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The objective was to evaluate the comparative effectiveness and safety of pharmacological and nonpharmacological management options for atrial fibrillation/atrial flutter with rapid ventricular response (AFRVR) in patients with acute decompensated heart failure (ADHF) in the acute care setting.This study was a systematic review of observational studies or randomized clinical trials (RCT) of adult patients with AFRVR and concomitant ADHF in the emergency department (ED), intensive care unit, or step-down unit. The primary effectiveness outcome was successful rate or rhythm control. Safety outcomes were adverse events, such as symptomatic hypotension and venous thromboembolism.A total of 6577 unique articles were identified. Five studies met inclusion criteria: one RCT in the inpatient setting and four retrospective studies, two in the ED and the other three in the inpatient setting. In the RCT of diltiazem versus placebo, 22 patients (100%) in the treatment group had a therapeutic response compared to 0/15 (0%) in the placebo group, with no significant safety differences between the two groups. For three of the observational studies, data were limited. One observation study showed no difference between metoprolol and diltiazem for successful rate control, but worsening heart failure symptoms occurred more frequently in those receiving diltiazem compared to metoprolol (19 patients [33%] vs. 10 patients [15%], p = 0.019). A single study included electrical cardioversion (one patient exposed with failure to convert to sinus rhythm) as nonpharmacological management. The overall risk of bias for included studies ranged from serious to critical. Missing data and heterogeneity of definitions for effectiveness and safety outcomes precluded the combination of results for quantitative meta-analysis.High-level evidence to inform clinical decision making regarding effective and safe management of AFRVR in patients with ADHF in the acute care setting is lacking.

BackgroundPatient flow directly affects quality of care, access and financial performance for hospitals. Multidisciplinary discharge-focused rounds have proven to minimise avoidable delays experienced by patients near discharge. The study objective was to support discharge-focused rounds by implementing a machine-learning-based discharge prediction model using real-time electronic health record (EHR) data. We aimed to evaluate model predictive performance and impact on hospital length-of-stay.MethodsDischarge prediction models were developed from hospitalised patients on four inpatient units between April 2016 and September 2018. Unit-specific models were implemented to make individual patient predictions viewable with the EHR patient track board. Predictive performance was measured prospectively for 12 470 patients (120 780 patient-predictions) across all units. A pre/poststudy design applying interrupted time series methods was used to assess the impact of the discharge prediction model on hospital length-of-stay.ResultsProspective discharge prediction performance ranged in area under the receiver operating characteristic curve from 0.70 to 0.80 for same-day and next-day predictions; sensitivity was between 0.63 and 0.83 and specificity between 0.48 and 0.80. Elapsed length-of-stay, counts of labs and medications, mobility assessments and measures of acute kidney injury were model features providing the most predictive value. Implementing the discharge predictions resulted in a reduction in hospital length-of-stay of over 12 hours on a medicine unit (pConclusionsIncorporating automated patient discharge predictions into multidisciplinary rounds can support decreases in hospital length-of-stay. Variation in execution and impact across inpatient units existed.

Study objective Acute kidney injury occurs commonly and is a leading cause of prolonged hospitalization, development and progression of chronic kidney disease, and death. Early acute kidney injury treatment can improve outcomes. However, current decision support is not able to detect patients at the highest risk of developing acute kidney injury. We analyzed routinely collected emergency department (ED) data and developed prediction models with capacity for early identification of ED patients at high risk for acute kidney injury. Methods A multisite, retrospective, cross-sectional study was performed at 3 EDs between January 2014 and July 2017. All adult ED visits in which patients were hospitalized and serum creatinine level was measured both on arrival and again with 72 hours were included. We built machine-learning-based classifiers that rely on vital signs, chief complaints, medical history and active medical visits, and laboratory results to predict the development of acute kidney injury stage 1 and 2 in the next 24 to 72 hours, according to creatinine-based international consensus criteria. Predictive performance was evaluated out of sample by Monte Carlo cross validation. Results The final cohort included 91,258 visits by 59,792 unique patients. Seventy-two–hour incidence of acute kidney injury was 7.9% for stages greater than or equal to 1 and 1.0% for stages greater than or equal to 2. The area under the receiver operating characteristic curve for acute kidney injury prediction ranged from 0.81 (95% confidence interval 0.80 to 0.82) to 0.74 (95% confidence interval 0.74 to 0.75), with a median time from ED arrival to prediction of 1.7 hours (interquartile range 1.3 to 2.5 hours). Conclusion Machine learning applied to routinely collected ED data identified ED patients at high risk for acute kidney injury up to 72 hours before they met diagnostic criteria. Further prospective evaluation is necessary.

Background Monocyte distribution width (MDW) is a novel marker of monocyte activation, which is known to occur in the immune response to viral pathogens. Our objective was to determine the diagnostic performance of MDW and other leukocyte parameters for SARS-CoV-2 and influenza infection. Methods This was a prospective cohort analysis of adult patients who underwent complete blood count (CBC) and SARS-CoV-2 or influenza testing in an Emergency Department (ED) between January 2020 and July 2021. The primary outcome was SARS-CoV-2 or influenza infection. Secondary outcomes were measures of severity of illness including inpatient hospitalization, critical care admission, hospital lengths of stay and mortality. Descriptive statistics and diagnostic performance measures were evaluated for monocyte percentage, MDW, white blood cell (WBC) count, and neutrophil to lymphocyte ratio (NLR). Results 3,425 ED patient visits were included. SARS-CoV-2 testing was performed during 1,923 visits with a positivity rate of 5.4%; influenza testing was performed during 2,090 with a positivity rate of 2.3%. MDW was elevated in patients with SARS-Cov-2 (median 23.0U; IQR 20.5–25.1) or influenza (median 24.1U; IQR 22.0-26.9) infection, as compared to those without (18.9U; IQR 17.4–20.7 and 19.1U; 17.4–21, respectively, p

Objective:We analyzed the efficacy, cost, and cost-effectiveness of predictive decision-support systems based on surveillance interventions to reduce the spread of carbapenem-resistant Enterobacteriaceae (CRE).Design:We developed a computational model that included patient movement between acute-care hospitals (ACHs), long-term care facilities (LTCFs), and communities to simulate the transmission and epidemiology of CRE. A comparative cost-effectiveness analysis was conducted on several surveillance strategies to detect asymptomatic CRE colonization, which included screening in ICUs at select or all hospitals, a statewide registry, or a combination of hospital screening and a statewide registry.Setting:We investigated 51 ACHs, 222 LTCFs, and skilled nursing facilities, and 464 ZIP codes in the state of Maryland.Patients or participants:The model was informed using 2013–2016 patient-mix data from the Maryland Health Services Cost Review Commission. This model included all patients that were admitted to an ACH.Results:On average, the implementation of a statewide CRE registry reduced annual CRE infections by 6.3% (18.8 cases). Policies of screening in select or all ICUs without a statewide registry had no significant impact on the incidence of CRE infections. Predictive algorithms, which identified any high-risk patient, reduced colonization incidence by an average of 1.2% (3.7 cases) without a registry and 7.0% (20.9 cases) with a registry. Implementation of the registry was estimated to save $572,000 statewide in averted infections per year.Conclusions:Although hospital-level surveillance provided minimal reductions in CRE infections, regional coordination with a statewide registry of CRE patients reduced infections and was cost-effective.

Rapid growth in emergency department (ED) triage literature has been accompanied by diversity in study design, methodology, and outcome assessment. We aim to synthesize existing ED triage literature by using a framework that enables performance comparisons and benchmarking across triage systems, with respect to clinical outcomes and reliability.PubMed, EMBASE, Scopus, and Web of Science were systematically searched for studies of adult ED triage systems through 2016. Studies evaluating triage systems with evidence of widespread adoption (Australian Triage Scale, Canadian Triage and Acuity Scale, Emergency Severity Index, Manchester Triage Scale, and South African Triage Scale) were cataloged and compared for performance in identifying patients at risk for mortality, critical illness and hospitalization, and interrater reliability. This study was performed and reported in adherence to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.A total of 6,160 publications were identified, with 182 meeting eligibility criteria and 50 with sufficient data for inclusion in comparative analysis. The Canadian Triage and Acuity Scale (32 studies), Emergency Severity Index (43), and Manchester Triage Scale (38) were the most frequently studied triage scales, and all demonstrated similar performance. Most studies (6 of 8) reported high sensitivity (90%) of triage scales for identifying patients with ED mortality as high acuity at triage. However, sensitivity was low (80%) for identification of patients who had critical illness outcomes and those who died within days of the ED visit or during the index hospitalization. Sensitivity varied by critical illness and was lower for severe sepsis (36% to 74%), pulmonary embolism (54%), and non-ST-segment elevation myocardial infarction (44% to 85%) compared with ST-segment elevation myocardial infarction (56% to 92%) and general outcomes of ICU admission (58% to 100%) and lifesaving intervention (77% to 98%). Some proportion of hospitalized patients (3% to 45%) were triaged to low acuity (level 4 to 5) in all studies. Reliability measures (κ) were variable across evaluations, with only a minority (11 of 42) reporting κ above 0.8.We found that a substantial proportion of ED patients who die postencounter or are critically ill are not designated as high acuity at triage. Opportunity to improve interrater reliability and triage performance in identifying patients at risk of adverse outcome exists.

Purpose To determine the risk for acute kidney injury (AKI) attributable to intravenous contrast media (CM) administration in septic patients. Materials and methods This was a single-center retrospective propensity matched cohort analysis performed in the emergency department (ED) of an academic medical center. All visits for patients ≥18 years who met sepsis diagnostic criteria and had serum creatinine (SCr) measured both on arrival to the ED and again 48 to 72 h later were included. Of 4171 visits, 1464 patients underwent contrast-enhanced CT (CECT), 976 underwent unenhanced CT and 1731 underwent no CT at all. Results The primary outcome was incidence of AKI. Logistic regression and between-groups odds ratios with and without propensity-score matching were used to test for an independent association between CM administration and AKI. Incidence of AKI was 7.2%, 9.4% and 9.7% in those who underwent CECT, unenhanced CT and no CT. CM administration was not associated with increased incidence of AKI. Conclusions Sepsis is a medical emergency proven to benefit from early diagnosis and rapid initiation of treatment, which is often aided by CECT. Our findings argue against withholding CM for fear of precipitating AKI in potentially septic patients.

Artificial intelligence (AI) refers to the performance of tasks by machines ordinarily associated with human intelligence. Machine learning (ML) is a subtype of AI; it refers to the ability of computers to draw conclusions (ie, learn) from data without being directly programmed. ML builds from traditional statistical methods and has drawn significant interest in healthcare epidemiology due to its potential for improving disease prediction and patient care. This review provides an overview of ML in healthcare epidemiology and practical examples of ML tools used to support healthcare decision making at 4 stages of hospital-based care: triage, diagnosis, treatment, and discharge. Examples include model-building efforts to assist emergency department triage, predicting time before septic shock onset, detecting community-acquired pneumonia, and classifying COVID-19 disposition risk level. Increasing availability and quality of electronic health record (EHR) data as well as computing power provides opportunities for ML to increase patient safety, improve the efficiency of clinical management, and reduce healthcare costs.

Background The availability of patient outcomes–based feedback is limited in episodic care environments such as the emergency department. Emergency medicine (EM) clinicians set care trajectories for a majority of hospitalized patients and provide definitive care to an even larger number of those discharged into the community. EM clinicians are often unaware of the short- and long-term health outcomes of patients and how their actions may have contributed. Despite large volumes of patients and data, outcomes-driven learning that targets individual clinician experiences is meager. Integrated electronic health record (EHR) systems provide opportunity, but they do not have readily available functionality intended for outcomes-based learning. Objective This study sought to unlock insights from routinely collected EHR data through the development of an individualizable patient outcomes feedback platform for EM clinicians. Here, we describe the iterative development of this platform, Linking Outcomes Of Patients (LOOP), under a human-centered design framework, including structured feedback obtained from its use. Methods This multimodal study consisting of human-centered design studios, surveys (24 physicians), interviews (11 physicians), and a LOOP application usability evaluation (12 EM physicians for ≥30 minutes each) was performed between August 2019 and February 2021. The study spanned 3 phases: (1) conceptual development under a human-centered design framework, (2) LOOP technical platform development, and (3) usability evaluation comparing pre- and post-LOOP feedback gathering practices in the EHR. Results An initial human-centered design studio and EM clinician surveys revealed common themes of disconnect between EM clinicians and their patients after the encounter. Fundamental postencounter outcomes of death (15/24, 63% respondents identified as useful), escalation of care (20/24, 83%), and return to ED (16/24, 67%) were determined high yield for demonstrating proof-of-concept in our LOOP application. The studio aided the design and development of LOOP, which integrated physicians throughout the design and content iteration. A final LOOP prototype enabled usability evaluation and iterative refinement prior to launch. Usability evaluation compared to status quo (ie, pre-LOOP) feedback gathering practices demonstrated a shift across all outcomes from “not easy” to “very easy” to obtain and from “not confident” to “very confident” in estimating outcomes after using LOOP. On a scale from 0 (unlikely) to 10 (most likely), the users were very likely (9.5) to recommend LOOP to a colleague. Conclusions This study demonstrates the potential for human-centered design of a patient outcomes–driven feedback platform for individual EM providers. We have outlined a framework for working alongside clinicians with a multidisciplined team to develop and test a tool that augments their clinical experience and enables closed-loop learning.

Importance Sepsis is a common syndrome with substantial morbidity and mortality. A combination of vitamin C, thiamine, and corticosteroids has been proposed as a potential treatment for patients with sepsis. Objective To determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis. Design, setting, and participants Multicenter, randomized, double-blind, adaptive-sample-size, placebo-controlled trial conducted in adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction. Participants were enrolled in the emergency departments or intensive care units at 43 hospitals in the United States between August 2018 and July 2019. After enrollment of 501 participants, funding was withheld, leading to an administrative termination of the trial. All study-related follow-up was completed by January 2020. Interventions Participants were randomized to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death. Participants could be treated with open-label corticosteroids by the clinical team, with study hydrocortisone or matching placebo withheld if the total daily dose was greater or equal to the equivalent of 200 mg of hydrocortisone. Main outcomes and measures The primary outcome was the number of consecutive ventilator- and vasopressor-free days in the first 30 days following the day of randomization. The key secondary outcome was 30-day mortality. Results Among 501 participants randomized (median age, 62 [interquartile range {IQR}, 50-70] years; 46% female; 30% Black; median Acute Physiology and Chronic Health Evaluation II score, 27 [IQR, 20.8-33.0]; median Sequential Organ Failure Assessment score, 9 [IQR, 7-12]), all completed the trial. Open-label corticosteroids were prescribed to 33% and 32% of the intervention and control groups, respectively. Ventilator- and vasopressor-free days were a median of 25 days (IQR, 0-29 days) in the intervention group and 26 days (IQR, 0-28 days) in the placebo group, with a median difference of -1 day (95% CI, -4 to 2 days; P = .85). Thirty-day mortality was 22% in the intervention group and 24% in the placebo group. Conclusions and relevance Among critically ill patients with sepsis, treatment with vitamin C, thiamine, and hydrocortisone, compared with placebo, did not significantly increase ventilator- and vasopressor-free days within 30 days. However, the trial was terminated early for administrative reasons and may have been underpowered to detect a clinically important difference. Trial registration ClinicalTrials.gov Identifier: NCT03509350.

Opportunity exists to decrease healthcare-related exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), preserve infection control resources, and increase care capacity by reducing the time to diagnosis of coronavirus disease 2019 (COVID-19). A retrospective cohort analysis was undertaken to measure the effect of targeted rapid molecular testing for SARS-CoV-2 on these outcomes. In comparison with standard platform testing, rapid testing was associated with a 65.6% reduction (12.6 h) in the median time to removal from the isolation cohort for patients with negative diagnostic results. This translated to an increase in COVID-19 treatment capacity of 3028 bed-hours and 7500 fewer patient interactions that required the use of personal protective equipment per week.

The COVID‐19 crisis has brought about new clinical questions, new workflows, and accelerated distributed healthcare needs. Although artificial intelligence (AI)‐based clinical decision support seemed to have matured, the application of AI‐based tools for COVID‐19 has been limited to date. In this perspective piece, the opportunities and requirements for AI‐based clinical decision support systems are identified and challenges that impact “AI readiness” for rapidly emergent healthcare challenges are highlighted., The COVID‐19 crisis has brought about new clinical questions, workflows, and accelerated healthcare needs. While artificial intelligence (AI)‐based clinical decision support seemed to have matured, the application of learning‐based tools for COVID‐19 has been limited to date. This essay identifies opportunities and requirements for AI‐based decision support systems and highlights challenges that impact “AI readiness” for rapidly emergent healthcare challenges.© 2020 WILEY‐VCH Verlag GmbH & Co. KGaA, WeinheimThis article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

This study characterizes the trends in rates of SARS-CoV-2 positive test results among individuals in the Baltimore–Washington, DC area by self-reported race/ethnicity.

Background Emergency departments (ED) are sites of prevalent imaging overuse; however, determinants that drive imaging in this setting are not well-characterized. We systematically reviewed the literature to summarize the determinants of imaging overuse in the ED. Methods We searched MEDLINE® and Embase® from January 1998 to March 2017. Studies were included if they were written in English, contained original data, pertained to a U.S. population, and identified a determinant associated with overuse of imaging in the ED. Results Twenty relevant studies were included. Fourteen evaluated computerized tomography (CT) scanning in patents presenting to a regional ED who were then transferred to a level 1 trauma center; incomplete transfer of data and poor image quality were the most frequently described reasons for repeat scanning. Unnecessary pre-transfer scanning or repeated scanning after transfer, in multiple studies, was highest among older patients, those with higher Injury Severity Scores (ISS) and those being transferred further. Six studies explored determinants of overused imaging in the ED in varied conditions, with overuse greater in older patients and those having more comorbid diseases. Defensive imaging reportedly influenced physician behavior. Less integration of services across the health system also predisposed to overuse of imaging. Conclusions The literature is heterogeneous with surprisingly few studies of determinants of imaging in minor head injury or of spine imaging. Older patient age and higher ISS were the most consistently associated with ED imaging overuse. This review highlights the need for precise definitions of overuse of imaging in the ED.

Background Esophageal foreign body (EFB) and impaction are common gastrointestinal emergencies. Detection with standard imaging can be challenging. Computed tomography is a commonly used non-invasive imaging modality, but is not 100% sensitive and not always feasible. Sensitivity of plain film x-ray varies widely and the addition of a barium swallow can obscure evaluation by subsequent esophagogastroduodenoscopy (EGD). Use of emergency ultrasound (EUS) for detection of EFB in adults has not been previously studied. Objective To evaluate the role of EUS in detection of EFB and to characterize sonographic findings. Methods A case control series of five patients with clinical suspicion of EFB underwent EUS, and findings were compared to five healthy controls. Patients were evaluated for persistent air-fluid levels after swallowing, esophageal dilatation, and visualization of EFB. Results: All patients with suspected EFB had esophageal dilatation (17.5mm vs 9.3mm in healthy controls; p =0.0011) and persistent air-fluid levels after swallowing. EFB was visualized on EUS in 60% of patients. All patients had EFB confirmed on EGD except one, who vomited a significant food bolus during EUS and prior to EGD. Conclusion In patients with suspected EFB, point-of-care ultrasound may identify those with impaction. Suggestive findings include cervical esophageal dilatation and persistent intraluminal air-fluid levels after swallowing. EUS is a rapid, convenient test with the potential to expedite definitive management while decreasing cost and radiation exposure in this patient population.

Background User- and time-stamped data from hospital electronic health records (EHRs) present opportunities to evaluate how healthcare worker (HCW)-mediated contact networks impact transmission of multidrug-resistant pathogens, such as vancomycin-resistant enterococci (VRE). Methods This is a retrospective analysis of incident acquisitions of VRE between July 1, 2016 and June 30, 2018. Clinical and demographic patient data were extracted from the hospital EHR system, including all recorded HCW contacts with patients. Contacts by an HCW with 2 different patients within 1 hour was considered a “connection”. Incident VRE acquisition was determined by positive clinical or surveillance cultures collected ≥72 hours after a negative surveillance culture. Results There were 2952 hospitalizations by 2364 patients who had ≥2 VRE surveillance swabs, 112 (4.7%) patients of which had incident nosocomial acquisitions. Patients had a median of 24 (interquartile range [IQR], 18–33) recorded HCW contacts per day, 9 (IQR, 5–16) of which, or approximately 40%, were connections that occurred Conclusions We demonstrated that EHR data can be used to quantify the impact of HCW-mediated patient connections on transmission of VRE in the hospital. Defining incident acquisition risk of multidrug-resistant organisms through HCWs connections from EHR data in real-time may aid implementation and evaluation of interventions to contain their spread.

Background Patients who develop acute kidney injury (AKI) have a 2-fold increased risk for major adverse events within 1 year. An estimated 19–26% of all cases of hospital-acquired AKI may be attributable to drug-induced kidney disease (DIKD). Patients evaluated in the emergency department (ED) are often prescribed potentially nephrotoxic drugs, yet the role of ED prescribing in DIKD is unknown. Objective We sought to measure the association between ED medication administration and development of AKI. Methods This was a retrospective 5-year cohort analysis at a single center. Patients with a serum creatinine measurement at presentation in the ED and 24–168 h later were included. Outcome was incidence of AKI as defined by Kidney Disease Improving Global Outcomes criteria in the 7 days after ED evaluation. Medication administration risk was estimated using Cox proportional hazards model. Results There were 46,965 ED encounters by 30,407 patients included in the study, of which 6461 (13.8%) patients met the criteria for AKI. For hospitalized patients, administration of a potentially nephrotoxic medication was associated with increased risk of AKI (hazard ratio [HR] 1.30 [95% confidence interval {CI} 1.20–1.41]). Diuretics were associated with the largest risk of AKI (HR 1.64 [95% CI 1.52–1.78]), followed by angiotensin-converting enzyme inhibitors (HR 1.39 [95% CI 1.26–1.54]) and antibiotics (HR 1.13 [95% CI 1.05–1.22]). For discharged patients, administration of antibiotics was strongly associated with increased risk of AKI (HR 3.19 [95% CI 1.08–9.43]). Conclusion ED administration of potentially nephrotoxic medications was associated with an increased risk of AKI in the following 7 days. Diuretics, angiotensin-converting enzyme inhibitors, and antibiotics were independently associated with increased risk of AKI. Nephroprotective practices in the ED may mitigate kidney injury and long-term adverse outcomes.

Shared decision making for diagnostic decisions is understudied and differs from treatment decision making. Zackary D Berger and colleagues discuss how uncertainty and stakes should shape the conversation

Introduction With emergency department crowding becoming an increasing problem across the globe, nursing triage to prioritize patients receiving care is ever more important. ESI is the most common triage system used in the United States and is increasingly used worldwide. This qualitative study that explores emergency nursing perceptions of the ESI identifies strengths, weaknesses, and barriers to implementation of the ESI internationally. Methods We conducted a cross-sectional qualitative analysis using semistructured interviews of 27 emergency triage nurses. Content analysis was performed by 2 independent coders, using NVivo software to identify and analyze important themes. Results Interview coding revealed 7 core themes related to use of the ESI (frequencies indicated in parentheses): ease of use (90), speed and efficiency (135), patient safety (12), accuracy and reliability (30), challenging patient characteristics (123), subjectivity and variability (173), and effect of triage system on team dynamics (100). Intercoder agreement was excellent (Cohen's unweighted kappa=0.84). Subjectivity and variability in ESI score assignment consistently emerged in all interviews and included variability in number and use of resources, definition of "high risk," nursing experience, and subjectivity in pain assessment. Discussion Although emergency nurses perceive the ESI as easy to use, there are concerns about the subjectivity and variability inherent in the ESI that can lead to a functional lack of triage and a burden of undifferentiated ESI level 3 patients. These limitations in separating critically ill patients and in stratifying patients based on anticipated required resources points to the need for improvement in the ESI algorithm or a more objective triage system that can predict patient outcomes.Image 1Contribution to Emergency Nursing Practice •This qualitative analysis of nursing perceptions of the emergency severity index (ESI) highlights the importance of nursing input when implementing triage systems and describes perceived barriers and strengths when using the ESI. •Knowledge of these specific factors may prove useful in the development and implementation of triage systems in emergency departments around the globe.

Study objective We assess accuracy and variability of triage score assignment by emergency department (ED) nurses using the Emergency Severity Index (ESI) in 3 countries. In accordance with previous reports and clinical observation, we hypothesize low accuracy and high variability across all sites. Methods This cross-sectional multicenter study enrolled 87 ESI-trained nurses from EDs in Brazil, the United Arab Emirates, and the United States. Standardized triage scenarios published by the Agency for Healthcare Research and Quality (AHRQ) were used. Accuracy was defined by concordance with the AHRQ key and calculated as percentages. Accuracy comparisons were made with one-way ANOVA and paired t test. Interrater reliability was measured with Krippendorff's α. Subanalyses based on nursing experience and triage scenario type were also performed. Results Mean accuracy pooled across all sites and scenarios was 59.2% (95% confidence interval [CI] 56.4% to 62.0%) and interrater reliability was modest (α=.730; 95% CI .692 to .767). There was no difference in overall accuracy between sites or according to nurse experience. Medium-acuity scenarios were scored with greater accuracy (76.4%; 95% CI 72.6% to 80.3%) than high- or low-acuity cases (44.1%, 95% CI 39.3% to 49.0% and 54%, 95% CI 49.9% to 58.2%), and adult scenarios were scored with greater accuracy than pediatric ones (66.2%, 95% CI 62.9% to 69.7% versus 46.9%, 95% CI 43.4% to 50.3%). Conclusion In this multinational study, concordance of nurse-assigned ESI score with reference standard was universally poor and variability was high. Although the ESI is the most popular ED triage tool in the United States and is increasingly used worldwide, our findings point to a need for more reliable ED triage tools.

Study objective The study objective was to determine whether intravenous contrast administration for computed tomography (CT) is independently associated with increased risk for acute kidney injury and adverse clinical outcomes. Methods This single-center retrospective cohort analysis was performed in a large, urban, academic emergency department with an average census of 62,179 visits per year; 17,934 ED visits for patients who underwent contrast-enhanced, unenhanced, or no CT during a 5-year period (2009 to 2014) were included. The intervention was CT scan with or without intravenous contrast administration. The primary outcome was incidence of acute kidney injury. Secondary outcomes included new chronic kidney disease, dialysis, and renal transplantation at 6 months. Logistic regression modeling and between-groups odds ratios with and without propensity-score matching were used to test for an independent association between contrast administration and primary and secondary outcomes. Treatment decisions, including administration of contrast and intravenous fluids, were examined. Results Rates of acute kidney injury were similar among all groups. Contrast administration was not associated with increased incidence of acute kidney injury (contrast-induced nephropathy criteria odds ratio=0.96, 95% confidence interval 0.85 to 1.08; and Acute Kidney Injury Network/Kidney Disease Improving Global Outcomes criteria odds ratio=1.00, 95% confidence interval 0.87 to 1.16). This was true in all subgroup analyses regardless of baseline renal function and whether comparisons were made directly or after propensity matching. Contrast administration was not associated with increased incidence of chronic kidney disease, dialysis, or renal transplant at 6 months. Clinicians were less likely to prescribe contrast to patients with decreased renal function and more likely to prescribe intravenous fluids if contrast was administered. Conclusion In the largest well-controlled study of acute kidney injury following contrast administration in the ED to date, intravenous contrast was not associated with an increased frequency of acute kidney injury.

Extensive evidence indicates that serum response factor (SRF) regulates muscle-specific gene expression and that myocardin family SRF cofactors are critical for smooth muscle cell differentiation. In a yeast two hybrid screen for novel SRF binding partners expressed in aortic SMC, we identified four and a half LIM domain protein 2 (FHL2) and confirmed this interaction by GST pull-down and coimmunoprecipitation assays. FHL2 also interacted with all three myocardin factors and enhanced myocardin and myocardin-related transcription factor (MRTF)-A-dependent transactivation of smooth muscle α-actin, SM22, and cardiac atrial natriuretic factor promoters in 10T1/2 cells. The expression of FHL2 increased myocardin and MRTF-A protein levels, and, importantly, this effect was due to an increase in protein stability not due to an increase in myocardin factor mRNA expression. Treatment of cells with proteasome inhibitors MG-132 and lactacystin strongly upregulated endogenous MRTF-A protein levels and resulted in a substantial increase in ubiquitin immunoreactivity in MRTF-A immunoprecipitants. Interestingly, the expression of FHL2 attenuated the effects of RhoA and MRTF-B on promoter activity, perhaps through decreased MRTF-B nuclear localization or decreased SRF-CArG binding. Taken together, these data indicate that myocardin factors are regulated by proteasome-mediated degradation and that FHL2 regulates SRF-dependent transcription by multiple mechanisms, including stabilization of myocardin and MRTF-A.

On the basis of our previous studies on RhoA signaling in smooth muscle cells (SMC), we hypothesized that RhoA-mediated nuclear translocalization of the myocardin-related transcription factors (MRTFs) was important for regulating SMC phenotype. MRTF-A protein and MRTF-B message were detected in aortic SMC and in many adult mouse organs that contain a large SMC component. Both MRTFs upregulated SMC-specific promoter activity as well as endogenous SM22α expression in multipotential 10T1/2 cells, although to a lesser extent than myocardin. We used enhanced green fluorescent protein (EGFP) fusion proteins to demonstrate that the myocardin factors have dramatically different localization patterns and that the stimulation of SMC-specific transcription by certain RhoA-dependent agonists was likely mediated by increased nuclear translocation of the MRTFs. Importantly, a dominant-negative form of MRTF-A (ΔB1/B2) that traps endogenous MRTFs in the cytoplasm inhibited the SM α-actin, SM22α, and SM myosin heavy chain promoters in SMC and attenuated the effects of sphingosine 1-phosphate and transforming growth factor (TGF)-β on SMC-specific transcription. Our data confirmed the importance of the NH2-terminal RPEL domains for regulating MRTF localization, but our analysis of MRTF-A/myocardin chimeras and myocardin RPEL2 mutations indicated that the myocardin B1/B2 region can override this signal. Gel shift assays demonstrated that myocardin factor activity correlated well with ternary complex formation at the SM α-actin CArGs and that MRTF-serum response factor interactions were partially dependent on CArG sequence. Taken together, our results indicate that the MRTFs regulate SMC-specific gene expression in at least some SMC subtypes and that regulation of MRTF nuclear localization may be important for the effects of selected agonists on SMC phenotype.

Sphingosine 1-phosphate (S1P) is a lipid agonist that regulates smooth muscle cell (SMC) and endothelial cell functions by activating several members of the S1P subfamily of G-protein-coupled Edg receptors. We have shown previously that SMC differentiation is regulated by RhoA-dependent activation of serum response factor (SRF). Because S1P is a strong activator of RhoA, we hypothesized that S1P would stimulate SMC differentiation. Treatment of primary rat aortic SMC cells with S1P activated RhoA as measured by precipitation with a glutathione S-transferase-rhotekin fusion protein. In SMC and 10T1/2 cells, S1P treatment up-regulated the activities of several transiently transfected SMC-specific promoters, and these effects were inhibited by the Rho-kinase inhibitor, Y-27632. S1P also increased smooth muscle alpha-actin protein levels in SMC but had no effect on SRF binding to the smooth muscle alpha-actin CArG B element. Quantitative reverse transcriptase-PCR showed that S1P treatment of SMC or 10T1/2 cells did not increase the mRNA level of either of the recently identified SRF co-factors, myocardin or myocardin-related transcription factor-A (MRTF-A). MRTF-A protein was expressed highly in SMC and 10T1/2 cultures, and importantly the effects of S1P were inhibited by a dominant negative form of MRTF-A indicating that S1P may regulate the transcriptional activity of MRTF-A. Indeed, S1P treatment increased the nuclear localization of FLAG-MRTF-A, and the effect of MRTF-A overexpression on smooth muscle alpha-actin promoter activity was inhibited by dominant negative RhoA. S1P also stimulated SMC growth by activating the early growth response gene, c-fos. This effect was not attenuated by Y-27632 but could be inhibited by the MEK inhibitor, UO126. S1P enhanced SMC growth through ERK-mediated phosphorylation of the SRF co-factor, Elk-1, as measured by gel shift and Elk-1 activation assays. Taken together these results demonstrate that S1P activates multiple signaling pathways in SMC and regulates proliferation by ERK-dependent activation of Elk-1 and differentiation by RhoA-dependent activation of MRTF-A.