Contribution of Potentially Inappropriate Medications to Polypharmacy-Associated Risk of Mortality in Middle-Aged Patients: A National Cohort Study.

BACKGROUND: The role of potentially inappropriate medications (PIMs) in mortality has been studied among those 65 years or older. While middle-aged individuals are believed to be less susceptible to the harms of polypharmacy, PIMs have not been as carefully studied in this group. OBJECTIVE: To estimate PIM-associated risk of mortality and evaluate the extent PIMs explain associations between polypharmacy and mortality in middle-aged patients, overall and by sex and race/ethnicity. DESIGN: Observational cohort study. SETTING: Department of Veterans Affairs (VA), the largest integrated healthcare system in the US. PARTICIPANTS: Patients aged 41 to 64 who received a chronic medication (continuous use of ≥ 90 days) between October 1, 2008, and September 30, 2017. MEASUREMENT: Patients were followed for 5 years until death or end of study period (September 30, 2019). Time-updated polypharmacy and hyperpolypharmacy were defined as 5-9 and ≥ 10 chronic medications, respectively. PIMs were identified using the Beers criteria (2015) and were time-updated. Cox models were adjusted for demographic, behavioral, and clinical characteristics. RESULTS: Of 733,728 patients, 676,935 (92.3%) were men, 479,377 (65.3%) were White, and 156,092 (21.3%) were Black. By the end of follow-up, 104,361 (14.2%) patients had polypharmacy, 15,485 (2.1%) had hyperpolypharmacy, and 129,992 (17.7%) were dispensed ≥ 1 PIM. PIMs were independently associated with mortality (HR 1.11, 95% CI 1.04-1.18). PIMs also modestly attenuated risk of mortality associated with polypharmacy (HR 1.07, 95% CI 1.03-1.11 before versus HR 1.05, 95% CI 1.01-1.09 after) and hyperpolypharmacy (HR 1.18, 95% CI 1.09-1.28 before versus HR 1.12, 95% CI 1.03-1.22 after). Patterns varied when stratified by sex and race/ethnicity. LIMITATIONS: The predominantly male VA patient population may not represent the general population. CONCLUSION: PIMs were independently associated with increased mortality, and partially explained polypharmacy-associated mortality in middle-aged people. Other mechanisms of injury from polypharmacy should also be studied.

Contemporary Management and Outcomes of Veterans Hospitalized With Alcohol Withdrawal: A Multicenter Retrospective Cohort Study.

OBJECTIVES: Few studies describe contemporary alcohol withdrawal management in hospitalized settings or review current practices considering the guidelines by the American Society of Addiction Medicine (ASAM). METHODS: We conducted a retrospective cohort study of patients hospitalized with alcohol withdrawal on medical or surgical wards in 19 Veteran Health Administration (VHA) hospitals between October 1, 2018, and September 30, 2019. Demographic and comorbidity data were obtained from the Veteran Health Administration Corporate Data Warehouse. Inpatient management and hospital outcomes were obtained by chart review. Factors associated with treatment duration and complicated withdrawal were examined. RESULTS: Of the 594 patients included in this study, 51% were managed with symptom-triggered therapy alone, 26% with fixed dose plus symptom-triggered therapy, 10% with front loading regimens plus symptom-triggered therapy, and 3% with fixed dose alone. The most common medication given was lorazepam (87%) followed by chlordiazepoxide (33%), diazepam (14%), and phenobarbital (6%). Symptom-triggered therapy alone (relative risk [RR], 0.68; 95% confidence interval [CI], 0.57-0.80) and front loading with symptom-triggered therapy (RR, 0.75; 95% CI, 0.62-0.92) were associated with reduced treatment duration. Lorazepam (RR, 1.20; 95% CI, 1.02-1.41) and phenobarbital (RR, 1.28; 95% CI, 1.06-1.54) were associated with increased treatment duration. Lorazepam (adjusted odds ratio, 4.30; 95% CI, 1.05-17.63) and phenobarbital (adjusted odds ratio, 6.51; 95% CI, 2.08-20.40) were also associated with complicated withdrawal. CONCLUSIONS: Overall, our results support guidelines by the ASAM to manage patients with long-acting benzodiazepines using symptom-triggered therapy. Health care systems that are using shorter acting benzodiazepines and fixed-dose regimens should consider updating alcohol withdrawal management pathways to follow ASAM recommendations.

Opioid prescription and risk of atrial fibrillation in younger veterans.

BACKGROUND: Opioids may play a part in the development of atrial fibrillation (AF). Understanding the relationship between opioid exposure and AF can help providers better assess the risk and benefits of prescribing opioids. OBJECTIVE: To assess the incidence of AF as a function of prescribed opioids and opioid type. DESIGN: We performed unadjusted and adjusted time-updated Cox regressions to assess the association between opioid exposure and incident AF. PARTICIPANTS: The national study sample was comprised of Veterans enrolled in the Veterans Health Administration (VHA) who served in support of post-9/11 operations. MAIN MEASURES: The main predictor of interest was prescription opioid exposure, which was treated as a time-dependent variable. The first was any opioid exposure (yes/no). Secondary was opioid type. The outcome, incident AF, was identified through ICD-9-CM diagnostic codes at any primary care visit after the baseline period. KEY RESULTS: A total of 609,763 veterans (mean age: 34 years and 13.24% female) were included in our study. Median follow-up time was 4.8 years. Within this cohort, 124,395 veterans (20.40%) were prescribed an opioid. A total of 1,455 Veterans (0.24%) were diagnosed with AF. In adjusted time-updated Cox regressions, the risk of incident AF was higher in the veterans prescribed opioids (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.38-1.57). In adjusted time-updated Cox regressions, both immunomodulating and nonimmunomodulating opioid type was associated with increased risk of incident AF (HR: 1.40; 95% CI: 1.25-1.57 and HR: 1.49; 95% CI: 1.39-1.60), compared to no opioid use, respectively. CONCLUSIONS: Our findings suggest opioid prescription may be a modifiable risk factor for the development of AF.

Relationship Between Pain and LGBT Status Among Veterans in Care in a Retrospective Cross-Sectional Cohort.

Background: Pain assessment is performed in many healthcare systems, such as the Veterans Health Administration, but prior studies have not assessed whether pain screening varies in sexual and gender minority populations that include individuals who identify as lesbian, gay, bisexual, and/or transgender (LGBT). Objective: The purpose of this study was to evaluate pain screening and reported pain of LGBT Veterans compared to non-LGBT Veterans. Methods: Using a retrospective cross-sectional cohort, data from the Corporate Data Warehouse, a national repository with clinical/administrative data, were analyzed. Veterans were classified as LGBT using natural language processing. We used a robust Poisson model to examine the association between LGBT status and binary outcomes of pain screening, any pain, and persistent pain within one year of entry in the cohort. All models were adjusted for demographics, mental health, substance use, musculoskeletal disorder(s), and number of clinic visits. Results: There were 1,149,486 Veterans (218,154 (19%) classified as LGBT) in our study. Among LGBT Veterans, 94% were screened for pain compared to 89% among those not classified as LGBT (non-LGBT) Veterans. In adjusted models, LGBT Veterans' probability of being screened for pain compared to non-LGBT Veterans was 2.5% higher (95% CI 2.3%, 2.6%); risk of any pain was 2.1% lower (95% CI 1.6%, 2.6%); and there was no significant difference between LGBT and non-LGBT Veterans in persistent pain (RR = 1.00, 95% CI (0.99, 1.01), p = 0.88). Conclusions: In a nationwide sample, LGBT Veterans were more likely to be screened for pain but had lower self-reported pain scores, though adjusted differences were small. It was notable that transgender and Black Veterans reported the greatest pain. Reasons for these findings require further investigation.

The Association of Prescribed Opioids and Incident Cardiovascular Disease.

Opioid prescribing remains common despite known overdose-related harms. Less is known about links to nonoverdose morbidity. We determined the association between prescribed opioid receipt with incident cardiovascular disease (CVD) using data from the Veterans Aging Cohort Study, a national prospective cohort of Veterans with/without Human Immunodeficiency Virus (HIV) receiving Veterans Health Administration care. Selected participants had no/minimal prior exposure to prescription opioids, no opioid use disorder, and no severe illness 1 year after the study start date (baseline period). We ascertained prescription opioid exposure over 3 years after the baseline period using outpatient pharmacy fill/refill data. Incident CVD ascertainment began at the end of the prescribed opioid exposure ascertainment period until the first incident CVD event, death, or September 30, 2015. We used adjusted Cox proportional hazards regression models with matching weights using propensity scores for opioid receipt to estimate CVD risk. Among 49,077 patients, 30% received opioids; the median age was 49 years, 97% were male, 49% were Black, and 47% were currently smoking. Prevalence of hypertension, diabetes, current smoking, alcohol and cocaine use disorder, and depression was higher in patients receiving opioids versus those not but were well-balanced by matching weights. Unadjusted CVD incidence rates per 1,000-person-years were higher among those receiving opioids versus those not: 17.4 (95% confidence interval [CI], 16.5-18.3) versus 14.7 (95% CI, 14.2-15.3). In adjusted analyses, those receiving opioids versus those not had an increased hazard of incident CVD (adjusted hazard ratio 1.16 [95% CI, 1.08-1.24]). Prescribed opioids were associated with increased CVD incidence, making opioids a potential modifiable CVD risk factor. PERSPECTIVE: In a propensity score weighted analysis of Veterans Administration data, prescribed opioids compared to no opioids were associated with an increased hazard of incident CVD. Higher opioid doses compared with lower doses were associated with increased hazard of incident CVD. Opioids are a potentially modifiable CVD risk factor.

Graded chronic pain scale revised: validation in a Veteran sample.

OBJECTIVE: The Graded Chronic Pain Scale (GCPS) is frequently used in pain research and treatment to classify mild, bothersome, and high impact chronic pain. This study's objective was to validate the revised version of the GCPS (GCPS-R) in a US Veterans Affairs (VA) healthcare sample to support its use in this high-risk population. METHODS: Data were collected from Veterans (n = 794) via self-report (GCPS-R and relevant health questionnaires) and electronic health record extraction (demographics and opioid prescriptions). Logistic regression, adjusting for age and gender, was used to test for differences in health indicators by pain grade. Adjusted odds ratio (AOR) with 95% confidence intervals (CIs) were reported with CIs not including an AOR of 1 indicating that the difference exceeded chance. RESULTS: In this population, the prevalence of chronic pain (pain present most or every day, prior 3 months) was 49.3%: 7.1% with mild chronic pain (mild pain intensity and lower interference with activities); 23.3% bothersome chronic pain (moderate to severe pain intensity with lower interference); and 21.1% high impact chronic pain (higher interference). Results of this study mirrored findings in the non-VA validation study; differences between bothersome and high impact were consistent for activity limitations and present but not fully consistent for psychological variables. Those with bothersome chronic pain or high impact chronic pain were more likely to receive long-term opioid therapy compared to those with no/mild chronic pain. CONCLUSIONS: Findings highlight categorical differences captured with the GCPS-R, and convergent validity supports use of the GCPS-R in US Veterans.

Enhanced Identification of Hispanic Ethnicity Using Clinical Data: A Study in the Largest Integrated United States Health Care System.

BACKGROUND: Collection of accurate Hispanic ethnicity data is critical to evaluate disparities in health and health care. However, this information is often inconsistently recorded in electronic health record (EHR) data. OBJECTIVE: To enhance capture of Hispanic ethnicity in the Veterans Affairs EHR and compare relative disparities in health and health care. METHODS: We first developed an algorithm based on surname and country of birth. We then determined sensitivity and specificity using self-reported ethnicity from the 2012 Veterans Aging Cohort Study survey as the reference standard and compared this to the research triangle institute race variable from the Medicare administrative data. Finally, we compared demographic characteristics and age-adjusted and sex-adjusted prevalence of conditions in Hispanic patients among different identification methods in the Veterans Affairs EHR 2018-2019. RESULTS: Our algorithm yielded higher sensitivity than either EHR-recorded ethnicity or the research triangle institute race variable. In 2018-2019, Hispanic patients identified by the algorithm were more likely to be older, had a race other than White, and foreign born. The prevalence of conditions was similar between EHR and algorithm ethnicity. Hispanic patients had higher prevalence of diabetes, gastric cancer, chronic liver disease, hepatocellular carcinoma, and human immunodeficiency virus than non-Hispanic White patients. Our approach evidenced significant differences in burden of disease among Hispanic subgroups by nativity status and country of birth. CONCLUSIONS: We developed and validated an algorithm to supplement Hispanic ethnicity information using clinical data in the largest integrated US health care system. Our approach enabled clearer understanding of demographic characteristics and burden of disease in the Hispanic Veteran population.

Human Immunodeficiency Virus Status, Tenofovir Exposure, and the Risk of Poor Coronavirus Disease 19 Outcomes: Real-World Analysis From 6 United States Cohorts Before Vaccine Rollout.

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. METHODS: Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). RESULTS: Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81]). CONCLUSIONS: Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH.

Estimated mortality with early empirical antibiotic coverage of methicillin-resistant Staphylococcus aureus in hospitalized patients with bacterial infections: a systematic review and meta-analysis.

OBJECTIVES: We performed a systematic review and meta-analysis to estimate the effect of early active empirical antibiotics for MRSA on mortality, both in patients admitted with MRSA infections and in patients admitted with common infectious syndromes, for whom the causative pathogen may not have been MRSA. METHODS: A systematic literature search was conducted using Embase, MEDLINE, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from the earliest entry through to 26 April 2022. We included studies of patients hospitalized with culture-proven MRSA infections that compared mortality rates depending on whether patients received active empirical antibiotics. The primary outcome was the adjusted OR for mortality with early active empirical antibiotics. After performing random-effects meta-analysis, we estimated the absolute risk reduction in mortality with initial empirical MRSA coverage for common infectious syndromes based on the prevalence of MRSA and baseline mortality rate for each syndrome, as reported in the medical literature. RESULTS: Of an initial 2136 unique manuscripts, 37 studies (11 661 participants) met our inclusion criteria. Fifteen studies (6066 participants) reported adjusted OR of mortality. The pooled adjusted OR for mortality was 0.64 (95% CI, 0.48-0.84), favouring active empirical antibiotics. The estimated absolute mortality benefit was 0% for patients with pneumonia, 0.1% (95% CI, 0.04-0.2) for non-critically ill patients with soft tissue infections, 0.04% (95% CI, 0.01-0.05) for non-critically ill patients with urinary tract infections, 0.6% (95% CI, 0.2-1.0) for patients with septic shock, and 1.0% (95% CI, 0.3-1.4) for patients with catheter-related infections admitted to ICUs. CONCLUSIONS: For the three most common infections in the hospital, the absolute benefit on mortality of empirical antibiotics against MRSA is 0.1% or less. Meaningful benefit of empirical antimicrobials against MRSA is limited to patients with approximately 30% mortality and 10% prevalence of MRSA. Avoiding empirical antibiotics against MRSA for low-risk infections would substantially reduce the use of anti-MRSA therapy.

What internal medicine attendings talk about at morning report: a multicenter study.

BACKGROUND: Morning report is a core educational activity in internal medicine resident education. Attending physicians regularly participate in morning report and influence the learning environment, though no previous study has described the contribution of attending physicians to this conference. This study aims to describe attending comments at internal medicine morning reports. METHODS: We conducted a prospective, observational study of morning reports conducted at 13 internal medicine residency programs between September 1, 2020, and March 30, 2021. Each attending comment was described including its duration, whether the comment was teaching or non-teaching, teaching topic, and field of practice of the commenter. We also recorded morning report-related variables including number of learners, report format, program director participation, and whether report was scripted (facilitator has advance knowledge of the case). A regression model was developed to describe variables associated with the number of attending comments per report. RESULTS: There were 2,344 attending comments during 250 conferences. The median number of attendings present was 3 (IQR, 2-5). The number of comments per report ranged across different sites from 3.9 to 16.8 with a mean of 9.4 comments/report (SD, 7.4). 66% of comments were shorter than one minute in duration and 73% were categorized as teaching by observers. The most common subjects of teaching comments were differential diagnosis, management, and testing. Report duration, number of general internists, unscripted reports, and in-person format were associated with significantly increased number of attending comments. CONCLUSIONS: Attending comments in morning report were generally brief, focused on clinical teaching, and covered a wide range of topics. There were substantial differences between programs in terms of the number of comments and their duration which likely affects the local learning environment. Morning report stakeholders that are interested in increasing attending involvement in morning report should consider employing in-person and unscripted reports. Additional studies are needed to explore best practice models of attending participation in morning report.

Delirium among people aging with and without HIV: Role of alcohol and Neurocognitively active medications.

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.

Factors Associated with Bothersome Symptoms in Individuals With and Without HIV Who Report Alcohol Use.

Bothersome symptoms potentially related to drinking are commonly reported by people with and without HIV (PWH/PWoH). However, the relationship between bothersome symptoms and level of alcohol use is often not appreciated by patients or providers. Therefore, among persons reporting prior-year alcohol use, we assessed whether alcohol use level (AUDIT-C score), HIV status, and demographic covariates influenced the likelihood of the patient reporting a bothersome symptom. We used the Veterans Aging Cohort Study (VACS) surveys (2002-2018), including a validated symptoms index. Among 3679 PWH and 3830 PWoH currently drinking alcohol, the most commonly reported symptoms were muscle/joint pain (52%), sleep disturbance (51%), and fatigue (50%). Level of alcohol use was independently associated with 18 of 20 bothersome symptoms, including seven symptoms more common among PWH. Results can help inform PWH/PWoH who drink alcohol about the strong relationship between level of alcohol use and bothersome symptoms, potentially motivating reduced use.

Temporal and Geographic Patterns of Documentation of Sexual Orientation and Gender Identity Keywords in Clinical Notes.

OBJECTIVE: Disclosure of sexual orientation and gender identity correlates with better outcomes, yet data may not be available in structured fields in electronic health record data. To gain greater insight into the care of sexual and gender-diverse patients in the Veterans Health Administration (VHA), we examined the documentation patterns of sexual orientation and gender identity through extraction and analyses of data contained in unstructured electronic health record clinical notes. METHODS: Salient terms were identified through authoritative vocabularies, the research team's expertise, and frequencies, and the use of consistency in VHA clinical notes. Term frequencies were extracted from VHA clinical notes recorded from 2000 to 2018. Temporal analyses assessed usage changes in normalized frequencies as compared with nonclinical use, relative growth rates, and geographic variations. RESULTS: Over time most terms increased in use, similar to Google ngram data, especially after the repeal of the "Don't Ask Don't Tell" military policy in 2010. For most terms, the usage adoption consistency also increased by the study's end. Aggregated use of all terms increased throughout the United States. CONCLUSION: Term usage trends may provide a view of evolving care in a temporal continuum of changing policy. These findings may be useful for policies and interventions geared toward sexual and gender-diverse individuals. Despite the lack of structured data, the documentation of sexual orientation and gender identity terms is increasing in clinical notes.

Differences in COVID-19 testing and adverse outcomes by race, ethnicity, sex, and health system setting in a large diverse US cohort.

BACKGROUND: Racial/ethnic disparities during the first six months of the COVID-19 pandemic led to differences in COVID-19 testing and adverse outcomes. We examine differences in testing and adverse outcomes by race/ethnicity and sex across a geographically diverse and system-based COVID-19 cohort collaboration. METHODS: Observational study among adults (≥18 years) within six US cohorts from March 1, 2020 to August 31, 2020 using data from electronic health record and patient reporting. Race/ethnicity and sex as risk factors were primary exposures, with health system type (integrated health system, academic health system, or interval cohort) as secondary. Proportions measured SARS-CoV-2 testing and positivity; attributed hospitalization and death related to COVID-19. Relative risk ratios (RR) with 95% confidence intervals quantified associations between exposures and main outcomes. RESULTS: 5,958,908 patients were included. Hispanic patients had the highest proportions of SARS-CoV-2 testing (16%) and positivity (18%), while Asian/Pacific Islander patients had the lowest portions tested (11%) and White patients had the lowest positivity rates (5%). Men had a lower likelihood of testing (RR = 0.90 [0.89-0.90]) and a higher positivity risk (RR = 1.16 [1.14-1.18]) compared to women. Black patients were more likely to have COVID-19-related hospitalizations (RR = 1.36 [1.28-1.44]) and death (RR = 1.17 [1.03-1.32]) compared with White patients. Men were more likely to be hospitalized (RR = 1.30 [1.16-1.22]) or die (RR = 1.70 [1.53-1.89]) compared to women. These racial/ethnic and sex differences were reflected in both health system types. CONCLUSIONS: This study supports evidence of disparities by race/ethnicity and sex during the COVID-19 pandemic that persisted even in healthcare settings with reduced barriers to accessing care. Further research is needed to understand and prevent the drivers that resulted in higher burdens of morbidity among certain Black patients and men.

Analysis of Severe Illness After Postvaccination COVID-19 Breakthrough Among Adults With and Without HIV in the US.

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.

Polypharmacy and medical intensive care unit (MICU) admission and 10-year all-cause mortality risk among hospitalized patients with and without HIV.

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.

Joint longitudinal trajectories of pain intensity and opioid prescription in veterans with back pain.

PURPOSE: We describe pain intensity and opioid prescription jointly over time in Veterans with back pain to better understand their relationship. METHODS: We performed a retrospective cohort study on electronic health record data from 117 126 Veterans (mean age 49.2 years) diagnosed with back pain in 2015. We used latent class growth analysis to jointly model pain intensity (0-10 scores) and opioid prescriptions over 2 years to identify classes of individuals similar in their trajectory of pain and opioid over time. Multivariable multinomial logit models assessed sociodemographic and clinical predictors of class membership. RESULTS: We identified six trajectory classes: a "no pain/no opioid" class (22.2%), a "mild pain/no opioid" class (45.0%), a "moderate pain/no opioid" class (24.6%), a "moderate, decreasing pain/decreasing opioid" class (3.3%), a "moderate pain/high opioid" class (2.6%), and a "moderate, increasing pain/increasing opioid" class (2.3%). Among those in moderate pain classes, being white (vs. non-white) and older were associated with higher odds of being prescribed opioids. Veterans with mental health diagnoses had increased odds of being in the painful classes versus "no pain/no opioid" class. CONCLUSION: We found distinct patterns in the long-term joint course of pain and opioid prescription in Veterans with back pain. Understanding these patterns and associated predictors may help with development of targeted interventions for patients with back pain.

Potentially inappropriate medication use by level of polypharmacy among US Veterans 49-64 and 65-70 years old.

BACKGROUND: Potentially inappropriate medications (PIMs) are medications contra-indicated in particular circumstances. We sought to characterize PIMs by level of polypharmacy by age, sex, and race/ethnicity. METHODS: We performed a cross-sectional drug dispensing study using electronic health records available through the US Department of Veterans Affairs. We extracted pharmacy fill and refill records during fiscal year 2016 (i.e., October 1, 2015-September 30, 2016) for all patients aged 49-70 who accessed care in the preceding fiscal year. PIMs were defined by the combined Beers and Laroche (henceforth Beers Laroche) criteria used for older patients and the PROMPT criteria used for middle-aged. RESULTS: In the 1 499 586 patients aged 49-64, PIMs prevalence by PROMPT in patients with 0-4, 5-9, and ≥10 medications was 14.0%, 62.2%, and 86.1%, respectively, and by Beers Laroche was 14.3%, 63.4%, and 85.7%, respectively. In the 1 249 119 patients aged 65-70, PIMs prevalence by Beers Laroche was 14.8%, 59.9%, and 83.3%, and by PROMPT was 13.9%, 57.4%, and 82.0%, respectively. Meaningful differences in prevalence were shown by sex and race/ethnicity according to both set of criteria (e.g. PROMPT in patients with 5-9 medications: 66.1% women vs. 59.3% men; standardized-mean-differences [SMD] = 0.14; 61.7% of White vs. 54.5% of non-White; SMD = 0.15). The most common PIMs were digestive, analgesic, antidiabetic, and psychotropic medications. CONCLUSION: Prevalence of PIMs was high and increased with polypharmacy. Beers Laroche and PROMPT provided similar estimations inside and outside their target age, suggesting that PIMs are common among those with polypharmacy regardless of age.