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Patients who have low-risk clinical features and negative cardiac troponin levels may be suitable for early discharge after a brief period of observation in the emergency department (ED). Little is known about the prevalence and severity of coronary artery disease in such patients, although this has implications for follow-up. Subjects included 570 patients who were at < or =7% risk of acute myocardial infarction (AMI), remained clinically stable (defined as the absence of new ischemic changes on their electrocardiograph, signs or symptoms of heart failure, the development of a cardiac arrhythmia or hypotension requiring either inotropes or volume repletion) and had cardiac troponin I (cTnI) levels

Brain ischemia and reperfusion engage multiple independently-fatal terminal pathways involving loss of membrane integrity in partitioning ions, progressive proteolysis, and inability to check these processes because of loss of general translation competence and reduced survival signal-transduction. Ischemia results in rapid loss of high-energy phosphate compounds and generalized depolarization, which induces release of glutamate and, in selectively vulnerable neurons (SVNs), opening of both voltage-dependent and glutamate-regulated calcium channels. This allows a large increase in cytosolic Ca(2+) associated with activation of mu-calpain, calcineurin, and phospholipases with consequent proteolysis of calpain substrates (including spectrin and eIF4G), activation of NOS and potentially of Bad, and accumulation of free arachidonic acid, which can induce depletion of Ca(2+) from the ER lumen. A kinase that shuts off translation initiation by phosphorylating the alpha-subunit of eukaryotic initiation factor-2 (eIF2alpha) is activated either by adenosine degradation products or depletion of ER lumenal Ca(2+). Early during reperfusion, oxidative metabolism of arachidonate causes a burst of excess oxygen radicals, iron is released from storage proteins by superoxide-mediated reduction, and NO is generated. These events result in peroxynitrite generation, inappropriate protein nitrosylation, and lipid peroxidation, which ultrastructurally appears to principally damage the plasmalemma of SVNs. The initial recovery of ATP supports very rapid eIF2alpha phosphorylation that in SVNs is prolonged and associated with a major reduction in protein synthesis. High catecholamine levels induced by the ischemic episode itself and/or drug administration down-regulate insulin secretion and induce inhibition of growth-factor receptor tyrosine kinase activity, effects associated with down-regulation of survival signal-transduction through the Ras pathway. Caspase activation occurs during the early hours of reperfusion following mitochondrial release of caspase 9 and cytochrome c. The SVNs find themselves with substantial membrane damage, calpain-mediated proteolytic degradation of eIF4G and cytoskeletal proteins, altered translation initiation mechanisms that substantially reduce total protein synthesis and impose major alterations in message selection, down-regulated survival signal-transduction, and caspase activation. This picture argues powerfully that, for therapy of brain ischemia and reperfusion, the concept of single drug intervention (which has characterized the approaches of basic research, the pharmaceutical industry, and clinical trials) cannot be effective. Although rigorous study of multi-drug protocols is very demanding, effective therapy is likely to require (1) peptide growth factors for early activation of survival-signaling pathways and recovery of translation competence, (2) inhibition of lipid peroxidation, (3) inhibition of calpain, and (4) caspase inhibition. Examination of such protocols will require not only characterization of functional and histopathologic outcome, but also study of biochemical markers of the injury processes to establish the role of each drug.

BackgroundThere is an urgent need for objective criteria adjunctive to standard clinical assessment of acute Traumatic Brain Injury (TBI). Details of the development of a quantitative index to identify structural brain injury based on brain electrical activity will be described. MethodsAcute closed head injured and normal patients (n=1470) were recruited from 16 US Emergency Departments and evaluated using brain electrical activity (EEG) recorded from forehead electrodes. Patients had high GCS (median=15), and most presented with low suspicion of brain injury. Patients were divided into a CT positive (CT+) group and a group with CT negative findings or where CT scans were not ordered according to standard assessment (CT-/CT_NR). Three different classifier methodologies, Ensemble Harmony, Least Absolute Shrinkage and Selection Operator (LASSO), and Genetic Algorithm (GA), were utilized. ResultsSimilar performance accuracy was obtained for all three methodologies with an average sensitivity/specificity of 97.5%/59.5%, area under the curves (AUC) of 0.90 and average Negative Predictive Validity (NPV)>99%. Sensitivity was highest for CT+ cases with potentially life threatening hematomas, where two of three classifiers were 100%. ConclusionSimilar performance of these classifiers suggests that the optimal separation of the populations was obtained given the overlap of the underlying distributions of features of brain activity. High sensitivity to CT+ injuries (highest in hematomas) and specificity significantly higher than that obtained using ED guidelines for imaging, supports the enhanced clinical utility of this technology and suggests the potential role in the objective, rapid and more optimal triage of TBI patients. The derivation of algorithms for the identification of structural TBI are described.EEG recordings were obtained using only forehead electrodes on a handheld device.Classifiers methodologies used included genetic algorithms and LASSO logistic regression.The classifiers achieved an average sensitivity/specificity of 97.5%/59.5%.Performance well surpasses that of standard clinical practice for CT scan referrals in TBI.

Background Pneumonia is among the foremost causes of hospitalization and mortality in patients residing in extended care facilities. Despite its prevalence, there is currently little literature focusing on the course and management of nursing home-acquired pneumonia (NHAP) in the emergency department (ED). Our objective was to investigate the ED presentation, course, management and outcomes in patients admitted through the ED with NHAP. Methods A retrospective chart review of nursing home patients with a presumptive or final diagnosis of pneumonia admitted through the ED was performed at two large hospitals in Detroit, Michigan. Results A total of 296 patients were included in the study from 2002 to 2007 with a mean age of 81.1 years (SD ± 10.95) and 55.4% females. Blood cultures were performed on 90.8% of patients in the ED; 17.8% of these revealed growths, but half of these were considered contaminants. Initial chest x-ray in the ED was read as possible pneumonia in 18.2% of patients; 73.9% were started on antibiotics (ABX) in the ED. Mean hospital length of stay (LOS) was 10.75 days (SD ± 9.35) and in-hospital mortality was 16.2%. Time until first ABX in univariate analysis was nearly significant (p = 0.053) for mortality prediction, and the appropriate versus inappropriate ABX (per the Infectious Diseases Society of America and American Thoracic Society guidelines) did not affect mortality. Patients treated with a single ABX had significantly increased LOS (p = 0.0089). There was poor correlation between LOS and time until first ABX as well as LOS and time until appropriate ABX with a correlation coefficient of -0.048 (p = 0.42) and -0.08 (p = 0.43), respectively. Conclusions In this data set of NHAP patients admitted through the ED, we found a surprisingly low prevalence of true-positive blood cultures, high incidence of antibiotic pre-treatment at nursing homes prior to admission, high hospital mortality and low immunization rates. There was a wide spectrum of pathogens grown in blood culture. Only two thirds of the patients had dyspnea at presentation, and less than half had either cough or fever. On physical examination, about one fourth had no clinical findings consistent with pneumonia. Further, less than one fifth of chest x-rays were interpreted as possible pneumonia.

Background Influenza causes over 200,000 hospitalizations a year in the United States, but few antiviral treatment studies have focused on patients hospitalized with influenza. This open-label, randomized study was initiated during the 2009 H1N1 pandemic to help assess the antiviral activity, safety and tolerability of 5–10 days treatment with two different dosing regimens of the intravenous neuraminidase inhibitor, peramivir, in hospitalized subjects with influenza. Methods Quantitative virology was done on nasopharyngeal swab specimens from subjects ≥6 years of age to measure change from baseline in tissue culture infective dose (primary end point) and quantitative viral RNA levels by real-time PCR. Clinical end points included time to clinical resolution, a composite end point of four vital signs and oxygen saturation. Results A total of 234 hospitalized patients were randomized to peramivir 300 mg twice daily or 600 mg once daily; 127 had laboratory confirmed influenza. In those with detectable virus at baseline, viral titres declined without differences between regimens. There were no significant differences in clinical or virological end points between treatment arms, and apparent differences were explained by baseline disease severity differences in the groups. Peramivir was generally safe and well tolerated for treated patients hospitalized with pandemic influenza with outcomes similar to those described in the literature. Conclusions This open-label trial of intravenous peramivir in subjects hospitalized predominantly with 2009 influenza A (H1N1) demonstrated that once- or twice-daily administration was associated with decreases in viral shedding and clinical improvement. ClinicalTrials.gov number NCT00957996.

Brain damage accompanying cardiac arrest and resuscitation is frequent and devastating. Neurons in the hippocampus CA1 and CA4 zones and cortical layers III and V are selectively vulnerable to death after injury by ischemia and reperfusion. Ultrastructural evidence indicates that most of the structural damage is associated with reperfusion, during which the vulnerable neurons develop disaggregation of polyribosomes, peroxidative damage to unsaturated fatty acids in the plasma membrane, and prominent alterations in the structure of the Golgi apparatus that is responsible for membrane assembly. Reperfusion is also associated with vulnerable neurons with prominent production of messenger RNAs for stress proteins and for the proteins of the activator protein-1 complex, but these vulnerable neurons fail to efficiently translate these messages into the proteins. The inhibition of protein synthesis during reperfusion involves alteration of translation initiation factors, specifically serine phosphorylation of the alpha-subunit of eukaryotic initiation factor-2 (elF-2 alpha). Growth factors--in particular, insulin--have the potential to reverse phosphorylation of elF-2 alpha, promote effective translation of the mRNA transcripts generated in response to ischemia and reperfusion, enhance neuronal defenses against radicals, and stimulate lipid synthesis and membrane repair. There is now substantial evidence that the insulin-class growth factors have neuron-sparing effects against damage by radicals and ischemia and reperfusion. This new knowledge may provide a fundamental basis for a rational approach to "cerebral resuscitation" that will allow substantial amelioration of the often dismal neurologic outcome now associated with resuscitation from cardiac arrest.

BACKGROUND:Mild traumatic brain injury (mTBI) is a significant healthcare burden and its diagnosis remains a challenge in the emergency department. Serum biomarkers and advanced magnetic resonance imaging (MRI) techniques have already demonstrated their potential to improve the detection of brain injury even in patients with negative computed tomography (CT) findings. The objective of this study was to determine the clinical value of a combinational use of both blood biomarkers and MRI in mTBI detection and their characterization in the acute setting (within 24 hours after injury). METHODS:Nine patients with mTBI were prospectively recruited from the emergency department. Serum samples were collected at the time of hospital admission and every 6 hours up to 24 hours post injury. Neuronal (Ubiquitin C-terminal Hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels were analyzed. Advanced MRI data were acquired at 9 ± 6.91 hours after injury. Patients' neurocognitive status was assessed by using the Standard Assessment of Concussion (SAC) instrument. RESULTS:The median serum levels of UCH-L1 and GFAP on admission were increased 4.9 folds and 10.6 folds, respectively, compared to reference values. Three patients were found to have intracranial hemorrhages on SWI, all of whom had very high GFAP levels. Total volume of brain white matter (WM) with abnormal fractional anisotropy (FA) measures of diffusion tensor imaging (DTI) were negatively correlated with patients' SAC scores, including delayed recall. Both increased and decreased DTI-FA values were observed in the same subjects. Serum biomarker level was not correlated with patients' DTI data nor SAC score. CONCLUSIONS:Blood biomarkers and advanced MRI may correlate or complement each other in different aspects of mTBI detection and characterization. GFAP might have potential to serve as a clinical screening tool for intracranial bleeding. UCH-L1 complements MRI in injury detection. Impairment at WM tracts may account for the patients' neurocognitive symptoms.

The neocortex and the hippocampus were examined for lipid peroxidation products and ultrastructural alterations by fluorescence and electron microscopy, respectively, in rats subjected to 10 min of cardiac arrest or 10 min cardiac arrest and either 90 or 360 min reperfusion. Lipid peroxidation products were observed after 90 min reperfusion in the perikarya and proximal dendrites of neocortical pyramidal neurons and in the hippocampal hilar cells and CA1, region; the fluorescence was most intense at the base of the apical dendrite, the region of the Golgi apparatus. After 90 min of reperfusion, the CA1, showed considerable stretches of rough endoplasmic reticulum devoid of ribosomes and the Golgi cisternae were shorter and widely dilated. The neocortex showed similar endoplasmic reticulum changes, but no significant alterations to the Golgi were noted. In addition there were areas where strings of ribosomes appear to be detaching from the endoplasmic reticulum. After 360 min reperfusion in both the neocortex and the hippocampus, the damage appeared more severe. The Golgi was fragmented into vacuoles, membranous whorls had appeared, and dense aggregates of smooth vesicles were seen coalescing with each other and the vacuoles. These observations suggest that early Golgi involvement is a more important marker of lethal injury than ribosome release from the endoplasmic reticulum. The areas of disturbed Golgi ultrastructure correspond to those areas that show evidence of lipid peroxidation and imply that lipid peroxidation may be causally related to the disturbance in Golgi ultrastructure.

The 2010 AHA Guidelines for CPR and ECC for the evaluation and management of acute coronary syndromes (ACS) are intended to define the scope of training for healthcare providers who treat patients with suspected or definite ACS within the first hours after onset of symptoms. These guidelines summarize key out-of-hospital, emergency department (ED), and related initial critical-care topics that are relevant to diagnosis and initial stabilization and are not intended to guide treatment beyond the ED. Emergency providers should use these contents to supplement other recommendations from the ACC/AHA Guidelines, which are used throughout the United States and Canada.1–3 As with any guidelines, these general recommendations must be considered within the context of local resources and their application to individual patients by knowledgeable healthcare providers. The healthcare providers managing the individual patients are best suited to determine the most appropriate treatment strategy. The primary goals of therapy for patients with ACS are to ● Reduce the amount of myocardial necrosis that occurs in patients with acute myocardial infarction (AMI), thus preserving left ventricular (LV) function, preventing heart failure, and limiting other cardiovascular complications ● Prevent major adverse cardiac events (MACE): death, nonfatal MI, and need for urgent revascularization ● Treat acute, life-threatening complications of ACS, such as ventricular fibrillation (VF), pulseless ventricular tachycardia (VT), unstable tachycardias, symptomatic bradycardias (See Part 8: “Advanced Cardiovascular Life Support”), pulmonary edema, cardiogenic shock and mechanical complications of AMI ● An overview of recommended care for the ACS patient is illustrated in Figure 1, the Acute Coronary Syndromes Algorithm. Part 10 provides details of the care highlighted in the numbered algorithm boxes; box numbers in the text correspond to the numbered boxes in the algorithm. In this part, the abbreviation “AMI” refers to acute myocardial infarction, whether associated with ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). The diagnosis and treatment of AMI, however, will often differ for patients with STEMI versus NSTEMI. Please note carefully which AMI type is being discussed.

ACADEMIC EMERGENCY MEDICINE 2010; 17:932–939 © 2010 by the Society for Academic Emergency Medicine Abstract 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.

Approximately 6 million patients are evaluated annually in US emergency departments for acute chest pain. The delineation of the presence or absence of acute coronary syndromes in these patients must be accurate and efficient in order to prevent missed diagnoses. Coronary computed tomography angiography has great promise as a tool to expedite the triage of patients with acute chest pain to early discharge or further inpatient diagnosis and treatment.

Measurable B-type natriuretic peptides (BNPs), which are largely produced by the left ventricle, include BNP and N-terminal prohormone BNP (NT-proBNP). These proteins are released by cardiomyocytes in response to wall tension and neurohumoral signals, and are established tools in the diagnosis and prognosis of heart failure (HF). We identified 32 articles for entry into evidence tables that presented original data on BNP and/or NT-proBNP in more than 100 patients with acute coronary syndromes (ACS) presenting with chest discomfort with or without dyspnea. Natriuretic peptide (NP) elevation was associated with older age, female sex, hypertension, diabetes, prior HF, prior ischemic heart disease, and reduced renal function. Clinical correlates of elevated blood NP levels included left main or 3-vessel coronary disease, lipid-rich plaques with large necrotic cores in proximal locations, large zones of myocardial ischemia or infarction, no-reflow and impaired perfusion after percutaneous intervention, reduced left ventricular ejection fraction, higher Killip classification, and the development of cardiogenic shock. All studies indicated that after adjustment for baseline predictors and clinical risk scores, elevated NP concentrations were independently predictive of the development of HF and all-cause mortality. In contrast, studies did not consistently demonstrate that NPs were predictive of myocardial infarction and rehospitalization for ACS. In addition to baseline measurement, there is consensus that repeat testing at 4 to 12 weeks and 6 to 12 months in follow-up is helpful in the anticipation of late cardiac sequelae and may assist in assessing prognosis and guiding management.

Brain damage initiated during global ischemia has been shown to be exacerbated by iron-dependent lipid peroxidation during early reperfusion. We hypothesized that other cellular components might be involved in similar free radical reactions. In this study we examined three brain protein fractions and ribosomal RNA for evidence of free radical damage during post-ischemic reperfusion. Global brain ischemia was induced by 20-min cardiac arrest. Dogs were divided into four groups: (1) non-ischemic controls; (2) 20-min cardiac arrest without reperfusion; (3) 20-min cardiac arrest and 2 h reperfusion; (4) 20-min cardiac arrest and 8 h reperfusion. Soluble proteins and proteins from ribosomes and synaptosomes were assayed by a dinitrophenylhydrazine method for carbonyl groups, which are characteristic products of protein peroxidation. The ribosomal RNA was also examined by electrophoresis. When proteins from each fraction were peroxidized in vitro by Fenton reagents, carbonyl content increased as [Fe2+] was increased from 0 to 100 microM. However, following reperfusion there was no significant accumulation of carbonyl content in either the soluble (ANOVA P = 0.92) or ribosome (P = 0.10) protein fractions. There was a significant decrease in the carbonyl content of the synaptosome protein fraction after 8 h of reperfusion (P = 0.03). Similarly, although ribosomal RNA fragmentation was observed in ethidium stained agarose gels following in vitro reaction with Fenton reagents, there was no evidence of ribosomal RNA fragmentation or cross-linking following reperfusion. These results suggest that reperfusion free radical reactions do not involve these cellular proteins or ribosomal RNA.

Background A modestly increased plasma B-type natriuretic peptide (BNP) level of greater than 80 pg/mL has been associated with increased mortality in patients with ST-segment elevation myocardial infarction (STEMI). However, the prognostic significance of larger increases in BNP during STEMI has not been reported. Methods A total of 420 patients with STEMI were identified from an administrative database, and 91 were found to have a BNP level measured within 24 hours of hospitalization. All patients underwent detailed angiographic and echocardiographic evaluation. Charts were abstracted in a blinded fashion to the BNP results. Results The mean ± SD age of the participants was 64 ± 13 years, and 53 (58%) of the participants were men. The median, 25th percentile, and 75th percentile of the BNP value were 366, 142, and 1011 pg/mL, respectively. The BNP level increased progressively in 1-, 2-, and 3-vessel coronary disease with medians of 253, 351, and 818 pg/mL, respectively ( P = .009). Patients with grade 3/4 diastolic dysfunction had significantly increased median BNP values vs all others, 786 vs 306 pg/mL ( P = .03). Eight (9%) patients died during their hospitalization. The median BNP values for 83 (91%) survivors and 8 (9%) nonsurvivors were 344 and 1420 pg/mL, respectively ( P = .007). By multiple logistic regression, BNP level more than 500 pg/mL was independently associated with female sex, increased number of vessels diseased (>75% stenosis), lower ejection fraction, higher creatine kinase level, and lower body mass index. Conclusion In patients with STEMI, markedly increased BNP level seems to reflect the extent of coronary disease, the degree of associated systolic and diastolic dysfunction, and a higher risk of in-hospital mortality.

Approximately 6 million patients are evaluated annually in United States emergency departments for acute chest pain (McCaig and Burt, National Hospital Ambulatory Medical Care Survey 2003. National Center for Health Statistics: Hyattsville, MD, 2005). Delineation of the presence or absence of an acute coronary syndrome must be accurate and efficient. The latest estimate is that 2% of patients with an acute coronary syndrome are inappropriately sent home from the emergency department (Pope et al. N Engl J Med 2000;342:1163–1170; Lee and Goldman, N Engl J Med 2000;342:1163–1170). These patients suffer higher morbidity than admitted patients. Missed ACS was the number one payout per case and that accounts for 41% of claims paid. So not surprisingly physicians do not want to miss ACS, resulting in an annual cost of US$10 to $13 billion to rule out ACS (McCaig and Burt, The National Hospital Ambulatory Medical Care Survey. Centers for Disease Control and Prevention’s National Center for Health Statistics, 2005).

Iron-mediated peroxidation of brain lipids is known to occur during reperfusion following cardiac arrest. Since in vitro damage to DNA is caused by similar iron-dependent peroxidation, we tested whether free radical damage to genomic DNA also develops during reperfusion following cardiac arrest and resuscitation. Genomic DNA was isolated from the cerebral cortex in (i) normal dogs, (ii)_dogs subjected to a 20-min cardiac arrest, and (iii)_dogs resuscitated from a 20-min cardiac arrest and then allowed to reperfuse for 2 or 8 h. DNA strand nicks were evaluated by in vitro labeling of newly created 3′ and 5′ termini. DNA base damage was evaluated utilizing with piperidine prior to labeling of 5′ termini. The 3t DNA termini were labeled before and after digestion with exonuclease III, and the 5′ DNA termini were labeled before and after treatment with piperidine. In vitro experiments with genomic DNA damaged by oxygen radicals verified that these labeling methods identified radical damage. In the experimental animal groups, terminal incorporation and electrophoretic mobility of brain nuclear DNA are not significantly changed either by 20 min of complete brain ischermia or during the first 8 h of reperfusion. We conclude that genomic DNA is not extensively damaged during cardiac arrest and early reperfusion, and therefore such DNA damage does not appear to be an important early aspect of the neurologic injury that accompanies cardiac arrest and resuscitation.

Coronary Computed Tomography Angiography (CCTA) is a diagnostic test shown to have a high negative predictive value for coronary artery disease and major cardiac events at three months. Many emergency department, (ED), protocols mandate serial enzymes prior to discharge to capture possible myocardial injury even with normal CCTAs. Determine the value of serial cardiac enzymes in low risk patients (TIMI Risk Score

James E Skinner1, Michael Meyer2, William C Dalsey3, Brian A Nester4, George Ramalanjaona5, Brian J O’Neil6, Antoinette Mangione7, Carol Terregino8, Abel Moreyra9, Daniel N Weiss10, Jerry M Anchin1, Una Geary11, Pamela Taggart121Vicor Technologies, Inc, Boca Raton, FL, USA; 2Max Planck Institute for Experimental Physiology, Goettingen, Germany; 3Kimbal Medical Center, Lakewood, NJ, USA; 4Lehigh Valley Hospital and Health Network, Allentown, PA, USA; 5St. Michaels Hospital, Newark, NJ, USA; 6William Beaumont Hospital, Royal Oak, MI, USA; 7Luitpolb Pharmaceuticals, Inc., Norristown, PA, USA; 8Cooper Medical Center, Camden, NJ, USA; 9Robert Wood Johnson Medical School, New Brunswick, NJ, USA; 10Florida Arrhythmia Consultants, Ft. Lauderdale, FL, USA; 11St. James Hospital, Dublin, Ireland; 12Albert Einstein Medical Center, Philadelphia, PA, USAAbstract: Heart rate variability (HRV) reflects both cardiac autonomic function and risk of sudden arrhythmic death (AD). Indices of HRV based on linear stochastic models are independent risk factors for AD in postmyocardial infarction (MI) cohorts. Indices based on nonlinear deterministic models have a higher sensitivity and specificity for predicting AD in retrospective data. A new nonlinear deterministic model, the automated Point Correlation Dimension (PD2i), was prospectively evaluated for prediction of AD. Patients were enrolled (N = 918) in 6 emergency departments (EDs) upon presentation with chest pain and being determined to be at risk of acute MI (AMI) >7%. Brief digital ECGs (>1000 heartbeats, ∼15 min) were recorded and automated PD2i results obtained. Out-of-hospital AD was determined by modified Hinkle-Thaler criteria. All-cause mortality at 1 year was 6.2%, with 3.5% being ADs. Of the AD fatalities, 34% were without previous history of MI or diagnosis of AMI. The PD2i prediction of AD had sensitivity = 96%, specificity = 85%, negative predictive value = 99%, and relative risk >24.2 (p ≤ 0.001). HRV analysis by the time-dependent nonlinear PD2i algorithm can accurately predict risk of AD in an ED cohort and may have both life-saving and resource-saving implications for individual risk assessment.Keywords: heart rate variability, sudden death, ventricular arrhythmias, chaos, non-linear

Summary. Backgound: Over-investigation of low-risk patients with suspected pulmonary embolism (PE) represents a growing problem. The combination of gestalt estimate of low suspicion for PE, together with the PE rule-out criteria [PERC()): age < 50 years, pulse < 100 beats min )1 ,S aO 2 ‡ 95%, no hemoptysis, no estrogen use, no surgery/trauma requiring hospitalization within 4 weeks, no prior venous thromboembolism (VTE), and no unilateral leg swelling], may reduce speculative testing for PE. We hypothesized that low suspicion and PERC()) would predict a post-test probability of VTE(+) or death below 2.0%. Methods: We enrolled outpatients with suspected PE in 13 emergency departments. Clinicians completed a 72-field, web-based data form at the time of test order. Low suspicion required a gestalt pretest probability estimate of

Study objective Point-of-care testing reduces time to cardiac marker results in patients evaluated for acute coronary syndromes, yet evidence this translates to a decreased length of stay is lacking. We hypothesized that point-of-care testing decreases length of stay in patients being evaluated for acute coronary syndromes in the emergency department (ED). Methods Patients being evaluated for possible acute coronary syndromes at 4 EDs in the United States were randomized to having point-of-care markers as well as central laboratory markers, or central laboratory markers only (laboratory arm). Point-of-care markers were obtained using early serial testing at presentation and at 90, 180, and 360 minutes as required by the treating physician. Evaluation, treatment, and disposition decisions were at the treating physician's discretion. Length of stay was from presentation to the time of departure from the ED, either to an inpatient setting or to home. Results There were 1,000 patients in each study arm. There were 520 patients discharged home from the ED. Median (interquartile range) time to discharge home was 4.6 hours (3.5 to 6.1 hours) in laboratory patients and 4.5 hours (3.5 to 6.1 hours) in point-of-care patients. Median (interquartile range) time to transfer to an inpatient setting for admitted patients was 5.5 hours (4.2 to 7.5 hours) in laboratory patients, and 5.4 hours (4.1 to 7.3 hours) in point-of-care patients. At one site, time to transfer to the floor was reduced in the point-of-care arm compared with the laboratory arm (difference in medians 0.45 hours; 95% confidence interval [CI] –0.14 to 1.04 hours). At one site, time to ED departure for discharged patients was higher in the point-of-care arm than the laboratory arm (difference in medians 1.25 hours; 95% CI 0.13 to 2.36 hours). Conclusion The effect of point-of-care testing on length of stay in the ED varies between settings. At one site, point-of-care testing decreased time to admission, whereas at another, point-of-care testing increased time to discharge. Potential effects of point-of-care testing on patient throughput should be considered in the full context of ED operations.

Hypothermia therapy improves neurological outcome following out-of-hospital cardiac arrest (OOHCA). Standard surface cooling (SC) with ice packs and cold water blankets is readily available, but is labor intensive and often overcools the patient. The Arctic Sun® (AS) surface cooling system uses enhanced energy transfer pads and close computer control of patient temperature (temp). The objective of this study was to compare the AS to SC for treatment of patients with OOHCA. We hypothesized that a greater proportion of patients treated using the AS would reach 34°C within 4 hours of starting cooling (primary outcome) and AS treated patients would be less likely to be out of target range (32–34°C) during 24 hours of cooling than patients treated with SC. This multicenter trial enrolled unresponsive, hemodynamically stable patients resuscitated from witnessed OOHCA of presumed cardiac cause, with any initial rhythm. After randomization, sedation and paralysis, cooling devices were set to a target temp of 33.5°C and core temperature was monitored continuously. Assuming that 60% of SC treated patients will reach 34°C within 4 hours, a sample size of 64 has 80%power (α = 0.05) to identify a 30% absolute increase in the primary outcome. Thirty-four AS and 30 SC subjects were enrolled; three (2 AS, 1 SC) were withdrawn prior to initiating cooling. Overall, 75% of AS patients vs. 55% of SC patients reached 34°C within 4 hours (95% CI of the increase -4% to 43%). The mean (SD) time to 34°C was 200 (78) min for the AS group and 275 (195) min for the SC group. While 28/29 SC patients had a recorded temp outside of range, only 9/32 AC patients were out of range (Relative Risk=3.4; 95% CI 2.0 to 6.0). The rates of serious adverse events during cooling were similar (13% AS, 22% SC; p=0.3). The rate of Cerebral Performance Category of 1 or 2 recorded at final follow-up was similar (47% AS, 34% SC, p=0.4). In conclusion, the AS and SC are both safe and effective for inducing hypothermia. The AS may cool more quickly, but a lower than expected primary outcome rate in both groups limited our power to evaluate the primary outcome difference. After reaching 34°, AS patients were less likely to be out of range. Long-term neurological outcome was good among these comatose survivors of cardiac arrest.

To prospectively evaluate the enhancement of coronary, pulmonary, and thoracic aortic vasculature by using biphasic single-acquisition 64-section computed tomographic (CT) angiography and to prospectively evaluate if differences in right side of the heart and coronary venous enhancement interfere with interpretation of coronary arteries.With internal review board approval and HIPAA compliance, 50 patients (16 men, 34 women; mean age, 51.5 years; range, 30-75 years) with atypical chest pain were referred from the emergency department and were imaged with a 64-section CT scanner after premedication with oral atenolol and/or intravenous metoprolol. Thoracic CT angiography with retrospective gating was subsequently performed with a single biphasic injection of 130 mL of iso-osmolar contrast material (100 mL at 5 mL/sec and 30 mL at 3 mL/sec) in caudal-to-cranial acquisition. Coronary, aortic, and pulmonary arterial attenuation values were obtained. Coronary venous and right atrial enhancement were evaluated to assess whether there was interference with coronary artery evaluation. A two-tailed Friedman test was used to evaluate differences among segments within each artery.Mean coronary arterial, pulmonary arterial, and aortic attenuation values were significantly higher than the 250-HU threshold (P.05). Mean pooled coronary arterial (288.9 HU +/- 64.8), pulmonary arterial (316.4 HU +/- 79.9), and aortic (329.9 HU +/- 63.3) attenuation values were significantly higher than the 250-HU threshold (P.0001). Coronary venous enhancement did not affect depiction or interpretation of coronary arteries. Right atrial streak artifact focally traversed the right coronary artery in only one study.The aforementioned thoracic CT angiographic protocol provides enhancement of coronary, aortic, and pulmonary vasculature in a single breath hold without interference from right side of the heart streak artifact or coronary venous enhancement.

Background Molecular mediators influencing the transition from acute to persistent musculoskeletal pain following common stress exposures such as motor vehicle collision (MVC) remain poorly understood. In this exploratory, proof of concept study, we compared circulating microRNA (miRNA) expression profiles in the early aftermath of MVC among individuals who did and did not subsequently develop persistent pain. Blood RNA samples were obtained from African American individuals (n = 53) who presented to the emergency department after MVC and were discharged to home after evaluation. The presence or absence of severe pain in the axial region, the most common and morbid region in which post-MVC pain occurs, was assessed 6 weeks following MVC via standardized questionnaire. miRNA expression was determined using miRNA-sequencing; nonparametric analyses were used to compare miRNA expression levels among individuals with and without persistent pain. Results Thirty-two mature miRNA were differentially expressed (p

[This corrects the article DOI: 10.1371/journal.pone.0127487.].

To compare the support for, and perceptions of, family-witnessed resuscitation (FWR) in urban and suburban emergency departments (ED).A convenience sample of ED personnel from two urban and two suburban midwestern hospitals in the United States were surveyed. Survey questions assessed respondents' opinions and experiences regarding the presence of family members during a resuscitation attempt. Data analysis was conducted using descriptive statistics, 95% confidence intervals (CI), and chi2 tests.There were 218 respondents to the survey (108 urban, 110 suburban) of which the majority (63.3%) were female, and a mean (S.D.) age of 36.9 (10.2). The majority [131 (60.1%)] were health care providers (i.e. physicians, nurses, and physician assistants) while the remainder included support staff (i.e. security, pastoral care, and social workers). Half (50.9%; 95% CI: 44.3-57.6) of all ED personnel felt it was appropriate for an escorted family member to be allowed to be present during a resuscitation attempt. However, ED personnel of urban settings were less likely to support FWR (38.9% urban versus 62.7% suburban; p0.001). Likewise, fewer urban than suburban personnel thought that the psychological impact of witnessing a failed resuscitation attempt would be beneficial for a family member (37.6% versus 61.7%; respectively, p = 0.001). Of note, a minority, yet substantial percentage of all ED personnel believed that the practice would increase the potential for malpractice litigation (28.7% urban versus 21.8% suburban; p = 0.242).Overall, there is divided support among ED personnel for FWR. The hospital setting appears to influence this support strongly, as well as the perceived benefit of FWR.

Intravenous phenytoin has come under increased scrutiny with the introduction of the prodrug, fosphenytoin. We evaluated adverse events and length-of-stay using parenteral the two drugs in routine emergency department use. Open-label randomization of phenytoin or fosphenytoin in 256 Emergency Department patients prescribed 279 parenteral doses of a phenytoin-equivalent. All phenytoin was administered intravenously, and fosphenytoin was given intravenously or intramuscularly (physician preference). Adverse events and Emergency Department length-of-stay were recorded; re-presentation to the Emergency Department within three months was reviewed for evidence of the purple glove syndrome. Nonparametric statistics were used to analyze the data. Seventy-seven patients received phenytoin and 202 fosphenytoin; 28 (10.0%) received intramuscular fosphenytoin. The mean phenytoin-equivalent dose was similar between the groups. Eighteen patients required reduction in infusion rates because of an adverse event (phenytoin = 6.5%, fosphenytoin = 6.4%; OR 0.9, 95% CI 0.4 2.6; p = 1.0). Adverse events occurred with similar frequency (phenytoin 9.1%, fosphenytoin 15.8%; OR 0.7, 95% CI 0.3 1.4; p = 0.3). The most common events were: pruritus, pain on infusion, and paresthesias. One patient developed hypotension (fosphenytoin); there were no other serious adverse events, including phlebitis. Median Emergency Department length-of-stay was 6.7 h for phenytoin and 5.7 h for fosphenytoin (p = 0.6). In routine Emergency Department use, our data do not support formulary conversion from phenytoin to fosphenytoin, based on the incidence of adverse events or Emergency Department length-of-stay.

The use of cardiac markers to identify high-risk patients in the observation unit is undeniable. As the literature reviewed here reveals, the history and ECG miss a significant portion of patients with acute cardiac ischemia. It appears that acute MI and some high-risk "unstable angina" observation unit patients can be identified within 6 hours of hospital presentation using a combination of cardiac markers. Testing these patients soon after symptom onset or on arrival in the ED for myoglobin, CK-MB subforms, or CK-MB delta appears to provide the best diagnostic usefulness. For testing later in the clinical course, CK-MB troponin I, or troponin T are of clear diagnostic and prognostic value. The markers currently used are unable to identify the significant subset of patients with "non-AMI" coronary syndromes, however. These patients require further testing with appropriate noninvasive or invasive diagnostic studies.

ContextA previous study suggested that the combination of a normal D-dimer assay and normal alveolar dead-space fraction is a highly sensitive screening test for pulmonary embolism (PE).ObjectiveTo determine if the combination of a normal alveolar dead-space fraction (volume of alveolar dead space/tidal volume ≤20%) and a normal whole-blood agglutination D-dimer assay can exclude PE in emergency department (ED) patients.DesignProspective, noninterventional study conducted in 1998-1999. Study data were obtained prior to standard testing for PE, consisting of radionuclide lung scanning or contrast-enhanced computed tomography and 6-month follow-up plus selective use of venous ultrasonography and pulmonary angiography. Imaging studies were interpreted by blinded observers.SettingSix urban teaching hospitals in the United States.PatientsA total of 380 hemodynamically stable ED patients aged 18 years or older with suspected acute PE.Main Outcome MeasuresSensitivity and specificity for PE with a positive test defined as having either alveolar dead-space fraction or D-dimer assay results abnormal. Alveolar dead-space fraction was determined by subtracting airway dead space from physiological dead space (determined using the modified Bohr equation) and D-dimer assay, assayed at bedside using 20 µL of arterial blood.ResultsPulmonary embolism was diagnosed in 64 patients (16.8%), of those 20 had an abnormal D-dimer assay result, 3 had an abnormal alveolar dead-space fraction, 40 had abnormal results in both, and 1 had normal results for both tests. The sensitivity for diagnosis of PE was 98.4% (95% confidence interval [CI], 91.6%-100.0%). Among the 316 patients without PE, both D-dimer and dead-space results were normal in 163, for a specificity of 51.6% (95% CI, 46.1%-57.1%). Posterior probability of PE with normal results on both tests was 0.75% (95% CI, 0%-3.4%).ConclusionIn this multicenter study of ED patients, a normal D-dimer assay result plus a normal alveolar dead-space fraction was associated with a low prevalence of PE.

Study objective: To determine if 15 min of open-chest cardiac massage (OC-CPR) versus closed-chest compressions (CC-CPR) improves 72-h survival and neurologic outcome (behavioral and histologic) after 5 min of untreated cardiac arrest. Methods: Mongrel dogs were anesthetized and instrumented. Cardiac arrest was induced by KCl injection and after a 5-min period of non-intervention, dogs were randomized to receive either CC-CPR (N = 7) or OC-CPR (N = 5) performed for 15 min. The dogs were then resuscitated and physiologic data was recorded. Surviving dogs were scored at 72 h using canine neurodeficit score of Safar et al. (NDS; 0 = behaviorally normal, 500 = brain death). Dogs that could not be resuscitated or died before 72 h were assigned a score of 500. Brain histology was performed on all survivors. Results: All OC-CPR dogs were successfully resuscitated and were behaviorally normal at 72 h (NDS = 0). Histology in OC-CPR dogs showed little to no injury. Only three out of the seven CC-CPR dogs survived to 72 h. Of the survivors, one dog exhibited minor ataxia (NDS = 15), and two had incapacitating deficits (both NDS = 180). Two dogs died within 24 h after extubation, and one could not be resuscitated and the other could not be weaned from the ventilator (each NDS = 500). Histology of the CC-CPR survivors revealed moderate to severe lesions. NDS between groups was statistically significant ( p < 0.0079). Conclusion: In our canine model of cardiac arrest, OC-CPR significantly improved 72-h survival and neurologic outcome when compared to CC-CPR.

These experiments examine the effects of arachidonate with respect to cell death, radical-mediated injury, Ca2+ mobilization, and formation of ser-51-phosphorylated eukaryotic initiation factor 2alpha [eIF2alpha(P)]. It is known that during brain ischemia the concentration of free arachidonate can reach 180 microM, and during reperfusion oxidative metabolism of arachidonate leads to generation of superoxide that can reduce stored ferric iron and promote lipid peroxidation. During early brain reperfusion, we have shown an approximately 20-fold increase in eIF2alpha(P) which maps to vulnerable neurons that display inhibition of protein synthesis. Here in neuronally differentiated NB-104 cells, equivalent cell death (assessed by LDH release) was induced by 40 microM arachidonate and 20 microM cumene hydroperoxide (CumOOH, a known alkoxyl radical generator). In these injury models (1) radical inhibitors (BHA, BHT, and the lipophilic iron chelator EMHP) block CumOOH-induced cell death but do not block arachidonate-induced death; (2) 40 microM arachidonate (but not up to 40 microM CumOOH) rapidly induces Ca2+ release from intracellular stores; (3) both 40 microM arachidonate and 20 microM CumOOH induce intense immunostaining for eIF2alpha(P); and (4) the elF2alpha(P) immunostaining induced by CumOOH but not that induced by arachidonate is completely blocked by anti-radical intervention with EMHP. Arachidonate-induced formation of eIF2alpha(P) and cell death do not require iron-mediated radical mechanisms and are associated with Ca2+ release from intracellular stores; however, radical-mediated injury also induces both eIF2alpha(P) and cell death without release of intracellular Ca2+. Our data link eIF2alpha(P) formation during brain reperfusion to two established injury mechanisms that may operate concurrently.

Animal research has provided important information about many aspects of the pathophysiol- ogy of human disease. Well-performed animal studies can determine the potential benefit of many proposed therapeutic interventions, and experimental results from animal studies have served as the basis for many landmark clinical trials. Many animal research models are described in the research literature, and choosing the appropriate model to answer a research question can be a daunting task. Even more chal- lenging is developing a new model when none of the existing systems are relevant to the proposed ques- tion. This article was prepared by members of the SAEM Research Committee to provide an overview of animal modeling. Important considerations in choos- ing, applying, and developing animal research models are outlined. Practical discussions of potential prob- lems with animal models are also provided. Key words: laboratory; animals; animal models; animal research. ACADEMIC EMERGENCY MEDICINE 1999; 6:75-82 A NIMAL models of acute disease have contrib- uted significantly to the advancement of sci- entific knowledge. Animal experimentation is typ- ically initiated prior to actual human investi- gation, and provides the background for human re- search. The strengths of animal modeling are the ability to control confounding variables and per- form extensive biochemical, biomechanical, and pathophysiologic assays. These techniques provide the foundation on which cause-and-effect associa- tions are built. The use of animal studies to study human dis- ease assumes that animal models adequately re- flect the pathophysiology of human disease and that the results obtained can be applied to hu- mans. These assumptions are not absolutely true, because animals do not respond exactly like hu- mans. However, well-designed animal studies still contribute to the basic knowledge of human dis- ease. There is no ideal animal species for modeling

The purpose of this study was to determine the impact on patient care and the cost effectiveness of testing for chlamydial infection in the emergency department. All patients tested for chlamydial infection in three emergency departments between October 1, 1993 and January 31, 1994 were retrospectively reviewed for charges and adequacy of therapy. In one hospital, the effectiveness of a call-back system to enhance proper therapy of inadequately treated patients was evaluated. Of 2,416 test results, 249 were positive, and 197 of these charts were available for review. All 16 male patients were treated appropriately at the initial visit; 105 of 181 female patients were inadequately treated at the initial visit. The charge to identify each patient inadequately treated was $981.22 ($103,000 for 105). Of the 28 inadequately treated patients receiving a follow-up call, 20 sought treatment. The high cost of testing patients cannot be justified without an adequate surveillance system to enhance proper follow-up treatment.