A standardized protocol using clinical adjudication to define true infection status in patients presenting to the emergency department with suspected infections and/or sepsis.

In absence of a "gold standard", a standardized clinical adjudication process was developed for a registrational trial of a transcriptomic host response (HR) test. Two physicians independently reviewed clinical data to adjudicate presence and source of bacterial and viral infections in emergency department patients. Discordant cases were resolved by a third physician. Agreement among 955 cases was 74.1% (708/955) for bacterial, 75.6% (722/955) for viral infections, and 71.2% (680/955) overall. Most discordances were minor (85.2%; 409/480) versus moderate (11.7%; 56/480) or complete (3.3%; 16/480). Concordance levels were lowest for bacterial skin and soft tissue infections (8.2%) and for viral respiratory tract infections (4.5%). This robust adjudication process can be used to evaluate HR tests and other diagnostics by regulatory agencies and for educating clinicians, laboratorians, and clinical researchers. Clinicaltrials.gov NCT04094818. SUMMARY: Without a gold standard for evaluating host response tests, clinical adjudication is a robust reference standard that is essential to determine the true infection status in diagnostic registrational clinical studies.

Effectiveness of a bivalent mRNA vaccine dose against symptomatic SARS-CoV-2 infection among U.S. Healthcare personnel, September 2022-May 2023.

BACKGROUND: Bivalent mRNA vaccines were recommended since September 2022. However, coverage with a recent vaccine dose has been limited, and there are few robust estimates of bivalent VE against symptomatic SARS-CoV-2 infection (COVID-19). We estimated VE of a bivalent mRNA vaccine dose against COVID-19 among eligible U.S. healthcare personnel who had previously received monovalent mRNA vaccine doses. METHODS: We conducted a case-control study in 22 U.S. states, and enrolled healthcare personnel with COVID-19 (case-participants) or without COVID-19 (control-participants) during September 2022-May 2023. Participants were considered eligible for a bivalent mRNA dose if they had received 2-4 monovalent (ancestral-strain) mRNA vaccine doses, and were ≥67 days after the most recent vaccine dose. We estimated VE of a bivalent mRNA dose using conditional logistic regression, accounting for matching by region and four-week calendar period. We adjusted estimates for age group, sex, race and ethnicity, educational level, underlying health conditions, community COVID-19 exposure, prior SARS-CoV-2 infection, and days since the last monovalent mRNA dose. RESULTS: Among 3,647 healthcare personnel, 1,528 were included as case-participants and 2,119 as control-participants. Participants received their last monovalent mRNA dose a median of 404 days previously; 1,234 (33.8%) also received a bivalent mRNA dose a median of 93 days previously. Overall, VE of a bivalent dose was 34.1% (95% CI, 22.6%-43.9%) against COVID-19 and was similar by product, days since last monovalent dose, number of prior doses, age group, and presence of underlying health conditions. However, VE declined from 54.8% (95% CI, 40.7%-65.6%) after 7-59 days to 21.6% (95% CI 5.6%-34.9%) after ≥60 days. CONCLUSIONS: Bivalent mRNA COVID-19 vaccines initially conferred approximately 55% protection against COVID-19 among U.S. healthcare personnel. However, protection waned after two months. These findings indicate moderate initial protection against symptomatic SARS-CoV-2 infection by remaining up-to-date with COVID-19 vaccines.

Factors associated with the decision to receive bivalent COVID-19 booster vaccination among health care personnel.

COVID-19 vaccination is effective at reducing SARS-CoV-2 complications, but uptake has been low. Our objective in this study was to compare the importance of factors reported to influence the decision to receive a bivalent COVID-19 booster vaccine among health care personnel (HCP) tested for SARS-CoV-2 between October 2022 and April 2023 in a 20-hospital vaccine effectiveness study in the United States (n = 1656). Compared with those who had not received the booster, the factors most likely to be reported to be important were concerns about contracting COVID-19 (84.0% of those who had received the bivalent booster vs. 47.5% of those who had not, difference 36.6% points (PP), 95% confidence interval [CI] 32.1 to 41.1%), spreading infection to family members (89.2% vs. 62.8%, difference 26.3 PP, 95% CI 22.3 to 30.4%), and spreading infection to colleagues at work (85.5% vs. 59.4%, difference 26.1 PP, 95% CI 21.7 to 30.5%). HCP who had received the booster more frequently cited the primary literature (61.7% vs. 31.8%, difference 29.9 PP, 95% CI 24.6 to 35.2%) and employer recommendations (48.3% vs. 29.8%, difference 18.5 PP, 95% CI 13.2 to 23.9%) as influencing their decision. This analysis provides insight into factors for targeting future vaccine messaging.

Effectiveness of a Messenger RNA Vaccine Booster Dose Against Coronavirus Disease 2019 Among US Healthcare Personnel, October 2021-July 2022.

Background: Protection against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]) can limit transmission and the risk of post-COVID conditions, and is particularly important among healthcare personnel. However, lower vaccine effectiveness (VE) has been reported since predominance of the Omicron SARS-CoV-2 variant. Methods: We evaluated the VE of a monovalent messenger RNA (mRNA) booster dose against COVID-19 from October 2021 to June 2022 among US healthcare personnel. After matching case-participants with COVID-19 to control-participants by 2-week period and site, we used conditional logistic regression to estimate the VE of a booster dose compared with completing only 2 mRNA doses >150 days previously, adjusted for multiple covariates. Results: Among 3279 case-participants and 3998 control-participants who had completed 2 mRNA doses, we estimated that the VE of a booster dose against COVID-19 declined from 86% (95% confidence interval, 81%-90%) during Delta predominance to 65% (58%-70%) during Omicron predominance. During Omicron predominance, VE declined from 73% (95% confidence interval, 67%-79%) 14-60 days after the booster dose, to 32% (4%-52%) ≥120 days after a booster dose. We found that VE was similar by age group, presence of underlying health conditions, and pregnancy status on the test date, as well as among immunocompromised participants. Conclusions: A booster dose conferred substantial protection against COVID-19 among healthcare personnel. However, VE was lower during Omicron predominance, and waning effectiveness was observed 4 months after booster dose receipt during this period. Our findings support recommendations to stay up to date on recommended doses of COVID-19 vaccines for all those eligible.

Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel.

BACKGROUND: The prioritization of U.S. health care personnel for early receipt of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), allowed for the evaluation of the effectiveness of these new vaccines in a real-world setting. METHODS: We conducted a test-negative case-control study involving health care personnel across 25 U.S. states. Cases were defined on the basis of a positive polymerase-chain-reaction (PCR) or antigen-based test for SARS-CoV-2 and at least one Covid-19-like symptom. Controls were defined on the basis of a negative PCR test for SARS-CoV-2, regardless of symptoms, and were matched to cases according to the week of the test date and site. Using conditional logistic regression with adjustment for age, race and ethnic group, underlying conditions, and exposures to persons with Covid-19, we estimated vaccine effectiveness for partial vaccination (assessed 14 days after receipt of the first dose through 6 days after receipt of the second dose) and complete vaccination (assessed ≥7 days after receipt of the second dose). RESULTS: The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer-BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (<50 years or ≥50 years), race and ethnic group, presence of underlying conditions, and level of patient contact. Estimates of vaccine effectiveness were lower during weeks 9 through 14 than during weeks 3 through 8 after receipt of the second dose, but confidence intervals overlapped widely. CONCLUSIONS: The BNT162b2 and mRNA-1273 vaccines were highly effective under real-world conditions in preventing symptomatic Covid-19 in health care personnel, including those at risk for severe Covid-19 and those in racial and ethnic groups that have been disproportionately affected by the pandemic. (Funded by the Centers for Disease Control and Prevention.).

Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel - 33 U.S. Sites, January-March 2021.

Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration: ClinicalTrials.gov: NCT04332991.

Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020.

Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.

Characteristics of Adult Outpatients and Inpatients with COVID-19 - 11 Academic Medical Centers, United States, March-May 2020.

Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3).

Supplemental thiamine for the treatment of acute heart failure syndrome: a randomized controlled trial.

BACKGROUND: The purpose of this pilot study was to determine if a definitive clinical trial of thiamine supplementation was warranted in patients with acute heart failure. We hypothesized that thiamine, when added to standard of care, would improve dyspnea (primary outcome) in hospitalized patients with acute heart failure. Peak expiratory flow rate, type B natriuretic peptide, free fatty acids, glucose, hospital length of stay, as well as 30-day rehospitalization and mortality were pre-planned secondary outcome measures. METHODS: This was a blinded experimental study at two urban academic hospitals. Consecutive patients admitted from the Emergency Department with a primary diagnosis of acute heart failure were recruited over 2 years. Patients on a daily dietary supplement were excluded. Randomization was stratified by type B natriuretic peptide and diabetes medication categories. Subjects received study drug (100 mg thiamine or placebo) in the evening of their first and second day. Outcome measures were obtained 8 h after study drug infusion. Dyspnea was measured on a 100-mm visual analog scale sitting up on oxygen, sitting up off oxygen, and lying supine off oxygen with 0 indicating no dyspnea. Data were analyzed using mixed-models as well as linear, negative binomial and logistic regression models to assess the impact of group on outcome measures. RESULTS: Of 130 subjects randomized, 118 had evaluable data (55 in the control and 63 in the treatment groups), 89% in both groups were adjudicated to have primarily AHF. Thiamine values increased significantly in the treatment group and were unchanged in the control group. One patient had thiamine deficiency. Only dyspnea measured sitting upright on oxygen differed significantly by group over time. No change was found for the other measures of dyspnea and all of the secondary measures. CONCLUSIONS: In mild-moderate acute heart failure patients without thiamine deficiency, a standard dosing regimen of thiamine did not improve dyspnea, biomarkers, or other clinical parameters. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00680706 , May 20, 2008 (retrospectively registered).

An example of medical device-based projection of clinical trial enrollment: Use of electrocardiographic data to identify candidates for a trial in acute coronary syndromes.

BACKGROUND: To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment. METHODS: To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals' electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial's enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals. RESULTS: Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs. CONCLUSION: Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.

Prevalence of Inconsistencies in the Recorded Outcomes of Clinical Evaluations.

OBJECTIVES: The aims of the study were to determine the prevalence of variations in the recorded outcomes of clinical evaluations by 2 different physicians during a single patient visit and to comment on observations of physician practices regarding history taking and physical examination. METHODS: Structured interviews were conducted with both junior and supervising physicians after they had evaluated patients in a pediatric emergency department who presented with complaints of fever (temperature, >100.4°F) in infants younger than 3 months, fever (temperature, >102.2°F) in infants aged 3 to 12 months, headache in patients older than 5 years, abdominal pain in patients older than 5 years, and head injury in patients younger than 18 years. Data were analyzed with descriptive statistics. RESULTS: Most of the data reported by both junior and supervising physicians showed response disagreement. The questions on fever (temperature, >102.2°F) in infants aged 3 to 12 months showed 29% (10/34) disagreement on fever duration and 45% (5/11) on fever height. Questions on abdominal pain in children older than 5 years showed 24% (24/100) disagreement on reporting right lower quadrant pain and 10% (11/106) on right lower quadrant tenderness on examination; however, the discrepancy rates were 56% (56/100) when considering less than complete agreement on all painful sites and 53% (56/106) on all tender sites. Supervising physicians questioned and examined patients presenting with abdominal pain more often than those presenting with other complaints. CONCLUSIONS: There are significant variations in the recorded outcome of clinical evaluations by 2 different physicians during a single patient visit. Supervising physicians are more cautious to question and examine patients presenting with abdominal pain compared with other chief complaints.

Corticosteroid therapy in refractory shock following cardiac arrest: a randomized, double-blind, placebo-controlled, trial.

BACKGROUND: The purpose of this study was to determine whether the provision of corticosteroids improves time to shock reversal and outcomes in patients with post-cardiac arrest shock. METHODS: We conducted a randomized, double-blind trial of post-cardiac arrest patients in shock, defined as vasopressor support for a minimum of 1 hour. Patients were randomized to intravenous hydrocortisone 100 mg or placebo every 8 hours for 7 days or until shock reversal. The primary endpoint was time to shock reversal. RESULTS: Fifty patients were included with 25 in each group. There was no difference in time to shock reversal between groups (hazard ratio: 0.83 [95% CI: 0.40-1.75], p = 0.63). We found no difference in secondary outcomes including shock reversal (52% vs. 60%, p = 0.57), good neurological outcome (24% vs. 32%, p = 0.53) or survival to discharge (28% vs. 36%, p = 0.54) between the hydrocortisone and placebo groups. Of the patients with a baseline cortisol < 15 ug/dL, 100% (6/6) in the hydrocortisone group achieved shock reversal compared to 33% (1/3) in the placebo group (p = 0.08). All patients in the placebo group died (100%; 3/3) whereas 50% (3/6) died in the hydrocortisone group (p = 0.43). CONCLUSIONS: In a population of cardiac arrest patients with vasopressor-dependent shock, treatment with hydrocortisone did not improve time to shock reversal, rate of shock reversal, or clinical outcomes when compared to placebo. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT00676585, registration date: May 9, 2008.

Randomized Controlled Trial of Electronic Care Plan Alerts and Resource Utilization by High Frequency Emergency Department Users with Opioid Use Disorder.

INTRODUCTION: There is a paucity of literature supporting the use of electronic alerts for patients with high frequency emergency department (ED) use. We sought to measure changes in opioid prescribing and administration practices, total charges and other resource utilization using electronic alerts to notify providers of an opioid-use care plan for high frequency ED patients. METHODS: This was a randomized, non-blinded, two-group parallel design study of patients who had 1) opioid use disorder and 2) high frequency ED use. Three affiliated hospitals with identical electronic health records participated. Patients were randomized into "Care Plan" versus "Usual Care groups". Between the years before and after randomization, we compared as primary outcomes the following: 1) opioids (morphine mg equivalents) prescribed to patients upon discharge and administered to ED and inpatients; 2) total medical charges, and the numbers of; 3) ED visits, 4) ED visits with advanced radiologic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) studies, and 5) inpatient admissions. RESULTS: A total of 40 patients were enrolled. For ED and inpatients in the "Usual Care" group, the proportion of morphine mg equivalents received in the post-period compared with the pre-period was 15.7%, while in the "Care Plan" group the proportion received in the post-period compared with the pre-period was 4.5% (ratio=0.29, 95% CI [0.07-1.12]; p=0.07). For discharged patients in the "Usual Care" group, the proportion of morphine mg equivalents prescribed in the post-period compared with the pre-period was 25.7% while in the "Care Plan" group, the proportion prescribed in the post-period compared to the pre-period was 2.9%. The "Care Plan" group showed an 89% greater proportional change over the periods compared with the "Usual Care" group (ratio=0.11, 95% CI [0.01-0.092]; p=0.04). Care plans did not change the total charges, or, the numbers of ED visits, ED visits with CT or MRI or inpatient admissions. CONCLUSION: Electronic care plans were associated with an incremental decrease in opioids (in morphine mg equivalents) prescribed to patients with opioid use disorder and high frequency ED use.

Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study.

OBJECTIVE: To determine if intravenous thiamine would reduce lactate in patients with septic shock. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Two US hospitals. PATIENTS: Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014. INTERVENTIONS: Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge. MEASUREMENTS AND MAIN RESULTS: The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4, 2.5] vs. 3.1 [1.9, 8.3], p = 0.03). There was a statistically significant decrease in mortality over time in those receiving thiamine in this subgroup (p = 0.047). CONCLUSION: Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate. In those with baseline thiamine deficiency, patients in the thiamine group had significantly lower lactate levels at 24 hours and a possible decrease in mortality over time.

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath.

BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes.

A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma.

BACKGROUND: Patients with frequent asthma exacerbations resulting in emergency department (ED) visits are at increased risk for future exacerbations. We examined the ability of 1 dose of benralizumab, an investigational antiinterleukin 5 receptor α monoclonal antibody, to reduce recurrence after acute asthma exacerbations. METHODS: In this randomized, double-blind, placebo-controlled study, eligible subjects presented to the ED with an asthma exacerbation, had partial response to treatment, and greater than or equal to 1 additional exacerbation within the previous year. Subjects received 1 intravenous infusion of placebo (n = 38) or benralizumab (0.3 mg/kg, n = 36 or 1.0 mg/kg, n = 36) added to outpatient management. The primary outcome was the proportion of subjects with greater than or equal to 1 exacerbation at 12 weeks in placebo vs the combined benralizumab groups. Other outcomes included the time-weighted rate of exacerbations at week 12, adverse events, blood eosinophil counts, asthma symptom changes, and health care resource utilization. RESULTS: The proportion of subjects with greater than or equal to 1 asthma exacerbation at 12 weeks was not different between placebo and the combined benralizumab groups (38.9% vs 33.3%; P = .67). However, compared with placebo, benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P = .01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P = .02) in the combined groups. Benralizumab reduced blood eosinophil counts but did not affect other outcomes, while demonstrating an acceptable safety profile. CONCLUSIONS: When added to usual care, 1 dose of benralizumab reduced the rate and severity of exacerbations experienced over 12 weeks by subjects who presented to the ED with acute asthma.

Emergency medicine residents' knowledge of mechanical ventilation.

BACKGROUND: Although Emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM) residency curricula. OBJECTIVES: The objective of this study was to quantify EM residents' education, experience, and knowledge regarding mechanical ventilation. METHODS: We developed a survey of residents' educational experiences with ventilators and an assessment tool with nine clinical questions. Correlation and regression analyses were performed to evaluate the relationship between residents' scores on the assessment instrument and their training, education, and comfort with ventilation. RESULTS: Of 312 EM residents, 218 responded (69.9%). The overall correct response rate for the assessment tool was 73.3%, standard deviation (SD) ± 22.3. Seventy-seven percent (n = 167) of respondents reported ≤ 3 h of mechanical ventilation education in their residency curricula over the past year. Residents reported frequently caring for ventilated patients in the ED, as 64% (n = 139) recalled caring for ≥ 4 ventilated patients per month. Fifty-three percent (n = 116) of residents endorsed feeling comfortable caring for mechanically ventilated ED patients. In multiregression analysis, the only significant predictor of total test score was residents' comfort with caring for mechanically ventilated patients (F = 10.963, p = 0.001). CONCLUSIONS: EM residents report caring for mechanically ventilated patients frequently, but receive little education on mechanical ventilation. Furthermore, as residents' performance on the assessment tool is only correlated with their self-reported comfort with caring for ventilated patients, these results demonstrate an opportunity for increased educational focus on mechanical ventilation management in EM residency training.

Body mass index and risk of hospitalization among adults presenting with asthma exacerbation to the emergency department.

RATIONALE: Studies have linked obesity to incident asthma and worse chronic severity/control. However, the relationship between obesity and acute asthma morbidity remains unclear. OBJECTIVES: To determine whether obese adults presenting to the emergency department (ED) with asthma exacerbation are at higher risk of hospitalization compared with normal-weight adults. METHODS: Multicenter chart review study of 48 EDs across 23 U.S. states. We identified ED patients aged 18 to 54 years with asthma exacerbation during 2011 to 2012. Primary outcome was hospitalization. MEASUREMENTS AND MAIN RESULTS: The analytic cohort comprised 1,227 patients. Of these, 323 patients (27%) were overweight (body mass index [BMI], 25-29.9 kg/m(2)), and 607 (50%) were obese (BMI ≥ 30 kg/m(2)). Among the 607 obese patients, 364 patients (60%) were severely obese (BMI ≥ 35 kg/m(2)). Several markers of chronic severity/control of asthma and acute severity did not differ across BMI groups. By contrast, compared with normal-weight patients, the risk of hospitalization was higher in patients who were overweight (11 vs. 18%; odds ratio [OR], 1.68; 95% confidence interval [CI], 1.05-2.68; P = 0.03) or obese (11 vs. 23%; OR, 2.30; 95% CI, 1.53-3.49; P < 0.001). In the adjusted analysis with multiple imputation, the association lost statistical significance in overweight patients (OR, 1.56; 95% CI, 0.90-2.71; P = 0.11) but persisted in obese patients (OR, 1.69; 95% CI, 1.02-2.81; P = 0.04). The latter finding was driven by an even higher risk of hospitalization in severely obese patients (OR, 1.95; 95% CI, 1.13-3.34; P = 0.02). CONCLUSIONS: In this multicenter study of ED patients with asthma exacerbation, we found that obese adults were at a higher risk of hospitalization compared with normal-weight adults.

Electrolyte profile of pediatric patients with hypertrophic pyloric stenosis.

OBJECTIVES: Recent investigations have demonstrated that the classic hypochloremic, hypokalemic, metabolic alkalosis of hypertrophic pyloric stenosis (HPS) is not a common finding.Some have suggested a trend over time, but none has investigated factors contributing to laboratory derangement, such as duration of vomiting or patient age at presentation. We sought to determine the proportion of patients with HPS with normal and abnormal laboratory findings as a function of year of presentation, duration of vomiting, and patient age. METHODS: This is a retrospective chart review of 205 patients younger than 6 months with operative diagnosis of HPS at a tertiary, regional pediatric center from 2000 to 2009. We examined the acid-base status and electrolyte levels (serum bicarbonate [CO2], serum potassium [K], and serum chloride [Cl]) at the time of the index visit to determine the proportion of normal, high, and low values for each as a function of year of presentation, duration of vomiting, and patient age. RESULTS: The proportion of HPS cases with normal CO2 was 62%; low serum CO2, 20%; and high CO2, 18%. The proportion with normal serum K was 57%; low K, 8%; and high K, 35%. The proportion with normal Cl was 69%; low Cl, 25%; and high Cl, 6%. Logistic regression analysis demonstrated that the prevalence of metabolic alkalosis increased across the decade, whereas the prevalence of metabolic acidosis decreased and that advancing age was associated with the presence of alkalosis. CONCLUSIONS: We observed that normal laboratory values are the most common finding in HPS and that metabolic alkalosis was found more commonly in the latter part of the decade and in older infants.