A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality.

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P < 0.05) in the joint meta-analysis with the HGI (Ncases = 44,820; Ncontrols = 1,775,827; OR, 0.97 [0.95-1.00]; P = 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 [0.72-0.93]; P = 0.001). Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.

Bridging information gaps in menopause status classification through natural language processing.

Objective: To use natural language processing (NLP) of clinical notes to augment existing structured electronic health record (EHR) data for classification of a patient's menopausal status. Materials and methods: A rule-based NLP system was designed to capture evidence of a patient's menopause status including dates of a patient's last menstrual period, reproductive surgeries, and postmenopause diagnosis as well as their use of birth control and menstrual interruptions. NLP-derived output was used in combination with structured EHR data to classify a patient's menopausal status. NLP processing and patient classification were performed on a cohort of 307 512 female Veterans receiving healthcare at the US Department of Veterans Affairs (VA). Results: NLP was validated at 99.6% precision. Including the NLP-derived data into a menopause phenotype increased the number of patients with data relevant to their menopausal status by 118%. Using structured codes alone, 81 173 (27.0%) are able to be classified as postmenopausal or premenopausal. However, with the inclusion of NLP, this number increased 167 804 (54.6%) patients. The premenopausal category grew by 532.7% with the inclusion of NLP data. Discussion: By employing NLP, it became possible to identify documented data elements that predate VA care, originate outside VA networks, or have no corresponding structured field in the VA EHR that would be otherwise inaccessible for further analysis. Conclusion: NLP can be used to identify concepts relevant to a patient's menopausal status in clinical notes. Adding NLP-derived data to an algorithm classifying a patient's menopausal status significantly increases the number of patients classified using EHR data, ultimately enabling more detailed assessments of the impact of menopause on health outcomes.

Causes of alcohol-attributable death and associated years of potential life lost among LGB and non-LGB veteran men and women in Veterans Health Administration.

BACKGROUND: Alcohol use is a significant concern nationally and research now highlights higher rates of alcohol attributable death (AAD) and years of potential life lost (YPLL) among lesbian, gay, and bisexual (LGB) veterans compared to non-LGB veterans. In this study, we examined specific causes of AAD and associated YPLL between LGB and non-LGB veteran men and women to highlight needed outreach, prevention, and treatment strategies. METHODS: Using data from the nationwide Veterans Health Administration electronic health record and National Death Index from 2014 to 2018, we examined the top ten ranked causes of AAD among LGB (n = 102,085) and non-LGB veteran (n = 5,300,521) men and women, as well as associated YPLL per AAD. RESULTS: We observed higher rates of AAD among men than women, but higher rates among LGB veterans relative to their same-sex non-LGB counterparts. We noted greater YPLL per AAD among LGB men and all women compared to non-LGB men, even when of similar or same rank in cause of death. Acute-cause AAD death (e.g., alcohol-related suicide, poisonings) was ranked higher among LGB men and all women. YPLL was greater for both acute- and chronic-cause AAD (e.g., liver disease) among LGB men and all women compared to non-LGB men. CONCLUSIONS: Causes of AAD differ between LGB and non-LGB men and women. The differences observed highlight disparities in acute- and chronic-cause AAD between groups help explain the higher number of YPLL per AAD that disfavor LGB men and women veterans, and essential next steps in primary and secondary prevention of hazardous drinking and mortality risk.

Racial Disparities in Uterine Fibroid Treatment Among Veterans Using VA Health Care.

INTRODUCTION: Uterine fibroids are common, nonmalignant tumors that disproportionately impact Black patients. We aimed to examine Black and White differences in receipt of any treatment and type of first treatment in the Department of Veterans Affairs, including effect modification by severity as approximated by anemia. METHODS: We used Department of Veterans Affairs administrative data to identify 5,041 Black and 3,206 White veterans with symptomatic uterine fibroids, identified by International Classification of Diseases, 9th edition, Clinical Modification, codes, between fiscal year 2010 and fiscal year 2012 and followed in the administrative data through fiscal year 2018 for outcomes. Outcomes included receipt of any treatment, hysterectomy as first treatment, and fertility-sparing treatment as first treatment. We stratified all analyses by age (<45, ≥45 years old), used generalized linear models with a log link and Poisson error distribution, included an interaction term between race and anemia, and used recycled predictions to estimate adjusted percentages for outcomes. RESULTS: There was evidence of effect modification by anemia for receipt of any treatment but not for any other outcomes. Across age and anemia sub-groups, Black veterans were less likely to receive any treatment than White veterans. Adjusted racial differences were most pronounced among veterans with anemia (<45 years, Black-White difference = -10.3 percentage points; 95% confidence interval, -15.9 to -4.7; ≥45 years, Black-White difference = -20.3 percentage points; 95% confidence interval, -27.8 to -12.7). Across age groups, Black veterans were less likely than White veterans to have hysterectomy and more likely to have a fertility-sparing treatment as their first treatment. CONCLUSIONS: We identified significant Black-White disparities in receipt of treatment for symptomatic uterine fibroids. Additional research that centers the experiences of Black veterans with uterine fibroids is needed to inform strategies to eliminate racial disparities in uterine fibroid care.

Sexual orientation-related disparities in health conditions that elevate COVID-19 severity.

PURPOSE: The Veterans Health Administration (VA) is the largest single integrated healthcare system in the US and is likely the largest healthcare provider for people with minoritized sexual orientations (e.g., gay, lesbian, bisexual). The purpose of this study was to use electronic health record (EHR) data to replicate self-reported survey findings from the general US population and assess whether sexual orientation is associated with diagnosed physical health conditions that may elevate risk of COVID-19 severity among veterans who utilize the VA. METHODS: A retrospective analysis of VA EHR data from January 10, 1999-January 07, 2019 analyzed in 2021. Veterans with minoritized sexual orientations were included if they had documentation of a minoritized sexual orientation within clinical notes identified via natural language processing. Veterans without minoritized sexual orientation documentation comprised the comparison group. Adjusted prevalence and prevalence ratios (aPR) were calculated overall and by race/ethnicity while accounting for differences in distributions of sex assigned at birth, age, calendar year of first VA visit, volumes of healthcare utilization, and VA priority group. RESULTS: Data from 108,401 veterans with minoritized sexual orientation and 6,511,698 controls were analyzed. After adjustment, veterans with minoritized sexual orientations had a statistically significant elevated prevalence of 10 of the 11 conditions. Amongst the highest disparities observed were COPD (aPR:1.24 [95% confidence interval:1.23-1.26]), asthma (1.22 [1.20-1.24]), and stroke (1.26 [1.24-1.28]). CONCLUSIONS: Findings largely corroborated patterns among the general US population. Further research is needed to determine if these disparities translate to poorer COVID-19 outcomes for individuals with minoritized sexual orientation.

Identifying Posttraumatic Stress Disorder and Disparity Among Transgender Veterans Using Nationwide Veterans Health Administration Electronic Health Record Data.

Purpose: The prevalence of posttraumatic stress disorder (PTSD) and other psychiatric disorders is high among military veterans and even higher among transgender veterans. Prior prevalence estimates have become outdated, and novel methods of estimation have since been developed but not used to estimate PTSD prevalence among transgender veterans. This study provides updated estimates of PTSD prevalence among transgender and cisgender veterans. Methods: We examined Veterans Health Administration (VHA) medical record data from October 1, 1999 to April 1, 2021 for 9995 transgender veterans and 29,985 cisgender veteran comparisons (1:3). We matched on age group at first VHA health care visit, sex assigned at birth, and year of first VHA visit. We employed both probabilistic and rule-based algorithms to estimate the prevalence of PTSD for transgender and cisgender veterans. Results: The prevalence of PTSD was 1.5-1.8 times higher among transgender veterans. Descriptive data suggest that the prevalence of depression, schizophrenia, bipolar disorder, alcohol and non-alcohol substance use disorders, current/former smoking status, and military sexual trauma was also elevated among transgender veterans. Conclusion: The PTSD and overall psychiatric burden observed among transgender veterans was significantly higher than that of their cisgender peers, especially among recent users of VHA care. These PTSD findings are consistent with prior literature and minority stress theory, and they were robust across probabilistic and two rule-based methods employed in this study. As such, enhanced and careful screening, outreach, and evidence-based practices are recommended to help reduce this disparity among transgender veterans.

Using electronic health records to streamline provider recruitment for implementation science studies.

BACKGROUND: Healthcare providers are often targeted as research participants, especially for implementation science studies evaluating provider- or system-level issues. Frequently, provider eligibility is based on both provider and patient factors. Manual chart review and self-report are common provider screening strategies but require substantial time, effort, and resources. The automated use of electronic health record (EHR) data may streamline provider identification for implementation science research. Here, we describe an approach to provider screening for a Veterans Health Administration (VHA)-funded study focused on implementing risk-aligned surveillance for bladder cancer patients. METHODS: Our goal was to identify providers at 6 pre-specified facilities who performed ≥10 surveillance cystoscopy procedures among bladder cancer patients in the 12 months prior to recruitment start on January 16, 2020, and who were currently practicing at 1 of 6 pre-specified facilities. Using VHA EHR data (using CPT, ICD10 procedure, and ICD10 diagnosis codes), we identified cystoscopy procedures performed after an initial bladder cancer diagnosis (i.e., surveillance procedures). Procedures were linked to VHA staff data to determine the provider of record, the number of cystoscopies they performed, and their current location of practice. To validate this approach, we performed a chart review of 105 procedures performed by a random sample of identified providers. The proportion of correctly identified procedures was calculated (Positive Predictive Value (PPV)), along with binomial 95% confidence intervals (CI). FINDINGS: We identified 1,917,856 cystoscopies performed on 703,324 patients from October 1, 1999-January 16, 2020, across the nationwide VHA. Of those procedures, 40% were done on patients who had a prior record of bladder cancer and were completed by 15,065 distinct providers. Of those, 61 performed ≥ 10 procedures and were currently practicing at 1 of the 6 facilities of interest in the 1 year prior to study recruitment. The random chart review of 7 providers found 101 of 105 procedures (PPV: 96%; 95% CI: 91% to 99%) were surveillance procedures and were performed by the selected provider on the recorded date. IMPLICATIONS: These results show that EHR data can be used for accurate identification of healthcare providers as research participants when inclusion criteria consist of both patient- (temporal relationship between diagnosis and procedure) and provider-level (frequency of procedure and location of current practice) factors. As administrative codes and provider identifiers are collected in most, if not all, EHRs for billing purposes this approach can be translated from provider recruitment in VHA to other healthcare systems. Implementation studies should consider this method of screening providers.

Alcohol-attributable deaths and years of potential life lost due to alcohol among veterans: Overall and between persons with minoritized and non-minoritized sexual orientations.

BACKGROUND: Unhealthy alcohol use is disproportionally experienced by individuals with minoritized sexual orientations. Unlike the general US population, for whom the burden of alcohol as it relates to mortality is consistently monitored across time with national survey data, the impact of unhealthy alcohol use among veterans with minoritized sexual orientations, for whom addressing substance use is a national priority, is largely unknown. METHODS: Using Alcohol Use Disorders Identification Test Consumption data from the Department of Veterans Affairs electronic health record and underlying cause of death from National Death Index from 2014 to 2018 we quantified alcohol consumption and related mortality among veterans with (n = 102,085) and without minoritized sexual orientations (n = 5300,521). Age adjusted rates of alcohol attributed deaths (AAD) per 100,000 persons and years of potential life lost (YPLL) were estimated by sexual orientation, sex, and sexual orientation stratified by sex. RESULTS: Alcohol attributable deaths (n = 21,861) were higher among veterans with minoritized sexual orientations than veterans without after adjustment for age (486.5 deaths/100,000 versus 309.7 deaths/100,000, respectively). Veterans with minoritized sexual orientations also experienced more YPLL (13,772.8 years/100,000 versus 7618.9 years/100,000). Years of potential life lost per AAD was higher in women (33.2 years) than men (18.7 years). CONCLUSIONS: Alcohol consumption results in substantial disability and death among veterans, particularly veterans with minoritized sexual orientations. Findings suggest need for increased alcohol-related services for all VA patients, and potential targeted approaches to for veterans with minoritized sexual orientations and women to offset risk for, and years of potential life lost from, alcohol attributable death.

Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

Importance: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear. Objective: To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19. Design, Setting, and Participants: COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129 848 SCT-negative individuals, of whom 13 488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021. Exposures: The hemoglobin beta S (HbS) allele (rs334-T). Main Outcomes and Measures: This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records. Results: Of the 132 577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P = .01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure. Conclusions and Relevance: In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity.

Estimating prevalence of PTSD among veterans with minoritized sexual orientations using electronic health record data.

Objective: Questionnaire studies show people with minoritized sexual orientations (MSOs) face increased risk for conditions including posttraumatic stress disorder (PTSD). This study replicated Harrington et al.'s (2019) electronic health record probabilistic algorithm to evaluate lifetime PTSD prevalence in Veterans Health Administration (VHA)-using veterans. Method: In 115,853 MSO veterans and a 1:3 matched (on sex assigned at birth, and age at and year of first VHA visit) sample of non-MSO veterans. Each veteran was given a probability of "likely PTSD" (0.0-1.0) and thresholds (e.g., 0.7) applied to minimize false positive classifications. Results: Veterans with MSO were 2.35 times, CI [2.33, 2.38], more likely to have "likely PTSD" than veterans with non-MSO. The prevalence of "likely PTSD" using the rule-based International Classification of Diseases (ICD) approach was 40.8% among the MSO group compared to 22.0% among the non-MSO group after excluding those with bipolar or schizophrenia diagnoses and those with limited VHA engagement. Without those exclusions, prevalence was slightly higher in both groups (46.1% vs. 24.3%, respectively; prevalence ratio: 1.90). Despite increased prevalence of exposure to military sexual trauma (MST; MSO = 20.7%; non-MSO = 8.3%) and double "likely PTSD" among MSO veterans, they were less likely to have a service-connected PTSD disability than their matched non-MSO (MSO = 78.1%; non-MSO = 87.6%) comparators. Conclusions: VHA-using veterans with MSO were twice as likely to have "likely PTSD" and exposure to MST than veterans with non-MSO. Veterans with MSO were less likely to be service connected for PTSD than non-MSO counterparts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Variation in Sexual Orientation Documentation in a National Electronic Health Record System.

Purpose: The purpose of this study was to determine variation in sexual minority (SM) sexual orientation documentation within the electronic medical records of the Veterans Health Administration (VHA). Methods: Documentation of SM sexual orientation was retrospectively extracted from clinical notes and administrative data in the VHA from October 1, 1999 to July 1, 2019. The rate of documentation overall and by calendar year was calculated, and differences across patient, provider, and clinic characteristics were evaluated. Results: Approximately 1.4% of all VHA Veterans (n = 115,911) had at least one documentation of SM sexual orientation, including 79,455 men and 36,456 women. The rate of documentation increased from 81.01/100,000 in 2000 to 568.84/100,000 in 2018. The majority of documentations (58.7%) occurred in mental health settings by non-MD mental health/social work counselors, whereas only 9.6% occurred in primary care settings. Although 99% of these Veterans had a primary care visit, only 19% had SM status recorded in that setting. Conclusion: Documentation patterns of SM sexual orientation varied considerably in the VHA with notable gaps in primary care. Diverse approaches to culturally competent training for primary care clinicians and patient-facing collection strategies could facilitate documentation of sexual orientation.

Positive Predictive Value of COVID-19 ICD-10 Diagnosis Codes Across Calendar Time and Clinical Setting.

PURPOSE: To estimate the positive predictive value (PPV) of International Classification of Diseases, Tenth Revision (ICD-10) code U07.1, COVID-19 virus identified, in the Department of Veterans of Affairs (VA). PATIENTS AND METHODS: Records of ICD-10 code U07.1 from inpatient, outpatient, and emergency/urgent care settings were extracted from VA medical record data from 4/01/2020 to 3/31/2021. A weighted, random sample of 1500 records from each quarter of the one-year observation period was reviewed by study personnel to confirm active COVID-19 infection at the time of diagnosis and classify reasons for false positive records. PPV was estimated overall and compared across clinical setting and quarters. RESULTS: We identified 664,406 records of U07.1. Among the 1500 reviewed, 237 were false positives (PPV: 84.2%, 95% CI: 82.4-86.0). PPV ranged from 77.7% in outpatient settings to 93.8% in inpatient settings and was 83.3% in quarter 1, 80.5% in quarter 2, 86.1% in quarter 3, and 83.6% in quarter 4. The most common reasons for false positive records were history of COVID-19 (44.3%) and orders for laboratory tests (21.5%). CONCLUSION: The PPV of ICD-10 code U07.1 is low, especially in outpatient settings. Directed training may improve accuracy of coding to levels that are deemed adequate for future use in surveillance efforts.

Evaluation of Suicide Mortality Among Sexual Minority US Veterans From 2000 to 2017.

Importance: Identification of subgroups at greatest risk for suicide mortality is essential for prevention efforts and targeting interventions. Sexual minority individuals may have an increased risk for suicide compared with heterosexual individuals, but a lack of sufficiently powered studies with rigorous methods for determining sexual orientation has limited the knowledge on this potential health disparity. Objective: To investigate suicide mortality among sexual minority veterans using Veterans Health Administration (VHA) electronic health record data. Design, Setting, and Participants: This retrospective population-based cohort study used data on 8.1 million US veterans enrolled in the VHA after fiscal year 1999 that were obtained from VHA electronic health records from October 1, 1999 to September 30, 2017. Data analysis was carried out from March 1, 2020 to October 31, 2020. Exposure: Veterans with documentation of a minority sexual orientation. Documentation of sexual minority status was obtained through natural language processing of clinical notes and extraction of structured administrative data for sexual orientation in VHA electronic health records. Main Outcomes and Measures: Suicide mortality rate using data on the underlying cause of death obtained from the National Death Index. Crude and age-adjusted mortality rates were calculated for all-cause death and death from suicide among sexual minority veterans compared with the general US population and the general population of veterans. Results: Among the 96 893 veterans with at least 1 sexual minority documentation in the electronic health record, the mean (SD) age was 46 (16) years, 68% were male, and 70% were White. Of the 12 591 total deaths, 3.5% were from suicide. Veterans had a significantly higher rate of mortality from suicide (standardized mortality ratio, 4.50; 95% CI, 4.13-4.99) compared with the general US population. Suicide was the fifth leading cause of death in 2017 among sexual minority veterans (3.8% of deaths) and the tenth leading cause of death in the general US population (1.7% of deaths). The crude suicide rate among sexual minority veterans (82.5 per 100 000 person-years) was higher than the rate in the general veteran population (37.7 per 100 000 person-years). Conclusions and Relevance: The results of this population-based cohort study suggest that sexual minority veterans have a greater risk for suicide than the general US population and the general veteran population. Further research is needed to determine whether and how suicide prevention efforts reach sexual minority veterans.