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Abstract Background A trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5. Methods We did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality. Results Among 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23–0.67], p

Abstract Background Clinical trials often involve some form of interim monitoring to determine futility before planned trial completion. While many options for interim monitoring exist (e.g., alpha-spending, conditional power), nonparametric based interim monitoring methods are also needed to account for more complex trial designs and analyses. The upstrap is one recently proposed nonparametric method that may be applied for interim monitoring. Methods Upstrapping is motivated by the case resampling bootstrap and involves repeatedly sampling with replacement from the interim data to simulate thousands of fully enrolled trials. The p-value is calculated for each upstrapped trial and the proportion of upstrapped trials for which the p-value criteria are met is compared with a pre-specified decision threshold. To evaluate the potential utility for upstrapping as a form of interim futility monitoring, we conducted a simulation study considering different sample sizes with several different proposed calibration strategies for the upstrap. We first compared trial rejection rates across a selection of threshold combinations to validate the upstrapping method. Then, we applied upstrapping methods to simulated clinical trial data, directly comparing their performance with more traditional alpha-spending and conditional power interim monitoring methods for futility. Results The method validation demonstrated that upstrapping is much more likely to find evidence of futility in the null scenario than the alternative across a variety of simulations settings. Our three proposed approaches for calibration of the upstrap had different strengths depending on the stopping rules used. Compared to O’Brien-Fleming group sequential methods, upstrapped approaches had type I error rates that differed by at most 1.7% and expected sample size was 2–22% lower in the null scenario, while in the alternative scenario power fluctuated between 15.7% lower and 0.2% higher and expected sample size was 0–15% lower. Conclusions In this proof-of-concept simulation study, we evaluated the potential for upstrapping as a resampling-based method for futility monitoring in clinical trials. The trade-offs in expected sample size, power, and type I error rate control indicate that the upstrap can be calibrated to implement futility monitoring with varying degrees of aggressiveness and that performance similarities can be identified relative to considered alpha-spending and conditional power futility monitoring methods.

ABSTRACT: Objectives: Bebtelovimab is an anti-SARS-CoV-2 monoclonal antibody active against Omicron lineage variants authorized to treat high-risk outpatients with COVID-19. We sought to determine the real-world effectiveness of bebtelovimab during the Omicron phases BA.2/BA2.12.1/BA4/BA5. Methods: We conducted a retrospective cohort study of adults with SARS-CoV-2 infection between April 6 and October 11, 2022, using health records linked to vaccine and mortality data. We used propensity scores to match of bebtelovimab-treated with untreated outpatients. The primary outcome was 28-day all-cause hospitalization. The secondary outcomes were 28-day COVID-19-related hospitalization, 28-day all-cause mortality, 28-day emergency department visits, maximum respiratory support level, intensive care unit admission, and in-hospital mortality among hospitalized patients. We used logistic regression to determine bebtelovimab treatment effectiveness. Results: Among 22,720 patients with SARS-COV-2 infection, 3739 bebtelovimab-treated patients were matched to 5423 untreated patients. Compared with no treatment, bebtelovimab was associated with lower odds of 28-day all-cause hospitalization (1.3% vs 2.1%, adjusted odds ratio: 0.53; 95% confidence interval: 0.37-0.74, P

Abstract Objectives To evaluate whether subcutaneous neutralizing monoclonal antibody (mAb) treatment given in the emergency department (ED) setting was associated with reduced hospitalizations, mortality, and severity of disease when compared to nontreatment among mAb‐eligible patients with coronavirus disease 2019 (COVID‐19). Methods This retrospective observational cohort study of ED patients utilized a propensity score‐matched analysis to compare patients who received subcutaneous casirivimab and imdevimab mAb to nontreated COVID‐19 control patients in November–December 2021. The primary outcome was all‐cause hospitalization within 28 days, and secondary outcomes were 90‐day hospitalization, 28‐ and 90‐day mortality, and ED length of stay (LOS). Results Of 1340 patients included in the analysis, 490 received subcutaneous casirivimab and imdevimab, and 850 did not received them. There was no difference observed for 28‐day hospitalization (8.4% vs. 10.6%; adjusted odds ratio [aOR] 0.79, 95% confidence intervals [CI] 0.53–1.17) or 90‐day hospitalization (11.6% vs. 12.5%; aOR 0.93, 95% CI 0.65–1.31). However, mortality at both the 28‐day and 90‐day timepoints was substantially lower in the treated group (28‐day 0.6% vs. 3.1%; aOR 0.18, 95% CI 0.08–0.41; 90‐day 0.6% vs. 3.9%; aOR 0.14, 95% CI 0.06–0.36). Among hospitalized patients, treated patients had shorter hospital LOS (5.7 vs. 11.4 days; adjusted rate ratio [aRR] 0.47, 95% CI 0.33–0.69), shorter intensive care unit LOS (3.8 vs. 10.2 days; aRR 0.22, 95% CI 0.14–0.35), and the severity of hospitalization was lower (aOR 0.45, 95% CI 0.21–0.97) compared to untreated. Conclusions Among ED patients who presented for symptomatic COVID‐19 during the Delta variant phase, ED subcutaneous casirivimab/imdevimab treatment was not associated with a decrease in hospitalizations. However, treatment was associated with lower mortality at 28 and 90 days, hospital LOS, and overall severity of illness.

Abstract Introduction In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day 28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs). Methods PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7 days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60 years, obesity [body mass index ≥ 30], or certain coexisting medical conditions). Patients received remdesivir intravenously (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. Results In this subgroup analysis, HTE of remdesivir by time from symptom onset at treatment initiation and number of baseline RFs was not detected. Treatment with remdesivir reduced COVID-19-related hospitalizations independent of stratification by time from symptom onset to randomization. Of patients enrolled ≤ 5 days from symptom onset, 1/201 (0.5%) receiving remdesivir and 9/194 (4.6%) receiving placebo were hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01–0.82). Of those enrolled at > 5 days from symptom onset, 1/78 (1.3%) receiving remdesivir and 6/89 (6.7%) receiving placebo were hospitalized (HR 0.19; 95% CI 0.02–1.61). Remdesivir was also effective in reducing COVID-19-related hospitalizations when stratified by number of baseline RFs for severe disease. Of patients with ≤ 2 RFs, 0/159 (0.0%) receiving remdesivir and 4/164 (2.4%) receiving placebo were hospitalized; of those with ≥ 3 RFs, 2/120 (1.7%) receiving remdesivir and 11/119 (9.2%) receiving placebo were hospitalized (HR 0.16; 95% CI 0.04–0.73). Conclusions In the outpatient setting, benefit of remdesivir initiated within 7 days of symptoms appeared to be consistent across patients with RFs. Therefore, it may be reasonable to broadly treat patients with remdesivir regardless of comorbidities. Trial Registration ClinicalTrials.gov number NCT04501952.

ABSTRACT: Objectives: Sotrovimab effectively prevented progression to severe disease and mortality following infection with pre-Omicron SARS-CoV-2 variants. We sought to determine whether sotrovimab is similarly effective against SARS-CoV-2 Omicron variant infection. Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from December 26, 2021, to March 10, 2022, using electronic health records from a statewide health system. We propensity-matched patients not receiving authorized treatment for each patient treated with sotrovimab. The primary outcome was 28-day hospitalization; secondary outcomes included mortality. We also propensity-matched sotrovimab-treated patients from the Omicron and Delta phases. Logistic regression was used to determine sotrovimab effectiveness during Omicron and between variant phases. Results: Of 30,247 SARS-CoV-2 Omicron variant infected outpatients, we matched 1542 receiving sotrovimab to 3663 not receiving treatment. Sotrovimab treatment was not associated with reduced odds of 28-day hospitalization (2.5% vs 3.2%; adjusted odds ratio [OR] 0.82, 95% CI 0.55, 1.19) or mortality (0.1% vs 0.2%; adjusted OR 0.62, 95% CI 0.07, 2.78). Between phases, the observed treatment OR was higher during Omicron than during Delta (OR 0.85 vs 0.39, respectively; interaction P-value = 0.053). Conclusion: Real-world evidence demonstrated that sotrovimab was not associated with reduced 28-day hospitalization or mortality among COVID-19 outpatients during the Omicron BA.1 phase.

Objectives: Effective and widely available therapies are still needed for outpatients with COVID-19. We aimed to evaluate the efficacy and safety of lopinavir/ritonavir (LPV/r) for early treatment of non-hospitalized individuals diagnosed with COVID-19. Methods: This randomized, placebo (Plb)-controlled, double-blind, multi-site decentralized clinical trial enrolled non-hospitalized adults with confirmed SARS-CoV-2 infection and six or fewer days of acute respiratory infection symptoms who were randomized to either twice-daily oral LPV/r (400 mg/100 mg) or Plb for 14 days. Daily surveys on study days 1 through 16 and again on study day 28 evaluated symptoms, daily activities, and hospitalization status. The primary outcome was longitudinal change in an ordinal scale based on a combination of symptoms, activity, and hospitalization status through day 15 and was analyzed by use of a Bayesian longitudinal proportional odds logistic regression model for estimating the probability of a superior recovery for LPV/r over Plb (odds ratio >1). Results: Between June 2020 and December 2021, 448 participants were randomized to receive either LPV/r (n = 216) or Plb (n = 221). The mean symptom duration before randomization was 4.3 days (SD 1.3). There were no differences between treatment groups through the first 15 days for the ordinal primary outcome (odds ratio 0.96; 95% credible interval: 0.66 to 1.41). There were 3.2% (n = 7) of LPV/r and 2.7% (n = 6) of Plb participants hospitalized by day 28. Serious adverse events did not differ between groups. Conclusion: LPV/r did not significantly improve symptom resolution or reduce hospitalization in non-hospitalized participants with COVID-19. Trial registration: ClinicalTrials.gov Identifier: NCT04372628

Abstract Background Neutralizing monoclonal antibodies (mAbs) are highly effective in reducing hospitalization and mortality among early symptomatic COVID-19 patients in clinical trials and real-world data. While resistance to some mAbs has since emerged among new variants, characteristics associated with treatment failure of mAbs remain unknown. Methods This multicenter, observational cohort study included patients with COVID-19 who received mAb treatment between November 20, 2020, and December 9, 2021. We utilized electronic health records from a statewide health system plus state-level vaccine and mortality data. The primary outcome was mAb treatment failure, defined as hospitalization or death within 28 days of a positive SARS-CoV-2 test. Results COVID-19 mAb was administered to 7406 patients. Hospitalization within 28 days of positive SARS-CoV-2 test occurred in 258 (3.5%) of all patients who received mAb treatment. Ten patients (0.1%) died within 28 days, and all but one were hospitalized prior to death. Characteristics associated with treatment failure included having two or more comorbidities excluding obesity and immunocompromised status (adjusted odds ratio [OR] 3.71, 95% confidence interval [CI] 2.52–5.56), lack of SARS-CoV-2 vaccination (OR 2.73, 95% CI 2.01–3.77), non-Hispanic black race/ethnicity (OR 2.21, 95% CI 1.20–3.82), obesity (OR 1.79, 95% CI 1.36–2.34), one comorbidity (OR 1.68, 95% CI 1.11–2.57), age ≥ 65 years (OR 1.62, 95% CI 1.13–2.35), and male sex (OR 1.56, 95% CI 1.21–2.02). Immunocompromised status (none, mild, or moderate/severe), pandemic phase, and type of mAb received were not associated with treatment failure (all p > 0.05). Conclusions Comorbidities, lack of prior SARS-CoV-2 vaccination, non-Hispanic black race/ethnicity, obesity, age ≥ 65 years, and male sex are associated with treatment failure of mAbs.

Abstract Background Deaths due to injuries exceed 4.4 million annually, with over 90% occurring in low-and middle-income countries. A key contributor to high trauma mortality is prolonged trauma-to-treatment time. Earlier receipt of medical care following an injury is critical to better patient outcomes. Trauma epidemiological studies can identify gaps and opportunities to help strengthen emergency care systems globally, especially in lower income countries, and among military personnel wounded in combat. This paper describes the methodology of the “Epidemiology and Outcomes of Prolonged Trauma Care (EpiC)” study, which aims to investigate how the delivery of resuscitative interventions and their timeliness impacts the morbidity and mortality outcomes of patients with critical injuries in South Africa. Methods The EpiC study is a prospective, multicenter cohort study that will be implemented over a 6-year period in the Western Cape, South Africa. Data collected will link pre- and in-hospital care with mortuary reports through standardized clinical chart abstraction and will provide longitudinal documentation of the patient’s clinical course after injury. The study will enroll an anticipated sample of 14,400 injured adults. Survival and regression analysis will be used to assess the effects of critical early resuscitative interventions (airway, breathing, circulatory, and neurologic) and trauma-to-treatment time on the primary 7-day mortality outcome and secondary mortality (24-h, 30-day) and morbidity outcomes (need for operative interventions, secondary infections, and organ failure). Discussion This study is the first effort in the Western Cape of South Africa to build a standardized, high-quality, multicenter epidemiologic trauma dataset that links pre- and in-hospital care with mortuary data. In high-income countries and the U.S. military, the introduction of trauma databases and registries has led to interventions that significantly reduce post-injury death and disability. The EpiC study will describe epidemiology trends over time, and it will enable assessments of how trauma care and system processes directly impact trauma outcomes to ultimately improve the overall emergency care system. Trial Registration: Not applicable as this study is not a clinical trial.

ABSTRACT Little is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in vaccinated immunocompromised patients, particularly after the emergence of the Omicron variant. In this retrospective cohort study with exact matching and propensity score adjustment within the U.S. Department of Veterans Affairs (VA) healthcare system, we selected immunocompromised veterans age ≥18 years as of 1 January 2022, receiving VA healthcare. We compared a cohort of 1,878 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to 7,014 matched controls selected from patients who met study criteria but were not treated. Patients were followed through 15 June 2022, or until death, whichever occurred earlier. The primary outcome was a composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used Cox proportional hazards modeling to estimate the hazard ratios (HRs) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes. Most (73%) tixagevimab/cilgavimab recipients were ≥65 years old, and 80% had ≥3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to matched controls, recipients had a lower incidence of the composite COVID-19 outcome (49/1,878 [2.6%] versus 312/7,014 [4.4%]; HR 0.35; 95% CI, 0.24–0.52), and individually SARS-CoV-2 infection (HR 0.44; 95% CI, 0.22–0.88), COVID-19 hospitalization (HR 0.24; 95% CI, 0.10–0.59), and all-cause mortality (HR 0.32; 95% CI, 0.19–0.55). In conclusion, tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection and severe COVID-19 during the Omicron BA.1, BA.2, and BA.2.12.1 surge. IMPORTANCE SARS-CoV-2 remains an ongoing global health crisis that justifies continued efforts to validate and expand, when possible, knowledge on the efficacy of available vaccines and treatments. Clinical trials have been limited due to fast tracking of medications for mitigation of the COVID-19 pandemic for the general population. We present a real-world analysis, using electronic health record data, of the effectiveness of tixagevimab/cilgavimab for the prevention of COVID-19 infection in the unique population of U.S. veterans. Unlike those in the PROVENT clinical trial from which the emergency use authorization for tixagevimab/cilgavimab as a preventative treatment arose, the veterans population is highly immunocompromised and nearly 96% totally vaccinated. These demographics allowed us to analyze the effectiveness of tixagevimab/cilgavimab in preventing COVID-19 under different conditions in a more fragile population than that of the initial clinical trial.

OBJECTIVE:. Hypotension affects approximately 40% of critically ill patients undergoing emergency intubation and is associated with an increased risk of death. The objective of this study was to examine the association between prophylactic vasopressor administration and the incidence of peri-intubation hypotension and other clinical outcomes. DESIGN:. A secondary analysis of two multicenter randomized clinical trials. The clinical effect of prophylactic vasopressor administration was estimated using a one-to-one propensity-matched cohort of patients with and without prophylactic vasopressors. SETTING:. Seven emergency departments and 17 ICUs across the United States. PATIENTS:. One thousand seven hundred ninety-eight critically ill patients who underwent emergency intubation at the study sites between February 1, 2019, and May 24, 2021. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary outcome was peri-intubation hypotension defined as a systolic blood pressure less than 90 mm Hg occurring between induction and 2 minutes after tracheal intubation. A total of 187 patients (10%) received prophylactic vasopressors prior to intubation. Compared with patients who did not receive prophylactic vasopressors, those who did were older, had higher Acute Physiology and Chronic Health Evaluation II scores, were more likely to have a diagnosis of sepsis, had lower pre-induction systolic blood pressures, and were more likely to be on continuous vasopressor infusions prior to intubation. In our propensity-matched cohort, prophylactic vasopressor administration was not associated with reduced risk of peri-intubation hypotension (41% vs 32%; p = 0.08) or change in systolic blood pressure from baseline (–12 vs –11 mm Hg; p = 0.66). CONCLUSIONS:. The administration of prophylactic vasopressors was not associated with a lower incidence of peri-intubation hypotension in our propensity-matched analysis. To address potential residual confounding, randomized clinical trials should examine the effect of prophylactic vasopressor administration on peri-intubation outcomes.

OBJECTIVES:. The use of hyperoxemia during cardiac surgery remains controversial. We hypothesized that intraoperative hyperoxemia during cardiac surgery is associated with an increased risk of postoperative pulmonary complications. DESIGN:. Retrospective cohort study. SETTING:. We analyzed intraoperative data from five hospitals within the Multicenter Perioperative Outcomes Group between January 1, 2014, and December 31, 2019. We assessed intraoperative oxygenation of adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Hyperoxemia pre and post CPB was quantified as the area under the curve (AUC) of Fio2 above 0.21 in minutes when the corresponding peripheral oxygen saturation was greater than 92% measured by pulse oximetry. We quantified hyperoxemia during CPB as the AUC of Pao2 greater than 200 mm Hg measured by arterial blood gas. We analyzed the association of hyperoxemia during all phases of cardiac surgery with the frequency of postoperative pulmonary complications within 30 days, including acute respiratory insufficiency or failure, acute respiratory distress syndrome, need for reintubation, and pneumonia. PATIENTS:. Twenty-one thousand six hundred thirty-two cardiac surgical patients. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. During 21,632 distinct cardiac surgery cases, 96.4% of patients spent at least 1 minute in hyperoxemia (99.1% pre-CPB, 98.5% intra-CPB, and 96.4% post-CPB). Increasing exposure to hyperoxemia was associated with an increased risk of postoperative pulmonary complications throughout three distinct surgical periods. During CPB, increasing exposure to hyperoxemia was associated with an increased odds of developing postoperative pulmonary complications (p < 0.001) in a linear manner. Hyperoxemia before CPB (p < 0.001) and after CPB (p = 0.02) were associated with increased odds of developing postoperative pulmonary complications in a U-shaped relationship. CONCLUSIONS:. Hyperoxemia occurs almost universally during cardiac surgery. Exposure to hyperoxemia assessed continuously as an AUC during the intraoperative period, but particularly during CPB, was associated with an increased incidence of postoperative pulmonary complications.

OBJECTIVES:. Tracheal intubation (TI) is a common procedure in critical care, often performed with a Macintosh curved blade used for direct laryngoscopy (DL). Minimal evidence informs the choice between Macintosh blade sizes during TI. We hypothesized that Macintosh 4 blade would have higher first-attempt success than Macintosh 3 blade during DL. DESIGN:. Retrospective analysis using a propensity score and inverse probability weighting of data from six prior multicenter randomized trials. SETTING AND PARTICIPANTS:. Adult patients who underwent nonelective TI at participating emergency departments and ICUs. We compared the first-pass success of TI with DL in subjects intubated with a size 4 Macintosh blade on the first TI attempt to subjects with a size 3 Macintosh blade on the first TI attempt. MAIN RESULTS:. Among 979 subjects, 592 (60.5%) had TI using DL with a Macintosh blade, of whom 362 (37%) were intubated with a size 4 blade and 222 (22.7%) with a size 3 blade. We used inverse probability weighting with a propensity score for analyzing data. We found that patients intubated with a size 4 blade had a worse (higher) Cormack-Lehane grade of glottic view than patients intubated with a size 3 blade (adjusted odds ratio [aOR], 1.458; 95% CI, 1.064–2.003; p = 0.02). Patients intubated with a size 4 blade had a lower first pass success than those with a size 3 blade (71.1% vs 81.2%; aOR, 0.566; 95% CI, 0.372–0.850; p = 0.01). CONCLUSIONS AND RELEVANCE:. In critically ill adults undergoing TI using DL with a Macintosh blade, patients intubated using a size 4 blade on first attempt had a worse glottic view and a lower first pass success than patients intubated with a size 3 Macintosh blade. Further prospective studies are needed to examine the optimal approach to selecting laryngoscope blade size during TI of critically ill adults.

Abstract Background Coronavirus disease 2019 (COVID-19) has a heterogeneous outcome in individuals from remaining asymptomatic to death. In a majority of cases, mild symptoms are present that do not require hospitalization and can be successfully treated in the outpatient setting, though symptoms may persist for a long duration. We hypothesize that drugs suitable for decentralized study in outpatients will have efficacy among infected outpatients Methods The TREAT NOW platform is designed to accommodate testing multiple agents with the ability to incorporate new agents in the future. TREAT NOW is an adaptive, blinded, multi-center, placebo-controlled superiority randomized clinical trial which started with two active therapies (hydroxychloroquine and lopinavir/ritonavir) and placebo, with the hydroxychloroquine arm dropped shortly after enrollment began due to external evidence. Each arm has a target enrollment of 300 participants who will be randomly assigned in an equal allocation to receive either an active therapy or placebo twice daily for 14 days with daily electronic surveys collected over days 1 through 16 and on day 29 to evaluate symptoms and a modified COVID-19 ordinal outcome scale. Participants are enrolled remotely by telephone and consented with a digital interface, study drug is overnight mailed to study participants, and data collection occurs electronically without in-person interactions. Discussion If effective treatments for COVID-19 can be identified for individuals in the outpatient setting before they advance to severe disease, it will prevent progression to more severe disease, reduce the need for hospitalization, and shorten the duration of symptoms. The novel decentralized, “no touch” approach used by the TREAT NOW platform has distinction advantages over traditional in-person trials to reach broader populations and perform study procedures in a pragmatic yet rigorous manner. Trial registration ClinicalTrials.gov NCT04372628. Registered on April 30, 2020. First posted on May 4, 2020.

Introduction: Patients experiencing traumatic shock are at a higher risk for death and complications. We previously designed a bundle of emergency medical services traumatic shock care (“EMS-TruShoC”) for prehospital providers in resource-limited settings. We assess how EMS-TruShoC changes clinical outcomes of critically injured prehospital patients. Methods: This is a quasi-experimental educational implementation of a simplified bundle of care using a pre-post design with a control group. The intervention was delivered to EMS providers in Western Cape, South Africa. Delta shock index (heart rate divided by systolic blood pressure, reported as change from the scene to facility arrival) from the 13 months preceding intervention were compared to the 13 months post-implementation. A difference-in-differences analysis examined the difference in mean shock index change between the groups. Results: Data were collected from 198 providers who treated 770 severe trauma patients. The patient groups had similar demographic and clinical characteristics at baseline. Over all time-points, both groups had an increase in mean delta shock index (worsening shock), with the largest difference occurring 4-months post-implementation (0.047 change in control arm, 0.004 change in intervention arm; −0.043 difference-in-differences, P = 0.27). In pre-specified subgroup analyses, there was a statistically significant improvement in delta shock index in the intervention arm in patients with penetrating trauma cared for by basic providers immediately post-implementation (−0.372 difference-in-differences, P = 0.02). Discussion: Overall, there was no significant difference in delta shock index between the EMS-TruShoC intervention versus control groups. However, significant improvement in shock index in one subgroup suggests the intervention may be more likely to benefit penetrating trauma patients and basic providers.

Abstract Introduction: Multi-level dissemination strategies are needed to increase equitable access to effective treatment for high-risk outpatients with COVID-19, particularly among patients from disproportionately affected communities. Yet assessing population-level impact of such strategies can be challenging. Methods: In collaboration with key contributors in Colorado, we conducted a retrospective cohort study to evaluate a multi-level dissemination strategy for neutralizing monoclonal antibody (mAb) treatment. Real-world data included county-level, de-identified output from a statewide mAb referral registry linked with publicly available epidemiological data. Outcomes included weekly number of mAb referrals, unique referring clinicians, and COVID-19 hospitalization rates. We assessed weekly changes in outcomes after dissemination strategies launched in July 2021. Results: Overall, mAb referrals increased from a weekly average of 3.0 to 15.5, with an increase of 1.3 to 42.1 additional referrals per county in each post-period week (p < .05). Number of referring clinicians increased from a weekly average of 2.2 to 9.7, with an additional 1.5 to 22.2 unique referring clinicians observed per county per week beginning 5 weeks post-launch (p < .001). Larger effects were observed in communities specifically prioritized by the dissemination strategies. There were no observed differences in COVID-19 hospitalization rates between counties with and without mAb treatment sites. Conclusion: Real-world data can be used to estimate population impact of multi-level dissemination strategies. The launch of these strategies corresponded with increases in mAb referrals, but no apparent population-level effects on hospitalization outcomes. Strengths of this analytic approach include pragmatism and efficiency, whereas limitations include inability to control for other contemporaneous trends.

Abstract Introduction: Racial and ethnic minority groups have higher rates of SARS-CoV-2 infection, severe illness, and death; however, they receive monoclonal antibody (mAb) treatment at lower rates than non-Hispanic White patients. We report data from a systematic approach to improve equitable provision of COVID-19 neutralizing monoclonal antibody treatment. Methods: Treatment was administered at a community health urgent care clinic affiliated with a safety-net urban hospital. The approach included a stable treatment supply, a same-day test and treat model, a referral process, patient outreach, and financial support. We analyzed the race/ethnicity data descriptively and compared proportions using a chi-square test. Results: Over 17 months, 2524 patients received treatment. Compared to the demographics of county COVID-19-positive cases, a greater proportion of patients who received mAb treatment were Hispanic (44.7% treatment vs. 36.5% positive cases, p < 0.001), a lower proportion were White Non-Hispanic (40.7% treatment vs. 46.3% positive cases, p < 0.001), equal proportion were Black (8.2% treatment vs. 7.4% positive cases, P = 0.13), and equal proportion occurred for other race patients. Discussion: Implementation of multiple systematic strategies to administer COVID-19 monoclonal antibodies resulted in an equitable race/ethnic distribution of treatment.

Abstract Background Targeted normoxia (SpO2 90–96% or PaO2 60–100 mmHg) may help to conserve oxygen and improve outcomes in critically ill patients by avoiding potentially harmful hyperoxia. However, the role of normoxia for critically ill trauma patients remains uncertain. The objective of this study is to describe the study protocol and statistical analysis plan for the Strategy to Avoid Excessive Oxygen for Critically Ill Trauma Patients (SAVE-O2) clinical trial. Methods Design, setting, and participants: Protocol for a multicenter cluster randomized, stepped wedge implementation trial evaluating the effectiveness of a multimodal intervention to target normoxia in critically ill trauma patients at eight level 1 trauma centers in the USA. Each hospital will contribute pre-implementation (control) and post-implementation (intervention) data. All sites will begin in the control phase with usual care. When sites reach their randomly assigned time to transition, there will be a one-month training period, which does not contribute to data collection. Following the 1-month training period, the site will remain in the intervention phase for the duration of the trial. Main outcome measures: The primary outcome will be supplemental oxygen-free days, defined as the number of days alive and not on supplemental oxygen. Secondary outcomes include in-hospital mortality to day 90, hospital-free days to day 90, ventilator-free days (VFD) to day 28, time to room air, Glasgow Outcome Score (GOS), and duration of time receiving supplemental oxygen. Discussion SAVE-O2 will determine if a multimodal intervention to improve compliance with targeted normoxia will safely reduce the need for concentrated oxygen for critically injured trauma patients. These data will inform military stakeholders regarding oxygen requirements for critically injured warfighters, while reducing logistical burden in prolonged combat casualty care. Trial registration ClinicalTrials.gov NCT04534959 . Registered September 1, 2020.

BackgroundAnimal studies have shown that midazolam can increase vulnerability to cardiac ischemia, potentially via circadian-mediated mechanisms. We hypothesized that perioperative midazolam administration is associated with an increased incidence of myocardial injury in patients undergoing non-cardiac surgery (MINS) and that circadian biology may underlie this relationship.MethodsWe analyzed intraoperative data from the Multicenter Perioperative Outcomes Group for the occurrence of MINS across 50 institutions from 2014 to 2019. The primary outcome was the occurrence of MINS. MINS was defined as having at least one troponin-I lab value ≥0.03 ng/ml from anesthesia start to 72 h after anesthesia end. To account for bias, propensity scores and inverse probability of treatment weighting were applied.ResultsA total of 1,773,118 cases were available for analysis. Of these subjects, 951,345 (53.7%) received midazolam perioperatively, and 16,404 (0.93%) met criteria for perioperative MINS. There was no association between perioperative midazolam administration and risk of MINS in the study population as a whole (odds ratio (OR) 0.98, confidence interval (CI) [0.94, 1.01]). However, we found a strong association between midazolam administration and risk of MINS when surgery occurred overnight (OR 3.52, CI [3.10, 4.00]) or when surgery occurred in ASA 1 or 2 patients (OR 1.25, CI [1.13, 1.39]).ConclusionPerioperative midazolam administration may not pose a significant risk for MINS occurrence. However, midazolam administration at night and in healthier patients could increase MINS, which warrants further clinical investigation with an emphasis on circadian biology.

Introduction: The first proposed emergency care alternative payment model seeks to reduce avoidable admissions from the emergency department (ED), but this initiative may increase risk of adverse events after discharge. Our study objective was to describe variation in ED discharge rates and determine whether higher discharge rates were associated with more ED revisits. Methods: Using all-payer inpatient and ED administrative data from the California Office of Statewide Health Planning and Development (OSHPD) 2017 database, we performed a retrospective cohort study of hospital-level ED discharge rates and ED revisits using conditions that have been previously described as having variability in discharge rates: abdominal pain; altered mental status; chest pain; chronic obstructive pulmonary disease exacerbation; skin and soft tissue infection; syncope; and urinary tract infection. We categorized hospitals into quartiles for each condition based on a covariate-adjusted discharge rate and compared the rate of ED revisits between hospitals in the highest and lowest quartiles. Results: We found a greater than 10% difference in the between-quartile median adjusted discharge rate for each condition except for abdominal pain. There was no significant association between adjusted discharge rates and ED revisits. Altered mental status had the highest revisit rate, at 34% for hospitals in the quartile with the lowest and 30% in hospitals with the highest adjusted discharge rate, although this was not statistically significant. Syncope had the lowest rate of revisits at 16% for hospitals in both the lowest and highest adjusted discharge rate quartiles. Conclusion: Our findings suggest that there may be opportunity to increase ED discharges for certain conditions without resulting in higher rates of ED revisits, which may be a surrogate for adverse events after discharge.

Abstract Background Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear. Methods The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200–399 mL) of COVID-19 convalescent plasma that has demonstrated neutralizing function using a SARS-CoV-2 chimeric virus neutralization assay. Study treatments are administered in a blinded fashion and patients are followed for 28 days. The primary outcome is clinical status 14 days after study treatment as measured on a 7-category ordinal scale assessing mortality, respiratory support, and return to normal activities of daily living. Key secondary outcomes include mortality and oxygen-free days. The trial is projected to enroll 1000 patients and is designed to detect an odds ratio ≤ 0.73 for the primary outcome. Discussion This trial will provide the most robust data available to date on the efficacy of COVID-19 convalescent plasma for the treatment of adults hospitalized with acute moderate to severe COVID-19. These data will be useful to guide the treatment of COVID-19 patients in the current pandemic and for informing decisions about whether developing a standardized infrastructure for collecting and disseminating convalescent plasma to prepare for future viral pandemics is indicated. Trial registration ClinicalTrials.gov NCT04362176 . Registered on 24 April 2020.

Abstract Background Annually, over 1 billion people sustain traumatic injuries, resulting in over 900,000 deaths in Africa and 6 million deaths globally. Timely response, intervention, and transportation in the prehospital setting reduce morbidity and mortality of trauma victims. Our objective was to describe the existing literature evaluating trauma morbidity and mortality outcomes as a function of prehospital care time to identify gaps in literature and inform future investigation. Main body We performed a scoping review of published literature in MEDLINE. Results were limited to English language publications from 2009 to 2020. Included articles reported trauma outcomes and prehospital time. We excluded case reports, reviews, systematic reviews, meta-analyses, comments, editorials, letters, and conference proceedings. In total, 808 articles were identified for title and abstract review. Of those, 96 articles met all inclusion criteria and were fully reviewed. Higher quality studies used data derived from trauma registries. There was a paucity of literature from studies in low- and middle-income countries (LMIC), with only 3 (3%) of articles explicitly including African populations. Mortality was an outcome measure in 93% of articles, predominantly defined as “in-hospital mortality” as opposed to mortality within a specified time frame. Prehospital time was most commonly assessed as crude time from EMS dispatch to arrival at a tertiary trauma center. Few studies evaluated physiologic morbidity outcomes such as multi-organ failure. Conclusion The existing literature disproportionately represents high-income settings and most commonly assessed in-hospital mortality as a function of crude prehospital time. Future studies should focus on how specific prehospital intervals impact morbidity outcomes (e.g., organ failure) and mortality at earlier time points (e.g., 3 or 7 days) to better reflect the effect of early prehospital resuscitation and transport. Trauma registries may be a tool to facilitate such research and may promote higher quality investigations in Africa and LMICs.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

Background Neutralizing monoclonal antibody (mAb) treatment for COVID-19 prevents hospitalization and death but is underused, especially in racial/ethnic minority and rural populations. Reasons for underuse and inequity may include community member lack of awareness or healthcare access barriers, among others. This study assessed mAbs community awareness and opportunities for improving equitable mAb access. Methods A concurrent mixed methods study including surveys and focus groups with adults with high-risk conditions or their proxy decision-makers. Surveys and focus group guides addressed diffusion of innovation theory factors. Descriptive statistics and Fisher’s exact method was used to report and compare survey findings by race and ethnicity. Rapid qualitative methods were used for focus group analysis. Results Surveys from 515 individuals (460 English, 54 Spanish, 1 Amharic), and 8 focus groups (6 English, 2 Spanish) with 69 participants, completed June 2021 to January 2022. Most survey respondents (75%) had heard little or nothing about mAbs, but 95% would consider getting mAb treatment. Hispanic/Latino and Non-Hispanic People of Color (POC) reported less awareness, greater concern about intravenous infusions, and less trust in mAb safety and effectiveness than White, Non-Hispanic respondents. Focus group themes included little awareness but high interest in mAb treatment and concerns about cost and access barriers such as lacking established sources of care and travel from rural communities. Focus groups revealed preferences for broad-reaching but tailored messaging strategies using multiple media and trusted community leaders. Conclusions Despite unfamiliarity with mAb treatment, most respondents were open to receiving mAbs or recommending mAbs to others. While mAb messaging should have broad reach “to everyone everywhere,” racial and geographic disparities in awareness and trust about mAbs underscore need for tailored messaging to promote equitable access. Care processes should address patient-level barriers like transportation, insurance, or primary care access. COVID-19 treatment dissemination strategies should promote health equity.

Abstract Background Prehospital (ambulance) care can reduce morbidity and mortality from trauma. Yet, there is a dearth of effective evidence-based interventions and implementation strategies. Emergency Medical Services Traumatic Shock Care (EMS-TruShoC) is a novel bundle of five core evidence-based trauma care interventions. High-Efficiency EMS Training (HEET) is an innovative training and sensitization program conducted during clinical shifts in ambulances. We assess the feasibility of implementing EMS-TruShoC using the HEET strategy, and feasibility of assessing implementation and clinical outcomes. Findings will inform a main trial. Methods We conducted a single-site, prospective cohort, multi-methods pilot implementation study in Western Cape EMS system of South Africa. Of the 120 providers at the study site, 12 were trainers and the remaining were eligible learners. Feasibility of implementation was guided by the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. Feasibility of assessing clinical outcomes was assessed using shock indices and clinical quality of care scores, collected via abstraction of patients’ prehospital trauma charts. Thresholds for progression to a main trial were developed a priori. Results The average of all implementation indices was 83% (standard deviation = 10.3). Reach of the HEET program was high, with 84% learners completing at least 75% of training modules. Comparing the proportion of learners attaining perfect scores in post- versus pre-implementation assessments, there was an 8-fold (52% vs. 6%) improvement in knowledge, 3-fold (39% vs. 12%) improvement in skills, and 2-fold (42% vs. 21%) increase in self-efficacy. Clinical outcomes data were successfully calculated—there were clinically significant improvements in shock indices and quality of prehospital trauma care in the post- versus pre-implementation phases. Adoption of HEET was good, evidenced by 83% of facilitator participation in trainings, and 100% of surveyed stakeholders indicating good programmatic fit for their organization. Stakeholders responded that HEET was a sustainable educational solution that aligned well with their organization. Implementation fidelity was very high; 90% of the HEET intervention and 77% of the implementation strategy were delivered as originally planned. Participants provided very positive feedback, and explained that on-the-job timing enhanced their participation. Maintenance was not relevant to assess in this pilot study. Conclusions We successfully implemented the EMS-TruShoC educational intervention using the HEET training strategy in a single-site pilot study conducted in a low-resource international setting. All clinical outcomes were successfully calculated. Overall, this pilot study suggests high feasibility of our future, planned experimental trial.

Abstract Background and Aims Improving the quality of pre‐hospital traumatic shock care, especially in low‐ and middle‐income countries, is particularly relevant to reducing the large global burden of disease from injury. What clinical interventions represent high‐quality care is an actively evolving field and often dependent on the specific injury pattern. A key component of improving the quality of care is having a consistent way to assess and measure the quality of shock care in the pre‐hospital setting. The objective of this study was to develop and validate a chart abstraction instrument to measure the quality of trauma care in a resource‐limited, pre‐hospital emergency care setting. Methods Traumatic shock was selected as the tracer condition. The pre‐hospital quality of traumatic shock care (QTSC) instrument was developed and validated in three phases. A content development phase utilized a rapid literature review and expert consensus to yield the contents of the draft instrument. In the instrument validation phase, the QTSC instrument was created and underwent end user and content validation. A pilot‐testing phase collected user feedback and performance characteristics to iteratively refine draft versions into a final instrument. Accuracy and inter‐ and intra‐rater agreement were calculated. Results The final QTSC instrument contains 10 domains of quality, each with specific criteria that determine how the domain is measured and the level of quality of care rendered. The instrument is over 90% accurate and has good inter‐ and intra‐rater reliability when used by trained pre‐hospital provider users in South Africa. Pre‐hospital provider user feedback indicates the tool is easy to learn and quick to use. Conclusion We created and validated a novel chart abstraction instrument that can reliably and accurately measure the quality of pre‐hospital traumatic shock care. We provide a systematic methodology for developing and validating a quality of care tool for resource‐limited care settings.

OBJECTIVES:. Hyperoxia is common among critically ill patients and may increase morbidity and mortality. However, limited evidence exists for critically injured patients. The objective of this study was to determine the association between hyperoxia and in-hospital mortality in adult trauma patients requiring ICU admission. DESIGN, SETTING, AND PARTICIPANTS:. This multicenter, retrospective cohort study was conducted at two level I trauma centers and one level II trauma center in CO between October 2015 and June 2018. All adult trauma patients requiring ICU admission within 24 hours of emergency department arrival were eligible. The primary exposure was oxygenation during the first 7 days of hospitalization. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Primary outcome was in-hospital mortality. Secondary outcomes were hospital-free days and ventilator-free days. We included 3,464 critically injured patients with a mean age of 52.6 years. Sixty-five percent were male, and 66% had blunt trauma mechanism of injury. The primary outcome of in-hospital mortality occurred in 264 patients (7.6%). Of 226,057 patient-hours, 46% were spent in hyperoxia (oxygen saturation > 96%) and 52% in normoxia (oxygen saturation 90–96%). During periods of hyperoxia, the adjusted risk for mortality was higher with greater oxygen administration. At oxygen saturation of 100%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 6.4 (3.5–11.8), 5.4 (3.4–8.6), 2.7 (1.7–4.1), and 1.5 (1.1–2.2), respectively. At oxygen saturation of 98%, the adjusted risk scores for mortality (95% CI) at Fio2 of 100%, 80%, 60%, and 50% were 7.7 (4.3–13.5), 6.3 (4.1–9.7), 3.2 (2.2–4.8), and 1.9 (1.4–2.7), respectively. CONCLUSIONS:. During hyperoxia, higher oxygen administration was independently associated with a greater risk of mortality among critically injured patients. Level of evidence: Cohort study, level III.

Objectives:. Given finite ICU bed capacity, knowledge of ICU bed utilization during the coronavirus disease 2019 pandemic is critical to ensure future strategies for resource allocation and utilization. We sought to examine ICU census trends in relation to ICU bed capacity during the rapid increase in severe coronavirus disease 2019 cases early during the pandemic. Design:. Observational cohort study. Setting:. Thirteen geographically dispersed academic medical centers in the United States. Patients/Subjects:. We obtained daily ICU censuses from March 26 to June 30, 2020, as well as prepandemic ICU bed capacities. The primary outcome was daily census of ICU patients stratified by coronavirus disease 2019 and mechanical ventilation status in relation to ICU capacity. Interventions:. None. Measurements and Main Results:. Prepandemic overall ICU capacity ranged from 62 to 225 beds (median 109). During the study period, the median daily coronavirus disease 2019 ICU census per hospital ranged from 1 to 84 patients, and the daily ICU census exceeded overall ICU capacity for at least 1 day at five institutions. The number of critically ill patients exceeded ICU capacity for a median (interquartile range) of 17 (12–50) of 97 days at these five sites. All 13 institutions experienced decreases in their noncoronavirus disease ICU population, whereas local coronavirus disease 2019 cases increased. Coronavirus disease 2019 patients reached their greatest proportion of ICU capacity on April 12, 2020, when they accounted for 44% of ICU patients across all participating hospitals. Maximum ICU census ranged from 52% to 289% of overall ICU capacity, with three sites less than 80%, four sites 80–100%, five sites 100–128%, and one site 289%. Conclusions:. From March to June 2020, the coronavirus disease 2019 pandemic led to ICU censuses greater than ICU bed capacity at fives of 13 institutions evaluated. These findings demonstrate the short-term adaptability of U.S. healthcare institutions in redirecting limited resources to accommodate a public health emergency.

Introduction: Approximately 16% of acutely ill older adults develop new, long-term cognitive impairment (LTCI), many of whom initially seek care in the emergency department (ED). Currently, no effective interventions exist to prevent LTCI after an acute illness. Identifying early and modifiable risk factors for LTCI is the first step toward effective therapy. We hypothesized that Vitamin D deficiency at ED presentation was associated with LTCI in older adults. Methods: This was an observational analysis of a prospective cohort study that enrolled ED patients ≥ 65 years old who were admitted to the hospital for an acute illness. All patients were enrolled within four hours of ED presentation. Serum Vitamin D was measured at enrollment and Vitamin D deficiency was defined as serum concentrations

Introduction: Despite significant morbidity and mortality from stroke, patient delays to emergency department (ED) presentation following the onset of stroke symptoms are one of the main contraindications to treatment for acute ischemic stroke (AIS). Our objective was to identify patient and environmental factors associated with delayed presentations to the ED after onset of stroke symptoms. Methods: This was a pre-planned secondary analysis of data from a multicenter, retrospective observational study at three hospitals in Colorado. We included consecutive adult patients if they were admitted to the hospital from the ED, and the ED diagnosed or initiated treatment for AIS. Patients were excluded if they were transferred from another hospital. Primary outcome was delayed presentation to the ED (> 3.5 hours) following onset stroke symptoms. Results: Among 351 patients, 63% presented to the ED more than 3.5 hours after onset of stroke symptoms. Adjusted results show that patients who presented in the evening hours (odds ratio [OR] [0.45], 95% confidence interval [CI] [0.3–0.8]), as compared to daytime, were significantly less likely to have a delayed presentation. Speaking a language other than English (Spanish [OR 3.3, 95% CI 1.2–8.9] and “other” [OR 9.1, 95% CI 1.2–71.0]), having known cerebrovascular risk factors (>2 risk factors [OR 2.4, 95% CI 1.05–5.4] and 1–2 risk factors [OR 2.3, 95% CI 1.03–5.1], compared to zero risk factors), and presenting to a rural hospital (OR 2.2, 95% CI 1.2–4.2), compared to urban, were significantly associated with delayed presentation. Conclusion: Important patient and environmental factors are significantly associated with delayed ED presentations following the onset of stroke symptoms. Identifying how best to educate patients on stroke risk and recognition remains critically important.

Introduction: Accurate field triage of critically injured patients to trauma centers is vital for improving survival. We sought to estimate the national degree of undertriage of trauma patients who die in emergency departments (EDs) by evaluating the frequency and characteristics associated with triage to non-trauma centers. Methods: This was a retrospective cross-sectional analysis of adult ED trauma deaths in the 2010 National Emergency Department Sample (NEDS). The primary outcome was appropriate triage to a trauma center (Level I, II or III) or undertriage to a non-trauma center. We subsequently focused on urban areas given improved access to trauma centers. We evaluated the associations of patient demographics, hospital region and mechanism of injury with triage to a trauma versus non-trauma center using multivariable logistic regression. Results: We analyzed 3,971 included visits, representing 18,464 adult ED trauma-related deaths nationally. Of all trauma deaths, nearly half (44.5%, 95% CI [43.0-46.0]) of patients were triaged to non-trauma centers. In a subgroup analysis, over a third of urban ED visits (35.6%, 95% CI [34.1-37.1]) and most rural ED visits (86.4%, 95% CI [81.5-90.1]) were triaged to non-trauma centers. In urban EDs, female patients were less likely to be triaged to trauma centers versus non-trauma centers (adjusted odds ratio [OR] 0.83, 95% CI [0.70-0.99]). Highest median household income zip codes (≥$67,000) were less likely to be triaged to trauma centers than lowest median income ($1-40,999) (OR 0.54, 95% CI [0.43-0.69]). Compared to motor vehicle trauma, firearm trauma had similar odds of being triaged to a trauma center (OR 0.90, 95% CI [0.71-1.14]); however, falls were less likely to be triaged to a trauma center (OR 0.50, 95 %CI [0.38-0.66]). Conclusion: We found that nearly half of all trauma patients nationally and one-third of urban trauma patients, who died in the ED, were triaged to non-trauma centers, and thus undertriaged. Sex and other demographic disparities associated with this triage decision represent targeted opportunities to improve our trauma systems and reduce undertriage.

Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 ± 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels