Postoperative Outcomes Associated with the Timing of Surgery After SARS-CoV-2 Infection.

OBJECTIVE: Examine the association between prior SARS-CoV-2 infection, interval from infection to surgery, and adverse surgical outcomes. SUMMARY BACKGROUND DATA: Earlier series have reported worse outcomes for surgery after COVID-19 illness, and these findings have led to routinely deferring surgery seven weeks after infection. METHODS: We created a retrospective cohort of patients from the US Veterans Health Administration facilities nationwide, April 2020 to September 2022, undergoing surgical procedures. Primary outcomes were 90-day all-cause mortality and 30-day complications. Within surgical procedure groupings, SARS-CoV-2 infected and uninfected patients were matched in a 1:4 ratio. We categorized patients by 2-week intervals from SARS-CoV-2 positive test to surgery. Hierarchical multilevel multivariable logistic regression models were used to estimate the association between infection to surgery interval versus no infection and primary end points. RESULTS: We identified 82,815 veterans undergoing eligible operations (33% general, 27% orthopedic, 13% urologic, 9% vascular), of whom 16,563 (20%) had laboratory-confirmed SARS-CoV-2 infection before surgery. The multivariable models demonstrated an association between prior SARS-CoV-2 infection and increased 90-day mortality (odds ratio (OR) 1.42, 95% CI: 1.08, 1.86) and complications (OR 1.32, 95% CI: 1.11, 1.57) only for patients having surgery within 14 days of infection. ASA-stratified multivariable models showed that the associations between increased 90-day mortality (OR 1.40, 95% CI: 1.12, 1.75) and complications (OR 1.73, 95% CI: 1.34, 2.24) for patients having surgery within 14 days of infection were confined to those with ASA 4-5. CONCLUSIONS: In a contemporary surgical cohort, patients with prior SARS-CoV-2 infection only had increased postoperative mortality or complications when they had surgery within 14 days after the positive test. These findings support revising timing recommendations between surgery and prior SARS-CoV-2 infection.

Clinical outcomes of elective robotic vs laparoscopic surgery for colon cancer utilizing a large national database.

BACKGROUND: Prior studies have shown comparable outcomes between laparoscopic and robotic approaches across a range of surgeries; however, these have been limited in size. This study investigates differences in outcomes following robotic (RC) vs laparoscopic (LC) colectomy across several years utilizing a large national database. METHODS: We analyzed data from ACS NSQIP for patients who underwent elective minimally invasive colectomies for colon cancer from 2012 to 2020. Inverse probability weighting with regression adjustment (IPWRA) incorporating demographics, operative factors, and comorbidities was used. Outcomes included mortality, complications, return to the operating room (OR), post-operative length of stay (LOS), operative time, readmission, and anastomotic leak. Secondary analysis was performed to further assess anastomotic leak rate following right and left colectomies. RESULTS: We identified 83,841 patients who underwent elective minimally invasive colectomies: 14,122 (16.8%) RC and 69,719 (83.2%) LC. Patients who underwent RC were younger, more likely to be male, non-Hispanic White, with higher body mass index (BMI) and fewer comorbidities (for all, P < 0.05). After adjustment, there were no differences between RC and LC for 30-day mortality (0.8% vs 0.9% respectively, P = 0.457) or overall complications (16.9% vs 17.2%, P = 0.432). RC was associated with higher return to OR (5.1% vs 3.6%, P < 0.001), lower LOS (4.9 vs 5.1 days, P < 0.001), longer operative time (247 vs 184 min, P < 0.001), and higher rates of readmission (8.8% vs 7.2%, P < 0.001). Anastomotic leak rates were comparable for right-sided RC vs LC (2.1% vs 2.2%, P = 0.713), higher for left-sided LC (2.7%, P < 0.001), and highest for left-sided RC (3.4%, P < 0.001). CONCLUSIONS: Robotic approach for elective colon cancer resection has similar outcomes to its laparoscopic counterpart. There were no differences in mortality or overall complications, however anastomotic leaks were highest after left RC. Further investigation is imperative to better understand the potential impact of technological advancement such as robotic surgery on patient outcomes.

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.

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.

Impact of frailty on complications and length of stay after minimally invasive adrenalectomy surgery.

BACKGROUND: Adrenal disease requiring surgery incidence increases with age, and minimally invasive adrenalectomy procedures have improved the safety of adrenal surgery. This study evaluates the perioperative outcomes of elective adrenalectomies when performed in older patients and how frailty affects such outcomes. METHODS: Patients undergoing elective minimally invasive adrenalectomy were identified using the American College of Surgeon's National Surgical Quality Improvement Program Participant Use Targeted File years 2005 to 2020. The surgical indication was categorized as a benign disease, an endocrine disorder, or a malignant disease. Frailty was defined using the 5-item modified frailty index. Multivariable regressions were used to model the relationship of age and frailty with surgical outcomes. RESULTS: In 8,693 minimally invasive adrenalectomy patients, 5,281 (61%) were female, 5,026 (58%) were White, and 1,924 (22%) were aged 65 years or older. Surgical indications were benign disease 5,487 (63%), endocrinopathy 2,850 (33%), and malignancy 356 (4%). Patients aged <65 years (compared to those aged ≥65) were more likely to have a 5-item modified frailty index = 0 (26% vs 14%, respectively) and less likely to have a 5-item modified frailty index = ≥3 (2% vs 4%, respectively; P < .001). OUTCOMES: 30-day mortality 20 (0.2%), complications 459 (5%), return to operating room 73 (0.8%), and median length of stay 2 days. Thirty-day mortality was associated with a 5-item modified frailty index ≥3 (P = .009) and endocrine disease (P = .005) but not with age. Complications were associated with a 5-item modified frailty index ≥2 (≤P < .001) and malignant disease (P = .002), but not with age. CONCLUSION: Minimally invasive adrenalectomy has low 30-day mortality and complication rates that increase with frailty and not age. Frailty is a better predictor than the age of most adverse outcomes after elective minimally invasive adrenalectomy.

Racial disparities in complications following elective colon cancer resection: Impact of laparoscopic versus robotic approaches.

BACKGROUND: We sought to examine differences in outcomes for Black and White patients undergoing robotic or laparoscopic colectomy to assess the potential impact of technological advancement. METHODS: We queried the ACS-NSQIP database for elective robotic (RC) and laparoscopic (LC) colectomy for cancer from 2012 to 2020. Outcomes included 30-day mortality and complications. We analyzed the association between outcomes, operative approach, and race using multivariable logistic regression. RESULTS: We identified 64,460 patients, 80.9% laparoscopic and 19.1% robotic. RC patients were most frequently younger, male, and White, with fewer comorbidities (P â€‹< â€‹0.001). After adjustment, there was no difference in mortality by approach or race. Black patients who underwent LC had higher complications (OR 1.10, 95% CI 1.03-1.08, P â€‹= â€‹0.005) than their White LC counterparts and RC patients. CONCLUSIONS: Robotic colectomy was associated with lower rates of complications in minority patients. Further investigation is required to identify the causal pathway that leads to our finding.

Integration of Veterans Affairs Medical Centers Into Neurosurgical Residency Programs.

Veterans Affairs (VA) medical centers serve as a unique training environment for US residency programs. In this study, we aim to explore the scope and details of VA integration into neurosurgery resident training. We used data from the Accreditation Council for Graduate Medical Education database to provide an overview of neurosurgery training programs with an active VA affiliation and developed a multi-institutional survey to gather information related to rotation design, operative volume, expectations, and core training values. Of the 116 neurosurgery residency programs, 40 have an active affiliation with a VA medical center (34%). Residents most frequently rotated at the VA during their third postgraduate year, with an average rotation length of 7.5 months (range 2-21). Nearly all programs reported a weekly mix of clinic and operative days (96%), with residents longitudinally following patients throughout their rotations. Attending neurosurgeons from VA-affiliated programs reported operative experience (100%), independent decision-making (89%), and continuity of care (81%) as core values of VA neurosurgery rotations. Surgical volume varied between programs with an average of 13.4 ± 6.4 (SD) cases per month per rotating resident. A significant portion of neurosurgery residency programs in the United States incorporate VA rotations into resident training. Although rotation details vary from program-to-program, shared values include a strong operative experience, independent decision-making, and continuity of care. This analysis provides a comprehensive assessment of VA rotation structure across the country, which is valuable for programs considering implementing a VA rotation into their training program or modifying an existing rotation.

Incidence, Microbiological Studies, and Factors Associated With Prosthetic Joint Infection After Total Knee Arthroplasty.

Importance: Despite the frequency of total knee arthroplasty (TKA) and clinical implications of prosthetic joint infections (PJIs), knowledge gaps remain concerning the incidence, microbiological study results, and factors associated with these infections. Objectives: To identify the incidence rates, organisms isolated from microbiological studies, and patient and surgical factors of PJI occurring early, delayed, and late after primary TKA. Design, Setting, and Participants: This cohort study obtained data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse on patients who underwent elective primary TKA in the VA system between October 1, 1999, and September 30, 2019, and had at least 1 year of care in the VA prior to TKA. Patients who met these criteria were included in the overall cohort, and patients with linked Veterans Affairs Surgical Quality Improvement Program (VASQIP) data composed the VASQIP cohort. Data were analyzed between December 9, 2021, and September 18, 2023. Exposures: Primary TKA as well as demographic, clinical, and perioperative factors. Main Outcomes and Measures: Incident hospitalization with early, delayed, or late PJI. Incidence rate (events per 10 000 person-months) was measured in 3 postoperative periods: early (≤3 months), delayed (between >3 and ≤12 months), and late (>12 months). Unadjusted Poisson regression was used to estimate incidence rate ratios (IRRs) with 95% CIs of early and delayed PJI compared with late PJI. The frequency of organisms isolated from synovial or operative tissue culture results of PJIs during each postoperative period was identified. A piecewise exponential parametric survival model was used to estimate IRRs with 95% CIs associated with demographic and clinical factors in each postoperative period. Results: The 79 367 patients (median (IQR) age of 65 (60-71) years) in the overall cohort who underwent primary TKA included 75 274 males (94.8%). A total of 1599 PJIs (2.0%) were identified. The incidence rate of PJI was higher in the early (26.8 [95% CI, 24.8-29.0] events per 10 000 person-months; IRR, 20.7 [95% CI, 18.5-23.1]) and delayed periods (5.4 [95% CI, 4.9-6.0] events per 10 000 person-months; IRR, 4.2 [95% CI, 3.7-4.8]) vs the late postoperative period (1.3 events per 10 000 person-months). Staphylococcus aureus was the most common organism isolated overall (489 [33.2%]); however, gram-negative infections were isolated in 15.4% (86) of early PJIs. In multivariable analyses, hepatitis C virus infection, peripheral artery disease, and autoimmune inflammatory arthritis were associated with PJI across all postoperative periods. Diabetes, chronic kidney disease, and obesity (body mass index of ≥30) were not associated factors. Other period-specific factors were identified. Conclusions and Relevance: This cohort study found that incidence rates of PJIs were higher in the early and delayed vs late post-TKA period; there were differences in microbiological cultures and factors associated with each postoperative period. These findings have implications for postoperative antibiotic use, stratification of PJI risk according to postoperative time, and PJI risk factor modification.

Adult glioblastoma multiforme survival in the temozolomide era: a population-based analysis of Surveillance, Epidemiology, and End Results registries.

BACKGROUND: Survival after a glioblastoma multiforme (GBM) diagnosis remained static during the several decades before 1999. We hypothesized that the progressive increase in temozolomide use for GBM treatment that began in 1999 in the United States would be paralleled by a corresponding improvement in survival. METHODS: We included 19,674 GBM cases, ages 20 years or greater, diagnosed 1993 to 2007 in the population-based Surveillance, Epidemiology, and End Results Program database. We used proportional hazards models to calculate calendar period hazard ratios (HR) and 95% confidence intervals (CI), adjusted for demographic covariates. We compared survival across periods using the Kaplan-Meier method. RESULTS: Starting with cases diagnosed in 1999 to 2001, we observed a progressive decrease in HRs compared with cases diagnosed in 1993 to 1995. The multivariate-adjusted HR for 2005 to 2007 versus 1993 to 1995 was 0.69 (95% CI, 0.65-0.72). Age-stratified analyses revealed that this progressive decrease occurred in all age groups except 80+ years. Two-year survival increased from 7% among cases diagnosed in 1993 to 1995 and 1996 to 1998 to 9% among cases diagnosed in 1999 to 2001, 13% in 2002 to 2004, and 17% in 2005 to 2007. The disparity in survival between young and old patients increased in the temozolomide era, with 2-year survival of 39% among cases diagnosed at ages 20 to 44 years and 1% among cases diagnosed at 80+ years in 2005 to 2007. CONCLUSIONS: We observed a modest, but meaningful, population-based survival improvement for GBM patients in the United States. Widespread adoption of temozolomide represents the most likely explanation, although other treatment advances, such as increased extent of surgical resection, also may have played a role.

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.

Glycemic control and infections in patients with diabetes undergoing noncardiac surgery.

OBJECTIVE: Examine the relationship between perioperative glucose control and postoperative infections in a nationwide sample of diabetic patients undergoing a wide variety of surgical procedures. SUMMARY OF BACKGROUND DATA: Perioperative glucose control has been linked to postoperative infections after selected surgical procedures. METHODS: Retrospective analysis of surgical outcomes data from 1999 to 2004 on 55,408 patients with diabetes undergoing a variety of noncardiac operations contained in the Veterans Heath Administration National Surgical Quality Improvement Program database, supplemented with the Veterans Heath Administration Decision Support Services hemoglobin A1c (HbA(1c)) and serum glucose data. Multivariate Poisson regression model of postoperative infection including demographics, comorbidities, functional status, preoperative laboratories, surgical data, and glucose control (diabetes medications, serum glucose, HbA(1c), mean serum glucose within 24 hours after surgery). RESULTS: The most common procedures were herniorrhaphy (10%), carotid endarterectomy (6.6%), and open colectomy (5.6%). Mean (SD) preoperative HbA1c concentration was 7.9% (2.3); 51% of patients had preoperative serum glucose concentrations more than 150 mg/dL; and 72% of patients had a mean 24 hour postoperative glucose concentration at least 150 mg/dL. The overall postoperative infection rate was 8.0%. Higher rates of postoperative infection were associated with mean 24 hour postoperative serum glucose concentrations of 150 to 250 mg/dL (incidence rate ratio 1.22, 95% confidence interval, 1.04-1.43; P = 0.01) and more than 250 mg/dL (incidence rate ratio: 1.43; 95% confidence interval, 1.19-1.71; P < 0.001). Preoperative HbA1c and glucose concentrations were not associated with increased infection rates. CONCLUSIONS: In a large nationwide sample of diabetic patients undergoing a variety of noncardiac surgical procedures, glucose control in the first 24 hours after surgery was poor, and mean serum glucose concentrations of 150 mg/dL and higher during this time period were associated with increased rates of postoperative infectious complications.

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.

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.

The duration of postoperative acute kidney injury is an additional parameter predicting long-term survival in diabetic veterans.

Acute kidney injury (AKI) is primarily defined and staged according to the magnitude of the rise in serum creatinine. Here we sought to determine if the duration of AKI adds additional prognostic information above that from the magnitude of injury alone. We prospectively studied 35,302 diabetic patients from 123 Veterans Affairs Medical Centers undergoing their first noncardiac surgery. The main outcome was long-term mortality in those who survived the index hospitalization. AKI was stratified by magnitude according to AKI Network stages and by the duration (short (less than 2 days), medium (3-6 days) or long (7 days or more)). Overall, 17.8% of patients experienced at least stage 1 AKI or greater following surgery. Both the magnitude and duration of AKI were significantly associated with long-term survival in a dose-dependent manner. Within each stage, longer duration of AKI was significantly associated with a graded higher rate of mortality. However, within each of the duration categories, the stage was not associated with mortality. When considered separately in multivariate analyses, both a higher stage and duration were independently associated with increased risk of long-term mortality. Hence, the duration of AKI adds additional information to predict long-term mortality.

Preoperative Urinary Tract Infection Increases Postoperative Morbidity in Spine Patients.

STUDY DESIGN: Retrospective review. OBJECTIVE: Compare postoperative infection rates and 30-day outcomes in spine surgery patients with and without a preoperative urinary tract infection (UTI). SUMMARY OF BACKGROUND DATA: There is mixed evidence regarding safety and risks when operating on spine patients with a preoperative UTI. METHODS: Using data from the American College of Surgeons National Surgical Quality Improvement Program, we identified all adult patients undergoing spine surgery between 2012 and 2017 with a preoperative UTI. Patients with other preoperative infections were excluded. Our primary outcome was any postoperative infection (pneumonia, sepsis, surgical site infection, and organ space infection). Our secondary outcomes included surgical site infections, non-infectious complications, return to operating room, and 30-day readmission and mortality. We used univariate, then multivariate Poisson regression models adjusted for demographics, comorbidities, laboratory values, and case details to investigate the association between preoperative UTI status and postoperative outcomes. RESULTS: A total of 270,371 patients who underwent spine surgery were analyzed. The most common procedure was laminectomy (41.9%), followed by spinal fusion (31.7%) and laminectomy/fusion (25.6%). Three hundred fourty one patients had a preoperative UTI (0.14%). Patients with a preoperative UTI were more likely to be older, female, inpatients, emergency cases, with a higher American Society of Anesthesiologists score, and a longer operating time (for all, P < 0.001). Patients with a preoperative UTI had higher rates of infectious and non-infectious complications, return to operating room, and unplanned readmissions (for all, P < 0.001). However, there was no significant difference in mortality (0.6% vs. 0.2%, P = 0.108). Even after controlling for demographics, comorbidities, labs, and case details, preoperative UTI status was significantly associated with more postoperative infectious complications (incidence rate ratio [IRR]: 2.88, 95% confidence interval [CI]: 2.25-3.70, P < 0.001). CONCLUSION: Preoperative UTI status is significantly associated with postoperative infections and worse 30-day outcomes. Spine surgeons should consider delaying or cancelling surgery in patients with a UTI until the infection has cleared to reduce adverse outcomes. LEVEL OF EVIDENCE: 3.

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.

Covid-19 by Race and Ethnicity: A National Cohort Study of 6 Million United States Veterans.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. OBJECTIVE: To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. DESIGN: Retrospective cohort study. SETTING: United States Department of Veterans Affairs (VA). PARTICIPANTS: 5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. Exposures: Self-reported race/ethnicity. MAIN OUTCOME MEASURES: We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. RESULTS: Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). CONCLUSIONS: Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.

Covid-19 Testing, Hospital Admission, and Intensive Care Among 2,026,227 United States Veterans Aged 54-75 Years.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United States. OBJECTIVE: To determine associations between demographic and clinical factors and testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study including all patients tested for Covid-19 between February 8 and March 30, 2020, inclusive. We extracted electronic health record data from the national Veterans Affairs Healthcare System, the largest integrated healthcare system in the United States, on 2,026,227 patients born between 1945 and 1965 and active in care. Exposures: Demographic data, comorbidities, medication history, substance use, vital signs, and laboratory measures. Laboratory tests were analyzed first individually and then grouped into a validated summary measure of physiologic injury (VACS Index). Main Outcomes and Measures: We evaluated which factors were associated with Covid-19+ among all who tested. Among Covid-19+ we identified factors associated with hospitalization or intensive care. We identified independent associations using multivariable and conditional multivariable logistic regression with multiple imputation of missing values. RESULTS: Among Veterans aged 54-75 years, 585/3,789 (15.4%) tested Covid-19+. In adjusted analysis (C-statistic=0.806) black race was associated with Covid-19+ (OR 4.68, 95% CI 3.79-5.78) and the association remained in analyses conditional on site (OR 2.56, 95% CI 1.89-3.46). In adjusted models, laboratory abnormalities (especially fibrosis-4 score [FIB-4] >3.25 OR 8.73, 95% CI 4.11-18.56), and VACS Index (per 5-point increase OR 1.62, 95% CI 1.43-1.84) were strongly associated with hospitalization. Associations were similar for intensive care. Although significant in unadjusted analyses, associations with comorbid conditions and medications were substantially reduced and, in most cases, no longer significant after adjustment. CONCLUSIONS AND RELEVANCE: Black race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure.

Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States.

IMPORTANCE: Deaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19. OBJECTIVE: To evaluate whether initiation of prophylactic anticoagulation within 24 hours of admission is associated with decreased risk of death among patients hospitalized with COVID-19. DESIGN: Observational cohort study. SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States. PARTICIPANTS: All patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation. EXPOSURES: Prophylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants. MAIN OUTCOMES AND MEASURES: 30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation. RESULTS: Of 4,297 patients hospitalized with COVID-19, 3,627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3,600) received subcutaneous heparin or enoxaparin. We observed 622 deaths within 30 days of admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospitalization. In inverse probability of treatment weighted analyses, cumulative adjusted incidence of mortality at 30 days was 14.3% (95% CI 13.1-15.5) among those receiving prophylactic anticoagulation and 18.7% (95% CI 15.1-22.9) among those who did not. Compared to patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30-day mortality (HR 0.73, 95% CI 0.66-0.81). Similar associations were found for inpatient mortality and initiating therapeutic anticoagulation. Quantitative bias analysis demonstrated that results were robust to unmeasured confounding (e-value lower 95% CI 1.77). Results persisted in a number of sensitivity analyses. CONCLUSIONS AND RELEVANCE: Early initiation of prophylactic anticoagulation among patients hospitalized with COVID-19 was associated with a decreased risk of mortality. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission.