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Emergency department (ED) crowding continues to be a major challenge and has important ramifications for patient care quality. One strategy to decrease ED crowding has been to implement alternative pathways to traditional hospital admission. Through a survey-based retrospective cohort study, we aimed to assess the patient experience for those who agreed to transfer and admission to an affiliated community hospital from a large, academic center’s ED. In all, 85% of participants rated their overall experience as either great or good, 92% did not find it hard to make the decision to be transferred, and 95% found the transfer process itself to be easy.

Objective Prior data suggest Emergency Department (ED) visits for many emergency conditions decreased during the initial COVID-19 surge. However, the pandemic's impact on the wide range of conditions seen in EDs, and the resources required for treating them, has been less studied. We sought to provide a comprehensive analysis of ED visits and associated resource utilization during the initial COVID-19 surge. Methods We performed a retrospective analysis from 5 hospitals in a large health system in Massachusetts, comparing ED encounters from 3/1/2020–4/30/2020 to identical weeks from the prior year. Data collected included demographics, ESI, diagnosis, consultations ordered, bedside procedures, and inpatient procedures within 48 h. We compared raw frequencies between time periods and calculated incidence rate ratios. Results ED volumes decreased by 30.9% in 2020 compared to 2019. Average acuity of ED presentations increased, while most non-COVID-19 diagnoses decreased. The number and incidence rate of all non-critical care ED procedures decreased, while the occurrence of intubations and central lines increased. Most subspecialty consultations decreased, including to psychiatry, trauma surgery, and cardiology. Most non-elective procedures related to ED encounters also decreased, including craniotomies and appendectomies. Conclusion Our health system experienced decreases in nearly all non-COVID-19 conditions presenting to EDs during the initial phase of the pandemic, including those requiring specialty consultation and urgent inpatient procedures. Findings have implications for both public health and health system planning.

Objective Understanding the pattern of population risk for coronavirus disease 2019 (COVID-19) is critically important for health systems and policy makers. The objective of this study was to describe the association between neighborhood factors and number of COVID-19 cases. We hypothesized an association between disadvantaged neighborhoods and clusters of COVID-19 cases. Methods We analyzed data on patients presenting to a large health care system in Boston during February 5–May 4, 2020. We used a bivariate local join-count procedure to determine colocation between census tracts with high rates of neighborhood demographic characteristics (eg, Hispanic race/ethnicity) and measures of disadvantage (eg, health insurance status) and COVID-19 cases. We used negative binomial models to assess independent associations between neighborhood factors and the incidence of COVID-19. Results A total of 9898 COVID-19 patients were in the cohort. The overall crude incidence in the study area was 32 cases per 10 000 population, and the adjusted incidence per census tract ranged from 2 to 405 per 10 000 population. We found significant colocation of several neighborhood factors and the top quintile of cases: percentage of population that was Hispanic, non-Hispanic Black, without health insurance, receiving Supplemental Nutrition Assistance Program benefits, and living in poverty. Factors associated with increased incidence of COVID-19 included percentage of population that is Hispanic (incidence rate ratio [IRR] = 1.25; 95% CI, 1.23-1.28) and percentage of households living in poverty (IRR = 1.25; 95% CI, 1.19-1.32). Conclusions We found a significant association between neighborhoods with high rates of disadvantage and COVID-19. Policy makers need to consider these health inequities when responding to the pandemic and planning for subsequent health needs.

INTRODUCTION: Emergency clinicians on the frontline of the coronavirus pandemic experience a range of emotions including anxiety, fear, and grief. Debriefing can help clinicians process these emotions, but the coronavirus pandemic makes it difficult to create a physically and psychologically safe space in the emergency department (ED) to perform this intervention. In response, we piloted a video-based debriefing program to support emergency clinician well-being. We report the details of our program and results of our evaluation of its acceptability and perceived value to emergency clinicians during the pandemic. METHODS: ED attending physicians, resident physicians, and non-physician practitioners (NPP) at our quaternary-care academic medical center were invited to participate in role-based, weekly one-hour facilitated debriefings using Zoom. ED attendings with experience in debriefing led each session and used an explorative approach that focused on empathy and normalizing reactions. At the end of the pilot, we distributed to participants an anonymous 10-point survey that included multiple-answer questions and visual analogue scales. RESULTS: We completed 18 debriefings with 68 unique participants (29 attending physicians, 6 resident physicians, and 33 NPPs. A total of 76% of participants responded to our survey and 77% of respondents participated in at least two debriefings. Emergency clinicians reported that the most common reasons to participate in the debriefings were "to enhance my sense of community and connection" (81%) followed by "to support colleagues" (75%). Debriefing with members of the same role group (92%) and the Zoom platform (81%) were considered to be helpful aspects of the debriefing structure. Although emergency clinicians found these sessions to be useful (78.8 +/- 17.6) interquartile range: 73-89), NPPs were less comfortable speaking up (58.5 +/- 23.6) than attending physicians (77.8 +/- 25.0) (p = < 0.008). CONCLUSION: Emergency clinicians participating in a video-based debriefing program during the coronavirus pandemic found it to be an acceptable and useful approach to support emotional well-being. Our program provided participants with a platform to support each other and maintain a sense of community and connection. Other EDs should consider implementing a debriefing program to safeguard the emotional well-being of their emergency clinician workforce.

Introduction: Central arterial pressure rises to much higher levels during heavy isometric exercise compared to other forms of exercise. For this reason, patients with bicuspid aortic valves (BAV) are often restricted from heavy isometric exercise. Although this approach may be theoretically appealing, no data exists regarding the efficacy of this activity restriction. Methods: Patients between the 12-19 years old with BAV were approached during a routine clinic visit. Patients were excluded if they had a diagnosed syndrome or had undergone a procedure involving the aortic valve. Patients were assumed to have been exercise restricted, regardless of aortic dimensions. Patients completed a questionnaire regarding frequency and intensity of isometric exercise during the 12-month period prior to the visit. We then compared aortic dimensions and qualitative (1-4 scale) estimates of aortic insufficiency (AI) from an echocardiogram performed during the current visit and one obtained 2-5 years previously, using paired t-tests and multivariable regression controlling for age, gender, and participation in isometric exercise. Results: In this unique data set of 37 individuals (41% female, average age 14.8 years), 6 (16%) participated in isometric exercise. There was no significant increase in the aortic root Z-score (0.004 [95 th CI -0.20, 0.21) or in the ascending aorta Z-score (0.11 [95 th CI, -0.15, 0.37], p=0.4) between the first and second visits. Further, there was no differences in the change aortic root Z-score (β=-0.39, p=0.39) and ascending aorta Z-score (β=-0.30, p-0.699) between those who participated in isometric exercise and those who did not. However, although the sample size in this preliminary group of patients was small, the increase in AI severity among those participating in isometric exercise was clinically significant and approached statistical significance (β=0.37, p=0.1). These results did not change even after controlling for age, gender, and time between echocardiograms. Conclusion: Most adolescents with BAV follow recommendations to limit isometric exercise. Time-related changes in aortic dimensions were similar among patients who refrained from isometric exercise and those who engaged in isometric exercise. AI however may have progressed more rapidly in those who participated in isometric exercise.

Background Variability in the management of atrial fibrillation ( AF ) in the emergency department ( ED ) leads to avoidable hospital admissions and prolonged length of stay ( LOS ). In a retrospective single‐center study, a multidisciplinary AF treatment pathway was associated with a reduced hospital admission rate and reduced LOS . To assess the applicability of the AF pathway across institutions, we conducted a 2‐center study. Methods and Results We performed a prospective, 2‐stage study at 2 tertiary care hospitals. During the first stage, AF patients in the ED received routine care. During the second stage, AF patients received care according to the AF pathway. The primary study outcome was hospital admission rate. Secondary outcomes included ED LOS and inpatient LOS . We enrolled 104 consecutive patients in each stage. Patients treated using the AF pathway were admitted to the hospital less frequently than patients who received routine care (15% versus 55%; P LOS was shorter in the AF pathway cohort than in the routine care cohort (64 versus 105 hours, respectively; P =0.01). There was no significant difference in the average ED LOS between AF pathway and routine care cohorts (14 versus 12 hours, respectively; P =0.32). Conclusions In this prospective 2‐stage, 2‐center study, utilization of a multidisciplinary AF treatment pathway resulted in a 3.7‐fold reduction in admission rate and a 1.6‐fold reduction in average hospital LOS for admitted patients. Utilization of the AF pathway was not associated with a significant change in ED LOS .

To evaluate the efficiency and safety of emergency department (ED) coronary computed tomography angiography (CTA) during a 3-year clinical experience. Single-center registry of coronary CTA in consecutive ED patients with suspicion of acute coronary syndrome (ACS). The primary outcome was efficiency of coronary CTA defined as the length of hospitalization. Secondary endpoints of safety were defined as the rate of downstream testing, normalcy rates of invasive coronary angiography (ICA), absence of missed ACS, and major adverse cardiac events (MACE) during follow-up, and index radiation exposure. One thousand twenty two consecutive patients were referred for clinical coronary CTA with suspicion of ACS. Overall, median time to discharge home was 10.5 (5.7-24.1) hours. Patient disposition was 42.7 % direct discharge from the ED, 43.2 % discharge from emergency unit, and 14.1 % hospital admission. ACS rate during index hospitalization was 9.1 %. One hundred ninety two patients underwent additional diagnostic imaging and 77 underwent ICA. The positive predictive value of CTA compared to ICA was 78.9 % (95 %-CI 68.1-87.5 %). Median CT radiation exposure was 4.0 (2.5-5.8) mSv. No ACS was missed; MACE at follow-up after negative CTA was 0.2 %. Coronary CTA in an experienced tertiary care setting allows for efficient and safe management of patients with suspicion for ACS. • ED Coronary CTA using advanced systems is associated with low radiation exposure. • Negative coronary CTA is associated with low rates of MACE. • CTA in ED patients enables short median time to discharge home. • CTA strategy is characterized by few downstream tests including unnecessary ICA.

Introduction: The objective of this study was to investigate the factors associated with first-pass success in pediatric intubation in the emergency department (ED). Methods: We analyzed the data from two multicenter prospective studies of ED intubation in 17 EDs between April 2010 and September 2014. The studies prospectively measured patient’s age, sex, principal indication for intubation, methods (e.g., rapid sequence intubation [RSI]), devices, and intubator’s level of training and specialty. To evaluate independent predictors of first-pass success, we fit logistic regression model with generalized estimating equations. In the sensitivity analysis, we repeated the analysis in children

Background The United States is battling obesity and heart failure (HF) epidemics. Although studies have suggested relationships between obesity and HF morbidity, little is known regarding the effects of substantial weight reduction in obese patients with HF. Objectives This study investigated whether bariatric surgery is associated with a decreased rate of HF exacerbation. Methods We performed a self-controlled case series study of obese patients with HF who underwent bariatric surgery, using the population-based emergency department (ED) and inpatient sample in California, Florida, and Nebraska. Primary outcome was ED visit or hospitalization for HF exacerbation from 2005 to 2011. We used conditional logistic regression to compare the outcome event rate during sequential 12-month periods, using pre-surgery months 13 to 24 as the reference period. Results We identified 524 patients with HF who underwent bariatric surgery. During the reference period, 16.2% of patients had an ED visit or hospitalization for HF exacerbation. The rate remained unchanged in the subsequent 12-month pre-surgery period (15.3%; p = 0.67). In the first 12-month period after bariatric surgery, we observed a nonsignificantly reduced rate (12.0%; p = 0.052). However, the rate was significantly lower in the subsequent 13 to 24 months after bariatric surgery (9.9%; adjusted odds ratio: 0.57; p = 0.003). By contrast, there was no significant reduction in the rate of HF exacerbation among obese patients who underwent nonbariatric surgery (i.e., cholecystectomy, hysterectomy). Conclusions Our findings indicate that bariatric surgery is associated with a decline in the rate of HF exacerbation requiring ED evaluation or hospitalization among obese patients with HF.

Background Development of emergency department (ED) triage systems that accurately differentiate and prioritize critically ill from stable patients remains challenging. We used machine learning models to predict clinical outcomes, and then compared their performance with that of a conventional approach—the Emergency Severity Index (ESI). Methods Using National Hospital and Ambulatory Medical Care Survey (NHAMCS) ED data, from 2007 through 2015, we identified all adult patients (aged ≥ 18 years). In the randomly sampled training set (70%), using routinely available triage data as predictors (e.g., demographics, triage vital signs, chief complaints, comorbidities), we developed four machine learning models: Lasso regression, random forest, gradient boosted decision tree, and deep neural network. As the reference model, we constructed a logistic regression model using the five-level ESI data. The clinical outcomes were critical care (admission to intensive care unit or in-hospital death) and hospitalization (direct hospital admission or transfer). In the test set (the remaining 30%), we measured the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and net benefit (decision curves) for each model. Results Of 135,470 eligible ED visits, 2.1% had critical care outcome and 16.2% had hospitalization outcome. In the critical care outcome prediction, all four machine learning models outperformed the reference model (e.g., AUC, 0.86 [95%CI 0.85–0.87] in the deep neural network vs 0.74 [95%CI 0.72–0.75] in the reference model), with less under-triaged patients in ESI triage levels 3 to 5 (urgent to non-urgent). Likewise, in the hospitalization outcome prediction, all machine learning models outperformed the reference model (e.g., AUC, 0.82 [95%CI 0.82–0.83] in the deep neural network vs 0.69 [95%CI 0.68–0.69] in the reference model) with less over-triages in ESI triage levels 1 to 3 (immediate to urgent). In the decision curve analysis, all machine learning models consistently achieved a greater net benefit—a larger number of appropriate triages considering a trade-off with over-triages—across the range of clinical thresholds. Conclusions Compared to the conventional approach, the machine learning models demonstrated a superior performance to predict critical care and hospitalization outcomes. The application of modern machine learning models may enhance clinicians’ triage decision making, thereby achieving better clinical care and optimal resource utilization. Electronic supplementary material The online version of this article (10.1186/s13054-019-2351-7) contains supplementary material, which is available to authorized users.

AIMS Studies have suggested relationships between obesity and cardiovascular disease (CVD) morbidity. However, little is known about whether substantial weight reduction affects the risk of CVD-related acute care use in obese patients with CVD. The objective of this study was to determine whether bariatric surgery is associated with decreased risk of CVD-related acute care use. METHODS AND RESULTS We performed a self-controlled case series study of obese adults with CVD who underwent bariatric surgery, using population-based emergency department (ED), and inpatient samples in California, Florida, and Nebraska from 2005 to 2011. The primary outcome was ED visit or unplanned hospitalization for CVD. We used conditional logistic regression to compare the risk during sequential 12-month periods, using pre-surgery months 13-24 as the reference period. We identified 11 106 obese adults with CVD who underwent bariatric surgery. During the reference period, 20.6% [95% confidence interval (CI), 19.8-21.3%] of patients had an ED visit or unplanned hospitalization for CVD. The risk did not significantly change in the subsequent 12-month pre-surgery period [adjusted odds ratio (aOR) 0.98; 95% CI, 0.93-1.04; P = 0.42]. By contrast, in the first 12-month period after bariatric surgery, the risk significantly decreased (aOR 0.91; 95% CI, 0.86-0.96; P = 0.002). The risk remained reduced in the subsequent 13-24 months post-bariatric surgery (aOR 0.84; 95% CI, 0.79-0.89; P < 0.001). There was no reduction in the risk in separate obese populations that underwent non-bariatric surgery (i.e. cholecystectomy, hysterectomy). By CVD category, the risk of acute care use for coronary artery disease (CAD), heart failure (HF), and hypertension decreased after bariatric surgery, whereas that of dysrhythmia and venous thromboembolism transiently increased (Bonferroni corrected P < 0.05 for all comparisons). CONCLUSION Bariatric surgery is associated with a lower risk of overall CVD-related ED visit or unplanned hospitalization. The decline was mainly driven by reduced risk of acute care use for CAD, HF, and hypertension after bariatric surgery.

Background Increasing the value of health care delivery is a national priority, and providers face growing pressure to reduce cost while improving quality. Ample opportunity exists to increase efficiency and quality simultaneously through the application of systems engineering science. Objective We examined the hypothesis that Lean-based reorganization of laboratory process flow would improve laboratory turnaround times (TAT) and reduce waste in the system. Methods This study was a prospective, before-after analysis of laboratory process improvement in a teaching hospital emergency department (ED). The intervention included a reorganization of laboratory sample flow based in systems engineering science and Lean methodologies, with no additional resources. The primary outcome was the median TAT from sample collection to result for 6 tests previously performed in an ED kiosk. Results After the intervention, median laboratory TAT decreased across most tests. The greatest decreases were found in "reflex tests" performed after an initial screening test: troponin T TAT was reduced by 33 minutes (86 to 53 minutes; 99% confidence interval, 30-35 minutes) and urine sedimentation TAT by 88 minutes (117 to 29 minutes; 99% confidence interval, 87-90 minutes). In addition, troponin I TAT was reduced by 12 minutes, urinalysis by 9 minutes, and urine human chorionic gonadotropin by 10 minutes. Microbiology rapid testing TAT, a "control," did not change. Conclusions In this study, Lean-based reorganization of laboratory process flow significantly increased process efficiency. Broader application of systems engineering science might further improve health care quality and capacity while reducing waste and cost.

Introduction: Our goal was to assess whether use of a standardized clinical protocol improves efficiency for patients who present to the emergency department (ED) with symptoms of transient ischemic attack (TIA). Methods: We performed a structured, retrospective, cohort study at a large, urban, tertiary care academic center. In July 2012 this hospital implemented a standardized protocol for patients with suspected TIA. The protocol selected high-risk patients for admission and low/intermediate-risk patients to an ED observation unit for workup. Recommended workup included brain imaging, vascular imaging, cardiac monitoring, and observation. Patients were included if clinical providers determined the need for workup for TIA. We included consecutive patients presenting during a six-month period prior to protocol implementation, and those presenting between 6-12 months after implementation. Outcomes included ED length of stay (LOS), hospital LOS, use of neuroimaging, and 90-day risk of stroke or TIA. Results: From 01/2012 to 06/2012, 130 patients were evaluated for TIA symptoms in the ED, and from 01/2013 to 06/2013, 150 patients. The final diagnosis was TIA or stroke in 45% before vs. 41% after (p=0.18). Following the intervention, the inpatient admission rate decreased from 62% to 24% (p

Introduction: While emergency department (ED) crowding has myriad causes and negative downstream effects, applying systems engineering science and targeting throughput remains a potential solution to increase functional capacity. However, the most effective techniques for broad application in the ED remain unclear. We examined the hypothesis that Lean-based reorganization of Fast Track process flow would improve length of stay (LOS), percent of patients discharged within one hour, and room use, without added expense. Methods: This study was a prospective, controlled, before-and-after analysis of Fast Track process improvements in a Level 1 tertiary care academic medical center with >95,000 annual patient visits. We included all adult patients seen during the study periods of 6/2010-10/2010 and 6/2011-10/2011, and data were collected from an electronic tracking system. We used concurrent patients seen in another care area used as a control group. The intervention consisted of a simple reorganization of patient flow through existing rooms, based in systems engineering science and modeling, including queuing theory, demand-capacity matching, and Lean methodologies. No modifications to staffing or physical space were made. Primary outcomes included LOS of discharged patients, percent of patients discharged within one hour, and time in exam room. We compared LOS and exam room time using Wilcoxon rank sum tests, and chi-square tests for percent of patients discharged within one hour. Results: Following the intervention, median LOS among discharged patients was reduced by 15 minutes (158 to 143 min, 95%CI 12 to 19 min, p

Background— Although most research on patients with acute heart failure syndrome (AHFS) has focused on readmissions, this may provide an incomplete picture of health-care utilization. We examined the proportion and characteristics of patients with frequent emergency department (ED) visits for AHFS and associated health-care utilization. Methods and Results— A retrospective cohort study of adults with at least 1 ED visit for AHFS between 2010 and 2011 was performed, derived from population-based multipayer data of state ED and inpatient databases for 2 large and diverse states, California and Florida. The analytic sample comprised 113 033 patients with 175 491 ED visits for AHFS. During the 1-year follow-up period, 30.8% of patients had ≥2 (frequent) visits, accounting for 55.4% (95% confidence interval, 55.2–55.5%) of all ED visits for AHFS. In the multivariable model, significant predictors of frequent ED visits were non-Hispanic black race, Hispanic ethnicity, Medicaid insurance, and lower median household income (all P Conclusions— In this large cohort study, we found that one third (31%) of ED patients with AHFS had frequent ED visits for this condition and that minority race/ethnicity and lower socioeconomic status were associated with frequent ED visits. Individuals with frequent ED visits accounted for the majority of ED visits, hospitalizations, and hospital charges.

Objectives The problem of emergency department (ED) crowding is well recognized; however, little data exist on the sustainability of potential solutions, including physician triage and screening. The authors hypothesized that a physician triage screening program (Supplemented Triage and Rapid Treatment [START]) sustainably improves standard ED performance metrics. Methods This retrospective, observational, before-and-after study compared performance measures over 4 years in a tertiary care urban academic medical center with approximately 90,000 annual ED visits. Patients seen between December 2006 and November 2010 were included. Outcome measures included length of stay (LOS) for ED patients, percentage of patients who left without completing assessment (LWCA), percentage of patients treated and dispositioned by START without using monitored beds, and door-to-room time. Descriptive statistics were used. Results Median LOS for START patients was 56 minutes/patient lower when comparing 2010 to 2007 (p

Objectives The study purpose was to determine the optimal use of lumbar puncture (LP) red blood cell (RBC) counts to identify subarachnoid hemorrhage (SAH) when some blood remains in the final tube. Methods A case series was performed at a tertiary emergency department (ED). Records of 4,496 consecutive adult patients billed for LPs between 2001 and 2009 were reviewed. Inclusion criteria were headache (HA), final tube RBCs ≥ 5, and neurovascular imaging within 2 weeks of the visit. Demographics, relevant history and physical examination components, LP results, and neuroimaging findings were recorded for 280 patients. True-positive (TP) and true-negative (TN) SAH were strictly defined. Primary outcomes were the areas under the receiver operating characteristic curves (AUC) for final tube RBC count, differential RBC count between the final and initial tubes, and absolute differential RBC count between the final and initial tubes divided by the mean RBC count of the two tubes (also called the percent change in RBC count). Results There were 26 TP and 196 TN results; 58 patients were neither. The TP group consisted of 19 patients with visible or possible SAH on imaging (17 on noncontrast head computed tomography [CT; 12 definite and five possible] and two on magnetic resonance imaging), six with xanthochromia and a vascular lesion (aneurysm or arteriovenous malformation [AVM] > 2 mm), and one with xanthochromia and polymerase chain reaction (PCR)-positive meningitis. As a test for SAH, final tube RBC AUC was 0.85 (95% confidence interval [CI] = 0.80 to 0.91). Interval likelihood ratios (LRs) for final tube RBC count were LR 0 (95% CI = 0 to 0.3) for RBCs 10,000. Differential RBC count was not associated with SAH, with AUC 0.45 (95% CI = 0.31 to 0.60). However, the percent change in RBC count between the final and initial tubes had an AUC 0.84 (95% CI = 0.78 to 0.90), and the optimal test threshold for SAH was 0.63, with positive LR 3.6 (95% CI = 2.7 to 4.7) and negative LR 0.10 (95% CI = 0.03 to 0.4) for percent change 63%, respectively. This test added additional independent information to the final tube RBC count based on improved logistic regression model fit and discriminatory ability as measured by the LR test and c statistic, respectively. Conclusions Final LP tube RBC count and the percent change in RBC count, but not the simple differential count between the final and initial tubes, were associated with SAH. In this sample, there were no patients with SAH who had RBCs 10,000 increased the odds of SAH by a factor of 6.

Introduction: The American College of Emergency Physicians (ACEP) Task Force on Boarding described high-impact initiatives to decrease crowding. Furthermore, some emergency departments (EDs) have implemented a novel initiative we term “vertical patient flow,” i.e. segmenting patients who can be safely evaluated, managed, admitted or discharged without occupying a traditional ED room. We sought to determine the degree that ACEP-identified high-impact initiatives for ED crowding and vertical patient flow have been implemented in academic EDs in the United States (U.S.). Methods: We surveyed the physician leadership of all U.S. academic EDs from March to May 2010 using a 2-minute online survey. Academic ED was defined by the primary site of an emergency residency program. Results: We had a response rate of 73% (106/145) and a completion rate of 71% (103/145). The most prevalent hospital-based initiative was inpatient discharge coordination (46% [47/103] of respondents) while the least fully initiated was surgical schedule smoothing (11% [11/103]). The most prevalent ED-based initiative was fast track (79% [81/103]) while the least initiated was physician triage (12% [12/103]). Vertical patient flow had been implemented in 29% (30/103) of responding EDs while an additional 41% (42/103) reported partial/in progress implementation. Conclusion: We found great variability in the extent academic EDs have implemented ACEP’s established high-impact ED crowding initiatives, yet most (70%) have adopted to some extent the novel initiative vertical patient flow. Future studies should examine barriers to implementing these crowding initiatives and how they affect outcomes such as patient safety, ED throughput and patient/provider satisfaction. [West J Emerg Med 2013;14(2):85-89.]

Early triage of patients presenting to the emergency department (ED) with the chief complaint of chest pain suggestive of acute coronary syndrome (ACS) remains a diagnostic challenge. Elements of the chest pain history are associated with increased or decreased likelihoods of ACS.1 Sensitive troponin assays and initial electrocardiogram (ECG) provide important information in the initial decision.2–4 However, clinical history, a single set of cardiac biomarkers, and the initial ECG alone or in combination cannot identify the group of patients who can be safely discharged without further diagnostic testing. The percentage of patients who present to the ED with ACS and are inappropriately discharged is low (around 2%).5 However, discharged subjects have a two to three times increased risk of dying.5 Therefore, the standard of care for subjects with acute chest pain typically includes serial ECG and cardiac biomarkers followed by a stress test with or without imaging.6–9 The standard work-up decreases the risk of diagnostic errors. However, the complete “rule-out myocardial infarction” protocol is time-consuming and costly. Clinical risk scores (e.g., Thrombolysis in Myocardial Infarction [TIMI],10 Goldman,11 and Sanchis12) and triage algorithms are available to predict adverse cardiac events and facilitate the triage decision.10–14 However, the performance of these tools is not optimal.15 Risk scores used for the prediction of future cardiovascular events (e.g., Framingham Risk Score) and risk factors for coronary artery disease (CAD) have only limited value for the confirmation or exclusion of ACS in the ED.16,17 Coronary computed tomography angiography (CTA) permits detection of coronary stenosis and atherosclerotic plaque with high sensitivity, specificity, and negative predictive value.18–22 In patients who present to the ED with acute chest pain, exclusion of a significant coronary stenosis and plaque by coronary CTA has a high negative predictive value for ACS.23–32 In contrast, patients with a significant coronary stenosis detected by computed tomography (CT) have a high likelihood of ACS. However, there is a significant proportion of patients in whom coronary atherosclerotic plaque is present, without significant stenosis. In the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial, we observed approximately one-third (113 of 368) of patients with nonobstructive plaque.28 The quantitative assessment of coronary plaque and the combination of coronary plaque burden with clinical risk scores could possibly improve the accuracy for the diagnosis as well as the exclusion of ACS. We determined the association of four dichotomized (low- vs. intermediate- to high-risk categories) clinical risk scores and of the coronary atherosclerotic plaque burden as detected by CT with the outcome of ACS in patients who presented to the ED with the chief complaint of chest pain and inconclusive initial evaluation (negative cardiac biomarkers, nondiagnostic ECG changes), and no history of CAD. We hypothesized that the combination of risk scores and plaque burden improves the discriminatory capacity for the diagnosis of ACS.

Despite substantial progress in understanding the cancer-signaling network, effective therapies remain scarce due to insufficient disruption of oncogenic pathways, drug resistance and drug-induced toxicity. This complexity of cancer defines an urgent goal for researchers and clinicians to develop novel therapeutic strategies. The discovery of microRNAs (miRNAs) provides new hope for accomplishing this task. Supported by solid evidence for a critical role in cancer and bolstered by a unique mechanism of action, miRNAs are likely to yield a new class of targeted therapeutics. In contrast to current cancer medicines, miRNA-based therapies function by subtle repression of gene expression on a yet large number of oncogenic factors and are, therefore, anticipated to be highly efficacious. After the completion of target validation for several candidates, the development of therapeutic miRNAs is now moving to a new stage that involves pharmacological drug delivery, preclinical toxicology and regulatory guidelines.

Cancer stem cells (CSCs), or tumor-initiating cells, are involved in tumor progression and metastasis. MicroRNAs (miRNAs) regulate both normal stem cells and CSCs, and dysregulation of miRNAs has been implicated in tumorigenesis. CSCs in many tumors--including cancers of the breast, pancreas, head and neck, colon, small intestine, liver, stomach, bladder and ovary--have been identified using the adhesion molecule CD44, either individually or in combination with other marker(s). Prostate CSCs with enhanced clonogenic and tumor-initiating and metastatic capacities are enriched in the CD44(+) cell population, but whether miRNAs regulate CD44(+) prostate cancer cells and prostate cancer metastasis remains unclear. Here we show, through expression analysis, that miR-34a, a p53 target, was underexpressed in CD44(+) prostate cancer cells purified from xenograft and primary tumors. Enforced expression of miR-34a in bulk or purified CD44(+) prostate cancer cells inhibited clonogenic expansion, tumor regeneration, and metastasis. In contrast, expression of miR-34a antagomirs in CD44(-) prostate cancer cells promoted tumor development and metastasis. Systemically delivered miR-34a inhibited prostate cancer metastasis and extended survival of tumor-bearing mice. We identified and validated CD44 as a direct and functional target of miR-34a and found that CD44 knockdown phenocopied miR-34a overexpression in inhibiting prostate cancer regeneration and metastasis. Our study shows that miR-34a is a key negative regulator of CD44(+) prostate cancer cells and establishes a strong rationale for developing miR-34a as a novel therapeutic agent against prostate CSCs.

MicroRNAs (miRNA), a class of natural RNA-interfering agents, have recently been identified as attractive targets for therapeutic intervention. The rationale for developing miRNA therapeutics is based on the premise that aberrantly expressed miRNAs play key roles in the development of human disease, and that correcting these miRNA deficiencies by either antagonizing or restoring miRNA function may provide a therapeutic benefit. Although miRNA antagonists are conceptually similar to other inhibitory therapies, restoring the function of a miRNA by miRNA replacement is a less well characterized approach. Here, we discuss the specific properties of miRNA replacement and review recent examples that explored the therapeutic delivery of miRNA mimics in animal models of cancer. Cancer Res; 70(18); 7027–30. ©2010 AACR.

Recent reports have linked the expression of specific microRNAs (miRNAs) with tumorigenesis and metastasis. Here, we show that microRNA (miR)-16, which is expressed at lower levels in prostate cancer cells, affects the proliferation of human prostate cancer cell lines both in vitro and in vivo. Transient transfection with synthetic miR-16 significantly reduced cell proliferation of 22Rv1, Du145, PPC-1, and PC-3M-luc cells. A prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic miR-16 to tumor cells on bone tissues in mice when injected into tail veins. In the therapeutic bone metastasis model, injection of miR-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. Cell model studies indicate that miR-16 likely suppresses prostate tumor growth by regulating the expression of genes such as CDK1 and CDK2 associated with cell-cycle control and cellular proliferation. There is a trend toward lower miR-16 expression in human prostate tumors versus normal prostate tissues. Thus, this study indicates the therapeutic potential of miRNA in an animal model of cancer metastasis with systemic miRNA injection and suggest that systemic delivery of miR-16 could be used to treat patients with advanced prostate cancer.

OBJECTIVES There is limited information on the financial implications of an emergency department ultrasound (ED US) program. The authors sought to perform a fiscal analysis of an integrated ED US program. METHODS A retrospective review of billing data was performed for fiscal year (FY) 2007 for an urban academic ED with an ED US program. The ED had an annual census of 80,000 visits and 1,101 ED trauma activations. The ED is a core teaching site for a 4-year emergency medicine (EM) residency, has 35 faculty members, and has 24-hour availability of all radiology services including formal US. ED US is utilized as part of evaluation of all trauma activations and for ED procedures. As actual billing charges and reimbursement rates are institution-specific and proprietary information, relative value units (RVUs) and reimbursement based on the Centers for Medicare & Medicaid Services (CMS) 2007 fee schedule (adjusted for fixed diagnosis-related group [DRG] payments and bad debt) was used to determine revenue generated from ED US. To estimate potential volume, assumptions were made on improvement in documentation rate for diagnostic scans (current documentation rates based on billed volume versus diagnostic studies in diagnostic image database), with no improvements assumed for procedural ED US. Expenses consist of three components-capital costs, training costs, and ongoing operational costs-and were determined by institutional experience. Training costs were considered sunken expenses by this institution and were thus not included in the original return on investment (ROI) calculation, although for this article a second ROI calculation was done with training cost estimates included. For the purposes of analysis, certain key assumptions were made. We utilized a collection rate of 45% and hospitalization rates (used to adjust for fixed DRG payments) of 33% for all diagnostic scans, 100% for vascular access, and 10% for needle placement. An optimal documentation rate of 95% was used to estimate potential revenue. RESULTS In FY 2007, 486 limited echo exams of abdomen (current procedural terminology [CPT] 76705) and 480 limited echo cardiac exams were performed (CPT 93308) while there were 78 exams for US-guided vascular access (CPT 76937) and 36 US-guided needle placements when performing paracentesis, thoracentesis, or location of abscess for drainage (CPT 76492). Applying the 2007 CMS fee schedule and above assumptions, the revenue generated was 578 RVUs and $35,541 ($12,934 in professional physician fees and $22,607 in facility fees). Assuming optimal documentation rates for diagnostic ED US scans, ED US could have generated 1,487 RVUs and $94,593 ($33,953 in professional physician fees and $60,640 in facility fees). Program expenses include an initial capital expense (estimated at $120,000 for two US machines) and ongoing operational costs ($68,640 per year to cover image quality assurance review, continuing education, and program maintenance). Based on current revenue, there would be an annual operating loss, and thus an ROI cannot be calculated. However, if potential revenue is achieved, the annual operating income will be $22,846 per year with an ROI of 4.9 years to break even with initial investment. CONCLUSIONS Determining an ROI is a required procedure for any business plan for establishing an ED US program. Our analysis demonstrates that an ED US program that captures charges for trauma and procedural US and achieves the potential billing volume breaks even in less than 5 years, at which point it would generate a positive margin.

Objectives This study was designed to determine the usefulness of coronary computed tomography angiography (CTA) in patients with acute chest pain. Background Triage of chest pain patients in the emergency department remains challenging. Methods We used an observational cohort study in chest pain patients with normal initial troponin and nonischemic electrocardiogram. A 64-slice coronary CTA was performed before admission to detect coronary plaque and stenosis (>50% luminal narrowing). Results were not disclosed. End points were acute coronary syndrome (ACS) during index hospitalization and major adverse cardiac events during 6-month follow-up. Results Among 368 patients (mean age 53 ± 12 years, 61% men), 31 had ACS (8%). By coronary CTA, 50% of these patients were free of coronary artery disease (CAD), 31% had nonobstructive disease, and 19% had inconclusive or positive computed tomography for significant stenosis. Sensitivity and negative predictive value for ACS were 100% (n = 183 of 368; 95% confidence interval [CI]: 98% to 100%) and 100% (95% CI: 89% to 100%), respectively, with the absence of CAD and 77% (95% CI: 59% to 90%) and 98% (n = 300 of 368, 95% CI: 95% to 99%), respectively, with significant stenosis by coronary CTA. Specificity of presence of plaque and stenosis for ACS were 54% (95% CI: 49% to 60%) and 87% (95% CI: 83% to 90%), respectively. Only 1 ACS occurred in the absence of calcified plaque. Both the extent of coronary plaque and presence of stenosis predicted ACS independently and incrementally to Thrombolysis In Myocardial Infarction risk score (area under curve: 0.88, 0.82, vs. 0.63, respectively; all p Conclusions Fifty percent of patients with acute chest pain and low to intermediate likelihood of ACS were free of CAD by computed tomography and had no ACS. Given the large number of such patients, early coronary CTA may significantly improve patient management in the emergency department.

MicroRNAs have been increasingly implicated in human cancer and interest has grown about the potential to use microRNAs to combat cancer. Lung cancer is the most prevalent form of cancer worldwide and lacks effective therapies. Here we have used both in vitro and in vivo approaches to show that the let-7 microRNA directly represses cancer growth in the lung. We find that let-7 inhibits the growth of multiple human lung cancer cell lines in culture, as well as the growth of lung cancer cell xenografts in immunodeficient mice. Using an established orthotopic mouse lung cancer model, we show that intranasal let-7 administration reduces tumor formation in vivo in the lungs of animals expressing a G12D activating mutation for the K-ras oncogene. These findings provide direct evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that this miRNA may be useful as a novel therapeutic agent in lung cancer.

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) binds to death receptors 4/5 and selectively induces caspase-dependent apoptosis. The RNA interference screening approach has led to the discovery and characterization of several TRAIL pathway components in human cells. Here, libraries of synthetic small interfering RNA (siRNA) and microRNAs (miRNA) were used to probe the TRAIL pathway. In addition to known genes, siRNAs targeting CDK4, PTGS1, ALG2, CLCN3, IRAK4, and MAP3K8 altered TRAIL-induced caspase-3 activation responses. Introduction of the miRNAs let-7c, mir-10a, mir-144, mir-150, mir-155, and mir-193 also affected the activation of the caspase cascade. Putative targets of these endogenous miRNAs included genes encoding death receptors, caspases, and other apoptosis-related genes. Among the novel genes revealed in the screen, CDK4 was selected for further characterization. CDK4 was the only member of the cyclin-dependent kinase gene family that bore a unique function in apoptotic signal transduction. [Cancer Res 2007;67(22):10782–8]

Background— Noninvasive assessment of coronary atherosclerotic plaque and significant stenosis by coronary multidetector computed tomography (MDCT) may improve early and accurate triage of patients presenting with acute chest pain to the emergency department. Methods and Results— We conducted a blinded, prospective study in patients presenting with acute chest pain to the emergency department between May and July 2005 who were admitted to the hospital to rule out acute coronary syndrome (ACS) with no ischemic ECG changes and negative initial biomarkers. Contrast-enhanced 64-slice MDCT coronary angiography was performed immediately before admission, and data sets were evaluated for the presence of coronary atherosclerotic plaque and significant coronary artery stenosis. All providers were blinded to MDCT results. An expert panel, blinded to the MDCT data, determined the presence or absence of ACS on the basis of all data accrued during the index hospitalization and 5-month follow-up. Among 103 consecutive patients (40% female; mean age, 54±12 years), 14 patients had ACS. Both the absence of significant coronary artery stenosis (73 of 103 patients) and nonsignificant coronary atherosclerotic plaque (41 of 103 patients) accurately predicted the absence of ACS (negative predictive values, 100%). Multivariate logistic regression analyses demonstrated that adding the extent of plaque significantly improved the initial models containing only traditional risk factors or clinical estimates of the probability of ACS (c statistic, 0.73 to 0.89 and 0.61 to 0.86, respectively). Conclusions— Noninvasive assessment of coronary artery disease by MDCT has good performance characteristics for ruling out ACS in subjects presenting with possible myocardial ischemia to the emergency department and may be useful for improving early triage.

Background: Although studies have suggested links between obesity and morbidities related to cardiovascular disease (CVD), little is known about whether substantial weight reduction affects the risk and cost of CVD-related healthcare utilizations. We aimed to determine whether bariatric surgery is

Emergency department (ED) visits for opioid overdose provide an important marker of acute morbidity. We sought to evaluate national trends of ED visits for opioid overdose.The National Hospital Ambulatory Medical Care Survey, 1993-2010, was used to identify ED visits for opioid overdose.Outcome measures were national ED visit rates for opioid overdose per 100,000 U.S. population and per 100,000 ED visits.From 1993 to 2010, there were approximately 731,000 ED visits (95% CI, 586,000-877,000 visits) for opioid overdose, representing an overall rate of 14 ED visits (95% CI, 12-17 visits) per 100,000 population and 37 ED visits (95% CI, 31-45 visits) per 100,000 ED visits. Of these, 41% (95% CI, 33-50%) were for prescription opioid overdose. Between 1993 and 2010, the national visit rate increased from 7 to 27 per 100,000 population (+307%; Ptrend = 0.03), and from 19 to 63 per 100,000 ED visits (+235%; Ptrend 0.001). Stratified analyses of the visit rate per population showed upward, but nonsignificant, trends across multiple demographic groups and U.S. regions. In stratified analyses of the visit rate per 100,000 ED visits, the rate increased significantly in several groups: age20 years (+1188%; Ptrend = 0.002), age 20-29 years (+155%; Ptrend = 0.04), age ≥50 years (+231%; Ptrend = 0.04), female (+234%; Ptrend = 0.001), male (+80%; Ptrend = 0.04), whites (+187%; Ptrend 0.001), and patients in the South (+371%; Ptrend 0.001).In a nationally representative database of U.S. ED visits, we found that the ED visit rate for opioid overdose quadrupled from 1993 to 2010. Our findings suggest that previous prevention measures may not be adequate.

To evaluate the rate of emergency department (ED) visits for opioid overdose and to examine whether frequent ED visits for opioid overdose are associated with more hospitalizations, near-fatal events, and health care spending.Retrospective cohort study of adults with at least 1 ED visit for opioid overdose between January 1, 2010, and December 31, 2011, derived from population-based data of State Emergency Department Databases and State Inpatient Databases for 2 large and diverse states: California and Florida. Main outcome measures were hospitalizations for opioid overdose, near-fatal events (overdose involving mechanical ventilation), and hospital charges during the year after the first ED visit.The analytic cohort comprised 19,831 unique patients with 21,609 ED visits for opioid overdose. During a 1-year period, 7% (95% CI, 7%-7%; n=1389 patients) of the patients had frequent (2 or more) ED visits, accounting for 15% (95% CI, 14%-15%; n=3167) of all opioid overdose ED visits. Middle age, male sex, public insurance, lower household income, and comorbidities (such as chronic pulmonary disease and neurological diseases) were associated with frequent ED visits (all P.01). Overall, 53% (95% CI, 52%-54%; n=11,412) of the ED visits for opioid overdose resulted in hospitalizations; patients with frequent ED visits for opioid overdose had a higher likelihood of hospitalization (adjusted odds ratio, 3.98; 95% CI, 3.38-4.69). In addition, 10.0% (95% CI, 10%-10%; n=2161) of the ED visits led to near-fatal events; patients with frequent ED visits had a higher likelihood of a near-fatal event (adjusted odds ratio, 2.27; 95% CI, 1.96-2.66). Total charges in Florida were $208 million (95% CI, $200-$219 million).In this population-based cohort, we found that frequent ED visits for opioid overdose were associated with a higher likelihood of future hospitalizations and near-fatal events.

To examine temporal trends in emergency departments (EDs) visits for bronchiolitis among US children between 2006 and 2010.Serial, cross-sectional analysis of the Nationwide Emergency Department Sample, a nationally representative sample of ED patients. We used International Classification of Diseases, Ninth Revision, Clinical Modification code 466.1 to identify children2 years of age with bronchiolitis. Primary outcome measures were rate of bronchiolitis ED visits, hospital admission rate and ED charges.Between 2006 and 2010, weighted national discharge data included 1,435,110 ED visits with bronchiolitis. There was a modest increase in the rate of bronchiolitis ED visits, from 35.6 to 36.3 per 1000 person-years (2% increase; Ptrend = 0.008), due to increases in the ED visit rate among children from 12 months to 23 months (24% increase;Ptrend0.001). By contrast, there was a significant decline in the ED visit rate among infants (4% decrease; Ptrend0.001). Although unadjusted admission rate did not change between 2006 and 2010 (26% in both years), admission rate declined significantly after adjusting for potential patient- and ED-level confounders (adjusted odds ratio for comparison of 2010 with 2006, 0.84; 95% confidence interval: 0.76-0.93; P0.001). Nationwide ED charges for bronchiolitis increased from $337 million to $389 million (16% increase; Ptrend0.001), adjusted for inflation. This increase was driven by a rise in geometric mean of ED charges per case from $887 to $1059 (19% increase; Ptrend0.001).Between 2006 and 2010, we found a divergent temporal trend in the rate of bronchiolitis ED visits by age group. Despite a significant increase in associated ED charges, ED-associated hospital admission rates for bronchiolitis significantly decreased over this same period.

OBJECTIVE: To examine temporal trend in the national incidence of bronchiolitis hospitalizations, use of mechanical ventilation, and hospital charges between 2000 and 2009. METHODS: We performed a serial, cross-sectional analysis of a nationally representative sample of children hospitalized with bronchiolitis. The Kids Inpatient Database was used to identify children RESULTS: The 4 separated years (2000, 2003, 2006, and 2009) of national discharge data included 544 828 weighted discharges with bronchiolitis. Between 2000 and 2009, the incidence of bronchiolitis hospitalization decreased from 17.9 to 14.9 per 1000 person-years among all US children aged CONCLUSIONS: Between 2000 and 2009, we found a significant decline in bronchiolitis hospitalizations among US children. By contrast, use of mechanical ventilation and hospital charges for bronchiolitis significantly increased over this same period.

BACKGROUND Little is known about the duration of symptoms and follow-up patterns of patients seen in emergency departments for abdominal or flank pain. OBJECTIVE We aimed to measure the duration of symptoms and follow-up rate of patients discharged home from the emergency department after presenting with non-traumatic abdominal or flank pain. METHODS We conducted a single-centre, prospective descriptive study of adult patients who presented to our emergency department with non-traumatic abdominal or flank pain and were discharged from the emergency department. We gathered clinical data during the index emergency department visit and conducted telephone interviews of subjects 2-5 weeks later. RESULTS We reached 63 of 90 subjects (70%). The median duration of pain was 3 days after the emergency department visit. During the follow-up period, only 41% had followed-up with their family physician or primary care provider, although an additional 21% had planned to. Persistence of symptoms was common in the 37% of subjects who did not follow-up. CONCLUSION Of subjects discharged from the emergency department after visits for non-traumatic abdominal or flank pain, most improve within several days. Fewer than half follow-up with a family practitioner or a primary care provider. Emergency department revisits are uncommon and often for unrelated problems.

MiRNAs regulate cancer cells, but their potential effects on cancer stem/progenitor cells are still being explored. In this study, we used quantitative real-time-PCR to define miRNA expression patterns in various stem/progenitor cell populations in prostate cancer, including CD44+, CD133+, integrin α2β1+, and side population cells. We identified distinct and common patterns in these different tumorigenic cell subsets. Multiple tumor-suppressive miRNAs were downregulated coordinately in several prostate cancer stem/progenitor cell populations, namely, miR-34a, let-7b, miR-106a, and miR-141, whereas miR-301 and miR-452 were commonly overexpressed. The let-7 overexpression inhibited prostate cancer cell proliferation and clonal expansion in vitro and tumor regeneration in vivo. In addition, let-7 and miR-34a exerted differential inhibitory effects in prostate cancer cells, with miR-34a inducing G1 phase cell-cycle arrest accompanied by cell senescence and let-7 inducing G2–M phase cell-cycle arrest without senescence. Taken together, our findings define distinct miRNA expression patterns that coordinately regulate the tumorigenicity of prostate cancer cells. Cancer Res; 72(13); 3393–404. ©2012 AACR.

Introduction: Little information exists regarding how accurately emergency physicians (EPs) predict the probability of acute coronary syndrome (ACS). Our objective was to determine if EPs can accurately predict ACS in a prospectively identified cohort of emergency department (ED) patients who met enrolment criteria for a study of coronary computed tomographic angiography (CCTA) and were admitted for a “rule out ACS” protocol. Methods: A prospective observational pilot study in an academic medical centre was carried out. EPs caring for patients with chest pain provided whole-number estimates of the probability of ACS after clinical review. This substudy was part of the now published Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) study, a study of CCTA and admission of patients for a rule out ACS protocol after a nondiagnostic evaluation. Predictions were grouped into probability groups based on the validated Goldman criteria. ACS was determined by an adjudication committee using American Heart Association/American College of Cardiology/European Society of Cardiology guidelines. Results: A total of 334 predictions were obtained for a study population with a mean age of 54 (SD 12) years, 63% of whom were male. There were 35 ACS events. EPs predicted ACS better than by chance, and increasingly higher estimates were associated with a higher incidence of ACS (p = 0.0004). The percentage of patients with ACS was 0%, 6%, 7%, and 17%, respectively, for very low, low, intermediate, and high probability groups. EPs' estimates had a sensitivity of 63% using a > 20% probability of ACS to define a positive test. Lowering this threshold to > 7% to define a test as positive increased the sensitivity of physician estimates to 89% but lowered specificity from 65% to 24% Conclusions: Our data suggest that for a selected ED cohort meeting eligibility criteria for a study of CCTA, EPs predict ACS better than by chance, with an increasing proportion of patients proving to have ACS with increasing probability estimates. Lowering the estimate threshold does not result in an overall sensitivity level that is sufficient to send patients home from the ED and is associated with a poor specificity.

Myocardial injury is common among patients with intracerebral hemorrhage (ICH). However, it is challenging for emergency physicians to recognize acute myocardial injury in this population, as electrocardiographic (ECG) abnormalities are common in this setting. Our objective is to examine whether ischemic-appearing ECG changes predict subsequent myocardial injury in the context of ICH.Consecutive patients with primary ICH presenting to a single academic center were prospectively enrolled. Electrocardiograms were retrospectively reviewed by 3 independent readers. Anatomical areas of ischemia were defined as I and aVL; II, III, and aVF; V(1) to V(4); and V(5) and V(6). Medical record review identified myocardial injury, defined as troponin I or T elevation (cutoff 1.5 and 0.1 ng/mL, respectively), within 30 days.Between 1998 and 2004, 218 patients presented directly to our emergency department and did not have a do-not-resuscitate/do-not-intubate order; arrival ECGs and troponin levels were available for 206 patients. Ischemic-appearing changes were noted in 41% of patients, and myocardial injury was noted in 12% of patients. Ischemic-appearing changes were more common in patients with subsequent injury (64% vs 37%; P = .02). After multivariable analysis controlling for age and cardiac risk factors, ischemic-appearing ECG changes independently predicted myocardial injury (odds ratio, 3.2; 95% confidence interval, 1.3-8.2). In an exploratory analysis, ischemic-appearing ECG changes in leads I and aVL as well as V(5) and V(6) were more specific for myocardial injury (P = .002 and P = .03, respectively).In conclusion, although a range of ECG abnormalities can occur after ICH, the finding of ischemic-appearing changes in an anatomical distribution can help predict which patients are having true myocardial injury.

MicroRNAs (miRNAs) are emerging as potential cancer therapeutics, but effective delivery mechanisms to tumor sites are a roadblock to utility. Here we show that systemically delivered, synthetic miRNA mimics in complex with a novel neutral lipid emulsion are preferentially targeted to lung tumors and show therapeutic benefit in mouse models of lung cancer. Therapeutic delivery was demonstrated using mimics of the tumor suppressors, microRNA-34a (miR-34a) and let-7, both of which are often down regulated or lost in lung cancer. Systemic treatment of a Kras-activated autochthonous mouse model of non-small cell lung cancer (NSCLC) led to a significant decrease in tumor burden. Specifically, mice treated with miR-34a displayed a 60% reduction in tumor area compared to mice treated with a miRNA control. Similar results were obtained with the let-7 mimic. These findings provide direct evidence that synthetic miRNA mimics can be systemically delivered to the mammalian lung and support the promise of miRNAs as a future targeted therapy for lung cancer.

In Reply: We very much appreciate the interest of our colleagues in this important topic, one that has yet to fully mature in the pantheon of emergency medicine literature. We also recognize and noted in our manuscript that the single-site nature of our work is a limitation. However, we disagree that this limitation makes scientific exploration and publication of this nature a fruitless endeavor as implied. Publication bias aside, the central tenet of Lean methodologies is the elimination of waste in all forms, and thus it is an inherently generalizable tool to improve any process in which waste exists. However, by definition the specific details relating to the underlying process and the implementation of Lean are of key importance, and its potential utility needs to be weighed in each individual setting. In addition, partly for this reason, we suggest that local processes not affected by the intervention may serve as reliable controls. We specifically used another area of our ED as a control group to avoid the recognized limitations of an analysis that was purely based on data that were obtained “before and after” the changes were implemented. Finally, Lean methodologies do not always have to be resource intensive as our colleagues suggest. For example, no external consultants or significant internal resources were utilized for this work, and in addition we were in fact able to decrease resource utilization as is common with successful Lean interventions. We respectfully suggest that it is often in this simplicity and focus that Lean interventions, and robust scientific studies describing them, have the potential to be so powerful.

Tumor suppressor microRNAs (miRNA) provide a new opportunity to treat cancer. This approach, “miRNA replacement therapy,” is based on the concept that the reintroduction of miRNAs depleted in cancer cells reactivates cellular pathways that drive a therapeutic response. Here, we describe the development of a therapeutic formulation using chemically synthesized miR-34a and a lipid-based delivery vehicle that blocks tumor growth in mouse models of non–small-cell lung cancer. This formulation is effective when administered locally or systemically. The antioncogenic effects are accompanied by an accumulation of miR-34a in the tumor tissue and downregulation of direct miR-34a targets. Intravenous delivery of formulated miR-34a does not induce an elevation of cytokines or liver and kidney enzymes in serum, suggesting that the formulation is well tolerated and does not induce an immune response. The data provide proof of concept for the systemic delivery of a synthetic tumor suppressor mimic, obviating obstacles associated with viral-based miRNA delivery and facilitating a rapid route for miRNA replacement therapy into the clinic. Cancer Res; 70(14); 5923–30. ©2010 AACR.

MicroRNAs (miRNAs) have recently emerged as an important new class of cellular regulators that control various cellular processes and are implicated in human diseases, including cancer. Here, we show that loss of let-7 function enhances lung tumor formation in vivo, strongly supporting the hypothesis that let-7 is a tumor suppressor. Moreover, we report that exogenous delivery of let-7 to established tumors in mouse models of non-small-cell lung cancer (NSCLC) significantly reduces the tumor burden. These results demonstrate the therapeutic potential of let-7 in NSCLC and point to miRNA replacement therapy as a promising approach in cancer treatment.

Background: Emergency departments (EDs) are traditionally designed to provide rapid evaluation and stabilization and are neither staffed nor equipped to provide prolonged care. Longer ED length of stay (LOS) may compromise quality of care and contribute to delays in the emergency evaluation of other patients. Objectives: The objective was to determine whether ED LOS increased between 2001 and 2005 and whether trends varied by patient and hospital factors. Methods: This was a retrospective analysis of a nationally representative sample of 138,569 adult ED visits from the National Hospital Ambulatory Medical Care Survey (NHAMCS), 2001 to 2005. ED LOS was measured from registration to discharge. Results: Median ED LOS increased 3.5% per year from 132 minutes in 2001 to 154 minutes in 2005 (p-value for trend

We read with interest the letter from Dr Bouzas-Mosquera about our published article.1 We appreciate both his comments and the opportunity to respond. We used a subjective assessment of the pretest probability of acute coronary syndrome (ACS) by the emergency department (ED) caregiver because it incorporates into a single metric all of the data available to decision makers before imaging. Its limitation is that it is too insensitive to use to discharge ED patients directly home without further testing for ACS. It was used because no well established, universally accepted, and validated risk score exists that can be applied to undifferentiated ED populations with chest pain. …

Objectives Cardiac multidetector computed tomography (CMCT) has potential to be used as a screening test for patients with acute chest pain, but several tools are already used to risk-stratify this population. Risk models exist that stratify need for intensive care (Goldman), short-term prognosis (Thrombolysis in Myocardial Infarction, TIMI), and 1-year events (Sanchis). We applied these cardiovascular risk models to candidates for CMCT and assessed sensitivity for prediction of in-hospital acute coronary syndrome (ACS). We hypothesized that none of the models would achieve a sensitivity of 90% or greater, thereby justifying use of CMCT in patients with acute chest pain. Methods We analyzed TIMI, Goldman, and Sanchis in 148 consecutive patients with chest pain, nondiagnostic electrocardiogram, and negative initial cardiac biomarkers who previously met inclusion and exclusion criteria for the Rule-Out Myocardial Infarction Using Coronary Artery Tomography Study. ACS was adjudicated, and risk scores were categorized based on established criteria. Risk score agreement was assessed with weighted κ statistics. Results Overall, 17 (11%) of 148 patients had ACS. For all risk models, sensitivity was poor (range, 35%-53%), and 95% confidence intervals did not cross above 77%. Agreement to risk-classify patients was poor to moderate (weighted κ range, 0.18-0.43). Patients categorized as "low risk" had nonzero rates of ACS using all 3 scoring models (range, 8%-9%). Conclusions Available risk scores had poor sensitivity to detect ACS in patients with acute chest pain. Because of the small number of patients in this data set, these findings require confirmation in larger studies.

Background— Cardiac magnetic resonance (CMR) imaging permits early triage of patients presenting to the emergency department with acute chest pain but has been limited by the inability to differentiate new from old myocardial infarction. Our objective was to evaluate a CMR protocol that includes T2-weighted imaging and assessment of left ventricular wall thickness in detecting patients with acute coronary syndrome in the emergency department. Methods and Results— In this prospective cohort observational study, we enrolled patients presenting to the emergency department with acute chest pain, negative cardiac biomarkers, and no ECG changes indicative of acute ischemia. The CMR protocol consisted of T2-weighted imaging, first-pass perfusion, cine function, delayed-enhancement magnetic resonance imaging, and assessment of left ventricular wall thickness. The clinical outcome (acute coronary syndrome) was defined by review of clinical charts by a consensus panel that used American Heart Association/American College of Cardiology guidelines. Among 62 patients, 13 developed acute coronary syndrome during the index hospitalization. The mean CMR time was 32±8 minutes. The new CMR protocol (with the addition of T2-weighted and left ventricular wall thickness) increased the specificity, positive predictive value, and overall accuracy from 84% to 96%, 55% to 85%, and 84% to 93%, respectively, compared with the conventional CMR protocol (cine, perfusion, and delayed-enhancement magnetic resonance imaging). Moreover, in a logistic regression analysis that contained information on clinical risk assessment (c-statistic=0.695) and traditional cardiac risk factors (c-statistic=0.771), the new CMR protocol significantly improved the c-statistic to 0.958 ( P Conclusions— The present study indicates that a new CMR protocol improves the detection of patients with acute coronary syndrome in the emergency department and adds significant value over clinical assessment and traditional cardiac risk factors.

MicroRNAs play important roles in animal development, cell differentiation, and metabolism and have been implicated in human cancer. The let-7 microRNA controls the timing of cell cycle exit and terminal differentiation in Caenorhabditis elegans and is poorly expressed or deleted in human lung tumors. Here, we show that let-7 is highly expressed in normal lung tissue, and that inhibiting let-7 function leads to increased cell division in A549 lung cancer cells. Overexpression of let-7 in cancer cell lines alters cell cycle progression and reduces cell division, providing evidence that let-7 functions as a tumor suppressor in lung cells. let-7 was previously shown to regulate the expression of the RAS lung cancer oncogenes, and our work now shows that multiple genes involved in cell cycle and cell division functions are also directly or indirectly repressed by let-7. This work reveals the let-7 microRNA to be a master regulator of cell proliferation pathways. [Cancer Res 2007;67(16):7713–22]