Excess Mortality Among Patients in the Veterans Affairs Health System Compared With the Overall US Population During the First Year of the COVID-19 Pandemic.

Importance: During the first year of the COVID-19 pandemic, there was a substantial increase in the rate of death in the United States. It is unclear whether those who had access to comprehensive medical care through the Department of Veterans Affairs (VA) health care system had different death rates compared with the overall US population. Objective: To quantify and compare the increase in death rates during the first year of the COVID-19 pandemic between individuals who received comprehensive medical care through the VA health care system and those in the general US population. Design, Setting, and Participants: This cohort study compared 10.9 million enrollees in the VA, including 6.8 million active users of VA health care (those with a visit in the last 2 years), with the general population of the US, with deaths occurring from January 1, 2014, to December 31, 2020. Statistical analysis was conducted from May 17, 2021, to March 15, 2023. Main Outcomes and Measures: Changes in rates of death from any cause during the COVID-19 pandemic in 2020 compared with previous years. Changes in all-cause death rates by quarter were stratified by age, sex, race and ethnicity, and region, based on individual-level data. Multilevel regression models were fit in a bayesian setting. Standardized rates were used for comparison between populations. Results: There were 10.9 million enrollees in the VA health care system and 6.8 million active users. The demographic characteristics of the VA populations were predominantly male (>85% in the VA health care system vs 49% in the general US population), older (mean [SD], 61.0 [18.2] years in the VA health care system vs 39.0 [23.1] years in the US population), and had a larger proportion of patients who were White (73% in the VA health care system vs 61% in the US population) or Black (17% in the VA health care system vs 13% in the US population). Increases in death rates were apparent across all of the adult age groups (≥25 years) in both the VA populations and the general US population. Across all of 2020, the relative increase in death rates compared with expected values was similar for VA enrollees (risk ratio [RR], 1.20 [95% CI, 1.14-1.29]), VA active users (RR, 1.19 [95% CI, 1.14-1.26]), and the general US population (RR, 1.20 [95% CI, 1.17-1.22]). Because the prepandemic standardized mortality rates were higher in the VA populations prior to the pandemic, the absolute rates of excess mortality were higher in the VA populations. Conclusions and Relevance: In this cohort study, a comparison of excess deaths between populations suggests that active users of the VA health system had similar relative increases in mortality compared with the general US population during the first 10 months of the COVID-19 pandemic.

Dexamethasone in hospitalised COVID-19 patients not on intensive respiratory support.

BACKGROUND: Dexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS. METHODS: We included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality. RESULTS: Of 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%) patients on low-flow nasal cannula (NC) only received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio (HR) 1.76, 95% CI 1.47-2.12); there was no association with mortality among patients on NC only (HR 1.08, 95% CI 0.86-1.36). CONCLUSIONS: In patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC only in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS.

Pharmacoepidemiology, Machine Learning, and COVID-19: An Intent-to-Treat Analysis of Hydroxychloroquine, With or Without Azithromycin, and COVID-19 Outcomes Among Hospitalized US Veterans.

Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ among patients hospitalized with COVID-19. We examined the effects of HCQ alone and in combination with azithromycin in a hospitalized population of US veterans with COVID-19, using a propensity score-adjusted survival analysis with imputation of missing data. According to electronic health record data from the US Department of Veterans Affairs health care system, 64,055 US Veterans were tested for the virus that causes COVID-19 between March 1, 2020 and April 30, 2020. Of the 7,193 veterans who tested positive, 2,809 were hospitalized, and 657 individuals were prescribed HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and there was an increased risk of intubation when HCQ was used in combination with azithromycin (hazard ratio = 1.55; 95% confidence interval: 1.07, 2.24). In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treatment of patients hospitalized with COVID-19, using a national sample of the US veteran population. Using rigorous study design and analytic methods to reduce confounding and bias, we found no evidence of a survival benefit from the administration of HCQ.

HIV care using differentiated service delivery during the COVID-19 pandemic: a nationwide cohort study in the US Department of Veterans Affairs.

INTRODUCTION: The Department of Veterans Affairs (VA) is the largest provider of HIV care in the United States. Changes in healthcare delivery became necessary with the COVID-19 pandemic. We compared HIV healthcare delivery during the first year of the COVID-19 pandemic to a prior similar calendar period. METHODS: We included 27,674 people with HIV (PWH) enrolled in the Veterans Aging Cohort Study prior to 1 March 2019, with ≥1 healthcare encounter from 1 March 2019 to 29 February 2020 (2019) and/or 1 March 2020 to 28 February 2021 (2020). We counted monthly general medicine/infectious disease (GM/ID) clinic visits and HIV-1 RNA viral load (VL) tests. We determined the percentage with ≥1 clinic visit (in-person vs. telephone/video [virtual]) and ≥1 VL test (detectable vs. suppressed) for 2019 and 2020. Using pharmacy records, we summarized antiretroviral (ARV) medication refill length (<90 vs. ≥90 days) and monthly ARV coverage. RESULTS: Most patients had ≥1 GM/ID visit in 2019 (96%) and 2020 (95%). For 2019, 27% of visits were virtual compared to 64% in 2020. In 2019, 82% had VL measured compared to 74% in 2020. Of those with VL measured, 92% and 91% had suppressed VL in 2019 and 2020. ARV refills for ≥90 days increased from 39% in 2019 to 51% in 2020. ARV coverage was similar for all months of 2019 and 2020 ranging from 76% to 80% except for March 2019 (72%). Women were less likely than men to be on ARVs or to have a VL test in both years. CONCLUSIONS: During the COVID-19 pandemic, the VA increased the use of virtual visits and longer ARV refills, while maintaining a high percentage of patients with suppressed VL among those with VL measured. Despite decreased in-person services during the pandemic, access to ARVs was not disrupted. More follow-up time is needed to determine whether overall health was impacted by the use of differentiated service delivery and to evaluate whether a long-term shift to increased virtual healthcare could be beneficial, particularly for PWH in rural areas or with transportation barriers. Programmes to increase ARV use and VL testing for women are needed.

Accuracy of the Veterans Health Administration COVID-19 (VACO) Index for predicting short-term mortality among 1307 US academic medical centre inpatients and 427 224 US Medicare patients.

BACKGROUND: The Veterans Health Administration COVID-19 (VACO) Index predicts 30-day all-cause mortality in patients with COVID-19 using age, sex and pre-existing comorbidity diagnoses. The VACO Index was initially developed and validated in a nationwide cohort of US veterans-we now assess its accuracy in an academic medical centre and a nationwide US Medicare cohort. METHODS: With measures and weights previously derived and validated in US national Veterans Health Administration (VA) inpatients and outpatients (n=13 323), we evaluated the accuracy of the VACO Index for estimating 30-day all-cause mortality using area under the receiver operating characteristic curve (AUC) and calibration plots of predicted versus observed mortality in inpatients at a single US academic medical centre (n=1307) and in Medicare inpatients and outpatients aged 65+ (n=427 224). RESULTS: 30-day mortality varied by data source: VA 8.5%, academic medical centre 17.5%, Medicare 16.0%. The VACO Index demonstrated similar discrimination in VA (AUC=0.82) and academic medical centre inpatient population (AUC=0.80), and when restricted to patients aged 65+ in VA (AUC=0.69) and Medicare inpatient and outpatient data (AUC=0.67). The Index modestly overestimated risk in VA and Medicare data and underestimated risk in Yale New Haven Hospital data. CONCLUSIONS: The VACO Index estimates risk of short-term mortality across a wide variety of patients with COVID-19 using data available prior to or at the time of diagnosis. The VACO Index could help inform primary and booster vaccination prioritisation, and indicate who among outpatients testing positive for SARS-CoV-2 should receive greater clinical attention or scarce treatments.

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study.

OBJECTIVE: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. DESIGN: Observational cohort study. SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. PARTICIPANTS: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. MAIN OUTCOME MEASURES: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. RESULTS: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. CONCLUSIONS: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index.

BACKGROUND: Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. METHODS AND FINDINGS: We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality-no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77-0.81), and in early (AUC = 0.81 95% CI: 0.78-0.83) and late (AUC = 0.84, 95% CI: 0.78-0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60-64 years, overall mortality was estimated at 9% (95% CI: 6-11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3-7%) to 21% (95% CI: 12-31%), depending on sex and comorbid disease. CONCLUSION: Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines.

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.