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Introduction and Objective: In COVID-19, the rapid prediction of the severity of a patient's condition using modern biomarkers can accelerate the implementation of appropriate therapy, and thus improve the patient's prognosis., Material and Methods: A meta-analysis was conducted of data available in the literature on the differences in baseline suPAR blood concentration between patients (1) who tested positive and negative for COVID-19, (2) who had severe and non-severe COVID-19, and (3) COVID-19 survivors and non-survivors., Results: SuPAR levels in SARS-CoV-2 negative and positive patients varied and amounted to 3.61±1.59 ng/ml vs. 6.45±3.13 ng/ml, respectively (MD = -3.18; 95%CI: -4.71 to -1.66; p<0.001). suPAR levels among non-severe and severe COVID-19 patients were 7.06±2.64 ng/ml and 5.06±3.16 ng/ml (MD = 0.18; 95%CI: -2.48 to 2.83; p=0.90), respectively. Pooled analysis showed that suPAR levels between severe versus critical COVID-19 patients to be 5.59±1.54 ng/ml and 6.49±1.43 ng/ml, respectively (MD = -1.00; 95%CI: -1.31 to -0.70; p<0.001). The suPAR levels between ICU survivors versus non-survivors amounted to 5.82±2.33 ng/ml and 8.43±4.66 ng/ml (MD = -3.59; 95%CI: -6.19 to -1.00; p=0.007). In the case of in-hospital mortality, the mean suPAR level among survivors to hospital discharge was 5.63±1.27 ng/ml, compared to 7.85±2.61 ng/ml for patients who did not survive (MD = -3.58; 95%CI: -5.42 to -1.74; p<0.001)., Conclusions: SuPAR levels are significantly elevated in severe COVID-19 illness and maybe useful in predicting mortality. Further studies are needed to determine cut-off points and clarify the association of suPAR levels with disease progression. This is of utmost importance given the ongoing pandemic and overburdened health care systems.

Background: Non-disabling stroke (NDS) and transient ischemic attack (TIA) herald the possibility of future, more debilitating vascular events. Evidence is conflicting about potency of exercise and education in reducing risk factors for second stroke., Methods: Three-site, single-blinded, randomized controlled trial with 184 participants <3 months of NDS or TIA (mean age, 65 years; 66% male) randomized to usual care (UC) or UC + 12-week program of exercise and education (PREVENT). Primary (resting systolic blood pressure) and secondary outcomes (diastolic blood pressure [DBPrest], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], TC/HDL, triglycerides, fasting glucose, and body mass index) were assessed at baseline, post-intervention, and 6- and 12-month follow-up. Peak oxygen consumption (VO 2 peak) was measured at baseline, post-intervention, 12-month assessments., Results: Significant between-group differences at post-intervention favored PREVENT group over UC: DBPrest (mean difference [MD]: -3.2 mmHg, 95% confidence interval [CI]: -6.3, -.2, P = .04) and LDL-C (MD: -.31 mmol/L, 95% CI: -.42, -.20, P = .02). Trends of improvement in PREVENT group were noted in several variables between baseline and 6-month follow-up but not sustained at 12-month follow-up. Of note, VO 2 peak did not change over time in either group., Conclusion: Impact of PREVENT on vascular risk factor reduction was more modest than anticipated, possibly because several outcome variables approximated normative values at baseline and training intensity may have been sub-optimal. Further investigation is warranted to determine when exercise and education programs are viable adjuncts to pharmaceutical management for reduction of risk factors for second stroke. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: #NCT00885456.

Hyperkalemia is a common electrolyte abnormality identified in the emergency department (ED) and potentially fatal. However, there is no consensus over the potassium threshold that warrants intervention or its treatment algorithm. Commonly used medications are at best temporizing measures, and the roles of binders are unclear in the emergent setting. As the prevalence of comorbid conditions altering potassium homeostasis rises, hyperkalemia becomes more common, and hence there is a need to standardize management. A panel was assembled to synthesize the available evidence and identify gaps in knowledge in hyperkalemia treatment in the ED. The panel was composed of 7 medical practitioners, including 5 physicians, a nurse, and a clinical pharmacist with collective expertise in the areas of emergency medicine, nephrology, and hospital medicine. This panel was sponsored by the American College of Emergency Physicians with a goal to create a consensus document for managing acute hyperkalemia. The panel evaluated the evidence on calcium for myocyte stabilization and potassium shifting and excretion. This article summarizes information on available therapies for hyperkalemia and proposes a hyperkalemia treatment algorithm for the ED practitioner based on the currently available literature and highlights diagnostic pitfalls and evidence gaps., Competing Interests: This manuscript is a consensus document of an expert panel on hyperkalemia management, sponsored by the American College of Emergency Physicians. ZR is a principal investigator for Relypsa Inc and a consultant to Relypsa Inc and AstraZeneca. FP has received consulting fees from AstraZeneca and Relypsa and grants to his institution from AstraZeneca and Relypsa. TA has nothing to disclose. JB reports personal fees from American College of Emergency Physicians, during the conduct of the study; grants from Beckman Coulter, grants from Comprehensive Research Associates, outside the submitted work; JD reports: I have presented continuing education sessions within the last year on the topic of hyperkalemia supported by educational grants from AstraZeneca. These programs were coordinated through WebMD. MW reports personal fees from Vifor, personal fees from AstraZeneca, personal fees from Boehringer‐Ingelheim, personal fees from Bayer, personal fees from Janssen, during the conduct of the study; JN reports a grant for his institution from Relypsa and consulting fees and honoraria from AstraZeneca., (© 2021 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Two cases of envenomation from the small, semi-fossorial, front-fanged colubrid Homoroselaps lacteus are presented and the recent literature reviewed. In addition to local oedema and lymphadenopathy, the development of significant subcutaneous loco-regional bruising suggest that damage to capillary basement membrane and possibly other underlying anti-haemostatic effects may pertain to the clinical syndrome. Although local clinical effects may appear dramatic, due to the small volumes of venom that can be injected, it is considered that envenomation is unlikely to cause life-threatening effects., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Risk scores including the Thrombolysis in Myocardial Infarction (TIMI) score; History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) score; and Simplified Emergency Department Assessment of Chest Pain Score (sEDACS) have been used to evaluate patients with symptoms suggestive of acute myocardial infarct (AMI). This study assessed prognostic utility of cardiac risk stratification scores when augmented with a high-sensitivity cardiac troponin-I assay (hs-cTnI)., Methods: This study enrolled 2,505 suspected AMI patients at 29 hospitals in the United States from April 2015 to April 2016. Blood samples were tested for hs-cTnI on the Atellica IM TnIH Assay (Siemens Healthineers). Patients were considered low risk for death/AMI with a TIMI score = 0, HEART ≤3, sEDACS ≤15, and hs-cTnI <45 ng/L (99th percentile) at time 0 and 2-3 hours., Results: There were 2,336 patients included after exclusions for ST-segment elevation myocardial infarction or incomplete data. At 30 days, 283 patients (12.1%) had been diagnosed with AMI, and there were 24 (1.0%) deaths and 213 (9.1%) revascularizations. Of 298 patients with death or AMI, 258 (86.6%) had elevated hs-cTnI. The HEART score and sEDACS identified 34.5% and 36.6% of patients as low risk, respectively. This was significantly more than the 12.1% identified by the TIMI score (P < .01)., Conclusions: The TIMI, HEART, and sEDACS scores all identify low-risk patients when combined with hs-cTnI measurements. The HEART score and sEDACS identified more low-risk patients compared to the TIMI score. These patients could be considered for discharge from the emergency department without further testing., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Although there is no consensus on how to use an electrocardiogram (ECG) in patients with hyperkalemia, physicians often obtain it in the acute setting when diagnosing and treating hyperkalemia. The objective of this study is to evaluate if physicians are able to detect hyperkalemia based on the ECG., Methods: The study was conducted at a large county hospital with a population of end stage renal disease (ESRD) patients who received hemodialysis (HD) solely on an emergent basis. Five hundred twenty eight ECGs from ESRD patients were evaluated. The prevalence of hyperkalemia was approximately 60% in this cohort, with at least half of them in the severe hyperkalemia range (K ≥ 6.5 mEq/L)., Results: The mean sensitivity and specificity of the emergency physicians detecting hyperkalemia were 0.19 (± 0.16) and 0.97(± 0.04) respectively. The mean positive predictive value of evaluators for detecting hyperkalemia was 0.92 (±0.13) and the mean negative predictive value was 0.46 (± 0.05). In severe hyperkalemia (K ≥ 6.5 mEq/L), the mean sensitivity improved to 0.29 (± 0.20), while specificity decreased to 0.95 (±0.07)., Conclusion: An ECG is not a sensitive method of detecting hyperkalemia and should not be relied upon to rule it out. However, the ECG has a high specificity for detecting hyperkalemia and could be used as a rule in test., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The TRUE-AHF is a randomized, double-blind, parallel-group, placebo-controlled trial which is evaluating the effects of a 48-h infusion of ularitide (15 ng/kg/min) on the short- and long-term clinical course of patients with acute heart failure. Noteworthy features of the study include the early enrolment of patients following their initial clinical presentation (within 12 h), and entry blood pressure criteria and thresholds for the adjustment of drug infusion rates, which aim to minimize the risk of hypotension. The trial has two primary endpoints: (i) cardiovascular mortality during long-term follow-up; and (ii) the clinical course of patients during their index hospitalization. Cardiovascular mortality is evaluated in this event-driven trial by following all randomized patients for the occurrence of death until the end of the entire study without truncation at an arbitrarily determined early time point. The clinical course during the index hospitalization is evaluated using the hierarchical clinical composite endpoint, which combines information regarding changes in symptoms and the occurrence of in-hospital worsening heart failure events and death into a single ranked metric that captures interval clinical events and minimizes the likelihood of missing data and confounding due to intensification of background therapy. The design of the TRUE-AHF trial capitalizes on lessons learned from earlier trials and aims to evaluate definitively the potential benefit of ularitide in patients with acute heart failure., Trial Registration: NCT01661634., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source., Main Hypothesis: In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily., Design: Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches., Summary: The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All of the coauthors have received financial remuneration from Bayer Pharma AG for service on the Steering Committee except H. Mundl, S. Berkowitz, C. Pater, G. Peters, and B. Kirsch who are all employees of the sponsors. All coauthors receive stipend and research support for participation in NAVIGATE ESUS from the industry sponsors.

D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

Observation Services (OS) was founded by emergency physicians in an attempt to manage "boarding" issues faced by emergency departments throughout the United States. As a result, OS have proven to be an effective strategy in reducing costs and decreasing lengths of stay while improving patient outcomes. When OS are appropriately leveraged for maximum efficiency, patients presenting to emergency departments with common disease processes can be effectively treated in a timely manner. A well-structured observation program will help hospitals reduce the number of inappropriate, costly inpatient admissions while avoiding the potential of inappropriate discharges. Observation medicine is a complicated multidimensional issue that has generated much confusion. This service is designed to provide the best possible patient care in a value-based purchasing environment where quality, cost, and patient satisfaction must continually be addressed. Observation medicine is a service not a status. Therefore, patients are admitted to the service as outpatients no matter whether they are placed in a virtual or dedicated observation unit. The key to a successful observation program is to determine how to maximize efficiencies. This white paper provides the reader with the foundational guidance for observational services. It defines how to set up an observational service program, which diagnoses are most appropriate for admission, and what the future holds. The goal is to help care providers from any hospital deliver the most appropriate level of treatment, to the most appropriate patient, in the most appropriate location while controlling costs.

Background: Worldwide, cardiovascular diseases and cancer account for ∼40% of deaths. Certain reports have shown a progressive decrease in mortality. Our main objective was to assess mortality trends related to myocardial infarction (MI), heart failure (HF) and pulmonary embolism (PE)., Methods: MI, HF and PE were studied as cause of death based on the analysis of death certificates in Canada (C), England and Wales (E), France (F) and Sweden (S). We also used a multiple cause approach. Age-standardized death rates (SDR) were calculated., Results: The SDR for MI, HF or PE as the underlying cause of death, all decreased during the last decade. The decrease in SDR secondary to MI exceeded that for HF or PE. Concerning multiple cause of death, a greater decrease was also found for MI, compared with HF or PE., Conclusions: We confirm the beneficial trends in SDR with MI, HF or PE both as underlying or multiple causes in the studied countries. For HF and PE, multiple cause approach seems more accurate to describe the burden of these two pathologies. Our study also suggests that more efforts should be dedicated to HF and PE in order to achieve similar trends than in MI., (© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this analysis was to assess the association between elevated blood glucose level and mortality in acute heart failure (AHF)., Background: Elevated blood glucose has been reported to be prognostically meaningful in patients with cardiac diagnoses, such as coronary artery disease. The short-term prognostic impact of hyperglycemia in AHF is unknown, however., Methods: In a multinational cohort of AHF, we examined the ability of blood glucose concentrations at presentation to predict all-cause mortality by 30 days. Fully adjusted models for prognosis included a previous diagnosis of diabetes mellitus as a covariate., Results: A total of 6,212 subjects with AHF (mean age, 72 years; 52.5% male) were studied; the median blood glucose concentration on arrival at the hospital was 7.5 mmol/l (135 mg/dl), and 41% had a previous diagnosis of diabetes mellitus (DM). After 30 days, 618 patients (10%) had died. Compared with survivors, decedents had significantly higher median blood glucose concentrations (8.9 mmol/l vs. 7.4 mmol/l; p < 0.0001). In the fully adjusted model, an elevated blood glucose level was an independent predictor of 30-day mortality in AHF (odds ratio: 2.19; 95% confidence interval: 1.69 to 2.83; p < 0.001). The risk associated with an elevated blood glucose level appeared consistent across all subgroups of patients, including patients with preserved (hazard ratio: 5.41; 95% confidence interval: 2.44 to 12.0; p < 0.0001) and impaired systolic function (hazard ratio: 2.37; 95% confidence interval: 1.57 to 3.59; p < 0.0001). Furthermore, in reclassification analyses, elevated blood glucose added significant prognostic information to clinical parameters alone (4.4% net reclassification improvement; p = 0.01)., Conclusions: Among patients with AHF, blood glucose concentrations at presentation are powerfully prognostic for 30-day mortality, independent of a diagnosis of diabetes mellitus or other clinical variables. Because blood glucose is easily modifiable, it may represent a valid target for therapeutic intervention., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Acute heart failure (AHF) is a common, poorly characterized manifestation of hypertensive emergency. We sought to describe characteristics, treatment, and outcomes of patients with severe hypertension complicated by AHF., Methods and Results: The observational retrospective Studying the Treatment of Acute hypertension (STAT) registry records data on emergency department and hospitalized patients receiving intravenous therapy for blood pressure (BP) greater than 180/110 mm Hg in 25 US hospitals. A subset of patients with HF was defined as pulmonary edema on chest x-ray (CXR) or an elevated B-type natriuretic peptide level (BNP > 500 or NTproBNP > 900 pg/mL) in patients with creatinine level 2.5 mg/dL or less. Remaining STAT patients, after excluding those with a primary neurologic diagnosis, constitute the non-HF cohort. An adverse composite outcome was defined as mechanical ventilation, intensive care unit (ICU) admission, hospital length of stay more than 1 week, or death within 30 days. Of 1199 patients, 302 (25.2%) had AHF. Acute HF patients and non-AHF patients were similar in age, sex, and overall mortality, but AHF patients were more commonly African American, with a history of HF, diabetes or chronic obstructive pulmonary disease, and prior hypertension admissions. Heart failure patients had higher creatinine and natriuretic peptide levels but lower ejection fraction. They were more likely admitted to the ICU; receive electrocardiograms, bilevel positive airway pressure ventilation, and CXRs; and be readmitted within 90 days. Finally, BP decreases lower than 120 mm Hg within 12 hours were associated with an increased rate of the composite adverse outcome., Conclusions: Acute HF as a manifestation of hypertensive emergency is common, more likely in African Americans, and requires more clinical resources than patients with non-HF-related severe hypertension. Accurate BP control is critical, as declines less than 120 mm Hg were associated with increased adverse event rates., (Copyright © 2011 Elsevier Inc. All rights reserved.)

B-type natriuretic peptide (BNP) and bioimpedance vector analysis (BIVA) are potential methods of assessing fluid status in patients. Their speed and ease of implementation allows them to be used at the point of care. Currently, BNP is pivotal in the diagnosis and prognosis of heart failure, and is starting to be implemented in other diseases (e.g. acute coronary syndrome and end-stage renal disease). Although it can be elevated from volume-overload-induced cardiac stress, when assessing volume this method is ultimately unreliable since it lacks adequate specificity and accuracy. Alternatively, BIVA is accurate and sensitive in the detection of fluid status, but cannot be used to tell the etiology of the volume aberration. Despite being relatively new, BIVA is becoming recognized as a superior method to assess volume., (Copyright © 2011 S. Karger AG, Basel.)

Acute severe hypertension occurs in approximately 50% of patients with acute heart failure (AHF). Clevidipine, the latest-generation dihydropyridine calcium channel blocker, may be useful in the treatment of this patient population. The Evaluation of the Effect of Ultra-Short-Acting Clevidipine in the Treatment of Patients With Severe Hypertension (VELOCITY) trial enrolled 126 patients with systolic blood pressure (SBP) >180 mm Hg for treatment with clevidipine to a patient-specific prespecified initial target range (ITR) of SBP to be achieved within 30 minutes. Of the enrolled patients, 19 had AHF on presentation. Primary end points were the percentage in whom ITR was achieved within 30 minutes and the number whose SBP was below the ITR after 3 minutes of clevidipine infusion. Among the 19 AHF patients in VELOCITY, median time to ITR was 11.3 minutes (95% confidence interval, 7-19). ITR was reached in most patients (94%) within 30 minutes. No patient had hypotension below the ITR, and heart rate remained stable. At 18 hours, 16 of 19 patients had received continuous clevidipine infusion, and their SBP was reduced by mean of 50 mm Hg (25%) from baseline. There were no treatment-related adverse events or adverse events that led to clevidipine discontinuation. Clevidipine safely decreases SBP in AHF and does not cause unexpected hypotension. The results of this post hoc subgroup analysis suggest that clevidipine is safe, well tolerated, and efficacious in AHF patients with hypertension.

In July of 2008, the National Heart, Lung, and Blood Institute convened experts in noninvasive cardiovascular imaging, outcomes research, statistics, and clinical trials to develop recommendations for future randomized controlled trials of the use of imaging in: 1) screening the asymptomatic patient for coronary artery disease; 2) assessment of patients with stable angina; 3) identification of acute coronary syndromes in the emergency room; and 4) assessment of heart failure patients with chronic coronary artery disease with reduced left ventricular ejection fraction. This study highlights several possible trial designs for each clinical situation.

Background: Because of possible adverse outcomes, many of the >6 million annual emergency department (ED) patients with suspected acute coronary syndromes (ACS) undergo extensive evaluations. To minimize medical errors, chest pain evaluations are structured to identify accurately nearly 100% of patients with ACS. This is at a cost of negative evaluation rates that can exceed 90%. Ischemia-modified albumin (IMA), a serum biomarker with a high negative predictive value (NPV) at ED presentation, may exclude ACS. Our objective was to perform a meta-analysis of IMA use for ACS risk stratification., Methods: By computer literature search and communication with authors of unpublished information, all IMA data were considered. This analysis included studies if they reported IMA results from an ED presentation for suspected ACS. We defined a negative triple prediction test (TPT) as a nondiagnostic electrocardiogram, negative troponin, and negative IMA., Results: Eight studies of >1800 patients met the entry criteria. The TPT sensitivity and NPV for acute ACS were 94.4% and 97.1% and, for longer-term outcomes, were 89.2% and 94.5%, respectively., Conclusions: A negative TPT of a nondiagnostic electrocardiogram, negative troponin, and negative IMA has a high NPV for excluding ACS in the ED.

Study Objectives: To determine the completeness of documentation and accuracy of medical evaluation for a sample of emergency psychiatric patients., Design: Descriptive, retrospective chart review., Setting: Nine hundred-bed community teaching hospital with a voluntary psychiatric inpatient unit., Type of Participants: Two hundred ninety-eight emergency department patients with psychiatric chief complaints, all of whom were admitted to the voluntary psychiatric unit of the same community teaching hospital., Interventions: None, Measurements and Main Results: There was failure to document mental status at triage in 56% of patients. The most frequent process deficiencies in the medical evaluation were in the neurological examination. Twelve patients (4%) required acute medical treatment within 24 hours of psychiatric admission, and the ED history and physical examination should have identified an acute condition in 83%. The chart was documented "medically clear" in 80% of patients in whom medical disease should have been identified. Patients less than 55 years old had a four times greater chance of a missed medical diagnosis., Conclusion: Process deficiencies in the medical history and physical examination accounted for the vast majority of missed acute medical conditions. The statement "medically clear" is inaccurate and should be replaced by a thorough discharge note.