National Veterans Affairs Health Care Research Articles

Rates and Factors Associated With Documentation of Diagnostic Codes for Long COVID in the National Veterans Affairs Health Care System

Some persons infected with SARS-CoV-2 experience symptoms or impairments many months after acute infection. To determine the rates, clinical setting, and factors associated with documented receipt of COVID-19-related care 3 or more months after acute infection. This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants included persons with a positive SARS-CoV-2 test between February 1, 2020, and April 30, 2021, who were still alive 3 months after infection and did not have evidence of reinfection. Data analysis was performed from February 2020 to December 2021. Positive SARS-CoV-2 test. Rates and factors associated with documentation of COVID-19-related International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (U07.1, Z86.16, U09.9, and J12.82) 3 or more months after acute infection (hereafter, long-COVID care), with follow-up extending to December 31, 2021. Among 198 601 SARS-CoV-2-positive persons included in the study, the mean (SD) age was 60.4 (17.7) years, 176 942 individuals (89.1%) were male, 133 924 (67.4%) were White, 44 733 (22.5%) were Black, and 19 735 (9.9%) were Hispanic. During a mean (SD) follow-up of 13.5 (3.6) months, long-COVID care was documented in a wide variety of clinics, most commonly primary care and general internal medicine (18 634 of 56 310 encounters [33.1%]), pulmonary (7360 of 56 310 encounters [13.1%]), and geriatrics (5454 of 56 310 encounters [9.7%]). Long-COVID care was documented in 26 745 cohort members (13.5%), with great variability across geographical regions (range, 10.8%-18.1%) and medical centers (range, 3.0%-41.0%). Factors significantly associated with documented long-COVID care included older age, Black or American Indian/Alaska Native race, Hispanic ethnicity, geographical region, high Charlson Comorbidity Index score, having documented symptoms at the time of acute infection (adjusted odds ratio [AOR], 1.71; 95% CI, 1.65-1.78) and requiring hospitalization (AOR, 2.60; 95% CI, 2.51-2.69) or mechanical ventilation (AOR, 2.46; 95% CI, 2.26-2.69). Patients who were fully vaccinated at the time of infection were less likely to receive long-COVID care (AOR, 0.78; 95% CI, 0.68-0.90). Long-COVID care was documented in a variety of clinical settings, with great variability across regions and medical centers and was documented more commonly in older persons, those with higher comorbidity burden, those with more severe acute COVID-19 presentation and those who were unvaccinated at the time of infection. These findings provide support and guidance for health care systems to develop systematic approaches to the evaluation and management of patients who may be experiencing long COVID.

555. Utilization of Remdesivir for COVID-19 in the National Veterans Affairs Healthcare System

BackgroundAs remdesivir (GS-5734) has become a leading treatment for COVID-19, we sought to assess remdesivir utilization patterns, including utilization of concomitant and supportive therapies, and heterogeneity in treatment approaches.MethodsOur retrospective cohort study included hospitalized Veterans with positive COVID-19 PCR tests treated with remdesivir, from 03/2020 through 4/2021. Using exposure mapping of barcode medication administration records and medication dispensings, we assessed other medications received by each patient on each day of remdesivir treatment. Heterogeneity was defined as patterns of treatment (drug & duration) not shared by any other patient.ResultsOur study included 13,665 patients with COVID-19 receiving remdesivir. The median time to remdesivir initiation from either positive test or hospital admission was 1 day (interquartile range [IQR] 0-4 and 0-1, respectively). The median duration of remdesivir treatment was 5 days (IQR 4-5 days). Median length of hospital stay was 7 days (IQR 4-13). Inpatient mortality was 13.9% and an additional 6.2% of patients died within 90 days of discharge. The most common concomitant and supportive therapies were anticoagulants/antiplatelets (94.8%; enoxaparin 72.6%, heparin 18.4%, apixaban 10.8%, clopidogrel 6.3%), corticosteroids (90.8%; dexamethasone 87.3%, prednisone 2.9%, methylprednisolone 5.5%), statins (55.8%; atorvastatin 38.2%, simvastatin 7.1%, rosuvastatin 6.0%), antibiotics (41.9%; azithromycin 25.6%, ceftriaxone 13.2%, doxycycline 6.0%, vancomycin 4.9%), angiotensin receptor blockers (11.9%) and angiotensin-converting enzyme inhibitors (20.4%), melatonin (29.7%), and aspirin (35.6%). Concomitant utilization of Janus kinase inhibitors (0.5%), interleukin-6 inhibitors (2.4%), and hydroxychloroquine (0.5%) was low. Heterogeneity in concomitant and supportive therapies during remdesivir treatment was 84.6% (68.3% when assessed as drug class/category). ConclusionAmong hospitalized patients with COVID-19 in the national VA Healthcare system receiving remdesivir, remdesivir was initiated early in the admission and substantial heterogeneity was observed in concomitant and supportive therapies during remdesivir treatment.Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi, Inc (Research Grant or Support)

Factors Associated With Hospitalization and Death After COVID-19 Diagnosis Among Patients With Rheumatic Disease: An Analysis of Veterans Affairs Data.

ObjectiveIndividuals with autoimmune rheumatic disease (RD) are considered to be at increased risk for infection. However, few US population‐based studies have assessed whether these patients are at increased risk of hospitalization or death due to COVID‐19 compared with those without RD.MethodsWe performed a retrospective cohort study using national Veterans Affairs Health Care System data for individuals who tested positive for SARS‐CoV‐2. Outcomes of interest were hospitalization or death due to any cause within 30 days of COVID‐19 diagnosis. Outcomes were compared among veterans with RD and those without RD by using propensity score matching (PSM) and mixed‐effects multivariate logistic regression.ResultsOf 26,116 veterans with COVID‐19, 501 (1.9%) had an underlying RD. Prior to matching, patients with RD were more likely to have poor outcomes compared with controls (37.7% vs. 28.5% hospitalized; 6.4% vs. 4.5% died). In the PSM analysis, RD was not a significant predictor for poor outcomes; however, patients with prescriptions for glucocorticoids had increased odds of poor outcomes in a dose‐dependent manner (odds ratio [95% confidence interval] for hospitalization or death: 1.33 [1.20‐1.48] for doses >0 and ≤10 mg/day; 1.29 [1.09‐1.52] for doses >10 mg/day).ConclusionAmong US veterans with COVID‐19, we did not find a significant association between RD and hospitalization or death. Poor outcomes appear to be mostly driven by age and other comorbidities, similar to the general veteran population. However, we observed an increased risk for poor outcomes among patients who received glucocorticoids, even at daily doses less than or equal to 10 mg.

Development, Validation, and Evaluation of a Simple Machine Learning Model to Predict Cirrhosis Mortality

Machine-learning algorithms offer better predictive accuracy than traditional prognostic models but are too complex and opaque for clinical use. To compare different machine learning methods in predicting overall mortality in cirrhosis and to use machine learning to select easily scored clinical variables for a novel cirrhosis prognostic model. This prognostic study used a retrospective cohort of adult patients with cirrhosis or its complications seen in 130 hospitals and affiliated ambulatory clinics in the integrated, national Veterans Affairs health care system from October 1, 2011, to September 30, 2015. Patients were followed up through December 31, 2018. Data were analyzed from October 1, 2017, to May 31, 2020. Potential predictors included demographic characteristics; liver disease etiology, severity, and complications; use of health care resources; comorbid conditions; and comprehensive laboratory and medication data. Patients were randomly selected for model development (66.7%) and validation (33.3%). Three different statistical and machine learning methods were evaluated: gradient descent boosting, logistic regression with least absolute shrinkage and selection operator (LASSO) regularization, and logistic regression with LASSO constrained to select no more than 10 predictors (partial pathway model). Predictor inclusion and model performance were evaluated in a 5-fold cross-validation. Last, the predictors identified in the most parsimonious (the partial path) model were refit using maximum-likelihood estimation (Cirrhosis Mortality Model [CiMM]), and its predictive performance was compared with that of the widely used Model for End Stage Liver Disease with sodium (MELD-Na) score. All-cause mortality. Of the 107 939 patients with cirrhosis (mean [SD] age, 62.7 [9.6] years; 96.6% male; 66.3% white, 18.4% African American), the annual mortality rate ranged from 8.8% to 15.3%. In total, 32.7% of patients died within 3 years, and 46.2% died within 5 years after the index date. Models predicting 1-year mortality had good discrimination for the gradient descent boosting (area under the receiver operating characteristics curve [AUC], 0.81; 95% CI, 0.80-0.82), logistic regression with LASSO regularization (AUC, 0.78; 95% CI, 0.77-0.79), and the partial path logistic model (AUC, 0.78; 95% CI, 0.76-0.78). All models showed good calibration. The final CiMM model with machine learning-derived clinical variables offered significantly better discrimination than the MELD-Na score, with AUCs of 0.78 (95% CI, 0.77-0.79) vs 0.67 (95% CI, 0.66-0.68) for 1-year mortality, respectively (DeLong z = 17.00; P < .001). In this study, simple machine learning techniques performed as well as the more advanced ensemble gradient boosting. Using the clinical variables identified from simple machine learning in a cirrhosis mortality model produced a new score more transparent than machine learning and more predictive than the MELD-Na score.

Adherence of Infusible Biologics During the Time of COVID-19 Among Patients With Inflammatory Bowel Disease: A Nationwide Veterans Affairs Cohort Study

Adherence of Infusible Biologics During the Time of COVID-19 Among Patients With Inflammatory Bowel Disease: A Nationwide Veterans Affairs Cohort Study

Association of Duration and Type of Surgical Prophylaxis With Antimicrobial-Associated Adverse Events

The benefits of antimicrobial prophylaxis are limited to the first 24 hours postoperatively. Little is known about the harms associated with continuing antimicrobial prophylaxis after skin closure. To characterize the association of type and duration of prophylaxis with surgical site infection (SSI), acute kidney injury (AKI), and Clostridium difficile infection. In this multicenter, national retrospective cohort study, all patients within the national Veterans Affairs health care system who underwent cardiac, orthopedic total joint replacement, colorectal, and vascular procedures and who received planned manual review by a trained nurse reviewer for type and duration of surgical prophylaxis and for SSI from October 1, 2008, to September 30, 2013, were included. Data were analyzed using multivariable logistic regression, with adjustments for covariates determined a priori to be associated with the outcomes of interest. Data were analyzed from December 2016 to December 2018. Duration of postoperative antimicrobial prophylaxis (<24 hours, 24-<48 hours, 48-<72 hours, and ≥72 hours). Surgical site infection, AKI, and C difficile infection. Of the 79 058 included patients, 76 109 (96.3%) were men, and the mean (SD) age was 64.8 (9.4) years. Among 79 058 surgical procedures in the cohort, all had SSI and C difficile outcome data available; 71 344 (90.2%) had AKI outcome data. After stratification by type of surgery and adjustment for age, sex, race, diabetes, smoking, American Society of Anesthesiologists score greater than 2, methicillin-resistant Staphylococcus aureus colonization, mupirocin, type of prophylaxis, and facility factors, SSI was not associated with duration of prophylaxis. Adjusted odds of AKI increased with each additional day of prophylaxis (cardiac procedure: 24-<48 hours: adjusted odds ratio [aOR], 1.03; 95% CI, 0.95-1.12; 48-<72 hours: aOR, 1.22; 95% CI, 1.08-1.39; ≥72 hours: aOR, 1.82; 95% CI, 1.54-2.16; noncardiac procedure: 24-<48 hours: aOR, 1.31; 95% CI, 1.21-1.42; 48-<72 hours: aOR, 1.72; 95% CI, 1.47-2.01; ≥72 hours: aOR, 1.79; 95% CI, 1.27-2.53). The risk of postoperative C difficile infection demonstrated a similar duration-dependent association (24-<48 hours: aOR 1.08; 95% CI, 0.89-1.31; 48-<72 hours: aOR, 2.43; 95% CI, 1.80-3.27; ≥72 hours: aOR, 3.65; 95% CI, 2.40-5.53). The unadjusted numbers needed to harm for AKI after 24 to less than 48 hours, 48 to less than 72 hours, and 72 hours or more of postoperative prophylaxis were 9, 6, and 4, respectively; and 2000, 90, and 50 for C difficile infection, respectively. Vancomycin receipt was also a significant risk factor for AKI (cardiac procedure: aOR, 1.17; 95% CI, 1.10-1.25; noncardiac procedure: aOR, 1.21; 95% CI, 1.13-1.30). Increasing duration of antimicrobial prophylaxis was associated with higher odds of AKI and C difficile infection in a duration-dependent fashion; extended duration did not lead to additional SSI reduction. These findings highlight the notion that every day matters and suggest that stewardship efforts to limit duration of prophylaxis have the potential to reduce adverse events without increasing SSI.

Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus.

Hepatitis C virus (HCV) infection is associated with diabetes and may worsen glycemic control in patients with diabetes. We aimed to investigate whether eradication of HCV infection with direct-acting antiviral (DAA) agents is associated with improved glycemic control in patients with diabetes. We identified 2,435 patients with diabetes who underwent interferon-free and ribavirin-free DAA-based antiviral treatment for HCV in the national Veterans Affairs health care system. Changes in average hemoglobin A1c (HbA1c) level and use of antidiabetic medications 1 year before and after antiviral treatment were compared between patients who achieved sustained virologic response (SVR) and those who did not. Among patients with elevated baseline HbA1c, the drop in HbA1c associated with antiviral treatment was greater in those who achieved SVR (0.98%) than in those who sustained treatment failure (0.65%) (adjusted mean difference 0.34, P = 0.02). Use of antidiabetic medications decreased more in patients who achieved SVR than in those who sustained treatment failure, especially for the use of insulin, which dropped significantly from 41.3% to 38% in patients achieving SVR compared with a slight increase from 49.8% to 51% in those who sustained treatment failure. DAA-based eradication of HCV is associated with improved glycemic control in patients with diabetes as evidenced by decreased mean HbA1c and decreased insulin use. These endocrine benefits of SVR provide additional justification for considering antiviral treatment in all patients with diabetes.

Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma

Hepatitis C virus (HCV) treatment for patients with hepatocellular carcinoma (HCC) was uncommon before direct-acting antiviral (DAA) medications. Real-world effectiveness of DAAs for HCV in patients with HCC is unclear. We describe rates of sustained virologic response (SVR) with DAA regimens by HCV genotype in patients with a history of HCC. We identified patients who initiated antiviral treatment between January 1, 2014 and June 30, 2015 in the national Veterans Affairs health care system. Regimens included sofosobuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin. HCC patients were divided into those who were treated with liver transplantation after HCC diagnosis ("HCC/LT" group) and those treated with other modalities prior to antiviral therapy ("HCC" group). Of 17,487 HCV treatment recipients, 624 (3.6%) had prior HCC, including 142 with HCC/LT and 482 with HCC. Overall SVR was 91.1% in non-HCC, 74.4% in HCC, and 94.0% in HCC/LT. Among HCC patients, genotype 1 had the highest SVR overall (79.1% in HCC and 96.4% in HCC/LT), and genotype 3 the lowest (47.0% in HCC and 88.9% in HCC/LT). After adjustment for confounders, the presence of HCC was associated with lower likelihood of SVR overall (AOR 0.38 [95% CI 0.29, 0.48], p<0.001). HCV can be cured with DAAs in the majority of patients with prior HCC, and in virtually all HCC patients post-liver transplant. Deferral of HCV treatment until the post-transplant setting may be considered among HCC patients listed for transplantation. Over three-quarters of patients with hepatocellular carcinoma who have hepatitis C can achieve viral cure with direct-acting antiviral drugs. Among patients with hepatocellular carcinoma who subsequently received liver transplantation, over 90% of patients can achieve viral cure.

Five-year downstream outcomes following prostate-specific antigen screening in older men.

Despite ongoing controversies surrounding prostate-specific antigen (PSA) screening, many men 65 years or older undergo screening. However, few data exist that quantify the chain of events following screening in clinical practice to better inform decisions. To quantify 5-year downstream outcomes following a PSA screening result exceeding 4.0 ng/mL in older men. Longitudinal cohort study in the national Veterans Affairs health care system. In total, 295,645 men 65 years or older who underwent PSA screening in the Veterans Affairs health care system in 2003 and were followed up for 5 years using national Veterans Affairs and Medicare data. Among men whose index screening PSA level exceeded 4.0 ng/mL, we determined the number who underwent prostate biopsy, were diagnosed as having prostate cancer, were treated for prostate cancer, and were treated for prostate cancer and were alive at 5 years according to baseline characteristics. Biopsy and treatment complications were also assessed. In total, 25,208 men (8.5%) had an index PSA level exceeding 4.0 ng/mL. During the 5-year follow-up period, 8313 men (33.0%) underwent at least 1 prostate biopsy, and 5220 men (62.8%) who underwent prostate biopsy were diagnosed as having prostate cancer, of whom 4284 (82.1%) were treated for prostate cancer. Performance of prostate biopsy decreased with advancing age and worsening comorbidity (P < .001), whereas the percentage treated for biopsy-detected cancer exceeded 75% even among men 85 years or older, those with a Charlson-Deyo Comorbidity Index of 3 or higher, and those having low-risk cancer. Among men with biopsy-detected cancer, the risk of death from non-prostate cancer causes increased with advancing age and worsening comorbidity (P < .001). In total, 468 men (5.6%) had complications within 7 days after prostate biopsy. Complications of prostate cancer treatment included new urinary incontinence in 584 men (13.6%) and new erectile dysfunction 588 men (13.7%). Performance of prostate biopsy is uncommon in older men with abnormal screening PSA levels and decreases with advancing age and worsening comorbidity. However, once cancer is detected on biopsy, most men undergo immediate treatment regardless of advancing age, worsening comorbidity, or low-risk cancer. Understanding downstream outcomes in clinical practice should better inform individualized decisions among older men considering PSA screening.