to index date; medications were classified as anticholinergic NCAM, non-anticholinergic NCAM, or non NCAM and counts generated. We used logistic regression to determine odds ratios (ORs) for delirium associated with medication counts stratified by HIV status and adjusted for demographics, severity of illness, and related diagnoses., Results: PWH experienced a higher incidence of delirium (5.6, [95% CI 5.3-5.9/1000 PY]) than PWoH (5.0, [95% CI 4.8-5.1/1000 PY]). In multivariable analysis, anticholinergic and non-anticholinergic NCAM counts and level of alcohol use demonstrated strong independent dose-response associations with delirium., Conclusions: Decreasing alcohol use and limiting the use of neurocognitively active medications may help decrease excess rates of delirium, especially among PWH., (© 2023 The American Geriatrics Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Persons living with human immunodeficiency virus (HIV) (PWH) on antiretroviral therapy (ART) are frequently admitted to the intensive care unit (ICU). Persons living with HIV on ART may be at higher risk for potential drug-drug interactions (pDDIs) due to polypharmacy in the ICU. We determined the prevalence of pDDI with ART in critically ill PWH. Objectives: The primary outcome was prevalence of pDDI between ART and ICU medications. Secondary outcomes included pDDI per ICU admission, pDDI severity, ICU, and hospital length of stay (LOS). Methods: A single-center, retrospective cohort evaluating PWH ≥ 18 years old admitted to the ICU for > 24 hours who received ART during ICU admission, between January 2013 and 2015 at a tertiary care hospital in the United States. Each ICU admission was counted as a separate encounter. Medication databases and chart review were used to identify pDDI. Results: We included 77 PWH encounters; mean age was 55 ± 9 years and 65% were male. We identified 208 pDDIs among 53/77 (68.8%), with a mean 4 ± 2 pDDI per ICU admission. Antipsychotics (20%), analgesics (20%), and anti-lipemics (11%) were the most common ICU medications with ART-related pDDI. Of the pDDI, 64% were major, 24% moderate, and 12% contraindicated. Median ICU and hospital LOS were 4 days (IQR: 3-5) and 11 days (IQR: 7-31), respectively. Conclusion: Most PWH had at least one pDDI during ICU admission. Collaborations among pharmacists, intensivists, and infectious disease/HIV specialists to develop effective, actionable strategies, such as electronic health record alerts, could reduce pDDIs for PWH on ART in the ICU.

Background: Race, ethnicity, and rurality-related disparities in coronavirus disease 2019 (COVID-19) vaccine uptake have been documented in the United States (US)., Objective: We determined whether these disparities existed among patients at the Department of Veterans Affairs (VA), the largest healthcare system in the US., Design Settings Participants Measurements: Using VA Corporate Data Warehouse data, we included 5,871,438 patients (9.4% women) with at least one primary care visit in 2019 in a retrospective cohort study. Each patient was assigned a single race/ethnicity, which were mutually exclusive, self-reported categories. Rurality was based on 2019 home address at the zip code level. Our primary outcome was time-to-first COVID-19 vaccination between December 15, 2020-June 15, 2021. Additional covariates included age (in years), sex, geographic region (North Atlantic, Midwest, Southeast, Pacific, Continental), smoking status (current, former, never), Charlson Comorbidity Index (based on ≥1 inpatient or two outpatient ICD codes), service connection (any/none, using standardized VA-cutoffs for disability compensation), and influenza vaccination in 2019-2020 (yes/no)., Results: Compared with unvaccinated patients, those vaccinated (n=3,238,532; 55.2%) were older (mean age in years vaccinated=66.3, (standard deviation=14.4) vs. unvaccinated=57.7, (18.0), p<.0001)). They were more likely to identify as Black (18.2% vs. 16.1%, p<.0001), Hispanic (7.0% vs. 6.6% p<.0001), or Asian American/Pacific Islander (AA/PI) (2.0% vs. 1.7%, P<.0001). In addition, they were more likely to reside in urban settings (68.0% vs. 62.8, p<.0001). Relative to non-Hispanic White urban Veterans, the reference group for race/ethnicity-urban/rural hazard ratios reported, all urban race/ethnicity groups were associated with increased likelihood for vaccination except American Indian/Alaskan Native (AI/AN) groups. Urban Black groups were 12% more likely (Hazard Ratio (HR)=1.12 [CI 1.12-1.13]) and rural Black groups were 6% more likely to receive a first vaccination (HR=1.06 [1.05-1.06]) relative to white urban groups. Urban Hispanic, AA/PI and Mixed groups were more likely to receive vaccination while rural members of these groups were less likely (Hispanic: Urban HR=1.17 [1.16-1.18], Rural HR=0.98 [0.97-0.99]; AA/PI: Urban HR=1.22 [1.21-1.23], Rural HR=0.86 [0.84-0.88]). Rural White Veterans were 21% less likely to receive an initial vaccine compared with urban White Veterans (HR=0.79 [0.78-0.79]). AI/AN groups were less likely to receive vaccination regardless of rurality: Urban HR=0.93 [0.91-0.95]; AI/AN-Rural HR=0.76 [0.74-0.78]., Conclusions: Urban Black, Hispanic, and AA/PI Veterans were more likely than their urban White counterparts to receive a first vaccination; all rural race/ethnicity groups except Black patients had lower likelihood for vaccination compared with urban White patients. A better understanding of disparities and rural outreach will inform equitable vaccine distribution.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends at least annual spirometry for patients with chronic obstructive pulmonary disease (COPD). Since spirometry acquisition is variable in clinical practice, identifying characteristics associated with annual spirometry may inform strategies to improve care for patients with COPD., Methods: We included veterans hospitalized for COPD at Veterans Health Administration (VHA) facilities from 10/2012 to 09/2015. Our primary outcome was spirometry within 1 year of COPD hospitalization. Patient demographics, health factors, and comorbidities as well as practice and geographic variables were identified using Corporate Data Warehouse; provider characteristics were obtained from the Survey of Healthcare Experiences of Patients. We used logistic regression with a random intercept to account for potential clustering within facilities., Results: Spirometry was completed 1 year before or after hospitalization for 20,683/38,148 (54.2%) veterans across 114 facilities. Patients with spirometry were younger, (mean=67.2 years (standard deviation (SD)=9.3) vs. 69.4 (10.3)), more likely non-white (21.3% vs. 19.7%), and more likely to have comorbidities (p<0.0001 for asthma, depression, and post-traumatic stress disorder). Pulmonary clinic visit was most strongly associated with spirometry (odds ratio (OR)=3.14 [95% confidence interval 2.99-3.30]). There was no association for facility complexity. In a secondary analysis including provider-level data (3862 patients), results were largely unchanged. There was no association between primary care provider age, gender, or type (physician vs. advanced practice registered nurse vs. physician assistant) and spirometry., Conclusion: In a cohort of high-risk COPD patients, just over half completed spirometry within 1 year of hospitalization. Pulmonary clinic visit was most strongly associated with 1-year spirometry, though provider variables were not. Spirometry completion for high-risk COPD patients remains suboptimal and strategies to improve post-hospitalization care for patients not seen in pulmonary clinic should be developed to ensure guideline concordant care., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Context: Consequent to increasing COVID-19 infection rates, the Palliative Care (PC) service at a large New England hospital shifted from in-person to telehealth-delivered PC (TPC)., Objectives: We compared the quality of TPC to in-person PC during the early COVID-19 pandemic., Methods: We conducted an electronic health record review of PC consultations of patients hospitalized during three periods: pre-COVID January, 2020-February, 2020 (in-person); peak-COVID March, 2020-June, 2020 (majority TPC); and post-peak September, 2020-October, 2020 (majority in-person). We examined the relationship between these periods and PC delivery characteristics and quality measures using descriptive and bivariate statistics., Results: Of 377 patients, 50 were pre-COVID (TPC=0%), 271 peak-COVID (TPC=79.3%), and 56 post-peak (TPC<2%) (representation of PC consult: pre- and post-peak=samples; peak-COVID=all consults). Mean age was 69.3 years (standard deviation=15.5), with 54.9% male, 68.7% White, and 22.8% Black. Age and sex did not differ by period. PC consultations were more likely for goals of care (pre=30.0% vs. peak=53.9% vs. post=57.1%; P = 0.005) or hospice (4.0% vs. 14.4% vs. 5.4%, P = 0.031) during peak-COVID compared to pre-COVID. Rates of assessment of physical (98.0% vs. 63.5% vs. 94.6%, P < 0.001) and psychological symptoms (90.0% vs. 33.1% vs. 67.9%, P < 0.001) were lower during peak relative to pre-COVID and post-peak periods. There were no differences in assessment of patients' social needs, family burden, or goals of care across periods., Conclusion: The PC service provided high-quality inpatient PC using TPC despite significant strain during the early COVID-19 pandemic. Developing and testing strategies to promote comprehensive symptom control using TPC remains a priority to adjust to potential unmet PC needs., (Published by Elsevier Inc.)

Background: Clinical practice guidelines recommend integrating palliative care (PC) into the care of patients with heart failure (HF) to address their many palliative needs. However, the incidence rates of PC use among HF subtypes are unknown. Methods: We conducted a retrospective cohort study of patients with the following HF subtypes in the Department of Veterans Affairs: reduced ejection fraction (HFrEF), mid-range ejection fraction (HFmEF), and preserved ejection fraction (HFpEF). Patients were included at the time of HF diagnosis from 2011 to 2015 and followed until a minimum of five years or death. Incidence rates of receipt of PC (primary outcome) were calculated using generalized estimating equations. We evaluated the time to incident PC by HF subtype with Kaplan-Meier analyses and with adjusted restricted mean survival time. Results: Of the 113,555 patients, 69% were ≥65 years, 98% were male, 73% White, and 18% Black; 58% had HFrEF, 7% HFmEF, and 34% HFpEF. Twenty percent received PC during follow-up, and 66% died. Adjusted PC incidence rates were higher among patients with HFrEF (47 per 1000 person-years, confidence interval [95% CI] 43-52) than for HFmEF and HFpEF (42 per 1000 person-years, CI 38-47 for both). Restricting follow-up to five years, patients with HFrEF received PC six weeks earlier than patients with HFpEF. There was no significant difference in time to PC between patients with HFmEF versus HFpEF. Conclusion: About 1 in 20 patients with HFrEF and 1 in 25 patients with HFmEF and HFpEF receive PC annually. Patients with HFrEF receive PC sooner than patients with HFmEF and HFpEF.

Objective: Medical intensive care unit (MICU) admissions have been declining in people with HIV infection (PWH), but frequency of outpatient polypharmacy (prescription of ≥5 chronic medications) has increased. Among those hospitalized, we examined whether outpatient polypharmacy is associated with subsequent 1-year MICU admission or 10-year all-cause mortality, and if the association varies by HIV status., Design: Retrospective cohort study., Methods: Using a national electronic health record cohort of Veterans in care, we ascertained outpatient polypharmacy during fiscal year (FY) 2009 and followed patients for 1-year MICU admission and 10-year mortality. We assessed associations of any polypharmacy (yes/no and categorized ≤4, 5-7, 8-9, and ≥10 medications) with 1-year MICU admission and 10-year mortality using logistic and Cox regressions, respectively, adjusted for demographics, HIV status, substance use, and severity of illness., Results: Among 9898 patients (1811 PWH) hospitalized in FY2010, prior outpatient polypharmacy was common (51%). Within 1 year, 1532 (15%) had a MICU admission and within 10 years, 4585 (46%) died. Polypharmacy was associated with increased odds of 1-year MICU admission, in both unadjusted (odds ratio (OR) 1.36 95% CI: (1.22, 1.52)) and adjusted models, aOR (95% CI) = 1.28 (1.14, 1.43) and with 10-year mortality in unadjusted, hazard ratio (HR) (95% CI) = 1.40 (1.32, 1.48), and adjusted models, HR (95% CI) = 1.26 (1.19, 1.34). Increasing levels of polypharmacy demonstrated a dose-response with both outcomes and by HIV status, with a stronger association among PWH., Conclusions: Among hospitalized patients, prior outpatient polypharmacy was associated with 1-year MICU admission and 10-year all-cause mortality after adjusting for severity of illness in PWH and PWoH., Competing Interests: The authors have declared that no competing interests exist.

Importance: Understanding the severity of postvaccination SARS-CoV-2 (ie, COVID-19) breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations., Objective: To estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection., Design, Setting, and Participants: In this cohort study, the Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration included adults (aged ≥18 years) with HIV who were receiving care and were fully vaccinated by June 30, 2021, along with PWoH matched according to date fully vaccinated, age group, race, ethnicity, and sex from 4 US integrated health systems and academic centers. Those with postvaccination COVID-19 breakthrough before December 31, 2021, were eligible., Exposures: HIV infection., Main Outcomes and Measures: The main outcome was severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Discrete time proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% CIs of severe breakthrough illness within 28 days of breakthrough COVID-19 by HIV status adjusting for demographic variables, COVID-19 vaccine type, and clinical factors. The proportion of patients who received mechanical ventilation or died was compared by HIV status., Results: Among 3649 patients with breakthrough COVID-19 (1241 PWH and 2408 PWoH), most were aged 55 years or older (2182 patients [59.8%]) and male (3244 patients [88.9%]). The cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs 6.7%; risk difference, -0.67%; 95% CI, -2.58% to 1.23%). The risk of severe breakthrough illness was 59% higher in PWH with CD4 cell counts less than 350 cells/μL compared with PWoH (aHR, 1.59; 95% CI, 0.99 to 2.46; P = .049). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 cell count were associated with increased risk of severe breakthrough illness, whereas previous COVID-19 was associated with reduced risk. Among 249 hospitalized patients, 24 (9.6%) were mechanically ventilated and 20 (8.0%) died, with no difference by HIV status., Conclusions and Relevance: In this cohort study, the risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. PWH with moderate or severe immune suppression had a higher risk of severe breakthrough infection and should be included in groups prioritized for additional vaccine doses and risk-reduction strategies.

We evaluated adverse drug events (ADEs) by chart review in a random national sample of 428 veterans with coronavirus disease 2019 (COVID-19) who received tocilizumab (n = 173 of 428). ADEs (median time, 5 days) occurred in 51 of 173 (29%) and included hepatoxicity (n = 29) and infection (n = 13). Concomitant medication discontinuation occurred in 22% of ADE patients; mortality was 39%.

Background: Dexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS., Methods: We included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality., Results: Of 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%) patients on low-flow nasal cannula (NC) only received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio (HR) 1.76, 95% CI 1.47-2.12); there was no association with mortality among patients on NC only (HR 1.08, 95% CI 0.86-1.36)., Conclusions: In patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC only in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS., Competing Interests: Conflict of interest: K. Crothers, R. DeFaccio, J. Tate, P.R. Alba, M.B. Goetz, B. Jones, J.T. King, M.E. Ohl, C.T. Rentsch, M.C. Rodriguez-Barradas, S. Shahrir, A.C. Justice and K.M. Akgün have no conflicts of interest to disclose. V. Marconi reports grant funding from Gilead, ViiV, CDC, NIH and VA; honoraria and travel support from Eli Lilly; and participation on a data safety monitoring board., (The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2022.)

While vaccine hesitancy is well documented in the literature among the Latinx community, little attention or effort is given to the nuances among the members of individual communities, such as country of origin, immigration status, generational status, primary language, race, age, sex, gender, or rural residence and how these complexities affect vaccine messaging and uptake. We have evidence that this heterogeneity causes differences in access to healthcare, attitudes towards vaccines, and degree of health disparities. In this review we will describe their impact on vaccination rates in the Latinx community, highlighting missed opportunities for public health outreach, and how targeted messaging could improve vaccine uptake., (Copyright ©2022, Yale Journal of Biology and Medicine.)

Two randomized trials have shown that lung cancer screening (LCS) with low dose computed tomography (LDCT) reduces lung cancer mortality in patients at high-risk for lung malignancy by identifying early-stage cancers, when local cure and control is achievable. The implementation of LCS in the United States has revealed multiple barriers to preventive cancer care. Rates of LCS are disappointingly low with estimates between 5%-18% of eligible patients screened. Equally concerning, follow-up after baseline screening is far lower than that of clinical trials (44-66% v >90%). To optimize the benefits of LCS, programs must identify and address factors related to LCS participation and follow-up while concurrently recognizing and mitigating barriers. As a relatively new screening test, the most effective processes for LCS are uncertain. Therefore, LCS programs have adopted a wide range of approaches without clearly established best practices to guide them, particularly in rural and resource-limited settings. In this narrative review, we identify barriers and facilitators to LCS, focusing on those studies in non-clinical trial settings - reflecting "real world" challenges. Our goal is to identify effective and scalable LCS practices that will increase LCS participation, improve adherence to follow-up, inform strategies for quality improvement, and support new research approaches., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Tobacco use/smoking for epidemiologic studies is often derived from electronic health record (EHR) data, which may be inaccurate. We previously compared smoking from the United States Veterans Health Administration (VHA) EHR clinical reminder data with survey data and found excellent agreement. However, the smoking clinical reminder items changed October 1, 2018. We sought to use the biomarker salivary cotinine (cotinine ≥30) to validate current smoking from multiple sources., Materials and Methods: We included 323 Veterans Aging Cohort Study participants with cotinine, clinical reminder, and self-administered survey smoking data from October 1, 2018 to September 30, 2019. We included International Classification of Disease (ICD)-10 codes F17.21 and Z72.0. Operating characteristics and kappa statistics were calculated., Results: Participants were mostly male (96%), African American (75%) and mean age was 63 years. Of those identified as currently smoking based on cotinine, 86%, 85%, and 51% were identified as currently smoking based on clinical reminder, survey, and ICD-10 codes, respectively. Of those identified as not currently smoking based on cotinine, 95%, 97%, and 97% were identified as not currently smoking based on clinical reminder, survey, and ICD-10 codes. Agreement with cotinine was substantial for clinical reminder (kappa = .81) and survey (kappa = .83), but only moderate for ICD-10 (kappa = .50)., Discussion: To determine current smoking, clinical reminder, and survey agreed well with cotinine, whereas ICD-10 codes did not. Clinical reminders could be used in other health systems to capture more accurate smoking information., Conclusions: Clinical reminders are an excellent source for self-reported smoking status and are readily available in the VHA EHR., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2022.)

Background: In 2013, the United States Preventive Services Taskforce instituted recommendations for annual lung cancer screening (LCS) with low-dose chest CT imaging for high-risk individuals. LCS reduces lung cancer mortality, with greater reduction observed in Black participants in clinical trials. Although racial disparities in lung cancer mortality have been well documented, less is known about disparities in LCS participation and adherence to follow-up in clinical practice., Research Question: What is the association between race and adherence to LCS follow-up?, Study Design and Methods: A systematic review was conducted through a search of published studies in MEDLINE, PubMed, EMBASE, Web of Science, and Cumulative Index to Nursing and Allied Health Literature Database from database inception through October 2020. We included studies that examined rates of adherence to LCS follow-up and compared rates by race. Studies were pooled using random-effects meta-analysis., Results: We screened 18,300 titles and abstracts, and 229 studies were selected for full-text review. Nine studies met inclusion criteria; seven were included in the meta-analysis. Median adherent follow-up rate was 37% (range, 16%-82%). Notable differences among the studies included the proportion of the Black population (range, 4%-47%) and the structure of the LCS programs. The meta-analyses showed lower adherence to LCS follow-up in the Black population (OR, 0.67; 95% CI, 0.55-0.80). This disparity persisted across all malignancy risk levels determined by initial screening results., Interpretation: Lower adherence to LCS follow-up in Black compared with White patients occurs despite the higher potential lung cancer mortality benefit. Literature specifically addressing race-related barriers to LCS adherence remains limited. To ensure equity in LCS benefits, greater outreach to eligible Black patients should be implemented through increased physician education and use of screening program coordinators to focus on this patient population., Trial Registry: PROSPERO; No.: CRD42020214213; URL: http://www.crd.york.ac.uk/PROSPERO., (Published by Elsevier Inc.)

Background: People with HIV (PWH) have a higher hospitalization rate than the general population. The Veterans Aging Cohort Study (VACS) Index at study entry well predicts hospitalization in PWH, but it is unknown if the time-updated parameter improves hospitalization prediction. We assessed the association of parameterizations of the VACS Index 2.0 with the 5-year risk of hospitalization., Setting: PWH ≥30 years old with at least 12 months of antiretroviral therapy (ART) use and contributing hospitalization data from 2000 to 2016 in North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included. Three parameterizations of the VACS Index 2.0 were assessed and categorized by quartile: (1) "baseline" measurement at study entry; (2) time-updated measurements; and (3) cumulative scores calculated using the trapezoidal rule., Methods: Discrete-time proportional hazard models estimated the crude and adjusted associations (and 95% confidence intervals [CIs]) of the VACS Index parameterizations and all-cause hospitalizations. The Akaike information criterion (AIC) assessed the model fit with each of the VACS Index parameters., Results: Among 7289 patients, 1537 were hospitalized. Time-updated VACS Index fitted hospitalization best with a more distinct dose-response relationship [score <43: reference; score 43-55: aHR = 1.93 (95% CI: 1.66 to 2.23); score 55-68: aHR = 3.63 (95% CI: 3.12 to 4.23); score ≥68: aHR = 9.98 (95% CI: 8.52 to 11.69)] than study entry and cumulative VACS Index after adjusting for known risk factors., Conclusions: Time-updated VACS Index 2.0 had the strongest association with hospitalization and best fit to the data. Health care providers should consider using it when assessing hospitalization risk among PWH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the incidence, presentation, and management of rheumatoid arthritis (RA) in patients with HIV, including the use of disease-modifying antirheumatic drugs (DMARDs) in this immunosuppressed population., Methods: Patients included in this study were from the Veterans Aging Cohort Study, a longitudinal cohort of veterans with HIV and age-, race-, and site-matched uninfected veterans. We identified all patients who had ≥1 rheumatologist-generated International Classification of Diseases, Ninth Revision (ICD-9) or Tenth Revision (ICD-10) code for RA and whose serum samples were tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. To further confirm the diagnosis of RA, medical charts were reviewed to verify whether patients met the American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 criteria for RA. We recorded DMARD use and adverse effects during the first contiguous course of treatment (i.e., >6 months of no interruption in DMARD treatment)., Results: This study included 56,250 patients with HIV and 116,944 uninfected individuals over 2,384,541 person-years. Of the 2,748 individuals in this cohort who were reviewed for a diagnosis of RA based on ICD-9 or ICD-10 codes, incident RA was identified in 215 individuals, including 21 patients with HIV. The incidence rate ratio of RA for patients with HIV compared to uninfected individuals was 0.29 (95% confidence interval 0.19-0.48). Most of the patients diagnosed as having RA (88%) were seropositive for RA-associated autoantibodies (RF and/or anti-CCP). However, high autoantibody titers were less frequent in RA patients with HIV compared to RA patients without HIV. In total, 5% of RA patients with HIV (1 of 21) had both high titers of anti-CCP and high titers of RF, compared to 41% of uninfected individuals (81 of 194). DMARDs were prescribed in 71% of RA patients with HIV (15 of 21) compared to 94% of RA patients without HIV (183 of 194). There was no indication that the DMARD safety profile was worse among RA patients with HIV who were prescribed DMARDs (n = 10 assessed) compared to RA patients without HIV who were prescribed DMARDs (n = 158 assessed)., Conclusion: In this cohort, incident RA was less common in patients with HIV compared to uninfected individuals. Moreover, compared to RA patients without HIV, the seropositivity rate and titers of RA-specific autoantibodies were lower among RA patients with HIV, and those with HIV were prescribed DMARDs less frequently than those without HIV., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Background: People with HIV (PWH) with access to antiretroviral therapy (ART) experience excess morbidity and mortality compared with uninfected patients, particularly those with persistent viremia and without CD4+ cell recovery. We compared outcomes for medical intensive care unit (MICU) survivors with unsuppressed (>500 copies/ml) and suppressed (≤500 copies/ml) HIV-1 RNA and HIV-uninfected survivors, adjusting for CD4+ cell count., Setting: We studied 4537 PWH [unsuppressed = 38%; suppressed = 62%; 72% Veterans Affairs-based (VA) and 10 531 (64% VA) uninfected Veterans who survived MICU admission after entering the Veterans Aging Cohort Study (VACS) between fiscal years 2001 and 2015., Methods: Primary outcomes were all-cause 30-day and 6-month readmission and mortality, adjusted for demographics, CD4+ cell category (≥350 (reference); 200-349; 50-199; <50), comorbidity and prior healthcare utilization using proportional hazards models. We also adjusted for severity of illness using discharge VACS Index (VI) 2.0 among VA-based survivors., Results: In adjusted models, CD4+ categories <350 cells/μl were associated with increased risk for both outcomes up to 6 months, and risk increased with lower CD4+ categories (e.g. 6-month mortality CD4+ 200-349 hazard ratio [HR] = 1.35 [1.12-1.63]; CD4+ <50 HR = 2.14 [1.72-2.66]); unsuppressed status was not associated with outcomes. After adjusting for VI in models stratified by HIV, VI quintiles were strongly associated with both outcomes at both time points., Conclusion: PWH who survive MICU admissions are at increased risk for worse outcomes compared with uninfected, especially those without CD4+ cell recovery. Severity of illness at discharge is the strongest predictor for outcomes regardless of HIV status. Strategies including intensive case management for HIV-specific and general organ dysfunction may improve outcomes for MICU survivors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Polypharmacy is associated with frailty in the general population, but little is known about polypharmacy among persons living with HIV (PLWH) on antiretroviral (ARV) therapy. We determined the association between polypharmacy and an adapted frailty-related phenotype (aFRP) via a cross-sectional study in FY 2009 of 1762 PLWH on ARV with suppressed viral load and 2679 uninfected participants in the Veterans Aging Cohort Study. The primary predictor was number of chronic outpatient non-ARV medications using pharmacy fill/refill data. The outcome was self-report of four aFRP domains: shrinking, exhaustion, slowness, low physical activity. Frailty was defined as reporting 3-4 domains while pre-frailty was 1-2. Frailty was uncommon (2% PLWH, 3% uninfected); a larger proportion demonstrated any aFRP domain (31% PLWH, 41% uninfected). Among PLWH and uninfected, median chronic non-ARV medications was 6 and 16 respectively if having any aFRP domain, and 4 and 10 when without aFRP domains. In adjusted analyses, each additional chronic non-ARV medication conferred an 11% increased odds of having any aFRP domain in PLWH (OR [95% CI] = 1.11 [1.08, 1.14]), and a 4% increase in those uninfected (OR [95% CI] = 1.04 [1.03, 1.04]). The stronger association between polypharmacy and frailty in PLWH warrants further study and potential deprescribing of medications.