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BackgroundThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.MethodsIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.ResultsThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio

BackgroundThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.MethodsIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.ResultsThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.ConclusionsIn noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

BackgroundThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.MethodsIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.ResultsThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio

BackgroundThe large-scale social distancing efforts to reduce SARS-CoV-2 transmission have dramatically changed human behaviors associated with traumatic injuries. Trauma centers have reported decreases in trauma volume, paralleled by changes in injury mechanisms. We aimed to quantify changes in trauma epidemiology at an urban Level I trauma center in a county that instituted one of the earliest shelter-in-place orders to inform trauma care during future pandemic responses.MethodsA single-center interrupted time-series analysis was performed to identify associations of shelter-in-place with trauma volume, injury mechanisms, and patient demographics in San Francisco, California. To control for short-term trends in trauma epidemiology, weekly level data were analyzed 6 months before shelter-in-place. To control for long-term trends, monthly level data were analyzed 5 years before shelter-in-place.ResultsTrauma volume decreased by 50% in the week following shelter-in-place (p < 0.01), followed by a linear increase each successive week (p < 0.01). Despite this, trauma volume for each month (March-June 2020) remained lower compared with corresponding months for all previous 5 years (2015-2019). Pediatric trauma volume showed similar trends with initial decreases (p = 0.02) followed by steady increases (p = 0.05). Reductions in trauma volumes were due entirely to changes in nonviolent injury mechanisms, while violence-related injury mechanisms remained unchanged (p < 0.01).ConclusionAlthough the shelter-in-place order was associated with an overall decline in trauma volume, violence-related injuries persisted. Delineating and addressing underlying factors driving persistent violence-related injuries during shelter-in-place orders should be a focus of public health efforts in preparation for future pandemic responses.Level of evidenceEpidemiological study, level III.

Care during mass casualty events (MCE) has improved during the last 15 years. Military and civilian collaboration has led to partnerships which augment the response to MCE. Much has been written about strategies to deliver care during an MCE, but there is little about how to transition back to normal operations after an event. A panel discussion entitled The Day(s) After: Lessons Learned from Trauma Team Management in the Aftermath of an Unexpected Mass Casualty Event at the 76th Annual American Association for the Surgery of Trauma meeting on September 13, 2017 brought together a cadre of military and civilian surgeons with experience in MCEs. The events described were the First Battle of Mogadishu (1993), the Second Battle of Fallujah (2004), the Bagram Detention Center Rocket Attack (2014), the Boston Marathon Bombing (2013), the Asiana Flight 214 Plane Crash (2013), the Baltimore Riots (2015), and the Orlando Pulse Night Club Shooting (2016). This article focuses on the lessons learned from military and civilian surgeons in the days after MCEs.

BackgroundThe Mangled Extremity Severity Score (MESS) was developed 25 years ago in an attempt to use the extent of skeletal and soft tissue injury, limb ischemia, shock, and age to predict the need for amputation after extremity injury. Subsequently, there have been mixed reviews as to the use of this score. We hypothesized that the MESS, when applied to a data set collected prospectively in modern times, would not correlate with the need for amputation.MethodsWe applied the MESS to patient data collected in the American Association for the Surgery of Trauma PROspective Vascular Injury Treatment registry. This registry contains prospectively collected demographic, diagnostic, treatment, and outcome data.ResultsBetween 2013 and 2015, 230 patients with lower extremity arterial injuries were entered into the PROspective Vascular Injury Treatment registry. Most were male with a mean age of 34 years (range, 4-92 years) and a blunt mechanism of injury at a rate of 47.4%. A MESS of 8 or greater was associated with a longer stay in the hospital (median, 22.5 (15, 29) vs 12 (6, 21); p = 0.006) and intensive care unit (median, 6 (2, 13) vs 3 (1, 6); p = 0.03). Of the patients' limbs, 81.3% were ultimately salvaged (median MESS, 4 (3, 5)), and 18.7% required primary or secondary amputation (median MESS, 6 (4, 8); p < 0.001). However, after controlling for confounding variables including mechanism of injury, degree of arterial injury, injury severity score, arterial location, and concomitant injuries, the MESS between salvaged and amputated limbs was no longer significantly different. Importantly, a MESS of 8 predicted in-hospital amputation in only 43.2% of patients.ConclusionTherapeutic advances in the treatment of vascular, orthopedic, neurologic, and soft tissue injuries have reduced the diagnostic accuracy of the MESS in predicting the need for amputation. There remains a significant need to examine additional predictors of amputation following severe extremity injury.Level of evidenceProspective, prognostic study, level III.

IntroductionAdvances in technology have made extensive monitoring of patient physiology the standard of care in intensive care units (ICUs). While many systems exist to compile these data, there has been no systematic multivariate analysis and categorization across patient physiological data. The sheer volume and complexity of these data make pattern recognition or identification of patient state difficult. Hierarchical cluster analysis allows visualization of high dimensional data and enables pattern recognition and identification of physiologic patient states. We hypothesized that processing of multivariate data using hierarchical clustering techniques would allow identification of otherwise hidden patient physiologic patterns that would be predictive of outcome.MethodsMultivariate physiologic and ventilator data were collected continuously using a multimodal bioinformatics system in the surgical ICU at San Francisco General Hospital. These data were incorporated with non-continuous data and stored on a server in the ICU. A hierarchical clustering algorithm grouped each minute of data into 1 of 10 clusters. Clusters were correlated with outcome measures including incidence of infection, multiple organ failure (MOF), and mortality.ResultsWe identified 10 clusters, which we defined as distinct patient states. While patients transitioned between states, they spent significant amounts of time in each. Clusters were enriched for our outcome measures: 2 of the 10 states were enriched for infection, 6 of 10 were enriched for MOF, and 3 of 10 were enriched for death. Further analysis of correlations between pairs of variables within each cluster reveals significant differences in physiology between clusters.ConclusionsHere we show for the first time the feasibility of clustering physiological measurements to identify clinically relevant patient states after trauma. These results demonstrate that hierarchical clustering techniques can be useful for visualizing complex multivariate data and may provide new insights for the care of critically injured patients.

Thromboembolism is an important complication in hospitalized patients with COVID-19. This trial sought to determine whether extended thromboprophylaxis after hospital discharge would reduce deaths and thromboembolic events. The trial was done during a time when the Omicron and Delta variants were circulating and COVID-19 hospitalization rates were decreasing. Visual Abstract. Thromboprophylaxis After COVID-19 Hospitalization.: Thromboembolism is an important complication in hospitalized patients with COVID-19. This trial sought to determine whether extended thromboprophylaxis after hospital discharge would reduce deaths and thromboembolic events. The trial was done during a time when the Omicron and Delta variants were circulating and COVID-19 hospitalization rates were decreasing. Background: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. Objective: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. Design: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087) Setting: Done during 2021 to 2022 among 127 U.S. hospitals. Participants: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. Intervention: 2.5 mg of apixaban versus placebo twice daily for 30 days. Measurements: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. Results: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. Limitations: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. Conclusion: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

The need to improve and integrate civilian and military casualty care and trauma systems in an effort to increase care and treatment of all types of injuries is discussed.

Objective: Multicenter data from 2 decades ago demonstrated that critically ill and injured patients spending more than 6 hours in the emergency department (ED) before transfer to the intensive care unit (ICU) had higher mortality rates. A contemporary analysis of ED length of stay in critically injured patients at American College of Surgeons’ Trauma Quality Improvement Program (ACS-TQIP) centers was performed to test whether prolonged ED length of stay is still associated with mortality. Methods: This was an observational cohort study of critically injured patients admitted directly to ICU from the ED in ACS-TQIP centers from 2010-2015. Spending more than 6 hours in the ED was defined as prolonged ED length of stay. Patients with prolonged ED length of stay were matched to those with non-prolonged ED length of stay and mortality was compared. Main Results: A total of 113,097 patients were directly admitted from the ED to the ICU following injury. The median ED length of stay was 167 minutes. Prolonged ED length of stay occurred in 15,279 (13.5%) of patients. Women accounted for 29.4% of patients with prolonged ED length of stay but only 25.8% of patients with non-prolonged ED length of stay, P < 0.0001. Mortality rates were similar after matching—4.5% among patients with prolonged ED length of stay versus 4.2% among matched controls. Multivariable logistic regression of the matched cohorts demonstrated prolonged ED length of stay was not associated with mortality. However, women had higher adjusted mortality compared to men Odds Ratio = 1.41, 95% Confidence Interval 1.28 -1.61, P < 0.0001. Conclusion: Prolonged ED length of stay is no longer associated with mortality among critically injured patients. Women are more likely to have prolonged ED length of stay and mortality. [ABSTRACT FROM AUTHOR]