Carol L. Clark

The Recidivism Characteristics of an Emergency Department Observation Unit

STUDY OBJECTIVE We describe the recidivism characteristics of an adult emergency department (ED) observation unit population and determine whether rates differ according to demographic or clinical features. METHODS This prospective observational cohort study of a protocol-driven ED observation unit reviewed all discharged ED observation unit patients who returned within 14 days of discharge for an unscheduled ED visit or direct inpatient admission to the study hospital, or a proximate affiliated hospital, during 6 consecutive months. Age, sex, initial ED observation unit diagnosis, ED observation unit length of stay, and return visit disposition were determined from hospital databases and confirmed by chart review. All return visits were classified as related or unrelated to the index visit. RESULTS There were 55,727 ED visits, with 4,348 patients admitted to the ED observation unit, of whom 80.7% (3,509) were discharged. Patients with or without a return visit were similar in terms of age (56.9 years [standard deviation (SD) 19.5 years]), percentage of male patients (40.0%), or initial ED observation unit length of stay (15.0 hours [SD 6.0 hours]). Of discharged ED observation unit patients, 375 (10.8%) had a return visit, of which 277 (7.9%) were related. Of return visits, 86.3% of patients had only 1 return visit, 11.6% had 2, and 2.1% had 3 or more; 4.2% of returns occurred at an affiliated hospital. Time to first return visit was clustered within the first week for related visits, with a mean time to return of 4.5 days (SD 3.9 days). On return visit, 40.2% of patients were treated and discharged from the ED, 36.2% were treated in the ED and admitted, 14.4% were treated in the ED and then the ED observation unit and discharged home, 12.3% were directly admitted to the hospital, and 2.5% were treated in the ED and then the ED observation unit and admitted. Among common conditions, related return visit rates were highest for headache (16.1%), back pain (13.8%), and abdominal pain (12.7%) and lowest for chest pain (3.6%). As a group, therapeutic protocols, and specifically painful conditions, had significantly higher related return visit rates than diagnostic protocols (10.8% versus 5.1%). CONCLUSION Patients who return after an ED observation unit visit are similar to patients who do not return in terms of age, sex, or initial length of stay. However, ED observation unit recidivism rates do differ according to observation category, with painful conditions showing the highest recidivism rates.

Evaluation of Intravenous Peramivir for Treatment of Influenza in Hospitalized Patients

BACKGROUND Seasonal influenza causes >200 000 annual hospitalizations in the United States. Current antiviral treatment options are limited to oral or inhaled agents. There is an urgent unmet need for intravenous antiviral treatments. METHODS Patients hospitalized with suspected influenza were randomized to 5-day treatment with intravenous peramivir (600 mg once daily) or placebo; all received the institutions standard of care (SOC) treatment. Time to clinical resolution and change in viral shedding in nasopharyngeal specimens were the primary and key secondary end points. RESULTS Influenza infection was confirmed in 338 of 405 enrolled patients. At the time of a preplanned interim analysis, the primary efficacy analysis population comprised 121 patients who did not receive a concurrent neuraminidase inhibitor as part of the SOC. The median (95% confidence interval) time to clinical resolution was 42.5 (34.0-57.9) hours for peramivir versus 49.5 (40.0-61.9) hours for placebo (P = .97). A larger treatment effect was observed in patients with history of symptoms <48 hours or admitted to an intensive care unit. Greater reductions in viral shedding, based on median tissue culture infective dose, were observed in patients who received peramivir than in placebo recipients, although this difference was not statistically significant. The incidence and severity of adverse events and laboratory abnormalities were similar between the 2 treatment groups. The study was terminated for futility after a preplanned interim analysis. CONCLUSIONS A significant clinical benefit was not demonstrated for peramivir plus SOC compared with placebo plus SOC. Peramivir was generally safe and well tolerated. These findings highlight the challenges in designing studies to evaluate influenza antiviral agents in a hospitalized setting. Clinical Trials Registration. NCT00958776.

Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial.

STUDY OBJECTIVE We compare the safety and efficacy of ecallantide with placebo in subjects undergoing assessment for acute angiotensin-converting enzyme inhibitor-induced angioedema (ACEIA) in an emergency department (ED). METHODS This was a multicenter, phase 2, double-blind study with subjects randomized to receive a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo plus physician-directed conventional therapy. The primary endpoint was defined as meeting predetermined discharge eligibility criteria within 6 hours of study drug administration. Discharge criteria included improvement of edema, stable vital signs, absence of stridor, absence of dyspnea or use of accessory muscles during respiration, absence of drooling, and ability to drink without difficulty. RESULTS An interim analysis showed that a high percentage of subjects met the primary endpoint, and the study was halted. Overall, 79 subjects were randomized and 76 had data for analysis. Most had mild (45%) or moderate (42%) ACEIA. The discharge eligibility endpoint was met by 72% of the placebo group and 85%, 89%, and 89% of the ecallantide 10-, 30-, and 60-mg groups, respectively. This difference in meeting discharge eligibility endpoint criteria between treatment groups was not statistically significant. The incidence of treatment-emergent adverse events was similar between placebo and active-treatment groups. CONCLUSION The addition of ecallantide to standard therapy does not appear to improve angioedema compared with placebo in ED patients with ACEIA. Our data suggest that most ED patients presenting with mild to moderate ACEIA are likely to meet our discharge eligibility criteria within 6 hours of treatment, regardless of intervention. Further studies to assess the utility of ecallantide in patients with more severe angioedema may be useful. No new safety signals related to ecallantide administration were identified.

Hospital Process Intervals, not Ems Time Intervals, are the Most Important Predictors of Rapid Reperfusion in Ems Patients with St-Segment Elevation Myocardial Infarction

Abstract Objective. To assess the relationship of emergency medical services (EMS) intervals and internal hospital intervals to the rapid reperfusion of patients with ST-segment elevation myocardial infarction (STEMI). Methods. We performed a secondary analysis of a prospectively collected database of STEMI patients transported to a large academic community hospital between January 1, 2004, and December 31, 2009. EMS and hospital data intervals included EMS scene time, transport time, hospital arrival to myocardial infarction (MI) team activation (D2Page), page to catheterization laboratory arrival (P2Lab), and catheterization laboratory arrival to reperfusion (L2B). We used two outcomes: EMS scene arrival to reperfusion (S2B) ≤90 minutes and hospital arrival to reperfusion (D2B) ≤90 minutes. Means and proportions are reported. Pearson chi-square and multivariate regression were used for analysis. Results. During the study period, we included 313 EMS-transported STEMI patients with 298 (95.2%) MI team activations. Of these STEMI patients, 295 (94.2%) were taken to the cardiac catheterization laboratory and 244 (78.0%) underwent percutaneous coronary intervention (PCI). For the patients who underwent PCI, 127 (52.5%) had prehospital EMS activation, 202 (82.8%) had D2B ≤90 minutes, and 72 (39%) had S2B ≤90 minutes. In a multivariate analysis, hospital processes EMS activation (OR 7.1, 95% CI 2.7, 18.4], Page to Lab [6.7, 95% CI 2.3, 19.2] and Lab arrival to Reperfusion [18.5, 95% CI 6.1, 55.6]) were the most important predictors of Scene to Balloon ≤ 90 minutes. EMS scene and transport intervals also had a modest association with rapid reperfusion (OR 0.85, 95% CI 0.78, 0.93 and OR 0.89, 95% CI 0.83, 0.95, respectively). In a secondary analysis, Hospital processes (Door to Page [OR 44.8, 95% CI 8.6, 234.4], Page 2 Lab [OR 5.4, 95% CI 1.9, 15.3], and Lab arrival to Reperfusion [OR 14.6 95% CI 2.5, 84.3]), but not EMS scene and transport intervals were the most important predictors D2B ≤90 minutes. Conclusions. In our study, hospital process intervals (EMS activation, door to page, page to laboratory, and laboratory to reperfusion) are key covariates of rapid reperfusion for EMS STEMI patients and should be used when assessing STEMI care.

Intravenous zanamivir or oral oseltamivir for hospitalised patients with influenza: an international, randomised, double-blind, double-dummy, phase 3 trial

BACKGROUND Neuraminidase inhibitors are effective for the treatment of acute uncomplicated influenza. However, there is an unmet need for intravenous treatment for patients admitted to hospital with severe influenza. We studied whether intravenous zanamivir was a suitable treatment in this setting. METHODS In this international, randomised, double-blind, double-dummy, phase 3 trial, we recruited patients aged 16 years or older with severe influenza admitted to 97 hospitals from 26 countries. We randomly assigned patients (1:1:1 stratified by symptom onset ≤4 days or 5-6 days) to receive 300 mg or 600 mg intravenous zanamivir, or standard-of-care (75 mg oral oseltamivir) twice a day for 5-10 days; patients were followed up for 28 days. The randomisation schedule, including stratification, was generated using GlaxoSmithKlines RandAll software. Patients, site study staff, and sponsor were masked to study treatment. The primary endpoint was time to clinical response-a composite of vital sign stabilisation and hospital discharge-in the influenza-positive population. The trial was powered to show an improvement of 1·5 days or greater with 600 mg intravenous zanamivir. Pharmacokinetic, safety, and virology endpoints were also assessed. This trial is registered with ClinicalTrials.gov, number NCT01231620. FINDINGS Between Jan 15, 2011, and Feb 12, 2015, 626 patients were randomly assigned to receive 300 mg intravenous zanamivir (n=201), 600 mg intravenous zanamivir (n=209), or 75 mg oral oseltamivir (n=205) twice a day; 11 patients discontinued the study before receiving any study treatment. 488 (78%) of 626 patients had laboratory-confirmed influenza. Compared with a median time to clinical response of 5·14 days in the 600 mg intravenous zanamivir group, the median time to clinical response was 5·87 days (difference of -0·73 days, 95% CI -1·79 to 0·75; p=0·25) in the 300 mg intravenous zanamivir group and 5·63 days (difference of -0·48 days, 95% CI -2·11 to 0·97; p=0·39) in the oseltamivir group. Four patients with influenza A/H1N1pdm09 in the oseltamivir group developed H275Y resistance mutations. Adverse events were reported in 373 (61%) of treated patients and were similar across treatment groups; the most common adverse events (300 mg intravenous zanamivir, 600 mg intravenous zanamivir, oseltamivir) were diarrhoea (10 [5%], 15 [7%], 14 [7%]), respiratory failure (11 [5%], 14 [7%], 11 [5%]), and constipation (7 [3%], 13 [6%], 10 [5%]). 41 (7%) treated patients died during the study (15 [7%], 15 [7%], 11 [5%]); the most common causes of death were respiratory failure and septic shock. INTERPRETATION Time to clinical response to intravenous zanamivir dosed at 600 mg was not superior to oseltamivir or 300 mg intravenous zanamivir. All treatments had a similar safety profile in hospitalised patients with severe influenza. FUNDING GlaxoSmithKline.

Incremental benefit of 80-lead electrocardiogram body surface mapping over the 12-lead electrocardiogram in the detection of acute coronary syndromes in patients without ST-elevation myocardial infarction: Results from the Optimal Cardiovascular Diagnostic Evaluation Enabling Faster Treatment of Myocardial Infarction (OCCULT MI) trial.

BACKGROUND The initial 12-lead (12L) electrocardiogram (ECG) has low sensitivity to detect myocardial infarction (MI) and acute coronary syndromes (ACS) in the emergency department (ED). Yet, early therapies in these patients have been shown to improve outcomes. OBJECTIVES The Optimal Cardiovascular Diagnostic Evaluation Enabling Faster Treatment of Myocardial Infarction (OCCULT-MI) trial was a multicenter trial comparing a novel 80-lead mapping system (80L) to standard 12L ECG in patients with chest pain and presumed ACS. This secondary analysis analyzed the incremental value of the 80L over the 12L in the detection of high-risk ECG abnormalities (ST-segment elevation or ST depression) in patients with MI and ACS, after eliminating all patients diagnosed with ST-elevation MI (STEMI) by 12L ECG. METHODS Chest pain patients presenting to one of 12 academic EDs were diagnosed and treated according to the standard care of that site and its clinicians; the clinicians were blinded to 80L results. MI was defined by discharge diagnosis of non-ST-elevation MI (NSTEMI) or unstable angina (UA) with an elevated troponin. ACS was defined as discharge diagnosis of NSTEMI or UA with at least one positive test result (troponin, stress test, angiogram) or revascularization procedure. RESULTS   Of the 1,830 patients enrolled in the trial, 91 patients with physician-diagnosed STEMI and 225 patients with missing 80L or 12L data were eliminated from the analysis; no discharge diagnosis was available for one additional patient. Of the remaining 1,513 patients, 408 had ACS, 206 had MI, and one had missing status. The sensitivity of the 80L was significantly higher than that of the 12L for detecting MI (19.4% vs. 10.4%, p = 0.0014) and ACS (12.3% vs. 7.1%, p = 0.0025). Specificities remained high for both tests, but were somewhat lower for 80L than for 12L for detecting both MI and ACS. Negative and positive likelihood ratios (LR) were not statistically different between groups. In patients with severe disease (defined by stenosis > 70% at catheterization, percutaneous coronary intervention, coronary artery bypass graft, or death from any cause), the 80L had significantly higher sensitivity for detecting MI (with equivalent specificity), but not ACS. CONCLUSIONS Among patients without ST elevation on the 12L ECG, the 80L body surface mapping technology detects more patients with MI or ACS than the 12L, while maintaining a high degree of specificity.

Minimizing Attrition for Multisite Emergency Care Research

Loss to follow-up of enrolled patients (a.k.a. attrition) is a major threat to study validity and power. Minimizing attrition can be challenging even under ideal research conditions, including the presence of adequate funding, experienced study personnel, and a refined research infrastructure. Emergency care research is shifting toward enrollment through multisite networks, but there have been limited descriptions of approaches to minimize attrition for these multicenter emergency care studies. This concept paper describes a stepwise approach to minimize attrition, using a case example of a multisite emergency department prospective cohort of over 3,000 patients that has achieved a 30-day direct phone follow-up attrition rate of <3%. The seven areas of approach to minimize attrition in this study focused on patient selection, baseline contact data collection, patient incentives, patient tracking, central phone banks, local enrollment site assistance, and continuous performance monitoring. Appropriate study design, including consideration of these methods to reduce attrition, will be time well spent and may improve study validity.

Reliability of clinical assessments in older adults with syncope or near syncope

OBJECTIVES Clinical prediction models for risk stratification of older adults with syncope or near syncope may improve resource utilization and management. Predictors considered for inclusion into such models must be reliable. Our primary objective was to evaluate the inter-rater agreement of historical, physical examination, and electrocardiogram (ECG) findings in older adults undergoing emergency department (ED) evaluation for syncope or near syncope. Our secondary objective was to assess the level of agreement between clinicians on the patients overall risk for death or serious cardiac outcomes. METHODS We conducted a cross-sectional study at 11 EDs in adults 60 years of age or older who presented with unexplained syncope or near syncope. We excluded patients with a presumptive cause of syncope (e.g., seizure) or if they were unable or unwilling to follow-up. Evaluations of the patients past medical history and current medication use were completed by treating provider and trained research associate pairs. Evaluations of the patients physical examination and ECG interpretation were completed by attending/resident, attending/advanced practice provider, or attending/attending pairs. All evaluations were blinded to the responses from the other rater. We calculated the percent agreement and kappa statistic for binary variables. Inter-rater agreement was considered acceptable if the kappa statistic was 0.6 or higher. RESULTS We obtained paired observations from 255 patients; mean (±SD) age was 73 (±9) years, 137 (54%) were male, and 204 (80%) were admitted to the hospital. Acceptable agreement was achieved in 18 of the 21 (86%) past medical history and current medication findings, none of the 10 physical examination variables, and three of the 13 (23%) ECG interpretation variables. There was moderate agreement (Spearman correlation coefficient, r = 0.40) between clinicians on the patients probability of 30-day death or serious cardiac outcome, although as the probability increased, there was less agreement. CONCLUSIONS Acceptable agreement between raters was more commonly achieved with historical rather than physical examination or ECG interpretation variables. Clinicians had moderate agreement in assessing the patients overall risk for a serious outcome at 30 days. Future development of clinical prediction models in older adults with syncope should account for variability of assessments between raters and consider the use of objective clinical variables.

ECG Predictors of Cardiac Arrhythmias in Older Adults With Syncope

Study objective: Cardiac arrhythmia is a life‐threatening condition in older adults who present to the emergency department (ED) with syncope. Previous work suggests the initial ED ECG can predict arrhythmia risk; however, specific ECG predictors have been variably specified. Our objective is to identify specific ECG abnormalities predictive of 30‐day serious cardiac arrhythmias in older adults presenting to the ED with syncope. Methods: We conducted a prospective, observational study at 11 EDs in adults aged 60 years or older who presented with syncope or near syncope. We excluded patients with a serious cardiac arrhythmia diagnosed during the ED evaluation from the primary analysis. The outcome was occurrence of 30‐day serous cardiac arrhythmia. The exposure variables were predefined ECG abnormalities. Independent predictors were identified through multivariate logistic regression. The sensitivities and specificities of any predefined ECG abnormality and any ECG abnormality identified on adjusted analysis to predict 30‐day serious cardiac arrhythmia were also calculated. Results: After exclusion of 197 patients (5.5%; 95% confidence interval [CI] 4.7% to 6.2%) with serious cardiac arrhythmias in the ED, the study cohort included 3,416 patients. Of these, 104 patients (3.0%; 95% CI 2.5% to 3.7%) had a serious cardiac arrhythmia within 30 days from the index ED visit (median time to diagnosis 2 days [interquartile range 1 to 5 days]). The presence of nonsinus rhythm, multiple premature ventricular conductions, short PR interval, first‐degree atrioventricular block, complete left bundle branch block, and Q wave/T wave/ST‐segment abnormalities consistent with acute or chronic ischemia on the initial ED ECG increased the risk for a 30‐day serious cardiac arrhythmia. This combination of ECG abnormalities had a similar sensitivity in predicting 30‐day serious cardiac arrhythmia compared with any ECG abnormality (76.9% [95% CI 67.6% to 84.6%] versus 77.9% [95% CI 68.7% to 85.4%]) and was more specific (55.1% [95% CI 53.4% to 56.8%] versus 46.6% [95% CI 44.9% to 48.3%]). Conclusion: In older ED adults with syncope, approximately 3% receive a diagnosis of a serious cardiac arrhythmia not recognized on initial ED evaluation. The presence of specific abnormalities on the initial ED ECG increased the risk for 30‐day serious cardiac arrhythmias.

Creation and Implementation of an Outpatient Pathway for Atrial Fibrillation in the Emergency Department Setting: Results of an Expert Panel

Atrial fibrillation and flutter (AF) is a common condition among emergency department (ED) patients in the United States. Traditionally, ED care for primary complaints related to AF focus on rate control, and patients are often admitted to an inpatient setting for further care. Inpatient care may include further telemetry monitoring and diagnostic testing, rhythm control, a search for identification of AF etiology, and stroke prophylaxis. However, many patients are eligible for safe and effective outpatient management pathways. They are widely used in Canada and other countries but less widely adopted in the United States. In this project, we convened an expert panel to create a practical framework for the process of creating, implementing, and maintaining an outpatient AF pathway for emergency physicians to assess and treat AF patients, safely reduce hospitalization rates, ensure appropriate stroke prophylaxis, and effectively transition patients to longitudinal outpatient treatment settings from the ED and/or observation unit. To support local pathway creation, the panel also reached agreement on a protocol development plan, a sample pathway, consensus recommendations for pathway components, sample pathway metrics, and a structured literature review framework using a modified Delphi technique by a technical expert panel of emergency medicine, cardiology, and other stakeholder groups.