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BackgroundTest-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls.MethodsAdults hospitalized at 21 medical centers in 18 states March 11-August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group.Results5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64years, VE was 93% (95% CI: 90-94) using syndrome-negative controls and 91% (95% CI: 88-93) using test-negative controls.ConclusionsDespite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.

The SARS-CoV-2 Omicron variant (B.1.1.529 or BA.1) became predominant in the United States by late December 2021 (1). BA.1 has since been replaced by emerging lineages BA.2 (including BA.2.12.1) in March 2022, followed by BA.4 and BA.5, which have accounted for a majority of SARS-CoV-2 infections since late June 2022 (1). Data on the effectiveness of monovalent mRNA COVID-19 vaccines against BA.4/BA.5-associated hospitalizations are limited, and their interpretation is complicated by waning of vaccine-induced immunity (2-5). Further, infections with earlier Omicron lineages, including BA.1 and BA.2, reduce vaccine effectiveness (VE) estimates because certain persons in the referent unvaccinated group have protection from infection-induced immunity. The IVY Network

During the COVID-19 pandemic, self-reported COVID-19 vaccination might facilitate rapid evaluations of vaccine effectiveness (VE) when source documentation (e.g., immunization information systems [IIS]) is not readily available. We evaluated the concordance of COVID-19 vaccination status ascertained by self-report versus source documentation and its impact on VE estimates.Hospitalized adults (≥18 years) admitted to 18 U.S. medical centers March-June 2021 were enrolled, including COVID-19 cases and SARS-CoV-2 negative controls. Patients were interviewed about COVID-19 vaccination. Abstractors simultaneously searched IIS, medical records, and other sources for vaccination information. To compare vaccination status by self-report and documentation, we estimated percent agreement and unweighted kappa with 95% confidence intervals (CIs). We then calculated VE in preventing COVID-19 hospitalization of full vaccination (2 doses of mRNA product ≥14 days prior to illness onset) independently using data from self-report or source documentation.Of 2520 patients, 594 (24%) did not have self-reported vaccination information to assign vaccination group; these patients tended to be more severely ill. Among 1924 patients with both self-report and source documentation information, 95.0% (95% CI: 93.9-95.9%) agreement was observed, with a kappa of 0.9127 (95% CI: 0.9109-0.9145). VE was 86% (95% CI: 81-90%) by self-report data only and 85% (95% CI: 81-89%) by source documentation data only.Approximately one-quarter of hospitalized patients could not provide self-report COVID-19 vaccination status. Among patients with self-report information, there was high concordance with source documented status. Self-report may be a reasonable source of COVID-19 vaccination information for timely VE assessment for public health action.

Background . Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. Methods . In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression. Results . After excluding patients receiving mRNA vaccines, among 3979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% confidence interval [CI]: 63–75%) overall, including 55% (29–72%) among immunocompromised patients, and 72% (64–77%) among immunocompetent patients, for whom VEs was similar at 14–90 days (73% [59–82%]), 91–180 days (71% [60–80%]), and 181–274 days (70% [54–81%]) postvaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18–65%) among immunocompetent patients. Conclusions . The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months postvaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.

Effective and widely available therapies are still needed for outpatients with COVID-19. We aimed to evaluate the efficacy and safety of lopinavir/ritonavir for early treatment of non-hospitalized individuals diagnosed with COVID-19.This randomized, placebo-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 lopinavir/ritonavir (400 mg/100 mg) or placebo 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 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 lopinavir/ritonavir over placebo (odds ratio [OR]1).Between June 2020 and December 2021, 448 participants were randomized to receive either lopinavir/ritonavir (n=216) or placebo (n=221). The mean symptom duration prior to 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 (OR 0.96; 95% CrI: 0.66 to 1.41). There were 3.2% (n=7) of lopinavir/ritonavir and 2.7% (n=6) of placebo participants hospitalized by day 28. Serious adverse events did not differ between groups.Lopinavir/ritonavir did not significantly improve symptom resolution or reduce hospitalization in non-hospitalized participants with COVID-19.ClinicalTrials.gov Identifier: NCT04372628.

Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p

To compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United States.Multicenter observational case-control study with a test negative design.Hospitals in 18 US states.4760 adults admitted to one of 21 hospitals with acute respiratory symptoms between 26 December 2021 and 30 June 2022, a period when the omicron variant was dominant. Participants included 2385 (50.1%) patients with laboratory confirmed covid-19 (cases) and 2375 (49.9%) patients who tested negative for SARS-CoV-2 (controls).The main outcome was vaccine effectiveness against hospital admission with covid-19 for a primary series plus booster doses and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. Vaccine effectiveness analyses were stratified by immunosuppression status (immunocompetent, immunocompromised). The primary analysis evaluated all covid-19 vaccine types combined, and secondary analyses evaluated specific vaccine products.Overall, median age of participants was 64 years (interquartile range 52-75 years), 994 (20.8%) were immunocompromised, 85 (1.8%) were vaccinated with a primary series plus two boosters, 1367 (28.7%) with a primary series plus one booster, and 1875 (39.3%) with a primary series alone, and 1433 (30.1%) were unvaccinated. Among immunocompetent participants, vaccine effectiveness for prevention of hospital admission with omicron related covid-19 for a primary series plus two boosters was 63% (95% confidence interval 37% to 78%), a primary series plus one booster was 65% (58% to 71%), and for a primary series alone was 37% (25% to 47%) (P0.001 for the pooled boosted regimens compared with a primary series alone). Vaccine effectiveness was higher for a boosted regimen than for a primary series alone for both mRNA vaccines (BNT162b2 (Pfizer-BioNTech): 73% (44% to 87%) for primary series plus two boosters, 64% (55% to 72%) for primary series plus one booster, and 36% (21% to 48%) for primary series alone (P0.001); mRNA-1273 (Moderna): 68% (17% to 88%) for primary series plus two boosters, 65% (55% to 73%) for primary series plus one booster, and 41% (25% to 54%) for primary series alone (P=0.001)). Among immunocompromised patients, vaccine effectiveness for a primary series plus one booster was 69% (31% to 86%) and for a primary series alone was 49% (30% to 63%) (P=0.04).During the first six months of 2022 in the US, booster doses of a covid-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing hospital admissions with omicron related covid-19.This article is a living test negative design study that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Introduction Angiotensin converting enzyme inhibitor (ACEi) associated angioedema is frequently encountered in the emergency department. Airway management is the primary treatment, but published evidence supporting the decision to intubate patients with this condition is extremely limited. Method We performed a retrospective study of all cases of ACEi associated angioedema encountered in a large, urban, tertiary referral emergency department. We classified demographics, duration of symptoms before presentation, physical exam findings and nasopharyngoscopy findings in patients that did and did not require intubation. Results We identified a total of 190 separate encounters from 183 unique patients who presented during the 3-year period of the study. Eighteen (9.5%) of these patients required intubation. Patients requiring intubation were more likely to present within 6 h of the onset of angioedema symptoms. Anterior tongue swelling, vocal changes, drooling, and dyspnea were significantly more common in patients requiring intubation. Isolated lip swelling was present in 54% of all patients and was the only finding significantly more common in the group that did not require intubation. Conclusions Rapid progression of symptoms within the first 6 h of angioedema onset, anterior tongue swelling, vocal changes, drooling and dyspnea are associated with intubation for ACEi associated angioedema. Isolated lip swelling is significantly more common in patients that do not require intubation. Our data provide risk stratification guidance for providers treating patients with suspected ACEi associated angioedema in the emergency department.

Objectives We previously reported gene expression-based endotypes of pediatric septic shock, endotypes A and B, and that corticosteroid exposure was independently associated with increased mortality among pediatric endotype A patients. The Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock trial tested the efficacy of vasopressin as initial vasopressor therapy for septic shock among adult patients, when compared with norepinephrine. Patients who reached a prespecified dose of either vasopressor were further randomized to receive hydrocortisone or placebo. A proportion of patients in the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock trial had transcriptomic data generated at baseline using whole blood-derived messenger RNA. We used the publicly available transcriptomic data from the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock trial to assign the study subjects to pediatric septic shock endotype A or B, and tested the hypothesis that hydrocortisone treatment is associated with increased mortality among patients in endotype A. Design Secondary analysis of publicly available transcriptomic data. Setting Multiple adult ICUs. Patients Adults with septic shock randomized to hydrocortisone (n = 47) or placebo (n = 50). Interventions Randomization to the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock trial experimental arms. Measurements and main results Endotype A patients receiving hydrocortisone had a mortality rate of 46%, whereas endotype A patients receiving placebo had a mortality rate of 22% (p = 0.105). In contrast, the mortality rates for endotype B patients receiving hydrocortisone or placebo were 19% and 22%, respectively. The odds of death were more than three times greater in endotype A patients receiving hydrocortisone than endotype A patients receiving placebo (p = 0.05). Conclusions This exploratory analysis provides further evidence that corticosteroid exposure may be associated with increased mortality among septic shock endotype A patients.

COVID-19 mRNA vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization.Case control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states March 11 - December 15, 2021, including COVID-19 case patients and RT-PCR-negative controls. We included adults who were unvaccinated or vaccinated with two doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (180 vs ≥180 days since dose two) and continuous time modeled using restricted cubic splines.10,078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (IQR 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE180 days was 90% (95%CI: 88-91) vs 82% (95%CI: 79-85) at ≥180 days (p 0.001). VE declined for Pfizer-BioNTech (88% to 79%, p 0.001) and Moderna (93% to 87%, p 0.001) products, for younger adults (18-64 years) [91% to 87%, p = 0.005], and for adults ≥65 years of age (87% to 78%, p 0.001). In models using restricted cubic splines, similar changes were observed.In a period largely pre-dating Omicron variant circulation, effectiveness of two mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months.

Background The study objective was to evaluate 2- and 3-dose coronavirus disease 2019 (COVID-19) mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients. Methods We conducted a 21-site case-control analysis of 10 425 adults hospitalized in March to December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (severe acute respiratory syndrome coronavirus 2-negative). Participants were classified as follows: SOT recipient (n = 440), other immunocompromising condition (n = 1684), or immunocompetent (n = 8301). The VE against COVID-19-associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls. Results Among SOT recipients, VE was 29% (95% confidence interval [CI], −19% to 58%) for 2 doses and 77% (95% CI, 48% to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI, 64% to 79%) for 2 doses and 92% (95% CI, 85% to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI, 87% to 90%) for 2 doses and 96% (95% CI, 83% to 99%) for 3 doses. Conclusions Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent adults and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses.

IMPORTANCE: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people. OBJECTIVE: To evaluate the association between vaccination with mRNA COVID-19 vaccines—mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)—and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease. DESIGN, SETTING, AND PARTICIPANTS: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021. EXPOSURES: COVID-19 vaccination. MAIN OUTCOMES AND MEASURES: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression. RESULTS: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P

BackgroundAs SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes.MethodsIn a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2.ResultsAmong 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%).ConclusionDuring March–May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

Background As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes. Methods In a multicenter case-control analysis of US adults hospitalized March 11–May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2. Results Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7–91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18–49 years (97.4%; 95% CI, 79.3–9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8–82.6) than without immunosuppression (91.3%; 95% CI, 85.6–94.8). Conclusion During March–May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination† with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

The benefit of corticosteroids for septic shock remains unclear, reflecting heterogeneity of treatment effect. We previously reported a binary septic shock endotype classification based on expression of 100 genes. This binary classification provides information regarding prognosis and corticosteroid responsiveness but does not capture the endotypes continuum. Here, we describe a continuous metric for endotype assignment, the Z value, and its relationship with septic shock outcomes and corticosteroid responsiveness. In a derivation cohort, a lower Z value was independently associated with increased odds of mortality. When the Z value was fit using cubic splines, the odds of mortality increased considerably below a Z value of 15 among patients exposed to corticosteroids. A similar interaction between Z value and corticosteroid exposure was observed when the model was applied to pediatric and adult validation cohorts. The Z value provides more detailed evidence of patients with septic shock in whom corticosteroids are harmful.

Background Interfacility transfers between emergency department (EDs) are common and at times unnecessary. We sought to examine the role of health insurance status with potentially avoidable transfers. Methods We conducted a retrospective observational analysis using hospital electronic administrative data of all interfacility ED‐to‐ED transfers to a single, quaternary care adult ED in 2018. We defined a potentially avoidable transfer as an ED‐to‐ED transfer in which the patient did not receive a procedure from a specialist at the receiving hospital and was discharged from the ED or the receiving hospital within 24 hours of arrival. We constructed a multivariable logistic regression model to examine whether insurance status was associated with potentially avoidable transfers among all ED‐to‐ED transfers adjusting for patient demographics, severity, mode of arrival, clinical condition, and rurality. Results Among 7508 transfers, 1862 (25%) were potentially avoidable and were more likely to be uninsured (20% vs 9%). In the multivariable analysis, among ED‐to‐ED transfers for adults aged 18–64 years old who were uninsured (vs any insurance) were significantly more likely to be potentially avoidable (adjusted odds ratio [aOR] 2.1 [1.7, 2.4]) and there is a significant interaction with age. Potentially avoidable transfers increased with younger age, male sex, black (vs white), small rural classification (vs urban), and arrival by ground ambulance (vs flight). Conclusions Potentially avoidable transfers comprised 1 in 4 transfers. Patients who lack insurance were more than twice as likely to be classified as potentially avoidable even after evaluating for confounders and interactions. This effect was most pronounced among younger patients. Further research is needed to explore why uninsured patients are disproportionately more likely to experience potentially avoidable transfers.

Individualized interactive instruction provides an opportunity for significant innovation and advances in curriculum design. We describe the development and implementation of virtual small group exercises into the curriculum of an emergency medicine residency training program using a free social media and communication platform (Slack). Two virtual small group exercises, one case‐based and one open‐ended, were trialed during the 2016 to 2017 academic year. We found that the exercises were feasible to implement in a learner group where 66% (41/62) had little or no prior experience with Slack. There was a trend toward a more favorable rating of the quality of the dialogue and of the task‐technology fit for the case‐based format as opposed to the open‐ended educational activity.

Background Symptoms of mild COVID‐19 illness are non‐specific and may persist for prolonged periods. Effects on quality of life of persistent poor physical or mental health associated with COVID‐19 are not well understood. Methods Adults aged ≥18 years with laboratory‐confirmed COVID‐19 and matched control patients who tested negative for SARS‐CoV‐2 infection at outpatient facilities associated with 11 medical centers in the United States were interviewed to assess symptoms, illness duration, and health‐related quality of life. Duration of symptoms, health‐related quality of life measures, and days of poor physical health by symptoms experienced during illness were compared between case patients and controls using Wilcoxon rank‐sum tests. Symptoms associated with COVID‐19 case status were evaluated by multivariable logistic regression. Results Among 320 participants included, 157 were COVID‐19 cases and 163 were SARS‐CoV‐2 negative controls. Loss of taste or smell was reported by 63% of cases and 6% of controls and was strongly associated with COVID‐19 in logistic regression models (adjusted odds ratio [aOR] = 32.4; 95% confidence interval [CI], 12.6‐83.1). COVID‐19 cases were more likely than controls to have experienced fever, body aches, weakness, or fatigue during illness, and to report ≥1 persistent symptom more than 14 days after symptom onset (50% vs 32%, P

ObjectivesTo characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant.DesignCase-control study.Setting21 hospitals across the United States.Participants11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022).Main outcome measuresVaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization’s clinical progression scale was compared among variants using proportional odds regression.ResultsEffectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85).ConclusionsmRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.

Background Mechanical thrombectomy (MT) is the preferred treatment for large vessel occlusion (LVO) ischemic stroke, and neurological outcome improves with earlier treatment. Patients with LVO frequently require inter-facility transfer to access MT but delays at transferring EDs may worsen neurological outcomes. Methods We conducted a retrospective observational study to evaluate the association of time spent and transferring EDs with 90-day neurological outcomes among patients who were transferred from an outside ED to the Comprehensive Stroke Center and received MT. Time intervals at transferring EDs were examined descriptively, and multivariable logistic regression modeling was used to examine the association of time spent in the ED with 90-day neurologic outcome (modified Rankin Scale; good ≤2, poor ≥3). Results Among 111 patients transferred to a stroke center for MT between 2013 and 2017, the time between CT scan and the stroke center transfer request was 44 (IQR 27,65) minutes, or 47% of transferring ED total duration. Duration at the transferring ED was not significantly associated with 90-day outcome. Only NIH Stroke Scale at the time of arrival to the stroke center was associated with good 90-day neurological outcome (aOR 0.84, 95%CI 0.77, 0.92, p Conclusions Among LVO patients transferred for MT, the total time spent at transferring EDs was not associated with 90-day neurologic outcome in patients with LVO. As therapies and their associated effectiveness improves over time, future investigations should further characterize the time between CT and transfer request to identify targets for process improvement and clinical outcomes.

Acute pain management is fundamental in prehospital trauma care. Early pain control may decrease the risk of developing post-traumatic stress disorder (PTSD) and chronic pain. Fentanyl and ketamine...

Importance: Acute heart failure (AHF) precipitates millions of hospital admissions worldwide, but previous registries have been country or region specific. Objective: To conduct a prospective contemporaneous comparison of AHF presentations, etiologic factors and precipitants, treatments, and in-hospital outcomes among global regions through the International Registry to Assess Medical Practice with Longitudinal Observation for Treatment of Heart Failure (REPORT-HF). Design, Setting, and Participants: A total of 18553 adults were enrolled during a hospitalization for AHF. Patients were recruited from the acute setting in Western Europe (WE), Eastern Europe (EE), Eastern Mediterranean and Africa (EMA), Southeast Asia (SEA), Western Pacific (WP), North America (NA), and Central and South America (CSA). Patients with AHF were approached for consent and excluded only if there was recent participation in a clinical trial. Patients were enrolled from July 23, 2014, to March 24, 2017. Statistical analysis was conducted from April 18 to June 29, 2018; revised analyses occurred between August 6 and 29, 2019. Main Outcomes and Measures: Heart failure etiologic factors and precipitants, treatments, and in-hospital outcomes among global regions. Results: A total of 18553 patients were enrolled at 358 sites in 44 countries. The median age was 67.0 years (interquartile range [IQR], 57-77), 11372 were men (61.3%), 9656 were white (52.0%), 5738 were Asian (30.9%), and 867 were black (4.7%). A history of HF was present in more than 50% of the patients and 40% were known to have a prior left-ventricular ejection fraction lower than 40%. Ischemia was a common AHF precipitant in SEA (596 of 2329 [25.6%]), WP (572 of 3354 [17.1%]), and EMA (364 of 2241 [16.2%]), whereas nonadherence to diet and medications was most common in NA (306 of 1592 [19.2%]). Median time to the first intravenous therapy was 3.0 (IQR, 1.4-5.6) hours in NA; no other region had a median time above 1.2 hours (P

Background: Understanding the prevalence of substance use disorder (SUD) in emergency department (ED) settings could facilitate prevention and treatment responses to the epidemic. However, little information is available on the true prevalence of SUD in the ED population. We characterized 1) methods for determining the prevalence of substance use and SUDs within an ED, and 2) the degree to which prevalence differs between geographically proximate EDs. Methods: This cross-sectional, multi-hospital study analyzed data from prior studies and electronic health records (EHR). Our data sources included 1) interviews of a population-based sample of ED patients, 2) chart review for a cohort of ED patients, and 3) ICD-9 codes from an urban, academic trauma center. In addition, ICD-9 codes were obtained for three geographically proximate hospitals of differing type. The sampling methods and ED settings were compared descriptively in terms of their population characteristics and estimated prevalence of SUDs. Results: Prevalence of SUDs at the urban academic center was extremely high, particularly when measured by prospective survey, but also with chart review. Use over the prior year (binge drinking, illicit drug use, or treatment for alcohol or drug use) as determined by self-report and chart review respectively was: 41.9% and 15.2% for alcohol, 36.2% and 21.6% for drugs, and 59.2% and 30.4% for either. Estimates using ICD-9 codes indicated a far lower prevalence of substance use and suggest differences between EDs. Conclusions: SUDs are highly prevalent in ED populations, though significant variability between EDs is likely. SUDs are infrequently coded, suggesting that clinicians may be unaware of SUDs, or that discharge coding is insufficient to understand and respond to SUDs. Feasible and efficacious methods of identification and documentation of SUDs is an urgent priority to aid efforts to facilitate health services planning and quality improvement, and enable pragmatic clinical trials.

Suboptimal ventilation may impact outcomes in patients with traumatic brain injury (TBI). This study compares the incidence of eucapnia between manually and mechanically ventilated patients with severe TBI during helicopter transport.This retrospective chart review included consecutive intubated adults with severe TBI (Glasgow Coma Scale score9) transported by helicopter from the scene of injury to a level 1 trauma center between 2009 and 2015. The primary outcome was the first venous partial pressure of carbon dioxide obtained in the emergency department. Hypocapnia, eucapnia, and hypercapnia were defined based on the normal range for the testing instrument. The Fisher exact test was used to compare groups.Of 1,070 trauma patients intubated and transported, 93 met the inclusion criteria with full data. The mean age was 43 years, 81 of 93 were white, and 70 of 93 were men. The mean Injury Severity Score was 29, and 26 of 93 were mechanically ventilated. Hypocapnia occurred in 4 of 93 and hypercapnia in 56 of 93. There was no difference in the rate of eucapnia in manually ventilated compared with mechanically ventilated patients (36% vs. 35%, P = 1.00).Eucapnia at emergency department arrival occurred in 36% of patients and was unaffected by whether ventilation was manually or mechanically controlled. Few patients were hypocapnic, indicating a low incidence of hyperventilation during helicopter transport.

Background Recovery from stroke-induced aphasia is typically protracted and involves complex functional reorganization. The relative contributions of the lesioned and non-lesioned hemispheres to this process have been examined in several cross-sectional studies but longitudinal studies involving several time-points and large numbers of subjects are scarce. Objective The aim of this study was to address the gaps in the literature by longitudinally studying the evolution of post-stroke lateralization and localization of language-related fMRI activation in the first year after single left hemispheric ischemic stroke. Method Seventeen patients with stroke-induced aphasia were enrolled to undergo detailed behavioral testing and fMRI at 2, 6, 12, 26, and 52 weeks post-stroke. Matched for age, handedness and sex participants were also enrolled to visualize canonical language regions. Results Behavioral results showed improvements over time for all but one of the behavioral scores (Semantic Fluency Test). FMRI results showed that the left temporal area participates in compensation for language deficits in the first year after stroke, that there is a correlation between behavioral improvement and the left cerebellar activation over time, and that there is a shift towards stronger frontal left-lateralization of the fMRI activation over the first year post-stroke. Temporary compensation observed in the initial phases of post-stroke recovery that involves the non-lesioned hemisphere may not be as important as previously postulated, since in this study the recovery was driven by activations in the left fronto-temporal regions. Conclusion Language recovery after left hemispheric ischemic stroke is likely driven by the previously involved in language and attention left hemispheric networks.

Background Intracerebral hemorrhage (ICH) is a severe neurologic condition with no proven treatment. Recent evidence suggests that monocytes, a heterogenous group of cells with M1 and M2 phenotypes, contribute to secondary damage following ICH. Microparticles are vesicles .1-1 µm in size that are released from cells. We hypothesized that M1 and M2 monocyte microparticles (mMP) would be differentially expressed in ICH cases and controls. Methods In a single-center, prospective, observational study, consecutive ICH cases were enrolled within 12 hours of symptom onset. Age (±5 years)-, race-, and sex-matched controls were recruited. M1 and M2 mMP numbers were determined in plasma samples using flow cytometry and protein biomarkers using standardized assays. The Mann–Whitney U test compared M1 and M2 mMP counts between cases and controls. Standardized regression coefficients compared M1 and M2 mMP with C-reactive protein (CRP) and serum amyloid A (SAA). Results Nineteen ICH case-control pairs were enrolled. The median number of M1 mMP was not significantly different between ICH cases (8.63 × 10 7 /milliliter (mL)) compared with controls (8.64 × 10 7 /mL), ( P = .525). The median number of M2 mMP was significantly higher in ICH cases (1.61 × 10 6 /mL) compared with controls (4.46 × 10 5 /mL) ( P = .027). There were no significant associations for M1 or M2 mMP with CRP or SAA. Conclusion Higher numbers of M2 mMP in ICH cases compared with controls is hypothesis generating. It may represent differences in the chronic inflammatory status in patients susceptible to ICH, such as cellular activation or apoptosis. Further research is needed, including serial plasma samples, to elucidate the pathophysiology of monocytes and mMP following ICH.

Objective: The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric sepsis risk model, uses biomarkers to estimate baseline mortality risk for pediatric septic shock. It is unknown how PERSEVERE performs within distinct septic shock phenotypes. We tested PERSEVERE in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF), and in those without new onset thrombocytopenia but with multiple organ failure (MOF). Design: PERSEVERE-based mortality risk was generated for each study subject (n = 660). A priori, we determined that if PERSEVERE did not perform well in both the TAMOF and the MOF cohorts, we would revise PERSEVERE to incorporate admission platelet counts. Setting: Multiple PICUs in the United States. Interventions: Standard care. Measurements and Main Results: PERSEVERE performed well in the TAMOF cohort (areas under the receiver operating characteristic curves [AUC], 0.84 [95% CI, 0.77–0.90]), but less well in the MOF cohort (AUC, 0.71 [0.61–0.80]). PERSEVERE was revised using 424 subjects previously reported in the derivation phase. PERSEVERE-II had an AUC of 0.89 (0.85–0.93) and performed equally well across TAMOF and MOF cohorts. PERSEVERE-II performed well when tested in 236 newly enrolled subjects. Sample size calculations for a clinical trial testing the efficacy of plasma exchange for children with septic shock and TAMOF indicated PERSEVERE-II–based stratification could substantially reduce the number of patients necessary, when compared with no stratification. Conclusions: Testing PERSEVERE in the context of septic shock phenotypes prompted a revision incorporating platelet count. PERSEVERE-II performs well upon testing, independent of TAMOF or MOF status. PERSEVERE-II could potentially serve as a prognostic enrichment tool.

Purpose Failure to obtain an accurate medication history can adversely affect patient care in the emergency department (ED) and propagate errors into the inpatient and outpatient settings. Obtaining an accurate medication history in the ED is challenging, however, due to limited time, a suboptimal environment for patient interaction, and inadequate information in the electronic health record (EHR). This article describes the development and initial evaluation of the PictureRx Medication History Application, a tablet computer-based program that queries patients' prescription fill data from the Surescripts Medication History service and renders it graphically for review and editing at the point of care. Methods A quasi-experimental trial of PictureRx was performed in a large academic ED. Adult patients taking at least 1 prescription medication were prospectively eligible for the intervention. Usual care control patients were retrospectively matched 1:1. The main outcomes were updates to the patients' existing pre-visit medication list in the EHR and patient perceptions of the application. Results The medication list was updated for 101/244 (41.4%) of the intervention group and for 43/244 (17.6%) of the control group (difference 23.8%, 95% confidence interval, 16.0-31.6%). Similar differences were observed for medication additions, removals, and corrections in dose. Approximately 80% of intervention patients "strongly agreed" that the application was easy to use, aided medication list accuracy, and the graphical features assisted with recall. Conclusion A novel tablet computer-based medication history application was feasible to implement in a busy academic ED. Use of the tool was associated with more updates to patients' EHR medication list.

BACKGROUND: Injury is a leading cause of child morbidity and mortality worldwide. Delivering injury prevention programs via mobile platforms, such as applications (apps), may reduce risky behaviors. iBsafe is an “interactive Bike and Bite safety” mobile game app founded in behavioral theory and designed to educate kindergarten-aged children about bicycle and dog-related safety. This study assessed the relationship of iBsafe game play and child safety knowledge and skills; hypothesizing that iBsafe increases safety knowledge with translation to practice. METHODS: This single-blinded, randomized, controlled field trial included sixty 5–6-year-old children. Parent-child dyads were randomly assigned to receive a weeklong field trial of iBsafe or control. Pre- and post-intervention safety knowledge tests were completed; post-intervention safety skills assessments occurred in a simulated safety lab using real props (i.e., safety street, bicycles, and live dogs). The primary outcome was child bicycle and dog-related safety knowledge and skills performance. Performance was assessed by blinded reviewers. Secondary outcomes included frequency of safety discussion in groups and iBsafe acceptability. RESULTS: Thirty children were randomized to each group; there were no substantial demographic differences between groups. Compared to controls, post-intervention iBsafe children had higher bicycle and dog-related safety knowledge scores (9.2±0.9 vs. 8.7±1.0, P=0.029 and 8.2±2.1 vs. 6.7±1.8, P=0.003, respectively); and they exhibited more safety skills (median number bicycle skills 5 vs. 4, P=0.007; median number dog-related skills 5 vs. 3, P

Background: Advanced airways (endotracheal tubes, supraglottic airways) are frequently placed by Emergency Medical Services (EMS) in patients with out-of-hospital cardiac arrest (OHCA). However, if an airway is to be placed, it is unknown whether this should occur early or late in the sequence of resuscitation events. This study evaluated the association between the timing of airway placement and the minute-to-minute probability of achieving return of spontaneous circulation (ROSC). Methods: This secondary analysis of Resuscitation Outcomes Consortium Prehospital Resuscitation using an Impedance Valve and Early versus Delayed (ROC PRIMED) study data included adult, non-traumatic, witnessed OHCA patients with airway placement by EMS before ROSC. The primary exposure variable was time from EMS arrival to advanced airway placement. The outcome was prehospital ROSC. Since resuscitations occur over time, a Cox proportional hazards model was fit to estimate the probability of ROSC as a function of the airway timing, adjusting for Utstein variables. Results: A total of 7,547 patients were included. Time to airway placement was 0–5 minutes in 12% of the cohort, >5–10 (36%), >10–15 (29%), >15–20 (14%), >20–25 (5%), >25–30 (2%), and >30 (2%). ROSC occurred in 43%. Time to airway had a statistically significant impact on ROSC. A negative association between the time to airway placement and the hazard of ROSC was observed, such that increasing intervals between EMS arrival and airway placement were associated with decreasing probabilities of ROSC, regardless of initial cardiac rhythm. Conclusions: EMS advanced airway placement has a time-dependent association with ROSC. In witnessed OHCA patients receiving advanced airways, early airway placement is associated with increased probability of ROSC.

OBJECTIVE: To evaluate the relationship between satisfaction with life (SWL) and functional outcome after traumatic brain injury (TBI). SETTING AND PARTICIPANTS: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study (TRACK-TBI Pilot) enrolled patients at three U.S. Level I trauma centers within 24hrs of TBI. DESIGN: Patients were grouped by outcome measure concordance (good-recovery/good-satisfaction, impaired-recovery/impaired-satisfaction) and discordance (good-recovery/impaired-satisfaction, impaired-recovery/good-satisfaction). Logistic regression was utilized to determine predictors of discordance. MAIN MEASURES: Functional outcome: Glasgow Outcome Scale-Extended (GOSE); SWL: Satisfaction with Life Scale (SWLS) RESULTS: Of the 586 enrolled subjects, 298 had completed both outcome measures at six-month follow-up; the correlation between GOSE and SWLS was 0.380. Patients with impaired-recovery (GOSE

Objectives Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality. Design Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated. Setting Multiple ICUs. Patients Adults with sepsis. Interventions None. Measurements and main results Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality. Conclusions Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information.

Study objective Opioid abuse and overdose constitute an ongoing health emergency. Many presume opioids have little potential for iatrogenic addiction when used as directed, particularly in short courses, as is typical of the emergency department (ED) setting. We preliminarily explore the possibility that initial exposure to opioids by EDs could be related to subsequent opioid misuse. Methods This cross-sectional study surveyed a convenience sample of patients reporting heroin or nonmedical opioid use at an urban, academic ED. We estimated the proportion whose initial exposure to opioids was a legitimate medical prescription and the proportion of those prescriptions that came from an ED. Secondary measurements included the proportion of patients receiving nonopioid substances before initial opioid exposure, the source of opioids between initial exposure and onset of regular nonmedical use, and time from initial prescription to opioid use disorder. Results Of 59 subjects, 35 (59%; 95% confidence interval [CI] 47% to 71%) reported they were first exposed to opioids by a legitimate medical prescription, and for 10 of 35 (29%; 95% CI 16% to 45%), the prescription came from an ED. Most medically exposed subjects (28/35; 80%; 95% CI 65% to 91%) reported nonopioid substance use or treatment for nonopioid substance use disorders preceding the initial opioid exposure. Emergency providers were a source of opioids between exposure and onset of regular nonmedical use in 11 of 35 cases (31%; 95% CI 18% to 48%). Thirty-one of the 35 medically exposed subjects reported the time of onset of nonmedical use; median time from exposure to onset of nonmedical use was 6 months for use to get high (N=25; interquartile range [IQR] 2 to 36), 12 months for regular use to get high (N=24; IQR 2 to 36), 18 months for use to avoid withdrawal (N=26; IQR 2 to 38), and 24 months for regular use to avoid withdrawal (N=27; IQR 2 to 48). Eleven subjects (36%; 95% CI 21% to 53%) began nonmedical use within 2 months, and 9 of 11 (82%; 95% CI 53% to 96%) reported nonopioid substance use or treatment for alcohol abuse before initial opioid exposure. Conclusion Although short-term opioid administration by emergency providers is unlikely to cause addiction by itself, ED opioid prescriptions may contribute to the development of addiction in some patients. There is an urgent need for further research to estimate long-term risks of short-course opioid therapy so that the risk of iatrogenic addiction can be appropriately balanced with the benefit of analgesia.

Traumatic brain injury (TBI) is responsible for nearly 30% of all injury-related deaths in the United States.1 Affecting 1.7 million U.S. people annually, TBI is a primary cause of death and disability.2 Approximately 75% of all TBIs are considered mild, defined as an acute injury to the head as a result of blunt force trauma or rapid acceleration/deceleration causing loss of consciousness (

Background Incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in complicated skin and skin structure infection (cSSSI) presenting to emergency departments (EDs). Treatment is heterogeneous and can require inpatient admission to an observation unit (OU). Vancomycin is commonly used in the OU for treatment, but increasing MRSA resistance to vancomycin suggests the need for alternatives. Daptomycin is an alternative but it is not known how it compares with vancomycin. Objective This study tested the hypothesis that daptomycin is noninferior to vancomycin for the treatment of cSSSI in an OU, using a relative risk (RR) of 1.3 as the noninferiority limit. Methods Subjects admitted to an ED-based OU with a diagnosis of cSSSI were eligible. Consenting subjects were randomized 1:1 to intravenous (i.v.) vancomycin at 15 mg/kg dosing every 12 h or i.v. daptomycin at 4 mg/kg once. Subjects were followed until they met objective criteria for discharge home or hospital admission. Discharged patients were prescribed 10–14 days of oral cephalexin and trimethoprim-sulfamethoxazole, or clindamycin if allergic to either of these medications. The primary endpoint was meeting objective discharge criteria with no change in antibiotic therapy or return to the ED for the same cellulitis within 30 days of OU discharge. Results There were 100 patients enrolled. RR for satisfying the endpoint was 1.07 (95% confidence interval 0.58–1.98) for daptomycin compared with vancomycin. Hospital admission rates were 36% and 32% for daptomycin and vancomycin treatment, respectively. Conclusion Daptomycin was not inferior to vancomycin in the treatment of cSSSI in an OU.

BACKGROUND: Delivering quality lectures is a critical skill for residents seeking careers in academia yet no validated tools for assessing resident lecture skills exist. OBJECTIVES: The authors sought to develop and validate a lecture assessment tool. METHODS: Using a nominal group technique, the authors derived a behaviorally anchored assessment tool. Baseline characteristics of resident lecturers including prior lecturing experience and perceived comfort with lecturing were collected. Faculty and senior residents used the tool to assess lecturer performance at weekly conference. A postintervention survey assessed the usability of the form and the quantity and quality of the feedback. Analysis of variance was used to identify relationships in performance within individual domains to baseline data. Generalizability coefficients and scatterplots with jitter were used to assess inter‐rater reliability. RESULTS: Of 64 residents assessed, most (68.8%) had previous lecturing experience and 6.3% had experience as a regional/national speaker. There was a significant difference in performance within the domains of Content Expertise (p

Objectives Hypertension is a leading cause of morbidity and mortality. The emergency department (ED) frequently serves populations with unmet health needs and could have a greater and more systematic role in secondary prevention for hypertension. This study sought to determine, among hypertensive patients discharged from the ED, the frequency that patients 1) received hypertension-specific education, and 2) followed-up with a primary care provider. We secondarily assessed participant beliefs about hypertension. Methods This non-experimental, observational study enrolled a convenience sample of consenting patients with asymptomatic, markedly elevated blood pressure (systolic ≥160 mmHg or diastolic ≥100 mmHg) with medium to low triage acuity discharged from an urban, academic ED. Discharge instructions were assessed through chart review. Patients followed up per their normal routine without intervention. Participants were interviewed by phone two to four weeks after ED discharge to ascertain outpatient follow-up and describe beliefs about hypertension. Results From April through June 2014, 200 patients were approached, of whom 90 were enrolled. Of these, 77% of patients reported a previous diagnosis of hypertension, and 60% reported current treatment with antihypertensive medications. Five patients (5.5%) received written instructions at discharge addressing hypertension, although 59 (65.6%) reported that they were informed about their elevated blood pressure during the ED visit. Follow-up with a primary care provider within 2–4 weeks of discharge was completed in 57% of cases. None of the patients who received hypertension-specific discharge instructions completed follow-up. Conclusions Over half of markedly hypertensive patients discharged from the ED followed up with primary care within four weeks. Nonetheless, missed opportunities for improved secondary prevention among ED patients with hypertension are common. There is an urgent need for evidence-based interventions to assist emergency departments in addressing this health threat.

Background Angiotensin-converting enzyme inhibitor–induced angioedema (ACEI-AE) is mediated by bradykinin. There remains an unmet treatment need because these patients, when presenting to the emergency department (ED), do not respond to conventional therapies, such as antihistamines and corticosteroids. Objective To estimate the treatment effect of ecallantide, a recombinant plasma kallikrein inhibitor, in ED patients with ACEI-AE in whom conventional therapy fails. Methods This was a triple-blind (patient, physician, and statistician), randomized, controlled, phase 2 study to estimate the magnitude of safety and efficacy signals for designing a definitive phase 3 trial comparing conventional therapy with ecallantide to conventional therapy with placebo. Patients were enrolled from April 1, 2010, through January 31, 2013. The primary efficacy study end point was achieving discharge criteria from the ED within 4 hours after initiating study-related treatment. Results Discharge criteria from the ED was met in 4 hours or less for 8 (31%) of 26 patients receiving ecallantide vs 5 of (21%) 24 patients receiving placebo (difference in proportions, 10%; 95% confidence interval, −14% to 34%). Ecallantide was well tolerated in both groups. Conclusion The results from this preliminary study reveal that ecallantide is safe to use and may increase the proportion of patients who meet early discharge criteria by approximately10%. A larger phase 3 study is necessary to confirm the efficacy and evaluate the cost-effectiveness of ecallantide use for ACEI-AE in the ED setting. Trial Registration clinicaltrials.gov Identifier: NCT01036659

Introduction: The degree to which individual patients use multiple emergency departments (EDs)is not well-characterized. We determined the degree of overlap in ED population between threegeographically proximate hospitals. Methods: This retrospective cohort study reviewed administrative hospital records from 2003 to2007 for patients registered to receive ED services at an urban academic, urban community, andsuburban community ED located within 10 miles of one another. We determined the proportion whosought care at multiple EDs and secondarily characterized patterns of repeat encounters. Results: There were 795,176 encounters involving 282,903 patients. There were 89,776 (31%)patients with multiple encounters to a single ED and 39,920 (14%) patients who sought care frommultiple EDs. The 39,920 patients who sought care from multiple EDs generated 185,629 (23%)of all encounters. Patients with repeat encounters involving multiple EDs were more likely to befrequent or highly frequent users (30%) than patients with multiple encounters to a single ED (14%). Conclusion: While only 14% of patients received care from more than one ED, they wereresponsible for a quarter of ED encounters. Patients who use multiple EDs are more oftenfrequent or highly frequent users than are repeat ED visitors to the same ED. Overlap between ED populations is sufficient to warrant consideration by multiple domains of research, practice, andpolicy. [West J Emerg Med. 2015;16(2):229–233.]

Status epilepticus is a life-threatening, time-sensitive emergency. Acquiring an electroencephalogram (EEG) in the emergency department (ED) could impact therapeutic and disposition decisions for patients with suspected status epilepticus.The objective of this study is to estimate the proportion of EEGs diagnostic for seizures in patients presenting to an ED with a complaint of seizures.This retrospective chart review included adults presenting to the ED of an urban, academic, tertiary care hospital with suspected seizures or status epilepticus, who received an EEG within 24 hours of hospital admission. Data abstraction was performed by a single, trained, nonblinded abstractor. Seizures were defined as an epileptologist's diagnosis of either seizures or status epilepticus on EEG. The proportion of patients with seizures is given with confidence interval95 (CI95).Of 120 included patients, 67 (56%) had a history of epilepsy. Mean age was 52 years (SD, 16), 58% were White, and 61% were male. Within 24 hours, 3% had an EEG diagnostic for seizures. Electroencephalogram was obtained in the ED in 32 (27%) of 120 (CI95, 19%-35%), and 2 (6%) of 32 (CI95, 1%-19%) had seizures. Electroencephalogram was performed inpatient for 88 (73%) of 120 (CI95, 65%-81%), and 2 (2%) of 88 (CI95, 0.5%-7.1%) had seizures.Only 3% of ED patients with suspected seizures or status epilepticus had EEG confirmation of seizures within 24 hours. Early EEG acquisition in the ED may identify a group of patients amenable to ED observation and subsequent discharge from the hospital.

Background Few studies have documented the possibility of treatment-induced improvements in language functions 12 months or longer after stroke. The purpose of the current study was to provide a preliminary estimate of efficacy of constraint-induced aphasia therapy (CIAT) when compared to no-intervention in patients with chronic (>1 year) post-stroke aphasia in order to provide the data needed to design an appropriately powered trial. Material/Methods This was a randomized, controlled, single-blinded, pilot trial. We identified 32 patients with chronic post-stroke aphasia. Of these, 27 were offered participation, and 24 were randomized (CONSORT diagram): 14 to CIAT and to 10 to no-intervention. CIAT groups received up to 4 hours/day of intervention for 10 consecutive business days (40 hours of therapy). Outcomes were assessed within 1 week of intervention and at 1 and 12 weeks after intervention and included several linguistic measures and a measure of overall subjective communication abilities (mini-Communicative Abilities Log (mini-CAL)). To maintain blinding, clinicians treating patients (CIAT group) did not communicate with other team members and the testing team members were blinded to treatment group assignment. Results Overall, the results of this pilot trial support the results of previous observational studies that CIAT may lead to improvements in linguistic abilities. At 12 weeks, the treatment group reported better subjective communication abilities (mini-CAL) than the no-intervention group (p=0.019). Other measures trended towards better performance in the CIAT group. Conclusions In this randomized, controlled, and blinded pilot study, intensive language therapy (CIAT) led to an improvement in subjective language abilities. The effects demonstrated allow the design of a definitive trial of CIAT in patients with a variety of post-stroke aphasia types. In addition, our experiences have identified important considerations for designing subsequent trial(s) of CIAT or other interventions for post-stroke aphasia.