Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes: A Multinational, Federated Analysis of LEGEND-T2DM.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head clinical trials. OBJECTIVES: The aim of this study was to compare the cardiovascular effectiveness of SGLT2is, GLP-1 RAs, dipeptidyl peptidase-4 inhibitors (DPP4is), and clinical sulfonylureas (SUs) as second-line antihyperglycemic agents in T2DM. METHODS: Across the LEGEND-T2DM (Large-Scale Evidence Generation and Evaluation Across a Network of Databases for Type 2 Diabetes Mellitus) network, 10 federated international data sources were included, spanning 1992 to 2021. In total, 1,492,855 patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy were identified who initiated 1 of 4 second-line agents (SGLT2is, GLP-1 RAs, DPP4is, or SUs). Large-scale propensity score models were used to conduct an active-comparator target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, on-treatment Cox proportional hazards models were fit for 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (3-point MACE plus heart failure hospitalization) risk and HR estimates were combined using random-effects meta-analysis. RESULTS: Over 5.2 million patient-years of follow-up and 489 million patient-days of time at risk, patients experienced 25,982 3-point MACE and 41,447 4-point MACE. SGLT2is and GLP-1 RAs were associated with lower 3-point MACE risk than DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98]) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88]). DPP4is were associated with lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). The pattern for 3-point MACE was also observed for the 4-point MACE outcome. There were no significant differences between SGLT2is and GLP-1 RAs for 3-point or 4-point MACE (HR: 1.06 [95% CI: 0.96-1.17] and 1.05 [95% CI: 0.97-1.13]). CONCLUSIONS: In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of SGLT2is and GLP-1 RAs should be prioritized as second-line agents in those with established CVD.

Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study.

Background: SGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head trials. Methods: Across the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis. Findings: Across cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]). Interpretation: In patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD. Funding: National Institutes of Health, United States Department of Veterans Affairs.

Healthcare service utilization for formerly homeless veterans in permanent supportive housing: Do neighborhoods matter?

Neighborhood characteristics are associated with residents' healthcare use. However, we understand less about these relationships among formerly homeless persons, who often have complex healthcare needs, including mental health and substance use disorders. Among formerly homeless Veterans, we examined: (a) how neighborhood characteristics are associated with Veteran Health Administration (VHA) healthcare use and, (b) if these relationships varied by Veterans' level of healthcare need. We obtained data on our cohort of 711 Veterans housed through VHA's permanent supportive housing program (HUD-VASH) in 2016-2017 from VHA's Homeless Registry, VHA's electronic health records, and the U.S. Census. We studied the relationships between neighborhood characteristics (% Veteran, % in poverty, % unemployed, % using public transportation, and % vacant properties) and VA healthcare use (primary care visits, outpatient mental health visits, and "high use" of emergency departments [> 4 visits]) using mixed-effects logistic and negative binomial regression models, controlling for patient demographics. We further examined moderation by patient healthcare need (calculated from cost and clinical data). We found that veterans in neighborhoods with higher percentages of residents who (a) were Veterans or (b) used public transportation were more likely to have high emergency department use. Those in neighborhoods with higher public transportation use had more primary care visits while those in neighborhoods with more property vacancies had more outpatient mental health visits. Among those with high healthcare needs, residents of areas with more Veterans had higher emergency department use. Promoting public transportation use and social engagement with other Veterans in residential neighborhoods may influence HUD-VASH Veterans' VA healthcare use. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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.

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.

Military Sexual Trauma and Adverse Mental and Physical Health and Clinical Comorbidity in Women Veterans.

INTRODUCTION: Military sexual trauma (MST)-exposure to sexual harassment or assault during military service-is a major health priority for the Veterans Health Administration (VHA). We examined the health correlates of MST in the largest sample of U.S. women veterans studied to date. METHODS: Using national VHA electronic medical record data, we identified 502,199 women veterans who enrolled in the VHA between January 1, 2000, and December 31, 2017, had at least one VHA visit, and were screened for MST (exclusive of those who declined to answer the screening). We conducted logistic regression analyses to examine associations of a positive MST screen with various mental and physical health conditions-defined by administrative diagnostic codes-and comorbidity of mental and/or physical health conditions. Models were adjusted for demographic and military service characteristics, along with duration in the VHA. RESULTS: Approximately 26% (n = 130,738) of women veterans screened positive for MST. In fully adjusted models, a positive MST screen was associated with greater risk of having all mental and physical health conditions examined, except cancer-related conditions, ranging from 9% greater odds of rheumatic disease to 5.4 times greater odds of post-traumatic stress disorder. MST was also associated with greater comorbidity, including greater odds of having ≥2 mental health conditions (odds ratio [OR], 3.28; 99% confidence interval [CI], 3.20-3.37), having ≥2 physical health conditions (OR, 1.26; 99% CI, 1.22-1.29), and having ≥1 mental health condition and ≥1 physical health condition (OR, 2.05; 99% CI, 2.00-2.11). CONCLUSIONS: Findings suggest that MST is common in women veterans and may play a role in the clinical complexity arising from comorbid conditions.

Association of Posttraumatic Stress Disorder and Incident Ischemic Heart Disease in Women Veterans.

Importance: Posttraumatic stress disorder (PTSD) is associated with greater risk of ischemic heart disease (IHD) in predominantly male populations or limited community samples. Women veterans represent a growing, yet understudied, population with high levels of trauma exposure and unique cardiovascular risks, but research on PTSD and IHD in this group is lacking. Objective: To determine whether PTSD is associated with incident IHD in women veterans. Design, Setting, and Participants: In this retrospective, longitudinal cohort study of the national Veterans Health Administration (VHA) electronic medical records, the a priori hypothesis that PTSD would be associated with greater risk of IHD onset was tested. Women veterans 18 years or older with and without PTSD who were patients in the VHA from January 1, 2000, to December 31, 2017, were assessed for study eligibility. Exclusion criteria consisted of no VHA clinical encounters after the index visit, IHD diagnosis at or before the index visit, and IHD diagnosis within 90 days of the index visit. Propensity score matching on age at index visit, number of prior visits, and presence of traditional and female-specific cardiovascular risk factors and mental and physical health conditions was conducted to identify women veterans ever diagnosed with PTSD, who were matched in a 1:2 ratio to those never diagnosed with PTSD. Data were analyzed from October 1, 2018, to October 30, 2020. Exposures: PTSD, defined by International Classification of Diseases, Ninth Revision (ICD-9), or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), diagnosis codes from inpatient or outpatient encounters. Main Outcomes and Measures: Incident IHD, defined as new-onset coronary artery disease, angina, or myocardial infarction, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient encounters, and/or coronary interventions based on Current Procedural Terminology codes. Results: A total of 398 769 women veterans, 132 923 with PTSD and 265 846 never diagnosed with PTSD, were included in the analysis. Baseline mean (SD) age was 40.1 (12.2) years. During median follow-up of 4.9 (interquartile range, 2.1-9.2) years, 4381 women with PTSD (3.3%) and 5559 control individuals (2.1%) developed incident IHD. In a Cox proportional hazards model, PTSD was significantly associated with greater risk of developing IHD (hazard ratio [HR], 1.44; 95% CI, 1.38-1.50). Secondary stratified analyses indicated that younger age identified women veterans with PTSD who were at greater risk of incident IHD. Effect sizes were largest for those younger than 40 years at baseline (HR, 1.72; 95% CI, 1.55-1.93) and decreased monotonically with increasing age (HR for ≥60 years, 1.24; 95% CI, 1.12-1.38). Conclusions and Relevance: This cohort study found that PTSD was associated with increased risk of IHD in women veterans and may have implications for IHD risk assessment in vulnerable individuals.

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.

Adherence to the Use of Home Telehealth Technologies and Emergency Room Visits in Veterans with Heart Failure.

Background: Prior studies have posited poor patient adherence to remote patient monitoring as the reason for observed lack of benefits. Introduction: The purpose of this study was to examine the relationship between average adherence to the daily use of home telehealth (HT) and emergency room (ER) visits in Veterans with heart failure. Materials and Methods: This was a retrospective study using administrative data of Veterans with heart failure enrolled in Veterans Affairs (VA) HT Program in the first half of 2014. Zero-inflated negative binomial regression was used to determine which predictors affect the probability of having an ER visit and the number of ER visits. Results: The final sample size was 3,449 with most being white and male. There were fewer ER visits after HT enrollment (mean ± standard deviation of 1.85 ± 2.8) compared with the year before (2.2 ± 3.4). Patient adherence was not significantly associated with ER visits. Age and being from a racial minority group (not white or black) and belonging to a large HT program were associated with having an ER visit. Being in poorer health was associated with higher expected count of ER visits. Discussion: Subgroups of patients (e.g., with depression, sicker, or from a racial minority group) may benefit from added interventions to decrease ER use. Conclusions: This study found that adherence was not associated with ER visits. Reasons other than adherence should be considered when looking at ER use in patients with heart failure enrolled in remote patient monitoring programs.

Why patients stop using their home telehealth technologies over time: Predictors of discontinuation in Veterans with heart failure.

BACKGROUND: Daily use of home telehealth (HT) technologies decreases over time. Barriers to continued use are unclear. PURPOSE: To examine predictors of drop-out from HT in Veterans with heart failure. METHODS: Data for Veterans with heart failure enrolled in the Veterans Affairs HT Program were analyzed using a mixed effects Cox regression model to determine risk of dropping-out over a 1-year period. FINDINGS: Older (hazard ratio [HR] 1.01), sicker (prior hospital readmission [HR 1.39]), higher probability of hospital admission/death [HR 1.23], functional impairments [1.14]) and white Veterans (compared to black; HR 1.41) had higher risk of drop-out in HT Programs. Users of VA's online patient portal (HR 0.90) had lower risk of drop-out. DISCUSSION: Older and sicker patients are at most risk of stopping HT use, yet use of a patient portal shows promise in improving continued use. Interventions targeting patients at high risk for HT discontinuation are needed to promote ongoing engagement.