Initial antiretroviral therapy regimen and risk of heart failure.

OBJECTIVES: Heart failure risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced heart failure risk. DESIGN: Cohort study. METHODS: PWH who initiated an ART regimen between 2000 and 2016 were identified from three integrated healthcare systems. We evaluated heart failure risk by protease inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitor (INSTI)-based ART, and comparing two common nucleotide reverse transcriptase inhibitors: tenofovir disoproxil fumarate (tenofovir) and abacavir. Follow-up for each pairwise comparison varied (i.e. 7 years for protease inhibitor vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors. RESULTS: Thirteen thousand six hundred and thirty-four PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The hazard ratio (95% CI) were: 2.5 (1.5-4.3) for protease inhibitor vs. NNRTI-based ART (reference); 0.5 (0.2-1.8) for protease inhibitor vs. INSTI-based ART (reference); 0.1 (0.1-0.8) for NNRTI vs. INSTI-based ART (reference); and 1.7 (0.5-5.7) for tenofovir vs. abacavir (reference). In more complex models of cumulative incidence that accounted for possible nonproportional hazards over time, the only remaining finding was evidence of a higher risk of heart failure for protease inhibitor compared with NNRTI-based regimens (1.8 vs. 0.8%; P  = 0.002). CONCLUSION: PWH initiating protease inhibitors may be at higher risk of heart failure compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted.

Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems.

BACKGROUND: Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. SETTING: Retrospective analyses of electronic health record data from 3 US integrated health care systems. METHODS: Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. RESULTS: Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). CONCLUSIONS: Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.

Transgender Care Experiences, Barriers, and Recommendations for Improvement in a Large Integrated Health Care System in the United States.

Purpose: Transgender individuals who pursue gender affirmation medical procedures often need to navigate a complex health system and interact with multiple health care providers in primary and specialty care. We sought to better understand patient, provider, and system level barriers to transgender care in a large integrated health care system in California. Methods: Three 90-min focus groups were conducted with 13 transgender individuals who received specialty care between April and August 2018 in Kaiser Permanente Southern California. Results: Participants cited common adversities such as misgendering and system-wide insensitivity during health care encounters and low levels of understanding of their transgender experience among primary care providers. Provider-patient relationship improvements were recommended for pre- and postsurgical care and service-provider sensitivity training. Suggestions include better care coordination, reducing redundancy in clearance for specialty care services, and enhancing patient support for navigation of gender affirmation services. Participants requested careful consideration when implementing systemwide routine processes such as using pronouns and names when calling patients in for visits or describing procedures on service invoices. Conclusions: Education and training programs for improving transgender care competency and enhancing care coordination between primary care and specialty care for transgender patients are warranted. Including transgender voices with lived-experience as active stakeholders in ongoing efforts such as community advisory boards to identify care gaps may facilitate patient-centered and culturally sensitive transgender care and increased patient satisfaction. Policy Implications: There is a need for systematic training for transgender care competent providers and enhancement of care coordination between primary care and specialty care.

Chronic and Sustained High-Dose Opioid Use in an Integrated Health System.

INTRODUCTION: The Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain released in 2016 had led to decreases in opioid prescribing. This study sought to examine chronic and sustained high-dose prescription opioid use in an integrated health system. METHODS: A serial cross-sectional study was conducted in 2021 to estimate the annual age-adjusted prevalence and incidence of chronic and high-dose opioid use among demographically diverse noncancer adults in an integrated health system in Southern California during 2013-2020. Interrupted time-series analysis with segmented regression was conducted to estimate changes in the trends in annual rates before (2013-2015) and after (2017-2020) the 2016 guideline, treating 2016 as a wash-out period. RESULTS: Prevalence and incidence of chronic use and sustained high-dose use had started to decrease after a health system intervention program before the 2016 Centers for Disease Control and Prevention guideline release and continued to decline after the guideline. Among those with sustained high-dose use, there was a substantial decrease in persons with an average daily dosage ≥90 morphine milligram equivalent and concurrent benzodiazepine use. An accelerated decrease in prevalent chronic use after the guideline was observed (slope change: -11.1 [95% CI= -20.3, -1.9] users/10,000 person-years, p=0.03). The incidence of chronic use and sustained high-dose use continued to decrease after the guideline release but at a slower pace. CONCLUSIONS: Implementing evidence-based prescribing guidelines was associated with a decrease in chronic and sustained high-dose prescription opioid use.

Factors Associated With Firearm Injury Among Pediatric Members of a Large Integrated Healthcare System.

BACKGROUND AND OBJECTIVES: Few studies have tested multiple socio-ecological risk factors assocated with firearm injury among pediatric populations and distinguished self-inflicted from non-self-inflicted injury. To address this gap, the current study examined demographic, individual psychosocial, and neighborhood variables as risk factors for firearm injury among a large cohort of children and adolescents. METHODS: Retrospective cohort study. Data were obtained from the electronic health records of a large integrated healthcare system. The cohort included children <18 years with at least one clinical encounter between January 1, 2010 and December 31, 2018. Poisson regression was used to examine demographic (age, gender, race and ethnicity, Medicaid status), psychosocial (depression, substance use disorder, medical comorbidities), and neighborhood education variables as potential risk factors for non-self-inflicted and self-inflicted firearm injuries. RESULTS: For non-self-inflicted injury, the highest relative risk was found for children age 12-17 years old compared to 0-5 year olds (RR = 37.57); other risk factors included male gender, Black and Hispanic race and ethnicity (compared to White race), being a Medicaid recipient, lower neighborhood education, and substance use disorder diagnosis. For self-inflicted injury, only age 12-17 years old and male gender were associated with increased risk. CONCLUSIONS: These results reinforce the established higher risk for firearm injury among adolescent males, highlight differences between self-inflicted and non-self-inflicted injuries, and the need to consider demographic, psychosocial, and neighborhood variables as risk factors to inform interventions aimed to reduce firearm injuries among children and adolescents.

Variation in Heart Failure Risk by HIV Severity and Sex in People With HIV Infection.

BACKGROUND: HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood. SETTING: Integrated health care system. METHODS: We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex. RESULTS: The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200-499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively). CONCLUSIONS: Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH.

Sexually Transmitted Infections Among Men and Transgender Women Using HIV Pre-exposure Prophylaxis in a Large Integrated Health System-A Cohort Study.

BACKGROUND: Sexually transmitted infections (STIs) are common in people using pre-exposure prophylaxis (PrEP). We examined risk and factors associated with STIs in a cohort of PrEP users in an integrated health system in the United States. SETTING: The Kaiser Permanente Southern California is a large integrated health system that provides comprehensive medical services to approximately 4.7 million demographically diverse members. METHODS: We identified men and transgender women initiating PrEP between January 1, 2014, and June 1, 2018, and followed through December 31, 2018. Demographic and clinical factors potentially associated with the risk of bacterial STIs during PrEP use were evaluated using Poisson regression models. RESULTS: Among 5042 individuals tested for STIs with 7198 person-years of follow-up, 1709 (33.9%) had at least one new STI. The estimated incidence of STIs was 48.3 per 100 person-years, and the most common STI was rectal chlamydia. Most repeat STIs (61.4%) occurred <180 days apart. In a multivariable analysis, an history of STIs in the prior 6 months through 7 days after the PrEP initiation was the most prominent risk factor of STIs during PrEP use (adjusted risk ratio: 1.78, 95% confidence intervals: 1.65 to 1.93). Other risk factors included younger age (<35 years), being Hispanic, and having a history of alcohol use disorder or drug use disorder. CONCLUSIONS: Quarterly STI testing and targeted intervention to mitigate STI risk are warranted for young and racial minority PrEP users, particularly for those with prior history of STIs and substance use disorders.

Identifying Suicidal Ideation and Attempt From Clinical Notes Within a Large Integrated Health Care System.

PURPOSE: The purpose of this study was to develop a natural language processing algorithm to identify suicidal ideation/attempt from free-text clinical notes. METHODS: Clinical notes containing prespecified keywords related to suicidal ideation/attempts from 2010 to 2018 were extracted from our organization's electronic health record system. A random sample of 864 clinical notes was selected and equally divided into 4 subsets. These subsets were reviewed and classified as 1 of the following 3 suicidal ideation/attempt categories (current, historical, and no) by experienced research chart abstractors. The first 3 data sets were used to develop the rule-based computerized algorithm sequentially and the fourth data set was used to evaluate the algorithm's performance. The validated algorithm was then applied to the entire study sample of clinical notes. RESULTS: The computerized algorithm correctly identified 23 of the 26 confirmed current suicidal ideation/attempts and all 10 confirmed historical suicidal ideation/attempts in the validation data set. It produced an 88.5% sensitivity and a 100.0% positive predictive value for current suicidal ideation/attempts, and a 100.0% sensitivity and positive predictive value for historical suicidal ideation/attempts. After applying the computerized algorithm to the entire set of study notes, we identified a total of 1,050,287 current ideation/attempt events and 293,037 historical ideation/attempt events documented in clinical notes. Those for which current ideation/attempt events were documented were more likely to be female (59.5%), 25-44 years old (28.3%), and White (43.4%). CONCLUSION: Our study demonstrated that a computerized algorithm can effectively identify suicidal ideation/attempts from clinical notes. This algorithm can be utilized in support of suicide prevention research programs and patient care quality improvement initiatives.

Brief Report: COVID-19 Testing, Characteristics, and Outcomes Among People Living With HIV in an Integrated Health System.

BACKGROUND: Understanding the attributes of COVID-19 clinical severity among people living with HIV (PLWH) compared with those in HIV-uninfected patients is critical for risk stratification and treatment strategies. METHODS: We conducted a retrospective study at Kaiser Permanente Southern California among PLWH aged 18 years or older. We compared the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization among PLWH and HIV-uninfected adults. A chart review was conducted for PLWH with COVID-19 to examine viral suppression of HIV and most recent CD4+ counts in the year before COVID-19 diagnosis, known exposures to COVID-19, and clinical presentation. RESULTS: Between March 1, 2020, and May 31, 2020, the incidence of SARS-CoV-2 molecular testing, COVID-19 diagnosis, and COVID-19 hospitalization was 551.2, 57.0, and 9.3 per 10,000 PLWH, respectively, compared with 268.4, 34.6, and 5.3 per 10,000 HIV-uninfected individuals, respectively. Among those with COVID-19, the distribution of race/ethnicity, smoking status, and comorbidities was similar in PLWH and HIV-uninfected patients; however, PLWH were mostly men, younger, and less obese than HIV-uninfected individuals. Health care utilization regarding emergency care and hospitalizations in the year before COVID-19-related hospitalization was similar between the groups. Overall, HIV was virologically suppressed in >95% of PLWH with COVID-19, and HIV viral load and CD4+ status did not differ between hospitalized and nonhospitalized patients. CONCLUSIONS: In this population of patients with well-controlled HIV infection, the incidence of testing, diagnosis, and hospitalization for COVID-19 was higher in PLWH than that in HIV-uninfected patients.

Referral Linkage to Preexposure Prophylaxis Care and Persistence on Preexposure Prophylaxis in an Integrated Health Care System.

BACKGROUND: Successful linkage to preexposure prophylaxis (PrEP) and retention in care are important for HIV prevention. We examined gaps in PrEP care following referral and factors associated with PrEP linkage and persistence in an integrated health care system in the United States. METHODS: We identified individuals referred for PrEP from 2014 to 2017 at the Kaiser Permanente Southern California using electronic health records and assessed linkage to care, PrEP prescription orders and fills, and PrEP persistence (medication possession ratio ≥80%) in the year after the first fill. We evaluated demographic and clinical factors potentially associated with PrEP linkage and persistence using a series of multivariable modified Poisson regression models. RESULTS: Of 2995 referred individuals, 74.9% were linked to PrEP care. Nearly all those linked to care were prescribed PrEP and filled a prescription, but only 47.4% of those who filled a prescription were persistent on PrEP. Individuals aged <25 years (vs ≥25 years), female subjects (vs males), and individuals with high-deductible insurance (vs no high deductible) were less likely to be linked to care. Individuals aged <25 years and Hispanics (vs non-Hispanic whites) were less likely to be persistent. Those with alcohol use disorder were more likely to be linked to PrEP care but less likely to be persistent. New HIV diagnoses occurred in 38 individuals, and only 1 had PrEP in possession at diagnosis. CONCLUSIONS: We observed PrEP care gaps and disparities among individuals referred for PrEP. Patient-centered interventions are needed in primary care to address barriers to successful PrEP linkage and persistence.

Human immunodeficiency virus infection and risks of morbidity and death in adults with incident heart failure.

Aims: Human immunodeficiency virus (HIV) increases the risk of heart failure (HF), but whether it influences subsequent morbidity and mortality remains unclear. Methods and results: We investigated the risks of hospitalization for HF, HF-related emergency department (ED) visits, and all-cause death in an observational cohort of incident HF patients with and without HIV using data from three large US integrated healthcare delivery systems. We estimated incidence rates and adjusted hazard ratios (aHRs) by HIV status at the time of HF diagnosis for subsequent outcomes. We identified 448 persons living with HIV (PLWH) and 3429 without HIV who developed HF from a frequency-matched source cohort of 38 868 PLWH and 386 586 without HIV. Mean age was 59.5 ± 11.3 years with 9.8% women and 31.8% Black, 13.1% Hispanic, and 2.2% Asian/Pacific Islander. Compared with persons without HIV, PLWH had similar adjusted rates of HF hospitalization [aHR 1.01, 95% confidence interval (CI): 0.81-1.26] and of HF-related ED visits [aHR 1.22 (95% CI: 0.99-1.50)], but higher adjusted rates of all-cause death [aHR 1.31 (95% CI: 1.08-1.58)]. Adjusted rates of HF-related morbidity and all-cause death were directionally consistent across a wide range of CD4 counts but most pronounced in the subset with a baseline CD4 count <200 or 200-499 cells/µL. Conclusion: In a large, diverse cohort of adults with incident HF receiving care within integrated healthcare delivery systems, PLWH were at an independently higher risk of all-cause death but not HF hospitalizations or HF-related ED visits. Future studies investigating modifiable HIV-specific risk factors may facilitate more personalized care to optimize outcomes for PLWH and HF.

Patient characteristics associated with treatment initiation and engagement among individuals diagnosed with alcohol and other drug use disorders in emergency department and primary care settings.

Background: Treatment initiation and engagement rates for alcohol and other drug (AOD) use disorders differ depending on where the AOD use disorder was identified. Emergency department (ED) and primary care (PC) are 2 common settings where patients are identified; however, it is unknown whether characteristics of patients who initiate and engage in treatment differ between these settings. Methods: Patients identified with an AOD disorder in ED or PC settings were drawn from a larger study that examined Healthcare Effectiveness Data and Information Set (HEDIS) AOD treatment initiation and engagement measures across 7 health systems using electronic health record data (n = 54,321). Multivariable generalized linear models, with a logit link, clustered on health system, were used to model patient factors associated with initiation and engagement in treatment, between and within each setting. Results: Patients identified in the ED had higher odds of initiating treatment than those identified in PC (adjusted odds ratio [aOR] = 1.89, 95% confidence interval [CI] = 1.73-2.07), with no difference in engagement between the settings. Among those identified in the ED, compared with patients aged 18-29, older patients had higher odds of treatment initiation (age 30-49: aOR = 1.25, 95% CI = 1.12-1.40; age 50-64: aOR = 1.42, 95% CI = 1.26-1.60; age 65+: aOR = 1.27, 95% CI = 1.08-1.49). However, among those identified in PC, compared with patients aged 18-29, older patients were less likely to initiate (age 30-49: aOR = 0.81, 95% CI = 0.71-0.94; age 50-64: aOR = 0.68, 95% CI = 0.58-0.78; age 65+: aOR = 0.47, 95% CI = 0.40-0.56). Women identified in ED had lower odds of initiating treatment (aOR = 0.80, 95% CI = 0.72-0.88), whereas sex was not associated with treatment initiation in PC. In both settings, patients aged 65+ had lower odds of engaging compared with patients aged 18-29 (ED: aOR = 0.61, 95% CI = 0.38-0.98; PC: aOR = 0.42, 95% CI = 0.26-0.68). Conclusion: Initiation and engagement in treatment differed by sex and age depending on identification setting. This information could inform tailoring of future AOD interventions.

The prevalence of Healthcare Effectiveness Data and Information Set (HEDIS) initiation and engagement in treatment among patients with cannabis use disorders in 7 US health systems.

Background: Cannabis use disorders (CUDs) have increased with more individuals using cannabis, yet few receive treatment. Health systems have adopted the Healthcare Effectiveness Data and Information Set (HEDIS) quality measures of initiation and engagement in alcohol and other drug (AOD) dependence treatment, but little is known about the performance of these among patients with CUDs. Methods: This cohort study utilized electronic health records and claims data from 7 health care systems to identify patients with documentation of a new index CUD diagnosis (no AOD diagnosis ≤60 days prior) from International Classification of Diseases, Ninth revision, codes (October 1, 2014, to August 31, 2015). The adjusted prevalence of each outcome (initiation, engagement, and a composite of both) was estimated from generalized linear regression models, across index identification settings (inpatient, emergency department, primary care, addiction treatment, and mental health/psychiatry), AOD comorbidity (patients with CUD only and CUD plus other AOD diagnoses), and patient characteristics. Results: Among 15,202 patients with an index CUD diagnosis, 30.0% (95% confidence interval [CI]: 29.2-30.7%) initiated, 6.9% (95% CI: 6.2-7.7%) engaged among initiated, and 2.1% (95% CI: 1.9-2.3%) overall both initiated and engaged in treatment. The adjusted prevalence of outcomes varied across index identification settings and was highest among patients diagnosed in addiction treatment, with 25.0% (95% CI: 22.5-27.6%) initiated, 40.9% (95% CI: 34.8-47.0%) engaged, and 12.5% (95% CI: 10.0-15.1%) initiated and engaged. The adjusted prevalence of each outcome was generally highest among patients with CUD plus other AOD diagnosis at index diagnosis compared with those with CUD only, overall and across index identification settings, and was lowest among uninsured and older patients. Conclusion: Among patients with a new CUD diagnosis, the proportion meeting HEDIS criteria for initiation and/or engagement in AOD treatment was low and demonstrated variation across index diagnosis settings, AOD comorbidity, and patient characteristics, pointing to opportunities for improvement.