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Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome. Understanding of the complex pathways involved in lung injury pathogenesis, resolution, and repair has grown considerably in recent decades. Nevertheless, to date, only therapies targeting ventilation-induced lung injury have consistently proven beneficial, and despite these gains, ARDS morbidity and mortality remain high. Many candidate therapies with promise in preclinical studies have been ineffective in human trials, probably at least in part due to clinical and biological heterogeneity that modifies treatment responsiveness in human ARDS. A precision medicine approach to ARDS seeks to better account for this heterogeneity by matching therapies to subgroups of patients that are anticipated to be most likely to benefit, which initially might be identified in part by assessing for heterogeneity of treatment effect in clinical trials. In October 2019, the US National Heart, Lung, and Blood Institute convened a workshop of multidisciplinary experts to explore research opportunities and challenges for accelerating precision medicine in ARDS. Topics of discussion included the rationale and challenges for a precision medicine approach in ARDS, the roles of preclinical ARDS models in precision medicine, essential features of cohort studies to advance precision medicine, and novel approaches to clinical trials to support development and validation of a precision medicine strategy. In this Position Paper, we summarise workshop discussions, recommendations, and unresolved questions for advancing precision medicine in ARDS. Although the workshop took place before the COVID-19 pandemic began, the pandemic has highlighted the urgent need for precision therapies for ARDS as the global scientific community grapples with many of the key concepts, innovations, and challenges discussed at this workshop.

Background: Antivirals are infrequently prescribed in primary care for influenza-like-illness (ILI), mostly because of perceived ineffectiveness in real world primary care, and as individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with ILI reduces time to recovery overall and in key subgroups. Methods: We conducted an open-label, pragmatic, randomized controlled trial of adding oseltamivir to usual care in patients aged one year and older consulting with ILI in primary care. The primary endpoint was time to recovery (return to usual activities, with fever, head- and muscle-ache minor/absent), following a Bayesian piece-wise exponential model. Baseline nasopharyngeal swabs were analyzed after study completion. Findings: We ascertained the primary outcome for 3059 of the 3266 participants recruited in 15 European countries during three seasonal influenza seasons (2015-2018); 52.0% (1590/3059) had PCR-confirmed influenza infection. Time to recovery was shorter in those given oseltamivir by 1.02 days (95% Bayesian CI: 0.73-1.32). Hazard ratios of proportional benefit were similar across pre-specified subgroups; absolute benefit in time to recovery varied, with an estimated benefit of >2 days in older patients, more severe illness, comorbidity, or longer prior illness duration. The effect was independent of influenza status. Fewer antibiotics were prescribed in the oseltamivir arm (9.3% vs 13.2%, mean difference 4.0; 95% CI: 1.7-6.3), while nausea and/or vomiting was shorter in usual care patients (HR 0.92; 95% CI: 0.85-1.00). Interpretation: Primary care patients with ILI treated with oseltamivir recovered sooner than those managed by usual care alone, irrespective of influenza virus test results. Older, sicker, patients with comorbidities and longer prior illness duration showed greater absolute benefit. Trial Registration: The trial is registered with the ISRCTN Registry, number ISRCTN27908921. Funding Statement: CB reports receiving advisory board fees from Roche Molecular Systems and grant support from Roche Molecular Diagnostics; CB was supported by funding from an NIHR Protection Research Unit on Health Care Associated Infections and Antimicrobial Resistance, by the NIHR MedTech and In Vitro Diagnostics Co-Operative at Oxford NHS Foundation Trust, and by an NIHR Senior Investigator Award. TV is PI in a project that is funded by Innovative Medicines Initiative (IMI) of the European Union, in which Janssen Pharmaceutica is a partner and researcher in another IMI project in which Biocartis, Janssen, Biomerieux and Berry Consultants are partners. In addition he is co PI of a NIHR funded RCT, and PI in several studies funded by the Netherlands Organization of Health Research and Development. CL has received advisory boards fees from MSD and grant support from GILEAD, Global Bridges, Servier, Galenica-Olvos. Declaration of Interests: CB reports receiving advisory board fees from Roche Molecular Systems and grant support from Roche Molecular Diagnostics; CB was supported by funding from an NIHR Protection Research Unit on Health Care Associated Infections and Antimicrobial Resistance, by the NIHR MedTech and In Vitro Diagnostics Co-Operative at Oxford NHS Foundation Trust, and by an NIHR Senior Investigator Award. TV is PI in a project that is funded by Innovative Medicines Initiative (IMI) of the European Union, in which Janssen Pharmaceutica is a partner and researcher in another IMI project in which Biocartis, Janssen, Biomerieux and Berry Consultants are partners. In addition he is co PI of a NIHR funded RCT, and PI in several studies funded by the Netherlands Organization of Health Research and Development. CL has received advisory boards fees from MSD and grant support from GILEAD, Global Bridges, Servier, Galenica-Olvos. All other authors declare no conflict of interest. Ethics Approval Statement: All participating countries gained national research ethics committees and CTA approval as required. Ethics Ref: 15/SC/0138.

Introduction The Pediatric Assessment Triangle (PAT) is a rapid evaluation tool that establishes a child's clinical status and his or her category of illness to direct initial management priorities. Recently the PAT has been incorporated widely into the pediatric resuscitation curriculum. Although intuitive, its performance characteristics have yet to be quantified. The purpose of this research is to determine quantitatively its accuracy, reliability, and validity as applied by nurses at triage. Methods In this prospective observational study, triage nurses performed the PAT on all patients presenting to the pediatric emergency department of an urban teaching hospital. Researchers performed blinded chart review using the physician's initial assessment and final diagnosis as the criterion standard for comparison. Results A total of 528 children were included in the analysis. Likelihood ratios (LRs) were found for instability and category of pathophysiology using the PAT. Children deemed stable by initial PAT were almost 10 times more likely to be stable on further assessment (LR 0.12, 95% confidence interval [CI] 0.06-0.25). The PAT further specified categories of pathophysiology: respiratory distress (LR+ 4, 95% CI 3.1-4.8), respiratory failure (LR+ 12, 95% CI 4.0-37), shock (LR+ 4.2, 95% CI 3.1-5.6), central nervous system/metabolic disorder (LR+ 7, 95% CI 4.3-11), and cardiopulmonary failure (LR+ 49, 95% CI 20-120). Discussion The structured assessment of the initial PAT, as performed by nurses in triage, readily and reliably identifies high-acuity pediatric patients and their category of pathophysiology. The PAT is highly predictive of the child's clinical status on further evaluation.

From the Department of Emergency Medicine, Harbor–UCLA Medical Center, Torrance, CA; theDavid Geffen School of Medicine at UCLA, Los Angeles, CA; and the Los Angeles BiomedicalResearch Institute, Torrance, CA.0196-0644/$-see front matterCopyright © 2010 by the American College of Emergency Physicians.doi:10.1016/j.annemergmed.2010.01.024

Los objetivos del presente estudio fueron determinar si podrian satisfacerse las guias de la National Kidney Foundation para la colocacion de una fistula arteriovenosa (FAV) nativa (como minimo un 50% de todos los nuevos pacientes con insuficiencia renal terminal [IRT] y el 40% de pacientes en hemodialisis prevalente) en la poblacion desatendida que se presenta en estadios avanzados de IRT. Tambien tratamos de determinar las tasas de permeabilidad de la FAV al ano y los factores asociados con trombosis inmediata. Durante el periodo 2003-2005 176 pacientes con una edad media de 51 anos se sometieron a cirugia de abordaje para hemodialisis. El 62% eran hombres y el 48% presentaban diabetes mellitus. Solo se efectuo un mapeo venoso ecografico en el 37%. Debido a su presentacion tardia, en 109 pacientes (62%) fue necesario un abordaje venoso central temporal. De los 160 pacientes que se sometieron a la creacion de un acceso vascular por primera vez, 137 (86%) recibieron una FAV nativa y en 23 (14%) se implanto una protesis arteriovenosa. En hombres se puso de relieve una mayor tasa de creacion de FAV (91% comparado con 75% para mujeres, p = 0,005). La permeabilidad primaria al ano fue del 90%. No se detectaron diferencias en las tasas de trombosis inmediata o permeabilidad al ano con respecto al sexo, edad, etnicidad, tipo de seguro medico, presencia de abordaje temporal o uso de mapeo venoso preoperatorio. En una poblacion desatendida, las guias de la NKF para un acceso vascular por primera vez con FAV nativa han quedado superadas con una excelente permeabilidad al ano, a pesar de la presentacion tardia.

The aims of this study were to determine whether National Kidney Foundation (NKF) guidelines for native arteriovenous fistula (AVF) creation (at least 50% of all new end-stage renal disease [ESRD] patients and 40% of prevalent hemodialysis patients) could be met in an underserved population who presented in late stages of ESRD. We also sought to determine 1-year AVF patency rates and factors associated with early thrombosis. One hundred seventy-six patients underwent hemodialysis access surgery during the period 2003-2005 with a mean age of 51 years. Sixty-two percent were male, and 48% had diabetes mellitus. Ultrasound vein mapping was performed in only 37%. Temporary central venous access was necessary in 109 patients (62%) due to late presentation. Of the 160 patients who were first-time access, 137 (86%) received a native AVF and 23 (14%) had an arteriovenous graft. There was a higher rate of AVF creation in males (91% vs. 75% for females, p = 0.005). The 1-year primary patency was 90%. There were no differences in early thrombosis or 1-year patency rates with respect to gender, age, ethnicity, insurance status, presence of temporary access, or use of preoperative vein mapping. In an underserved population, NKF guidelines for native AVF for first-time access can be superseded with an excellent 1-year patency, despite late presentation.

Le but de ce travail etait de determiner si les recommandations de la National Kidney Foundation (NKF) pour la creation de fistule arterio-veineuse (FAV) native (au moins 50% de tous les malades en insuffisance renale terminale (IRT) et 40% des malades hemodialyses) pouvaient etre observees dans une population de malades defavorises se presentant a des stades tardifs de l'IRC. Nous avons egalement cherche a determiner la permeabilite a un an des FAV et les facteurs associes a la thrombose precoce. Cent soixante-seize malades ont eu un acces pour hemodialyse au cours de la periode 2003-2005, avec un âge moyen de 51 ans. Soixante-deux pour cent etaient de sexe masculin et 48% etaient diabetiques. Une cartographie veineuse par echographie n'a ete realisee que chez 37% des malades. Un acces veineux central temporaire a ete necessaire chez 109 malades (62%) en raison d'une presentation tardive. Parmi les 160 malades ayant un premier acces, 137 (86%) ont eu une FAV native et 23 (14%) un pontage arterio-veineux. Il y a eu un taux plus eleve de creation de FAV chez les hommes (91% versus 75% chez les femmes, p = 0,005). Le taux de permeabilite primaire a un an a ete de 90%. Il n'y avait pas de difference concernant les thromboses precoces ou de la permeabilite a un an en fonction du sexe, de l'âge, de l'ethnie, du mode d'assurance, de la presence d'un acces temporaire ou de l'utilisation d'une cartographie veineuse pre-operatoire. Dans une population defavorisee, les recommandations de la NKF pour des FAV natives lors du premier acces pour hemodialyse peuvent etre super adoptees avec une excellente permeabilite a un an, malgre une presentation tardive.

In this month’s issue of Annals, Kline et al report the creation and validation of a Bayesian network designed to identify a low-risk subset of patients suspected of having a venous thromboembolism, using only readily available clinical data. During validation, they found that half of their patients were categorized as low risk by the network and that 98.5% (95% confidence interval [CI] 97.2% to 99.2%) of these patients were determined to be free of disease. The clinical significance of this work is readily apparent: if data from our initial assessment (ie, history, physical examination, pulse oximetry) can comfortably exclude venous thromboembolism in half of the patients in whom we consider the diagnosis, then the potential savings to the patient and the health care system may be quite substantial. We would be able to reserve the use of D-dimer tests and lower extremity and pulmonary imaging studiesdwhich have their own inherent costs in terms of time, pain, associated risks, and potential false positive resultsdfor patients not in this low-risk category. In addition to its potential clinical utility, this research is noteworthy for the authors’ implementation of a Bayesian network, an important step forward in the application of Bayesian thinking to the clinical practice of medicine. In this editorial, we describe how evaluations of diagnostic tools have become more ‘‘Bayesian’’ over time, where the Bayesian network approach fits in this evolution, and how the Bayesian network captures much of the essence of clinical reasoning.

Study objective The purpose of this study is to define the prevalence and significance of apparent life-threatening events among infants in the out-of-hospital setting.

Study objective We determine the efficacy of prophylactic phenytoin in preventing early posttraumatic seizures in children with moderate to severe blunt head injury. Methods Children younger than 16 years and experiencing moderate to severe blunt head injury were randomized to receive phenytoin or placebo within 60 minutes of presentation at 3 pediatric trauma centers. The primary endpoint was posttraumatic seizures within 48 hours; secondary endpoints were survival and neurologic outcome 30 days after injury. A Bayesian decision-theoretic clinical trial design was used to determine the probability of remaining posttraumatic seizure free for each treatment group. Results One hundred two patients were enrolled, with a median age of 6.1 years. Sixty-eight percent were boys. The 2 treatment groups were well matched. During the 48-hour observation period, 3 (7%) of 46 patients given phenytoin and 3 (5%) of 56 patients given placebo experienced a posttraumatic seizure. There were no significant differences between the treatment groups in survival or neurologic outcome after 30 days. According to these results, the probability that phenytoin has the originally hypothesized effect of reducing the rate of early posttraumatic seizures by 12.5% is 0.0053. The probability that phenytoin has any prophylactic efficacy is 0.383. The median effect size in this trial was −0.015 (seizure rate increased by 1.5% in the phenytoin group), 95% probability interval −0.127 to 0.091 (12.7% higher rate of posttraumatic seizures to a 9.1% lower rate of posttraumatic seizures with phenytoin). Conclusion The rate of early posttraumatic seizures in children may be much lower than previously reported. Phenytoin did not substantially reduce that rate.

Background: Drugs administered endotracheally are effectively absorbed during normal spontaneous cardiac activity. However, animal cardiac arrest studies and limited clinical investigations do not support either the use of endotracheal (ET) drugs in doses currently recommended for adults or the method of direct endotracheal instillation. The purpose of this study was to compare the effect of intravenous (IV) and ET drug therapy on outcome from out-of-hospital cardiac arrest secondary to all cardiac arrest rhythms. Design: Five and one-half year retrospective cohort study. Setting: Municipal, university affiliated hospital. Patients: Consecutive patients >18 years of age in nontraumatic out-of-hospital cardiac arrest who received advanced cardiac life support (ACLS) medications by only the ET or IV route were included. Interventions: None. Results: Five hundred and ninety-six patients met inclusion criteria (IV drugs=495, ET drugs=101). There was no difference between groups in the rate of witnessed arrest and the frequency of bystander cardiopulmonary resuscitation (CPR). In the ET drug group, a significantly greater number of patients had an initial documented arrest rhythm of asystole compared to the IV drug group (56 vs 37%, P =0.01). The rate of return of spontaneous circulation (27 vs 15%, P =0.01) and survival to hospital admission rate (20 vs 9%, P =0.01) were significantly greater in the IV drug group. No patient who received ET drugs survived to hospital discharge compared to 5% of those receiving IV drugs ( P =0.01). Conclusion: For our out-of-hospital advanced rescuer system, ET drugs at recommended doses (twice the IV dose) injected into an ET tube during cardiac arrest and CPR were of no benefit.

In 1996, the US Food and Drug Administration (FDA) enacted Rule 21 CFR section 50.24, which allows a narrow exception to the requirement for prospective informed consent from human research subjects in clinical trials investigating potentially beneficial therapies for acute, life-threatening conditions. The first clinical trial to be conducted under this rule was sponsored by Baxter Healthcare Corporation and approved by the FDA on November 21, 1996. This large, multicenter, randomized clinical trial was designed to compare the addition of diaspirin cross-linked hemoglobin (DCLHb) with standard care in the initial resuscitation of adults experiencing severe, uncompensated, traumatic hemorrhagic shock. Before the first planned interim analysis of the data, review of fatal adverse events revealed an imbalance in mortality between the 2 treatment groups. The Data Monitoring Committee (DMC) recommended suspension of patient enrollment 24 days later. Additional data collection and analyses confirmed the excess number of deaths in patients treated with DCLHb but failed to reveal the cause of these deaths. The trial was formally terminated after only 112 of the planned 850 patients had been enrolled. We review the events leading up to and the rationale behind the DMC recommendations for suspension of patient enrollment and trial termination. Although the DCLHb trial was unsuccessful in achieving its goals, the monitoring process worked well. Emergency research was facilitated by DMC oversight, and the interests of research subjects were protected by the actions of the DMC.

From the Medical Device Safety Institute, Beth Israel Deaconess Medical Center, Boston, MA (Maisel); and the Department of EmergencyMedicine, Harbor-UCLA Medical Center, the Los Angeles Biomedical Research Institute, Torrance, CA, and the David Geffen School of Medicine atUCLA, Los Angeles, CA (Lewis).

Objective: Biphasic waveforms for transthoracic defibrillation (DF) have been tested extensively after brief (15 s) episodes of VF in animal models and in patients undergoing electrophysiologic testing. The purpose of this study was to compare the effects mono- and biphasic waveforms for DF on postdefibrillation ST segments and left ventricular pressure, markers of myocardial injury, after more extended periods of VF (30 and 90 s). Methods: 21 anesthetized and instrumented swine were randomized to truncated exponential monophasic or biphasic waveform DF. VF was induced electrically and 30 s later, DF with the designated waveform was attempted with a shock dose of 200 J. If unsuccessful, 300 J and then 360 J were administered if necessary. Following return to control hemodynamic values and normalization of the surface ECG, VF was again induced and, after 90 s, DF was attempted as in the 30 s VF period. CPR was not performed during VF and each animal was countershocked with only one waveform for both VF episodes. Waveforms were compared for frequency of first shock defibrillation success, surface ECG indicators of myocardial injury (ST segment changes at 10, 20, and 30 s after countershock) and time to return to pre-VF hemodynamics after successful DF, an indicator of postshock ventricular function. Results: Successful first shock conversion rates at 30 and 90 s were 60 and 63% for monophasic and 64 and 82% for biphasic (NS). Biphasic DF after 30 s produced ST segment changes (measured 10 s after DF) in 1/10 animals while six of eight animals in the monophasic group showed ST segment changes ( P =0.013). After 90 s of VF, ST segment changes were observed in 6/8 in the monophasic group and 2/10 in the biphasic group ( P =0.054). Differences in the time to hemodynamic recovery (return to control peak left ventricular pressure) were not observed between biphasic and monophasic waveforms after 30 or 90 s of VF. Conclusions: Monophasic and biphasic transthoracic defibrillation are equally effective in terminating VF of 30 and 90 s duration and restoring a perfusing rhythm. The biphasic waveform produced less ECG evidence of transient myocardial injury. However, there was no difference in the rate of return to control hemodynamics. ST segment changes following countershock of VF of brief duration are transient and of questionable significance.

Purpose: This study assessed in a prospective, blinded fashion whether a reversible defect on dipyridamole-thallium (DTHAL)/sestamibi (DMIBI) can predict adverse cardiac events after elective vascular surgery in patients with one or more clinical risk factors. Methods: Consecutive patients with one or more clinical risk factors underwent a preoperative blinded DTHAL/DMIBI. Patients with recent congestive heart failure (CHF) or myocardial infarction (MI) or severe or unstable angina were excluded. Results: Eighty patients (78% men; mean age, 65 years) completed the study. Diabetes mellitus was the most frequent clinical risk factor (73%), followed by age older than 70 years (41%), angina (29%), Q wave on electrocardiogram (26%), history of CHF (7%), and ventricular ectopy (3%). The results of DTHAL/DMIBI were normal in 36 patients (45%); a reversible plus or minus fixed defect was demonstrated in 28 patients (36%), and a fixed defect alone was demonstrated in 15 patients (19%). Nine adverse cardiac events (11%) occurred, including three cases of CHF, and one case each of unstable angina, Q wave MI, non-Q wave MI, and cardiac arrest (successfully resuscitated). Two cardiac deaths occurred (2% overall mortality), one after a Q wave MI and one after CHF and a non-Q wave MI. The cardiac event rate was 14% for reversible defect and 9.8% without reversible defect ( P =.71). The cardiac event rate was 12.5% (one of eight cases) for two or more reversible defects, versus 11.1% (eight of 72 cases) for fewer than two reversible defects ( P = 1.0). The sensitivity rate of two or more areas of redistribution was 11% (95% CI, 0.3%-48%), the specificity rate was 90%, and the positive and negative predictive values were 12.5% and 89%, respectively. Conclusion: Our study demonstrated no association between reversible defects on DTHAL/DMIBI and adverse cardiac events in moderate-risk patients undergoing elective vascular surgery. (J Vasc Surg 2000;32:77-89.)

Background: Initial nonoperative treatment for patients with periappendiceal mass has been shown to be safe and effective. Our goal was to evaluate the safety and efficacy of initial nonoperative management for perforated appendicitis not accompanied by a palpable mass. Methods: The study population consisted of 77 patients with appendicitis treated initially nonoperatively between 1992 and 1998. All had localized abdominal tenderness and computed tomography findings of abscess or phlegmon. None had a palpable abdominal mass. Outcome parameters evaluated were rate of failure, complication, and recurrence. Results: There were 49 males and 28 females with a mean age of 35 years (range 16 to 75). Initial nonoperative management was successful in 95% of patients. Complications occurred in 12% of patients. Recurrent appendicitis developed in 6.5% of patients after an average follow-up of 30 weeks. Conclusions: Perforated appendicitis patients with localized abdominal tenderness and abscess or phlegmon can safely and effectively be treated in an initial nonoperative fashion.

In 1996, the Food and Drug Administration (FDA) and the Department of Health and Human Services established regulations that defined a narrow set of circumstances in which incapacitated and critically ill subjects could be enrolled in interventional clinical trials without their individual, prospective, informed consent. These regulations are commonly referred to as the “emergency exception from informed consent,” and the FDA has published a draft guidance about their implementation. Because individuals enrolled in clinical trials under the exception do not have the opportunity to individually consent to their participation, the regulations require protections and safeguards beyond those required in the usual circumstances. These protections include (1) a requirement that the planned study be publicly disclosed “to the communities in which the clinical investigation will be conducted and from which the subjects will be drawn” (“public disclosure”); (2) consultation “with representatives of the communities in which the clinical investigation will be conducted and from which the subjects will be drawn” (“community consultation”); (3) publication of the final study results once the trial is completed (“poststudy disclosure”); and (4) the use of an independent data monitoring committee or data and safety monitoring board to independently oversee the trial. The purposes of public disclosure and community consultation are quite different. The goal of public disclosure is to ensure that potential subjects are aware of the proposed research, whereas the goal of community consultation is to inform the institutional review board considering approval of the protocol about the patterns and diversity of community opinions regarding the acceptability of the proposed research. Commonly used methods of community consultation include hosting meetings for community members, Web-based methods, and telephone call-in systems. In addition, many investigators provide information and question-and-answer sessions at regularly scheduled community meetings.

The ability of the Eagle criteria (age70 years, angina, diabetes, Q wave on EKG, history of congestive heart failure) to predict adverse cardiac events following major vascular surgery has previously been demonstrated. However, the utility of these criteria for lower-extremity amputation is not well established. To determine the value of the Eagle criteria for predicting cardiac morbidity and operative mortality following major lower-extremity amputation, we reviewed 214 consecutive procedures performed at two institutions over a 3-year period. Mean age was 62.7 years and 85% of the patients were male. Diabetes was the most frequent Eagle criterion (74%). The mean number of Eagle criteria was 1.6. Fifty-six percent of the amputations were below the knee, 24% were above the knee, and 20% were guillotine. On multivariate regression analysis, the presence of two or more Eagle criteria (16% vs. 4%, p = 0.04) and decompensated heart failure (39% vs. 7%, p = 0.003) were predictive of adverse cardiac events. The only predictor of postoperative mortality was the presence of two or more Eagle criteria (15% vs. 4%, p = 0.004). Our evaluation of the results of this study led us to conclude that patients requiring major lower-extremity amputation for major vascular disease who have multiple Eagle criteria or decompensated congestive heart failure are at high risk for adverse cardiac events and postoperative death. These findings should be used to guide perioperative cardiac evaluation and therapy.

The long-term goals of developing research within the specialty of emergency medicine (EM) include the following: 1) to continue to improve the quality and quantity of EM research in order to ultimately improve emergency patient care; 2) to maximize the research potential of emergency health care professionals in order to develop new emergency research talent and enthusiasm; and 3) to establish the academic research credentials of the specialty of EM in order to become competitive for federal research funding, and further improve emergency patient care. This article addresses the process by which the infrastructure for EM research can be developed at academic medical centers and provides recommendations. The roles of the academic chair, research director, senior researcher, and departmental faculty are discussed.

Eighty-nine male veterans presenting to a vascular surgery clinic with symptomatic lower extremity atherosclerosis were prospectively screened by duplex scan for asymptomatic carotid artery stenosis (CAS). Their chief complaint was: claudication (90%), rest pain (6%), and ischemic ulcer or gangrene (4%). The mean ankle-brachial index (ABI) was 0.77. Twenty-five CAS50% were detected in 18 (20%) patients. Twelve CAS75% were detected in 11 (12%) patients. There was no difference between patients with and without CAS50% with regards to mean ABI, history of angina, diabetes, hypertension, prior coronary artery bypass, or history of smoking. Carotid bruit was associated with ipsilateral CAS50% [p0.0001, sensitivity (52%), specificity (88%), positive predictive value (41%), negative predictive value (92%)]. As a result of the screening, eight elective carotid endarterectomies have been performed to date in six (7%) patients with one transient twelfth cranial nerve paresis as the only postoperative complication. We conclude that: (1) male patients presenting with symptomatic lower extremity atherosclerosis have a 20% prevalence of asymptomatic CAS50%, (2) there is no correlation between the degree of lower extremity ischemia and CAS50%, (3) carotid bruit is significantly associated with CAS50%, but has a low sensitivity, and (4) routine CAS screening should be considered for all male patients with symptomatic lower extremity atherosclerosis regardless of whether a bruit is present.

Dipyridamole-sestamibi (PMIBI) is recommended prior to vascular surgery in patients with > or = 1 Eagle criteria (Q waves, history of ventricular ectopy, diabetes, advanced age, and/or angina). To review our cardiac morbidity and mortality and the need for preoperative PMIBI, we reviewed 109 consecutive patients with a mean age of 59 years who underwent 145 elective major vascular procedures over a 1-year period. Seventy patients (with a mean of 0.8 Eagle criteria) underwent 92 vascular procedures without preoperative PMIBI and without coronary revascularization. Thirty-one patients (with a mean of 1.1 Eagle criteria) underwent 39 procedures without coronary revascularization following PMIBI, which showed reversible ischemia in seven and a fixed defect in 10; findings were normal in 14. Preoperative coronary bypass or angioplasty was limited to eight patients (14 procedures, mean of 1.6 Eagle criteria) who had unstable angina with (2 patients) or without (6 patients) acute myocardial infarction. There were four perioperative myocardial infarctions (2.8%), seven cardiac events overall (4.8%), and one cardiac death (0.7%). Three (43%) of the seven cardiac events occurred in patients with a normal scan or fixed defect on PMIBI imaging. In the absence of unstable angina, PMIBI had a sensitivity of only 25% and a specificity of 80% for cardiac events. We conclude that among patients without severe cardiac symptoms (1) PMIBI has a very limited ability to identify patients at risk for cardiac complications, and (2) preoperative PMIBI is neither necessary nor cost-effective.

The goal of emergency medicine is to improve health while preventing and treating disease and illness in patients seeking emergency medical care. Improvements in emergency medical care and the delivery of this care can be achieved through credible and meaningful research efforts. Improved delivery of emergency medical care through research requires careful planning and the wise use of limited resources. To achieve this goal, emergency medicine must provide appropriate training of young investigators and attract support for their work. Promotion of multidisciplinary research teams will help the specialty fulfill its goals. The result will be the improvement of emergency medical care, which will benefit not only the patients emergency physicians serve but also, ultimately, the nation's health.

Study objective We identify differences in the process of care for admitted patients who board in the emergency department (ED) compared with admitted patients who are transferred to an inpatient care area. Methods This is a retrospective study of a random sample of adult patients admitted through the ED at one urban teaching hospital. Patients who boarded in the ED for at least 6 hours after the decision to admit were matched to similar control patients. Data were collected by 2 trained medical students using a standardized data abstraction tool. All physician orders placed in the first 24 hours after admission orders were signed were identified. The medical record was searched for documentation of order completion. Each order was classified as being executed on time, delayed, or missed. Results Of 848 patients screened for inclusion in the study, a total of 145 matched case-control pairs were included, making a total of 290 patients. A total of 9,260 distinct orders were identified. Use of a generalized estimating equation that controlled for correlation within subjects showed that orders were less likely to be completed on time for boarders than for controls (odds ratio [OR] 0.46; 95% confidence interval [CI] 0.38 to 0.55). Among boarders, orders were more likely to be either delayed (OR 1.84; 95% CI 1.46 to 2.30) or missed entirely (OR 2.58; 95% CI 1.94 to 3.42). Boarders missed a median of 11 orders during their first 24 hours of admission compared with 6 orders for control patients. Conclusion This study detected an important process difference between boarded patients compared with control patients, which could explain previously suggested outcome differences between these 2 groups. This provides additional support for efforts to move patients to inpatient care areas in a timely fashion rather than board in the ED.

Study objectives: To determine whether admission to an acute care hospital is medically justified for all patients with acute stroke or transient ischemic attack (TIA) and whether those patients for whom admission is justified can be identified in the emergency department. Design: Retrospective descriptive study. Setting: Urban county teaching hospital. Participants: Consecutive adult patients seen in an ED with nonhemorrhagic stroke, TIA, or hemorrhagic stroke. Methods: Admission to an acute care hospital was deemed medically justified when the patient had any of the following criteria: another diagnosis that warranted admission, an inadequate home situation, altered mental status, or an adverse event during hospitalization or if they underwent hospital-based treatment that could not be provided on an outpatient basis. Results: One hundred sixty-eight patients were seen during a 1-year period: 120 had an ED diagnosis of nonhemorrhagic stroke, 22 had a diagnosis of TIA, and 26 had a diagnosis of hemorrhagic stroke. One hundred sixty-one patients (96%) were admitted to our hospital. Sixty-three of the 161 admissions (39%) were retrospectively categorized as medically justified. Seventeen of the 63 patients (27%) whose admissions were medically justified developed the criteria justifying their admission after leaving the ED. Conclusion: The practice of admitting all patients with nonhemorrhagic stroke, TIA, or hemorrhagic stroke to an acute care hospital is medically justified because the ED evaluation cannot reliably identify patients whose condition will worsen. [Henneman PL, Lewis RJ: Is admission medically justified for all patients with acute stroke or transient ischemic attack? Ann Emerg Med April 1995;25:458-463.]

Study objectives: To determine which adult patients with new-onset seizures require admission and whether those who require admission can be identified in the emergency department. Design: Retrospective chart review of patients seen during a 5-yearperiod. Setting: Urban county teaching hospital in southern California. Participants: Three hundred thirty-three adult patients with new-onset seizures. Patients were excluded if they had acute head trauma, hypoglycemia from diabetic therapy, or alcohol- or recreational drug-related seizures. Interventions: Standardized medical evaluation including physical examination, CBC, SMA-7 (electrolytes, blood urea nitrogen, creatinine, glucose), calcium, cranial computed tomography (CT), lumbar puncture if indicated, and admission to the hospital. Results: Forty-six percent of patients (136 of 294) admitted toour hospital required admission as judged by a retrospective evaluation of the ED and hospital course. The numbers of patients who had a clinically significant result with each part of the evaluation were: physical examination, 75 of 333 (23%); CBC, 25 of 319 (8%); SMA-7, 21 of 329 (6%); calcium, 2 of 208 (1%); CT, 134 of 325 (41%); and lumbar puncture, 19 of 227 (8%). Ninety-five percent of patients requiring admission (129 of 136) were detected by the standardized medical evaluation. Conclusion: One half of patients with new-onset seizures require admission. Patients with new-onset seizures who require admission can usually be detected by a standardized medical evaluation in the ED.

Study objective: The present epidemic of tuberculosis has increased the risk of transmission of tuberculosis to health care workers in general and emergency department staff in particular, who often treat patients with tuberculosis before their diagnosis. The purpose of this study was to determine the risk of tuberculosis exposure among the nursing and physician staff of an urban ED. Design: Observational study of self-reported purified protein derivative (PPD) skin test results and tuberculosis exposure. Setting: Urban, public ED. Participants: Attending physicians, resident physicians, and registered nurses. Interventions: None Results: Questionnaires were sent to all attending physicians, resident physicians, and registered nurses in the ED at Harbor-UCLA Medical Center requesting information on the subject's present and prior PPD status, known exposure to tuberculosis, and duration of time and average number of hours worked in the ED. Ninety-six of 129 questionnaires (74%) were returned. Five of the respondents had been immunized with Bacillus of Calmette and Guerin vaccine (BCG) and 10 of the respondents were PPD positive before beginning work in the ED. Of the other 81 respondents, 31% (25 of 81) had become PPD positive while working in the ED. The majority of these conversions (15 of 25) occurred in the first 6 months of 1993. A Kaplan-Meier survival analysis revealed nearly a 40% risk of PPD conversion after 60 months of full-time work in the ED. Conclusion: As measured by self-reported PPD status, a high rate of exposure to tuberculosis has been observed among the ED staff at Harbor-UCLA Medica Center. The highest rate of PPD conversion has been noted most recently, suggesting that there has been a significant increase in staff exposure to tuberculosis during 1992 and the beginning of 1993. Systematic monitoring of PPD conversion rates among ED staff is necessary to determine the adequacy of ED respiratory isolation procedures during the current tuberculosis epidemic.

Study objective: To determine the efficacy and feasibility of adenosine for the treatment of paroxysmal supraventricular tachycardia (PSVT) in the prehospital setting. Design: Prospective case series. Setting: Large, urban, advanced life support emergency medical services system. Participants: One hundred twenty-nine adult patients with PSVT, as identified by paramedic personnel. Pregnant patients and those taking carbamazepine or dipyridamole were excluded. Interventions: Dose of 12 mg adenosine by rapid IV push followed by a 5-mL saline flush and a repeat dose of 12 mg adenosine IV push if the patient's rhythm remained unchanged. Measurements and main results: Six-second lead II rhythm strips and vital signs were documented before and 2 minutes after the administration of adenosine. Demographic information, past medical history, medications, number of adenosine doses given, and complications were recorded by the paramedic on a case-report form. One hundred six of 129 (82%) of the case-report forms included the rhythm strips from before and after adenosine administration. Actual initial rhythms were determined by a consensus panel. The initial rhythms were PSVT in 79% (84 of 106) of patients, atrial fibrillation in 12% (13 of 106), sinus tachycardia in 5% (five of 106), atrial flutter in 2% (two of 106), and ventricular tachycardia in 2% (two of 106). Eighty-five percent (71 of 84) of patients in PSVT were successfully converted to sinus rhythms; four (5.6%) of these patients required a second 12-mg dose. One patient in atrial fibrillation spontaneously converted to normal sinus rhythm and one patient in ventricular tachycardia converted after adenosine. All other patients not initially in PSVT remained in their initial rhythm. Complications occurred in 12 of 129 patients and included chest pain (five), flushing (three), shortness of breath (two), nausea (one), anxiety (one), dizziness (one), headache (one), and seizure (one). All complications were transient and required no treatment. Prior history of PSVT was the only variable associated with a higher rate of conversion ( P =.029). Conclusion: Paramedics are able to accurately identify PSVT using a single lead. Adenosine is safe and effective treatment for PSVT in the prehospital setting. This series is the largest prehospital study of adenosine use to date. [Gausche M, Persse DE, Sugarman T, Shea SR, Palmer GL, Lewis RJ, Brueske PJ, Mahadevan S, Melio FR, Kuwata JH, Niemann JT: Adenosine for the prehospital treatment of paroxysmal supraventricular tachycardia. Ann Emerg Med August 1994;24:183-189.]

To determine the hospital characteristics associated with patients leaving emergency departments prior to physician evaluation.Cross-sectional design with data collection by mail and telephone survey.Los Angeles County, California.Convenience sample of four public and 26 private hospital EDs with a combined monthly volume of 92,570.None.Questionnaires were returned from 83% of EDs surveyed. During 1990, 4.2% of patients at these EDs left without being seen by a physician. In all, 7.3% of public hospital patients left without being seen, and 2.4% of private hospital patients left without being seen (P.001). The percentage of patients who left without being seen was significantly higher at EDs with longer waiting times, higher fraction of uninsured patients, and at hospitals with accredited residency training programs (P.001 for each comparison). A logistic regression model, used to simultaneously evaluate the effects of multiple correlated factors, revealed that waiting time, fraction of patients uninsured, and teaching status had independent positive associations with patients who left without being seen.More than 4% of patients who seek care at EDs in Los Angeles County leave without being seen by a physician. A greater proportion of patients leave without medical evaluation from EDs with long waiting times for ambulatory patients and from those that serve uninsured populations. These findings should be interpreted in light of existing data on the health consequences faced by patients who leave hospital EDs without treatment.

To determine the clinical characteristics associated with early post-traumatic seizures in children with head trauma. DESIGN, SETTING, AND TYPE OF PARTICIPANTS: Retrospective chart review; urban trauma center/pediatric emergency department. Trauma patients aged 3 months to 15 years given discharge diagnosis ICD-9-CM codes indicating head trauma and seen from 1988 to 1990 were eligible for the study.None.Of 194 patients, 96% suffered blunt trauma and 53% had a loss of consciousness. Fifty-one percent of 141 computed tomography (CT) scans of the head were abnormal, most frequently demonstrating skull fractures (34%), subdural hematomas (15%), and cerebral contusions (14%). Eighteen patients (9.3%) suffered post-traumatic seizures. A loss of consciousness, a low Glasgow Coma Scale (GCS) score (3 to 8), and an abnormal CT scan were associated with post-traumatic seizures (P.02, .001, and .02, respectively). However, only a low GCS score was predictive of post-traumatic seizures when these factors were considered simultaneously (P.001), with 38.7% of patients with low GCS scores suffering post-traumatic seizures and 3.8% of patients with high GCS scores suffering post-traumatic seizures. In children with low GCS scores, treatment with phenytoin was associated with a decrease in post-traumatic seizures.In the pediatric head trauma patient, a GCS score of 3 to 8 appears to be predictive of post-traumatic seizures. The data from this retrospective study are consistent with the hypothesis that prophylactic phenytoin reduces post-traumatic seizures in the pediatric head trauma patient with a low GCS score.

An understanding of statistical concepts and methods is essential for the clinician who wishes to interpret the results of clinical studies. In this article the concepts of descriptive statistics, classical hypothesis testing, P values, a priori information, and Type I and Type II errors are discussed with examples to illustrate their application to the interpretation of clinical trials. In addition, descriptions of Student's t test, the chi-squared test, Fisher's exact test, the rank sum test, and sequential methods are given.

Study objective Subgroup analyses examine associations (eg, between treatment and outcome) within subsets of a larger study sample. The traditional approach evaluates the data in each of the subgroups independently. More accurate answers, however, may be expected when the rest of the data are considered in the analysis of each subgroup, provided there are 3 or more subgroups. Methods We present a conceptual introduction to subgroup analysis that makes use of all the available data and then illustrate the technique by applying it to a previously published study of pediatric airway management. Using WinBUGS, freely available computer software, we perform an empirical Bayesian analysis of the treatment effect in each of the subgroups. This approach corrects the original subgroup treatment estimates toward a weighted average treatment effect across all subjects. Results The revised estimates of the subgroup treatment effects demonstrate markedly less variability than the original estimates. Further, using these estimates will reduce our total expected error in parameter estimation compared with using the original, independent subgroup estimates. Although any particular estimate may be adjusted inappropriately, adopting this strategy will, on average, lead to results that are more accurate. Conclusion When multiple subgroups are considered, it is often inadvisable to ignore the rest of the study data. Authors or readers who wish to examine associations within subgroups are encouraged to use techniques that reduce the total expected error.

Study objective There is currently no validated method for assessing hospital disaster preparedness. We determine the degree of correlation between the results of 3 methods for assessing hospital disaster preparedness: administration of an on-site survey, drill observation using a structured evaluation tool, and video analysis of team performance in the hospital incident command center. Methods This was a prospective, observational study conducted during a regional disaster drill, comparing the results from an on-site survey, a structured disaster drill evaluation tool, and a video analysis of teamwork, performed at 6 911-receiving hospitals in Los Angeles County, CA. The on-site survey was conducted separately from the drill and assessed hospital disaster plan structure, vendor agreements, modes of communication, medical and surgical supplies, involvement of law enforcement, mutual aid agreements with other facilities, drills and training, surge capacity, decontamination capability, and pharmaceutical stockpiles. The drill evaluation tool, developed by Johns Hopkins University under contract from the Agency for Healthcare Research and Quality, was used to assess various aspects of drill performance, such as the availability of the hospital disaster plan, the geographic configuration of the incident command center, whether drill participants were identifiable, whether the noise level interfered with effective communication, and how often key information (eg, number of available staffed floor, intensive care, and isolation beds; number of arriving victims; expected triage level of victims; number of potential discharges) was received by the incident command center. Teamwork behaviors in the incident command center were quantitatively assessed, using the MedTeams analysis of the video recordings obtained during the disaster drill. Spearman rank correlations of the results between pair-wise groupings of the 3 assessment methods were calculated. Results The 3 evaluation methods demonstrated qualitatively different results with respect to each hospital's level of disaster preparedness. The Spearman rank correlation coefficient between the results of the on-site survey and the video analysis of teamwork was –0.34; between the results of the on-site survey and the structured drill evaluation tool, 0.15; and between the results of the video analysis and the drill evaluation tool, 0.82. Conclusion The disparate results obtained from the 3 methods suggest that each measures distinct aspects of disaster preparedness, and perhaps no single method adequately characterizes overall hospital preparedness.

Study objectives: We prospectively validate a previously published out-of-hospital clinical decision rule (based on Glasgow Coma Scale [GCS] score, passenger space intrusion, and restraint use) to identify severely injured children involved in motor vehicle crashes (MVCs) with a population-based sample. Methods: We selected 20 Los Angeles County fire stations (paramedic squad and engine company) according to pediatric MVC call volume during the previous year and geographic diversity, and 21 hospitals clustered around the fire stations. All stations (60 shifts) were trained in data collection and study background. Immediately after a pediatric MVC call, each engine or paramedic squad completed a data form (14 variables, including vital signs, GCS score, and vehicular and crash characteristics) for children evaluated at the scene of a crash during a 24-month period. Outcomes were assessed by retrospective medical record review. We performed surveillance at all hospitals to identify nontransported children presenting within 7 days of the crash. Results: The primary outcome was an Injury Severity Scale (ISS) score of 16 or greater, with a secondary outcome of the need for specialized trauma care (emergency intubation, operative intervention, or death in the first 24 hours). We calculated the sensitivity and specificity of the validation sample, including binominal confidence intervals (CIs). One hundred seventy-five children were prospectively enrolled in the study; 34 children were excluded because of lack of hospital participation (n=10) and missing hospital records (n=24). There were 4 (3%) children with ISS score of 16 or greater, 6 (4%) children requiring specialized trauma care, and 7 (5%) with 1 of the 2 outcomes. The sensitivity and specificity of the rule for each outcome was 100% (95% CI 40% to 100%) and 73% (95% CI 65% to 80%) for severe injury and 67% (95% CI 22% to 96%) and 73% (95% CI 64% to 80%) for specialized trauma care. All previously published rules would have missed 1 child requiring emergency surgery. Conclusion: Although there were a small number of severely injured children in this sample, the decision rule identified all of them with less combined under- and overtriage than any previously published pediatric triage rule. The decision rule was less sensitive for identifying children requiring specialized trauma care. Larger validation studies are needed to adequately assess the utility of this rule before implementation.

Study objectives: We characterize disaster preparedness among a cohort of hospitals, focusing on practice variation, plan characteristics, and surge capacity. Methods: This was a descriptive, cross-sectional study using an in-person hospital survey and a 117-item questionnaire in Los Angeles County, CA. The study included 45 of the 81 designated 911 receiving hospitals, including private and tertiary care facilities. Observations include a description of hospital disaster plans, modes of intra- and interhospital communication, community and interagency involvement, decontamination capability and training, drills, pharmaceutical stockpiles, and each facility's surge capacity (assessed by monthly emergency department [ED] diversion status, number of available beds, ventilators, and negative pressure isolation rooms). Additional measures of preparedness included whether hospitals had the following: mutual aid agreements with other hospitals, long-term care facilities, and medical vendors; protocols for canceling elective surgeries and early in-patient discharge; surveillance systems; ongoing training with local emergency medical services and fire departments; communication with the public health department; volunteer credentialing systems; and a protocol for mass fatality incidents. Results: Ninety-five percent had adopted the Hospital Emergency Incident Command System, and 100% used the ReddiNet, a radio-based communications network. Ninety-five percent had memoranda of understanding with medical suppliers. However, 67% never had joint training programs with local police and fire agencies, and only 16% and 7% had written mutual aid agreements with other hospitals and long-term care facilities, respectively. Eighty-eight percent of hospitals had level B and/or C personal protective equipment, and 44% had decontamination facilities suitable in inclement weather. Ninety-six percent of respondents noted a nurse shortage, 58% had a monthly ED diversion rate of greater than 20%, and 69% estimated a surge capacity of less than 20 beds. Fifty-eight percent of responding hospitals had fewer than 10 negative pressure isolation rooms, only 36% had more than 10 ventilators, and 55% did not keep a stockpile of antibiotics or antidotes. Although 93% and 98%, respectively, had protocols for canceling elective surgeries and early in-patient discharge, only 64% had plans in place for a mass fatality incident. Conclusion: There are no objective measures of “hospital preparedness” or “hospital surge capacity.” In addition to establishing such standards, focus must be placed on enhancing interagency and interhospital communications. Current numbers of available hospital beds, ventilators, isolation rooms, and pharmaceuticals may be insufficient to effectively care for victims of large-scale disasters and other public health emergencies.

Study objectives: We determine whether the use of ultrasonographic localization of spinal landmarks performed by emergency physicians affects the performance of lumbar puncture. Methods: This study was performed in an urban county teaching hospital. Adults 18 years or older who were to receive a lumbar puncture for routine clinical care in the emergency department were included. Target patient enrollment was set at 100. Patients were randomized to either undergo preprocedural ultrasonographic localization of the puncture site by the treating emergency physician or to have the puncture site determined by the usual landmark palpation method. Patients were assessed by the treating physician with respect to ease with which puncture-site landmarks could be palpated: easily palpable, difficult to palpate, or unable to palpate. The primary endpoint was success of the procedure as defined by return of cerebrospinal fluid; secondary endpoints were the number of needle passes, pain associated with the procedure, time to perform the procedure, and patient satisfaction with the procedure. The primary analysis compared use of ultrasonography versus palpation alone for all endpoints using the χ 2 test, Fisher's exact test, and the Wilcoxon rank sum test, as appropriate. A subgroup analysis was performed by dividing patients into subgroups according to ease of landmark palpation. No consideration was given to terminating this study according to this interim analysis. Results: Sixty-six patients have been enrolled to date. Median age of the patients was 39 years, and 48% were men. Thirty-three (50%) of the patients were considered easy to palpate, 21 (32%) were difficult to palpate, and 12 (18%) were designated as having landmarks that were not palpable. Thirty-three (50%) patients were randomized into each of the 2 study groups. There were no significant differences between the 2 groups in terms of age, sex, body mass index, or ease of palpation of landmarks. For the primary outcome, procedural success, there were no significant differences between those undergoing ultrasonographic localization and those with palpation alone. The only secondary outcome that was significantly different was the median time to perform the procedure, with palpation at 2.8 minutes (interquartile ratio [IQR] 4.8 to 14.2) versus ultrasonography at 7.9 minutes (IQR 0.9 to 14.0; P =.03). Subgroup analysis showed that in the group of patients whose landmarks were either difficult to palpate or not palpable, there was a trend toward improved success rate using ultrasonography. Success rate for ultrasonography group was 100% (14 of 14) versus 84% for the palpation-only group (16 of 19; P =.24). In this subgroup, there were no significant differences between groups for number of needle attempts, pain scores, patient satisfaction, or time of procedure. Conclusion: Preliminary data do not suggest any advantage to the routine use of ultrasonography in patients who require lumbar puncture. There may be an improved success rate in those patients whose spinal landmarks are either difficult to palpate or not palpable. Use of ultrasonography for lumbar puncture localization adds 5.1 minutes to the median time required to perform the procedure.