Pathogenesis and host control of gammaherpesviruses: lessons from the mouse.

Gammaherpesviruses are lymphotropic viruses that are associated with the development of lymphoproliferative diseases, lymphomas, as well as other nonlymphoid cancers. Most known gammaherpesviruses establish latency in B lymphocytes. Research on Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68/γHV68/MHV4) has revealed a complex relationship between virus latency and the stage of B cell differentiation. Available data support a model in which gammaherpesvirus infection drives B cell proliferation and differentiation. In general, the characterized gammaherpesviruses exhibit a very narrow host tropism, which has severely limited studies on the human gammaherpesviruses EBV and Kaposi's sarcoma-associated herpesvirus. As such, there has been significant interest in developing animal models in which the pathogenesis of gammaherpesviruses can be characterized. MHV68 represents a unique model to define the effects of chronic viral infection on the antiviral immune response.

Electroencephalography Measures are Useful for Identifying Large Acute Ischemic Stroke in the Emergency Department.

BACKGROUND: Early diagnosis of stroke optimizes reperfusion therapies, but behavioral measures have incomplete accuracy. Electroencephalogram (EEG) has high sensitivity for immediately detecting brain ischemia. This pilot study aimed to evaluate feasibility and utility of EEG for identifying patients with a large acute ischemic stroke during Emergency Department (ED) evaluation, as these data might be useful in the prehospital setting. METHODS: A 3-minute resting EEG was recorded using a dense-array (256-lead) system in patients with suspected acute stroke arriving at the ED of a US Comprehensive Stroke Center. RESULTS: An EEG was recorded in 24 subjects, 14 with acute cerebral ischemia (including 5 with large acute ischemic stroke) and 10 without acute cerebral ischemia. Median time from stroke onset to EEG was 6.6 hours; and from ED arrival to EEG, 1.9 hours. Delta band power (P = .004) and the alpha/delta frequency band ratio (P = .0006) each significantly distinguished patients with large acute ischemic stroke (n = 5) from all other patients with suspected stroke (n = 19), with the best diagnostic utility coming from contralesional hemisphere signals. Larger infarct volume correlated with higher EEG power in the alpha/delta frequency band ratio within both the ipsilesional (r = -0.64, P = .013) and the contralesional (r = -0.78, P = .001) hemispheres. CONCLUSIONS: Within hours of stroke onset, EEG measures (1) identify patients with large acute ischemic stroke and (2) correlate with infarct volume. These results suggest that EEG measures of brain function may be useful to improve diagnosis of large acute ischemic stroke in the ED, findings that might be useful to pre-hospital applications.

Thrombosis of Inferior Vena Cava Diagnosed Using Point-of-Care Ultrasound After Pediatric Near-Syncope.

BACKGROUND: Venous thromboembolism (VTE) is extremely rare but under recognized in the pediatric population. Although the literature on the use of ultrasound to detect VTEs in adults is plentiful, little has been documented on its use in the pediatric population. CASE REPORT: We present a case of a healthy 16-year-old female who presented to our emergency department with 3 months of dyspnea on exertion and one episode of near-syncope. Point-of-care cardiac ultrasound identified an inferior vena cava thrombosis. Subsequent computed tomography angiography diagnosed concurrent bilateral pulmonary emboli (PE). The patient's identical twin sister presented with similar symptoms shortly thereafter and was also diagnosed with VTE and bilateral PE. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case demonstrates an instance of VTE and pulmonary embolism in twin adolescent girls. Physical examination findings, electrocardiogram, chest x-ray study, and several previous evaluations did not reveal the diagnosis. Point of care ultrasound was used to correctly diagnosis VTE and for heightened concern for a pulmonary embolism.

Immune modulation during latent herpesvirus infection.

Nearly all human beings, by the time they reach adolescence, are infected with multiple herpesviruses. At any given time, this family of viruses accounts for 35-40 billion human infections worldwide, making herpesviruses among the most prevalent pathogens known to exist. Compared to most other viruses, herpesviruses are also unique in that infection lasts the life of the host. Remarkably, despite their prevalence and persistence, little is known about how these viruses interact with their hosts, especially during the clinically asymptomatic phase of infection referred to as latency. This review explores data in human and animal systems that reveal the ability of latent herpesviruses to modulate the immune response to self and environmental antigens. From the perspective of the host, there are both potentially detrimental and surprisingly beneficial effects of this lifelong interaction. The realization that latent herpesvirus infection modulates immune responses in asymptomatic hosts forces us to reconsider what constitutes a 'normal' immune system in a healthy individual.

Spinal Cord Injuries and Helicopter Emergency Medical Services, 6,929 Patients: A Multicenter Analysis.

OBJECTIVE: Traumatic spinal cord injury (SCI) impacts quality of life for patients and caregivers, generating lifetime costs in the millions. Previous studies show delayed treatment of SCI patients at specialized centers is linked to complicated outcomes and extended hospitalizations. This study characterizes helicopter emergency medical service (HEMS) use in SCI and develops a methodology to study large volumes of HEMS electronic medical record data from multiple providers. METHODS: This descriptive study used deidentified data of HEMS providers that use Golden Hour Data Systems, Inc (San Diego, CA) software service from 34 states in the United States from 2004 to 2011. Demographic and logistical data underwent a deidentification protocol developed specifically for this study before analysis. RESULTS: Six thousand nine hundred twenty-nine SCI patients were transported. HEMS use increased but decreased relative to total transports from 2004 to 2011. The average patient was 39 ± 21 years old, male, and had a 63-minute total transport time. The largest age bracket was 15 to 25 years. CONCLUSION: HEMS improved access for SCI patients to all localities and generally took under 2 hours. SCI patients are mostly young adult males, thus supporting the loss of years of productivity and also supporting the high lifetime cost for care for SCI. This study created a methodology for future multicenter aggregate data studies.

Type I interferon signaling enhances CD8+ T cell effector function and differentiation during murine gammaherpesvirus 68 infection.

UNLABELLED: CD8(+) T cell responses are critical to the control of replication and reactivation associated with gammaherpesvirus infection. Type I interferons (IFNs) have been shown to have direct and indirect roles in supporting CD8(+) T cell development and function during viral infection; however, the role of type I interferons during latent viral infection has not been examined. Mice deficient in type I IFN signaling (IFNAR1(-/-) mice) have high levels of reactivation during infection with murine gammaherpesvirus 68 (MHV68), a murine gammaherpesvirus model for Epstein-Barr virus. We hypothesized that type I IFNs function to enhance the anti-gammaherpesvirus CD8(+) T cell response. To test this, IFNAR1(-/-) mice were infected with MHV68 and the CD8(+) T cell response was analyzed. In the absence of type I IFN signaling, there was a marked increase in short-lived effector CD8(+) T cells, and MHV68-specific CD8(+) T cells had upregulated expression of PD-1 and reduced tumor necrosis factor alpha (TNF-α), gamma IFN (IFN-γ), and interleukin-2 (IL-2) production. Suppressing MHV68 replication early in infection using the antiviral cidofovir rescued CD8(+) T cell cytokine production and reduced PD-1 expression. However, suppressing high levels of reactivation in IFNAR1(-/-) mice failed to improve CD8(+) T cell cytokine production during latency. T cell-specific abrogation of type I IFN signaling showed that the effects of type I IFNs on the CD8(+) T cell response during MHV68 infection are independent of direct type I IFN signaling on T cells. Our findings support a model in which type I IFNs likely suppress MHV68 replication, thus limiting viral antigen and facilitating an effective gammaherpesvirus-directed CD8(+) T cell response. IMPORTANCE: The murine gammaherpesvirus MHV68 has both genetic and biologic homology to the human gammaherpesvirus Epstein-Barr virus (EBV), which infects over 90% of humans. Latent EBV infection and reactivation are associated with various life-threatening diseases and malignancies. Host suppression of gammaherpesvirus latency and reactivation requires both CD8(+) T cells as well as type I interferon signaling. Type I IFNs have been shown to critically support the antiviral CD8(+) T cell response in other virus models. Here, we identify an indirect role for type I IFN signaling in enhancing gammaherpesvirus-specific CD8(+) T cell cytokine production. Further, this function of type I IFN signaling can be partially rescued by suppressing viral replication during early MHV68 infection. Our data suggest that type I IFN signaling on non-T cells can enhance CD8(+) T cell function during gammaherpesvirus infection, potentially through suppression of MHV68 replication.

Gammaherpesvirus latency differentially impacts the generation of primary versus secondary memory CD8+ T cells during subsequent infection.

UNLABELLED: Unlike laboratory animals, humans are infected with multiple pathogens, including the highly prevalent herpesviruses. The purpose of these studies was to determine the effect of gammaherpesvirus latency on T cell number and differentiation during subsequent heterologous viral infections. Mice were first infected with murine gammaherpesvirus 68 (MHV68), a model of Epstein-Barr virus (EBV) infection, and then after latency was established, they were challenged with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV). The initial replication of LCMV was lower in latently infected mice, and the maturation of dendritic cells was abated. Although the number of LCMV-specific effector CD8(+) T cells was not altered, they were skewed to a memory phenotype. In contrast, LCMV-specific effector CD4(+) T cells were increased in latently infected mice compared to those in mice infected solely with LCMV. When the memory phase was reached, latently infected mice had an LCMV-specific memory T cell pool that was increased relative to that found in singly infected mice. Importantly, LCMV-specific memory CD8(+) T cells had decreased CD27 and increased killer cell lectin-like receptor G1 (KLRG1) expression. Upon secondary challenge, LCMV-specific secondary effector CD8(+) T cells expanded and cleared the infection. However, the LCMV-specific secondary memory CD8(+) T cell pool was decreased in latently infected animals, abrogating the boosting effect normally observed following rechallenge. Taken together, these results demonstrate that ongoing gammaherpesvirus latency affects the number and phenotype of primary versus secondary memory CD8(+) T cells during acute infection. IMPORTANCE: CD8(+) T cells are critical for the clearance of intracellular pathogens, including viruses, certain bacteria, and tumors. However, current models for memory CD8(+) T cell differentiation are derived from pathogen-free laboratory mice challenged with a single pathogen or vaccine vector. Unlike laboratory animals, all humans are infected with multiple acute and chronic pathogens, including the highly prevalent herpesviruses Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex viruses (HSV), and varicella-zoster virus (VZV). The purpose of these studies was to determine the effect of gammaherpesvirus latency on T cell number and differentiation during subsequent heterologous viral infections. We observed that ongoing gammaherpesvirus latency affects the number and phenotype of primary versus secondary memory CD8(+) T cells during acute infection. These results suggest that unlike pathogen-free laboratory mice, infection or immunization of latently infected humans may result in the generation of T cells with limited potential for long-term protection.

Stroke and Helicopter Emergency Medical Service Transports: An Analysis of 25,332 Patients.

OBJECTIVE: Helicopter emergency medical services (HEMS) are effective in time-sensitive illnesses, including stroke. Intravenous tissue plasminogen activator is beneficial for ischemic stroke within 4.5 hours of onset. This study analyzed the largest repository of US HEMS electronic medical record data characterizing demographic and logistical trends during stroke center accreditation. This study developed a methodology to aggregate, analyze, and report data from multiple providers. METHODS: This is a descriptive study of aggregate, deidentified data from 67 US providers from 2004 to 2011. Retrospective data including age, ethnicity, total transport time, mission type, and locality were analyzed. The effect of primary stroke center (PSC) designation was assessed for 2011. RESULTS: A total of 25,332 patients were transported for "stroke." Stroke increased from 1.4% to 3.9% during the study. Ninety-six percent of transports arrived at definitive care within 2 hours. Seventy-two percent of transports were "interfacility," and 58% were from "rural" or "super-rural" localities. Seventy-nine percent of 2011 transports were to PSCs. Ethnicity and age were significant barriers to transport to PSCs (P < .001). CONCLUSIONS: HEMS has increased access to stroke care for super-rural, rural, and urban communities offering timely transport within the treatment window if symptoms are recognized within 2.5 hours of onset. This study created a methodology for future multicenter aggregate data studies.

Physiologic field triage criteria for identifying seriously injured older adults.

OBJECTIVE: To evaluate the ability of out-of-hospital physiologic measures to predict serious injury for field triage purposes among older adults and potentially reduce the undertriage of seriously injured elders to non-trauma hospitals. METHODS: This was a retrospective cohort study involving injured adults 55 years and older transported by 94 emergency medical services (EMS) agencies to 122 hospitals (trauma and non-trauma) in 7 regions of the western United States from January 1, 2006 to December 31, 2008. We evaluated initial out-of-hospital Glasgow Coma Scale (GCS) score, systolic blood pressure (SBP), respiratory rate, heart rate, shock index (SBP ÷ heart rate), out-of-hospital procedures, mechanism of injury, and patient demographics. The primary outcome was "serious injury," defined as Injury Severity Score (ISS) ≥ 16, as a measure of trauma center need. We used multivariable regression models, fractional polynomials and binary recursive partitioning to evaluate appropriate physiologic cut-points and the value of different physiologic triage criteria. RESULTS: A total of 44,890 injured older adults were evaluated and transported by EMS, of whom 2,328 (5.2%) had ISS ≥ 16. Nonlinear associations existed between all physiologic measures and ISS ≥ 16 (unadjusted and adjusted p ≤ 0.001 for all,), except for heart rate (adjusted p = 0.48). Revised physiologic triage criteria included GCS score ≤ 14; respiratory rate < 10 or > 24 breaths per minute or assisted ventilation; and SBP < 110 or > 200 mmHg. Compared to current triage practices, the revised criteria would increase triage sensitivity from 78.6 to 86.3% (difference 7.7%, 95% CI 6.1-9.6%), reduce specificity from 75.5 to 60.7% (difference 14.8%, 95% CI 14.3-15.3%), and increase the proportion of patients without serious injuries transported to major trauma centers by 60%. CONCLUSIONS: Existing out-of-hospital physiologic triage criteria could be revised to better identify seriously injured older adults at the expense of increasing overtriage to major trauma centers.

A gammaherpesvirus cooperates with interferon-alpha/beta-induced IRF2 to halt viral replication, control reactivation, and minimize host lethality.

The gammaherpesviruses, including Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), establish latency in memory B lymphocytes and promote lymphoproliferative disease in immunocompromised individuals. The precise immune mechanisms that prevent gammaherpesvirus reactivation and tumorigenesis are poorly defined. Murine gammaherpesvirus 68 (MHV68) is closely related to EBV and KSHV, and type I (alpha/beta) interferons (IFNαß) regulate MHV68 reactivation from both B cells and macrophages by unknown mechanisms. Here we demonstrate that IFNß is highly upregulated during latent infection, in the absence of detectable MHV68 replication. We identify an interferon-stimulated response element (ISRE) in the MHV68 M2 gene promoter that is bound by the IFNαß-induced transcriptional repressor IRF2 during latency in vivo. The M2 protein regulates B cell signaling to promote establishment of latency and reactivation. Virus lacking the M2 ISRE (ISREΔ) overexpresses M2 mRNA and displays uncontrolled acute replication in vivo, higher latent viral load, and aberrantly high reactivation from latency. These phenotypes of the ISREΔ mutant are B-cell-specific, require IRF2, and correlate with a significant increase in virulence in a model of acute viral pneumonia. We therefore identify a mechanism by which a gammaherpesvirus subverts host IFNαß signaling in a surprisingly cooperative manner, to directly repress viral replication and reactivation and enforce latency, thereby minimizing acute host disease. Since we find ISREs 5' to the major lymphocyte latency genes of multiple rodent, primate, and human gammaherpesviruses, we propose that cooperative subversion of IFNαß-induced IRFs to promote latent infection is an ancient strategy that ensures a stable, minimally-pathogenic virus-host relationship.

Herpesvirus latency confers symbiotic protection from bacterial infection.

All humans become infected with multiple herpesviruses during childhood. After clearance of acute infection, herpesviruses enter a dormant state known as latency. Latency persists for the life of the host and is presumed to be parasitic, as it leaves the individual at risk for subsequent viral reactivation and disease. Here we show that herpesvirus latency also confers a surprising benefit to the host. Mice latently infected with either murine gammaherpesvirus 68 or murine cytomegalovirus, which are genetically highly similar to the human pathogens Epstein-Barr virus and human cytomegalovirus, respectively, are resistant to infection with the bacterial pathogens Listeria monocytogenes and Yersinia pestis. Latency-induced protection is not antigen specific but involves prolonged production of the antiviral cytokine interferon-gamma and systemic activation of macrophages. Latency thereby upregulates the basal activation state of innate immunity against subsequent infections. We speculate that herpesvirus latency may also sculpt the immune response to self and environmental antigens through establishment of a polarized cytokine environment. Thus, whereas the immune evasion capabilities and lifelong persistence of herpesviruses are commonly viewed as solely pathogenic, our data suggest that latency is a symbiotic relationship with immune benefits for the host.

Variation in prehospital use and uptake of the national Field Triage Decision Scheme.

BACKGROUND: The Field Triage Decision Scheme is a national guideline that has been implemented widely for prehospital emergency medical services (EMS) and trauma systems. However, little is known about the uptake, modification, or variation in field application of triage criteria between trauma systems. OBJECTIVE: To describe and compare the use of field triage criteria by EMS personnel in six regions, including the timing of guideline uptake and the use of nonguideline criteria. METHODS: This was a retrospective cohort study of injured children and adults transported by 48 EMS agencies to 105 hospitals (trauma centers and non-trauma centers) in six Western U.S. regions from 2006 through 2008. We used probabilistic linkage to match patient-level prehospital information from multiple sources, including EMS records, base-hospital phone communication records, and trauma registry data files. Triage criteria were evaluated individually and grouped by "steps" (physiologic, anatomic, mechanism, and special considerations). We used descriptive statistics to compare the frequency of triage criteria use (overall and between regions) and to evaluate the timing of guideline uptake across multiple versions of the guidelines. RESULTS: A total of 260,027 injured patients were evaluated and transported by EMS over the three-year study period, of whom 46,414 (18%) met at least one field triage criterion and formed the primary sample for analysis. The three most common criteria cited (of 33 in use) were EMS provider judgment (26%), age <5 or >55 years (10%), and Glasgow Coma Scale (GCS) score <14 (9%). Of the 33 criteria in use, five (15%) were previously retired from the guidelines and seven (21%) were never included in the guidelines. 11,048 (24%) patients had more than one criterion applied (range 1-21). There was large variation in the type and frequency of criteria used between systems, particularly among the nonphysiologic triage steps. Only one of six regions had translated the most recent guidelines into field use within two years after release. CONCLUSION: There is large variation between regions in the frequency and type of field triage criteria used. Field uptake of guideline revisions appears to be slow and variable, suggesting opportunities for improvement in dissemination and implementation of updated guidelines.

Emergency Medicine resident anesthesia training in a private vs. academic setting.

BACKGROUND: Airway management is an essential part of any Emergency Medicine (EM) training program. Academic centers typically provide training to many learners at various training levels in a number of medical specialties during anesthesiology rotations. This potentially creates competition for intubation procedures that may negatively impact individual experiences. OBJECTIVES: We hypothesized that residents would report higher numbers of intubations and improved educational value in a private practice, rather than an academic, anesthesiology rotation. METHODS: EM residents' anesthesiology training was evaluated pre and post a change in training setting from an academic institution to a private practice institution. Outcome measures included the number of self-reported intubations, resident ratings of the rotation, and the number of positive comments. Residents' evaluation was measured with: a 14-item evaluation; subjective comments, which two blinded reviewers rated as positive, negative, or neutral; and transcripts from structured interviews to identify themes related to training settings. RESULTS: The number of intubations increased significantly in the private practice setting (4.6 intubations/day vs. 1.5 intubations/day, p < 0.001). Resident evaluations improved significantly with the private practice experience (mean scores of 3.83 vs. 2.23, p-values <0.05). Residents' impressions were also significantly higher for the private practice setting with respect to increased educational value, greater use of adjunct airway devices, and directed teaching. CONCLUSIONS: Number of intubations performed and residents' rating of the educational value were more favorable for a private practice anesthesiology rotation. Alternative settings may provide benefit for training in areas that have competition among trainees.

Production of rAAV by plasmid transfection induces antiviral and inflammatory responses in suspension HEK293 cells.

Recombinant adeno-associated virus (rAAV) is a clinically proven viral vector for delivery of therapeutic genes to treat rare diseases. Improving rAAV manufacturing productivity and vector quality is necessary to meet clinical and commercial demand. These goals will require an improved understanding of the cellular response to rAAV production, which is poorly defined. We interrogated the kinetic transcriptional response of HEK293 cells to rAAV production following transient plasmid transfection, under manufacturing-relevant conditions, using RNA-seq. Time-series analyses identified a robust cellular response to transfection and rAAV production, with 1,850 transcripts differentially expressed. Gene Ontology analysis determined upregulated pathways, including inflammatory and antiviral responses, with several interferon-stimulated cytokines and chemokines being upregulated at the protein level. Literature-based pathway prediction implicated multiple pathogen pattern sensors and signal transducers in up-regulation of inflammatory and antiviral responses in response to transfection and rAAV replication. Systematic analysis of the cellular transcriptional response to rAAV production indicates that host cells actively sense vector manufacture as an infectious insult. This dataset may therefore illuminate genes and pathways that influence rAAV production, thereby enabling the rational design of next-generation manufacturing platforms to support safe, effective, and affordable AAV-based gene therapies.

GlideScope versus flexible fiber optic for awake upright laryngoscopy.

STUDY OBJECTIVES: We compare laryngoscopic quality and time to highest-grade view between a face-to-face approach with the GlideScope and traditional flexible fiber-optic laryngoscopy in awake, upright volunteers. METHODS: This was a prospective, randomized, crossover study in which we performed awake laryngoscopy under local anesthesia on 23 healthy volunteers, using both a GlideScope video laryngoscopy face-to-face technique with the blade held upside down and flexible fiber-optic laryngoscopy. Operator reports of Cormack-Lehane laryngoscopic views and video-reviewed time to highest-grade view, as well as number of attempts, were recorded. RESULTS: Ten women and 13 men participated. A grade II or better view was obtained with GlideScope video laryngoscopy in 22 of 23 (95.6%) participants and in 23 of 23 (100%) participants with flexible fiber-optic laryngoscopy (relative risk GlideScope video laryngoscopy versus flexible fiber-optic laryngoscopy 0.96; 95% confidence interval 0.88 to 1.04). Median time to highest-grade view for GlideScope video laryngoscopy was 16 seconds (interquartile range 9 to 34) versus 51 seconds (interquartile range 35 to 96) for flexible fiber-optic laryngoscopy. A distribution of interindividual differences demonstrated that GlideScope video laryngoscopy was, on average, 39 seconds faster than flexible fiber-optic laryngoscopy (95% confidence interval 0.2 to 76.9 seconds). CONCLUSION: GlideScope video laryngoscopy can be used to obtain a Cormack-Lehane grade II or better view in the majority of awake, healthy volunteers when an upright face-to-face approach is used and was slightly faster than traditional flexible fiber-optic laryngoscopy. However, flexible fiber-optic laryngoscopy may be more reliable at obtaining high-grade views of the larynx. Awake, face-to-face GlideScope use may offer an alternative approach to the difficulty airway, particularly among providers uncomfortable with flexible fiber-optic laryngoscopy.

Evaluating age in the field triage of injured persons.

STUDY OBJECTIVE: We evaluate trauma undertriage by age group, the association between age and serious injury after accounting for other field triage criteria and confounders, and the potential effect of a mandatory age triage criterion for field triage. METHODS: This was a retrospective cohort study of injured children and adults transported by 48 emergency medical services (EMS) agencies to 105 hospitals in 6 regions of the western United States from 2006 through 2008. We used probabilistic linkage to match EMS records to hospital records, including trauma registries, state discharge databases, and emergency department databases. The primary outcome measure was serious injury, as measured by an Injury Severity Score greater than or equal to 16. We assessed undertriage (Injury Severity Score ≥16 and triage-negative or transport to a nontrauma center) by age decile and used multivariable logistic regression models to estimate the association (linear and nonlinear) between age and Injury Severity Score greater than or equal to 16, adjusted for important confounders. We also evaluated the potential influence of age on triage efficiency and trauma center volume. RESULTS: Injured patients (260,027) were evaluated and transported by EMS during the 3-year study period. Undertriage increased for patients older than 60 years, reaching approximately 60% for those older than 90 years. There was a strong nonlinear association between age and Injury Severity Score greater than or equal to 16. For patients not meeting other triage criteria, the probability of serious injury was most notable after 60 years. A mandatory age triage criterion would have decreased undertriage at the expense of overtriage, with 1 patient with Injury Severity Score greater than or equal to 16 identified for every 60 to 65 additional patients transported to major trauma centers. CONCLUSION: Trauma undertriage increases in patients older than 60 years. Although the probability of serious injury increases among triage-negative patients with increasing age, the use of a mandatory age triage criterion appears inefficient for improving field triage.

Prospective evaluation of an ED observation unit protocol for trauma activation patients.

BACKGROUND: The University of Utah emergency department (ED) observation unit (EDOU) cares for over 2500 patients each year, with a significant portion of these patients being trauma activation patients. We evaluated the safety and efficacy of our EDOU trauma protocol and described patient characteristics and outcomes of trauma patients managed in an EDOU. METHODS: We performed a prospective observational study of all trauma patients admitted to the EDOU over a 1-year period. Patient disposition, interventions, and adverse events during observation were recorded. Thirty-day follow-up was performed by telephone and chart review to evaluate for missed injuries, repeat hospitalizations, or repeat traumatic events. RESULTS: A total of 259 trauma patients were admitted to the EDOU during the study period and were contacted at least 30 days after discharge. There were no deaths, intubations, or other adverse events. At 30-day follow-up, there was 1 missed injury, which did not result in an adverse outcome. Ten patients were reevaluated in the ED or required hospitalization for events occurring after their initial EDOU stay but related to their initial trauma evaluation. The inpatient admission rate from the EDOU was 10.4%, and 3.1% of patients reported another traumatic event during the 30-day follow-up period. CONCLUSIONS: There were no adverse outcomes in trauma patients admitted to the EDOU, and our inpatient admission rate was within the generally accepted admission rate for patients in observation status. The EDOU appears to be a safe alternative to inpatient admission for the evaluation of minimally injured trauma activation patients.

Characteristics of the first two years of applicants to a new emergency medicine residency program.

BACKGROUND: To the best of our knowledge, no study has compared the effect of using the Electronic Residency Application Service (ERAS) on applicant pool characteristics for a new emergency medicine (EM) residency program. OBJECTIVE: We sought to compare applicants in an EM residency program's first year, in which the ERAS is not typically used, to applicants in year 2 (using ERAS). METHODS: We reviewed the applications to the new University of Utah EM residency program for the entering classes of 2005 (year 1) and 2006 (year 2). RESULTS: In total, 130 and 458 prospective residents applied during year 1 and year 2, respectively. Applicants using and not using ERAS were similar in average Step 1 score (211.8 vs. 212.4, respectively; p = 0.791), previously failed Step 1 or Step 2 attempt (12.1% vs. 11.0%, respectively; p = 0.729), previous failure to match in a residency program (8.6% vs. 4.6%, respectively; p = 0.083), previous residency training (18.8% vs. 14.9%, respectively; p = 0.288), and the percent who had completed an EM clerkship (95.3% vs. 93.0%, respectively; p = 0.342). Applicants not using ERAS were more likely to have been remediated in medical school (13.2% vs. 4.2%; p < 0.001) and to have a Standardized Letter of Recommendation (SLOR) (87% vs. 78%; p = 0.024). Applicants using ERAS were more likely to have a SLOR match estimate of "very competitive" (38.2% vs. 54.1%; p = 0.004). Applicants were similar in having attended a "top tier" medical school (44.5% vs. 41.3%, p = 0.508). CONCLUSION: Despite significantly fewer applicants, those applying without the use of ERAS to a new EM residency program were generally comparable to the applicant pool that did permit the use of ERAS. The larger number of applicants the second year likely reflects the use of ERAS.

EDOU staffing by PAs: what are the effects on patient outcomes?

OBJECTIVE: An emergency department observation unit (EDOU) opened in April 2006 staffed by physician assistants (PAs) and nurse practitioners (NPs). This study describes the complexity and outcomes of the EDOU patients to determine the effectiveness of staffing by PAs. METHODS: A retrospective chart review was performed of chest pain and trauma patients in the EDOU from April 2006 through May 2007. Patient characteristics, length of stay (LOS), and admission rates were recorded. Adverse events were monitored, and trauma patients were followed for 30 days to evaluate for missed injuries. RESULTS: 531 chest pain patients and 364 trauma patients were admitted to the EDOU during the study period. Average chest pain patient LOS was 14 hours and 32 minutes, and 12.2% of patients were admitted from the EDOU to an inpatient unit. For trauma patients, average LOS was 12 hours and 46 minutes, and 11.5% of patients were admitted to an inpatient unit. There were no deaths, intubations, or loss of vital signs. In 30-day follow-up, there were no significant missed injuries among trauma patients. CONCLUSION: PAs effectively cared for patients of moderate complexity in the two largest groups of utilizers of the EDOU.

Air ambulance transport times and advanced cardiac life support interventions during the interfacility transfer of patients with acute ST-segment elevation myocardial infarction.

OBJECTIVES: To characterize transport times for the interfacility air ambulance transport of patients with acute ST-segment elevation myocardial infarction (STEMI), to estimate the proportion of patients at risk of in-transport clinical decompensation, and to explore associated risk factors for such. METHODS: The electronic medical records of 35 air ambulance programs in the United States from December 2003 through December 2008 were reviewed. We defined clinical decompensation during transport as the combined outcome of either cardiopulmonary arrest or the receipt of any of a prespecified set of advanced life support (ALS) interventions. Multiple logistic regression employing generalized estimating equations to model autocorrelation of measures within air ambulance programs was used to explore the relationship between time from dispatch to transport and the outcome of interest. RESULTS: Three thousand seven hundred sixty-seven transports of STEMI patients were identified during the period of interest. Eighty-five percent of rotor wing transports (median 80 minutes, interquartile range [IQR] 66-104) and 7% of fixed-wing transports (median 162 minutes, IQR 142-210) attained a total transfer time of < or = 2 hours. Clinical decompensation in transport occurred in 182 of 3,767 (4.8%, 95% confidence interval [CI] 4.2-5.6%) transports. The most frequent critical ALS interventions were the administration of antiarrhythmics and the initiation of vasopressors. The odds ratios (ORs) for clinical decompensation comparing higher pretransport time quartiles with the lowest quartile (i.e., Q1: 6-50 minutes) were as follows: Q4: 82-1,500 minutes, OR 2.5 (95% CI 1.3-4.8, p = 0.007); Q3: 64-81 minutes, OR 1.9 (95% CI 1.0-3.6, p = 0.0499); and Q2: 51-63 minutes, OR 1.45 (95% CI 0.7-3.1, p = 0.34). Cardiac arrest or need for an ALS intervention prior to transport and a history of diabetes were also predictive of the outcome of interest. CONCLUSIONS: The majority of interfacility rotor-wing air ambulance transfers of patients with STEMI achieved a total transfer time of < or = 2 hours. Clinical decompensation requiring ALS treatment occurred in a small percentage of patients. Diabetes, prior arrest or decompensation, and delays to transport were associated with clinical decompensation in the air. Efforts to reduce delays to transport may reduce this risk in transported patients.