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Background: Dignitary medicine is an emerging field of training that involves the specialized care of diplomats, heads of state, and other high-ranking officials. In an effort to provide guidance on training in this nascent field, we convened a panel of experts in dignitary medicine and using the Delphi methodology, created a consensus curriculum for training in dignitary medicine., Methods: A three-round Delphi consensus process was performed with 42 experts in the field of dignitary medicine. Predetermined scores were required for an aspect of the curriculum to advance to the next round. The scores on the final round were used to determine the components of the curriculum. Scores below the threshold to advance were dropped in the subsequent round., Results: Our panel had a high degree of agreement on the required skills needed to practice dignitary medicine, with active practice in a provider's baseline specialty, current board certification, and skills in emergency care and resuscitation being the highest rated skills dignitary medicine physicians need. Skills related to vascular and emergency ultrasound and quality improvement were rated the lowest in the Delphi analysis. No skills were dropped from consideration., Conclusions: The results of our work can form the basis of formal fellowship training, continuing medical education, and publications in the field of dignitary medicine. It is clear that active medical practice and knowledge of resuscitation and emergency care are critical skills in this field, making emergency medicine physicians well suited to practicing dignitary medicine.

Introduction: Claims data raises the possibility that on demand telemedicine programs might increase new utilization, offsetting the cost benefits described in some retrospective analyses. We prospectively evaluated the cost of a synchronous audio-video on-demand telemedicine taking into account both what patients would have done instead of the telemedicine visit as well as the care patients received after the visit., Materials and Methods: We conducted a prospective observational study of patients who received care from an on-demand telemedicine program. At the time of the visit, we surveyed patients about the alternative care that would have been requested, if they had not done the telemedicine visit. We also obtained information following the visit about what further care was received. Using cost data derived from the literature we performed a sensitivity analysis to determine the cost impact of the on-demand telemedicine visit., Results: There were 650 patients enrolled with a mean age of 37 who were 68% female; 74% had their care concerns resolved on the telemedicine visit; only 16% would have "done nothing" if they had not done the telemedicine visit, representing possible new utilization. Net cost savings per telemedicine visit was calculated to range from $19-$121 per visit., Conclusions: In our on-demand telemedicine program, we found the majority of health concerns could be resolved in a single consultation and new utilization was infrequent. Synchronous audio-video telemedicine consults resulted in short-term cost savings by diverting patients from more expensive care settings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The optimal approach to prehospital care of trauma patients is controversial, and thought to require balancing advanced field interventions with rapid transport to definitive care., Objective: We sought principally to examine any association between the amount of prehospital IV fluid (IVF) administered and mortality., Methods: We conducted a retrospective cohort analysis of trauma registry data patients who sustained penetrating trauma between January 2008 and February 2011, as identified in the Pennsylvania Trauma Systems Foundation registry with corresponding prehospital records from the Philadelphia Fire Department. Analyses were conducted with logistic regression models and instrumental variable analysis, adjusted for injury severity using scene vital signs before the intervention was delivered., Results: There were 1966 patients identified. Overall mortality was 22.60%. Approximately two-thirds received fluids and one-third did not. Both cohorts had similar Trauma and Injury Severity Score-predicted mortality. Mortality was similar in those who received IVF (23.43%) and those who did not (21.30%) (p = 0.212). Patients who received IVF had longer mean scene times (10.82 min) than those who did not (9.18 min) (p < 0.0001), although call times were similar in those who received IVF (24.14 min) and those who did not (23.83 min) (p = 0.637). Adjusted analysis of 1722 patients demonstrated no benefit or harm associated with prehospital fluid (odds ratio [OR] 0.905, 95% confidence interval [CI] 0.47-1.75). Instrumental variable analysis utilizing variations in use of IVF across different Emergency Medical Services (EMS) units also found no association between the unit's percentage of patients that were provided fluids and mortality (OR 1.02, 95% CI 0.96-1.08)., Conclusions: We found no significant difference in mortality or EMS call time between patients who did or did not receive prehospital IVF after penetrating trauma., (Published by Elsevier Inc.)

Background: Wide variation in out-of-hospital cardiac arrest (OHCA) survival has been reported, with low survival in urban settings. We sought to describe the epidemiology of OHCA in Philadelphia, Pennsylvania, the fifth largest U.S. city, and identify potential areas for targeted interventions to improve survival., Methods and Results: Retrospective chart review of adult, non-traumatic, OHCA occurring in Philadelphia between 2008 and 2012. We determined incidence and epidemiological factors including: demographics, initial cardiac rhythm, bystander cardiopulmonary resuscitation, automated external defibrillator use, return of spontaneous circulation and 30-day survival. 5198 cases of adult, non-traumatic OHCA were identified. The incidence was 81.5/100,000. The majority of cases occurred in a residence (76.2%); 30.4% were witnessed events; the initial cardiac rhythm was pulseless ventricular tachycardia or ventricular fibrillation in 6.2% of cases, pulseless electrical activity in 21.0%, asystole in 38.3% and was unknown or undocumented in the remaining 34.5%. Multivariate logistic regression analysis demonstrated increased 30-day survival with younger age, shockable cardiac rhythms, and daytime arrest. 30-day survival was 8.1% for EMS-assessed patients and 8.6% for EMS-transported patients., Conclusions: Philadelphia's reported incidence is consistent with urban settings although the survival rate is higher than other urban centers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Survival from out-of-hospital cardiac arrest (OHCA) is generally poor and varies by geography. Variability in automated external defibrillator (AED) locations may be a contributing factor. To inform optimal placement of AEDs, we investigated AED access in a major US city relative to demographic and employment characteristics., Methods and Results: This was a retrospective analysis of a Philadelphia AED registry (2,559 total AEDs). The 2010 US Census and the Local Employment Dynamics database by ZIP code was used. Automated external defibrillator access was calculated as the weighted areal percentage of each ZIP code covered by a 400-m radius around each AED. Of 47 ZIP codes, only 9% (4) were high-AED-service areas. In 26% (12) of ZIP codes, less than 35% of the area was covered by AED service areas. Higher-AED-access ZIP codes were more likely to have a moderately populated residential area (P = .032), higher median household income (P = .006), and higher paying jobs (P =. 008)., Conclusions: The locations of AEDs vary across specific ZIP codes; select residential and employment characteristics explain some variation. Further work on evaluating OHCA locations, AED use and availability, and OHCA outcomes could inform AED placement policies. Optimizing the placement of AEDs through this work may help to increase survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Study Objective: Two decades ago, Philadelphia began allowing police transport of patients with penetrating trauma. We conduct a large, multiyear, citywide analysis of this policy. We examine the association between mode of out-of-hospital transport (police department versus emergency medical services [EMS]) and mortality among patients with penetrating trauma in Philadelphia., Methods: This is a retrospective cohort study of trauma registry data. Patients who sustained any proximal penetrating trauma and presented to any Level I or II trauma center in Philadelphia between January 1, 2003, and December 31, 2007, were included. Analyses were conducted with logistic regression models and were adjusted for injury severity with the Trauma and Injury Severity Score and for case mix with a modified Charlson index., Results: Four thousand one hundred twenty-two subjects were identified. Overall mortality was 27.4%. In unadjusted analyses, patients transported by police were more likely to die than patients transported by ambulance (29.8% versus 26.5%; OR 1.18; 95% confidence interval [CI] 1.00 to 1.39). In adjusted models, no significant difference was observed in overall mortality between the police department and EMS groups (odds ratio [OR] 0.78; 95% CI 0.61 to 1.01). In subgroup analysis, patients with severe injury (Injury Severity Score >15) (OR 0.73; 95% CI 0.59 to 0.90), patients with gunshot wounds (OR 0.70; 95% CI 0.53 to 0.94), and patients with stab wounds (OR 0.19; 95% CI 0.08 to 0.45) were more likely to survive if transported by police., Conclusion: We found no significant overall difference in adjusted mortality between patients transported by the police department compared with EMS but found increased adjusted survival among 3 key subgroups of patients transported by police. This practice may augment traditional care., (Copyright © 2014 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Study Objective: Collective knowledge and coordination of vital interventions for time-sensitive conditions (ST-segment elevation myocardial infarction [STEMI], stroke, cardiac arrest, and septic shock) could contribute to a comprehensive statewide emergency care system, but little is known about population access to the resources required. We seek to describe existing clinical management strategies for time-sensitive conditions in Pennsylvania hospitals., Methods: All Pennsylvania emergency departments (EDs) open in 2009 were surveyed about resource availability and practice patterns for time-sensitive conditions. The frequency with which EDs provided essential clinical bundles for each condition was assessed. Penalized maximum likelihood regressions were used to evaluate associations between ED characteristics and the presence of the 4 clinical bundles of care. We used geographic information science to calculate 60-minute ambulance access to the nearest facility with these clinical bundles., Results: The percentage of EDs providing each of the 4 clinical bundles in 2009 ranged from 20% to 57% (stroke 20%, STEMI 32%, cardiac arrest 34%, sepsis 57%). For STEMI and stroke, presence of a board-certified/board-eligible emergency physician was significantly associated with presence of a clinical bundle. Only 8% of hospitals provided all 4 care bundles. However, 53% of the population was able to reach this minority of hospitals within 60 minutes., Conclusion: Reliably matching patient needs to ED resources in time-dependent illness is a critical component of a coordinated emergency care system. Population access to critical interventions for the time-dependent diseases discussed here is limited. A population-based planning approach and improved coordination of care could improve access to interventions for patients with time-sensitive conditions., (Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Background: More than 300 000 out-of-hospital cardiac arrests (OHCA) occur each year in the United States. The relationship between time of day and OHCA outcomes in the prehospital setting is unknown. Any such association may have important implications for emergency medical services resource allocation., Methods and Results: We performed a retrospective review of cardiac arrest data from a large, urban emergency medical services system. Included were OHCA occurring in adults from January 2008 to February 2012. Excluded were traumatic arrests and cases in which resuscitation measures were not performed. Day was defined as 8 am to 7:59 pm; night, as 8 pm to 7:59 am. A relative risk regression model was used to evaluate the association between time of day and prehospital return of spontaneous circulation and 30-day survival, with adjustment for clinically relevant predictors of survival. Among the 4789 included cases, 1962 (41.0%) occurred at night. Mean age was 63.8 years (SD, 17.4 years); 54.5% were male. Patients with an OHCA occurring at night did not have significantly lower rates of prehospital return of spontaneous circulation compared with patients having daytime arrests (11.6% versus 12.8%; P=0.20). However, rates of 30-day survival were significantly lower at night (8.56% versus 10.9%; P=0.02). After adjustment for demographics, presenting rhythm, field termination, duration of call, dispatch-to-scene interval, automated external defibrillator application, bystander cardiopulmonary resuscitation, and location, 30-day survival remained significantly higher after daytime OHCA, with a relative risk of 1.10 (95% confidence interval, 1.02-1.18)., Conclusion: Rates of 30-day survival were significantly higher for OHCA occurring during the day compared with at night, even after adjustment for patient, event, and prehospital care differences.

Background: Previous studies have demonstrated lower mortality among patients transported to single urban trauma centers by private vehicle (PV) compared with Emergency Medical Services (EMS). We sought to describe the characteristics and outcomes of injured patients transported by PV in a state trauma system compared to patients transported by EMS., Methods: We performed a retrospective cohort study of state trauma registry data for patients admitted to all Pennsylvania trauma centers over 5 years (1/2003 to 12/2007). Our primary exposure of interest was prehospital mode of transport and our primary outcome of interest was in-hospital mortality. Unadjusted analyses were performed as were adjusted analyses controlling for injury severity. Data are presented as percents, odds ratios (ORs), and 95% confidence intervals., Results: Of the 91132 patients analyzed, 9.6% were transported to the emergency department by PV and 90.4% by EMS. Overall Injury Severity Score (ISS) was 13.3 ± 11.0 (ISS for EMS 13.7 ± 11.3, PV 9.2 ± 7.1, P < .001), and 6.6% of patients died (EMS 7.1%, PV 1.5%, P < .001). After adjusting for injury severity, patients transported by EMS were more likely to die than PV patients (OR 1.9 [95% CI 1.5-2.4]). This effect persisted in blunt, penetrating, advanced life support, and basic life support subgroups, but not in the severely injured (ISS >15, ISS >25) subgroups., Conclusions: Nearly 10% of injured patients arrive at trauma centers by private vehicle. Transport of injured patients by EMS was associated with higher mortality than PV transport. This may reflect the effects of prehospital time, prehospital interventions, or other confounders., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Dignitary Protection Medicine (DPM) is a new area of medical expertise that incorporates elements of virtually all medical and surgical specialties, drawing heavily from travel, tactical and expedition medicine. The fundamentals of DPM stem from the experiences of White House, State Department and other physicians who have traveled extensively with dignitaries. Furthermore, increased international travel of business executives and political dignitaries has mandated a need for proficiency in this realm. We sought to define the requisite knowledge base and skill sets that form the foundation of this new area of specialization., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: The objective was to identify the correlates of willingness to pay for ambulance transports from a rural city to a regional hospital in Guatemala., Methods: An innovative methodology that utilizes a novel randomization technique and satellite imagery was used to select a sample of homes in Santiago Atitlán, Guatemala. The respondents were surveyed at these homes about their willingness to pay for ambulance transport to a regional hospital. A price ladder was used to elicit respondents' willingness to pay for ambulance transport, depending on the level of severity of three types of emergencies: life-threatening emergencies, disability-causing emergencies, and simple emergencies. Simple and multiple linear regression modeling was used to identify the social and economic correlates of respondents' willingness to pay for ambulance transport and to predict demand for ambulance transport at a variety of price levels. Beta coefficients (β) expressed as percentages with 95% confidence intervals (CIs) were estimated., Results: The authors surveyed 134 respondents (response rate=3.3%). In the multivariable regression models, three variables correlated with willingness to pay: household income, location of residence (rural district vs. urban district), and respondents' education levels. Correlates for ambulance transport in life-threatening emergencies included greater household daily income (β=1.32%, 95% CI=0.63% to 2.56%), rural location of residence (β=-37.3%, 95% CI=-51.1% to -137.5%), and higher educational levels (β=4.41%, 95% CI=1.00% to 6.36%). Correlates of willingness to pay in disability-causing emergencies included greater household daily income (β=1.59%, 95% CI=0.81% to 3.19%) and rural location of residence (β=-19.4%, 95% CI=-35.7% to -89.4%). Correlates of willingness to pay in simple emergencies included rural location of residence (β=59.4%, 95% CI=37.9% to 133.7%) and higher educational levels (β=7.96%, 95% CI=1.96% to 11.8%). At all price levels, more individuals were willing to pay for transport for a life-threatening emergency than a disability-causing emergency. Respondents' willingness to pay was more responsive to price changes for transport during disability-causing emergencies than for transport during life-threatening emergencies., Conclusions: The primary correlates of willingness to pay for ambulance transport in Santiago Atitlán, Guatemala, are household income, location of residence (rural district vs. urban district), and respondents' education levels. Furthermore, severity of emergency significantly appears to influence how much individuals are willing to pay for ambulance transport. Willingness-to-pay information may help public health planners in resource-poor settings develop price scales for health services and achieve economically efficient allocations of subsidies for referral ambulance transport., (© 2012 by the Society for Academic Emergency Medicine.)

Objectives: The objective was to evaluate the effect of arrival to the emergency department (ED) by emergency medical services (EMS) on time to initiation of antibiotics, time to initiation of intravenous fluids (IVF), and in-hospital mortality in patients with severe sepsis and septic shock., Methods: The authors performed an evaluation of prospectively collected registry data of patients with a diagnosis of severe sepsis or septic shock who presented to an urban academic ED during a 2-year period from January 1, 2005, to December 31, 2006. Descriptive and multivariate analytic methods were used to analyze the data. Using unadjusted and adjusted models, out-of-hospital patients who presented to the ED by ambulance (EMS) were compared to control patients who arrived by alternative means (non-EMS). Primary outcomes measured were ED time to initiation of antibiotics, ED time to initiation of IVF, and in-hospital mortality., Results: A total of 963 severe sepsis patients were enrolled in the registry. Median time to antibiotics was 116 minutes for EMS (interquartile range [IQR] = 66 to 199) vs. 152 minutes for non-EMS (IQR = 92 to 252, p ≤ 0.001). Median time to initiation of IVF was 34 minutes for EMS (IQR = 10 to 88) and 68 minutes for non-EMS (IQR = 25 to 121, p ≤ 0.001). After adjustment for the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, age, and initial serum lactate level, no significant differences in hospital mortality were seen (adjusted relative risk [aRR] for EMS vs. non EMS = 1.24, 95% confidence interval [CI] = 0.92 to 1.66, p = 0.16). The Cox proportional hazard ratio (HR) comparing EMS to non-EMS care after similar adjustment was HR = 1.27 for IVF (95% CI = 1.10 to 1.47, p = 0.004) and HR = 1.25 for antibiotics (95% CI = 1.08 to 1.44, p = 0.003)., Conclusions: Out-of-hospital care was associated with improved in-hospital processes for the care of critically ill patients. Despite shortened ED treatment times for septic patients who arrive by EMS, a mortality benefit could not be demonstrated., (© 2011 by the Society for Academic Emergency Medicine.)

Background: Capnocytophaga canimorsus is a Gram-negative, fusiform, rod-shaped organism that is part of the normal oral flora of dogs, cats, and other animals. A significant number of Emergency Department (ED) patients are surgically or functionally asplenic and may be at marked risk for overwhelming post-splenectomy infection (OPSI). OPSI has a mortality rate estimated to be up to 70%. The risk of sepsis is estimated to be 30-60 times greater after splenectomy, and C. canimorsus is one of the organisms that can cause catastrophic OPSI., Objectives: To describe a case of C. canimorsus septic shock in a post-splenectomy patient and review the epidemiology of OPSI, the role of the spleen in protecting the body from infection, and the potential role of early goal-directed therapy in the resuscitation of patients with OPSI., Case Report: A 52 year-old man with a past medical history significant for idiopathic thrombocytopenic purpura (status post-splenectomy), and non-Hodgkin lymphoma (treated for cure), was brought to the ED with the chief complaints of light-headedness, malaise, and a rapidly spreading rash. He was found to be hypotensive, tachycardic, and tachypneic, and had a marked lactic acidosis. He was aggressively resuscitated with large volume fluid resuscitation and treated empirically with broad-spectrum antibiotics for septic shock of unclear etiology. His clinical course was complicated by acute lung injury and renal failure. Blood cultures grew C. canimorsus; he was extubated on hospital day 7 and discharged home several days later in good condition., Conclusions: Patients status-post-splenectomy are at greatly increased risk for infection from encapsulated organisms and other organisms, including C. canimorsus, which is part of the normal oral flora of dogs, cats, and other animals. It can be spread to humans by bites, scratches, or less invasive forms of animal-human contact. C. canimorsus infection can lead to OPSI. Early recognition and aggressive clinical management, including early goal-directed therapy and rapid administration of antibiotics, may minimize the morbidity and mortality of this condition and other etiologies of severe sepsis and septic shock., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: More than a decade ago, the city of Philadelphia began allowing police transport of penetrating trauma patients., Objectives:   The objective was to determine the relation between prehospital mode of transport (police department [PD] vs. Philadelphia Fire Department (PFD) emergency medical services [EMS]) and survival in subjects with proximal penetrating trauma., Methods: The authors performed a retrospective cohort study of prospectively collected trauma registry data. All subjects who sustained proximal penetrating trauma and who presented to a Level I urban trauma center over a 5-year period (January 1, 2003, to December 31, 2007) were included. Mortality for subjects presenting by EMS was compared to that of those who arrived by PD transport in unadjusted and adjusted analyses. Unadjusted analyses were performed using the chi-square test, Wilcoxon rank sum test, and Student's t-test. Adjusted analyses were performed using logistic regression using the Trauma Injury Severity Score (TRISS) methodology. Data are presented as percentages, odds ratios (ORs), and 95% confidence intervals (CIs). Total hospital length of stay was examined as a secondary outcome., Results: Of the 2,127 subjects, 26.8% were transported to the emergency department (ED) by PD, and 73.2% by EMS. The mean(±standard deviation [SD]) age of PD subjects was 26.3 (±9.1) years and 92% were male versus EMS subjects whose mean (±SD) age was 31.5 (±11.8) years and of whom 87% were male. Overall, 70.8% sustained a gunshot wound (GSW), and 29.2% sustained a stab wound (SW). Overall Injury Severity Score (ISS) was 11.21 (ISS for PD, 14.2±17.5; for EMS, 10.1±14.5; p<0.001), and 16.6% of the subjects died (PD, 21.4±0.41%; EMS, 14.8±0.36%; p<0.001). In unadjusted analyses, PD subjects were more likely to die than EMS subjects (OR=1.6, 95% CI=1.2 to 2.0; p<0.001). When adjusting for injury severity using TRISS, there was no difference in survival between PD and EMS subjects (OR=1.01, 95% CI=0.63 to 1.61). Median length of hospital stay was 1 day and did not differ according to mode of prehospital transport (p=0.159)., Conclusions: Although unadjusted mortality appears to be higher in PD subjects, these findings are explained by the more severely injured population transported by PD. The current practice of permitting police officers to transport penetrating trauma patients should be continued., (© 2010 by the Society for Academic Emergency Medicine.)

Purpose: Early recognition and treatment in severe sepsis improve outcomes. However, out-of-hospital patient characteristics and emergency medical services (EMS) care in severe sepsis is understudied. Our goals were to describe out-of-hospital characteristics and EMS care in patients with severe sepsis and to evaluate associations between out-of-hospital characteristics and severity of organ dysfunction in the emergency department (ED)., Materials and Methods: We performed a secondary data analysis of existing data from patients with severe sepsis transported by EMS to an academic medical center. We constructed multivariable linear regression models to determine if out-of-hospital factors are associated with serum lactate and sequential organ failure assessment (SOFA) in the ED., Results: Two hundred sixteen patients with severe sepsis arrived by EMS. Median serum lactate in the ED was 3.0 mmol/L (interquartile range, 2.0-5.0) and median SOFA score was 4 (interquartile range, 2-6). Sixty-three percent (135) of patients were transported by advanced life support providers and 30% (62) received intravenous fluid. Lower out-of-hospital Glasgow Coma Scale score was independently associated with elevated serum lactate (P < .01). Out-of-hospital hypotension, greater respiratory rate, and lower Glasgow Coma Scale score were associated with greater SOFA (P < .01)., Conclusions: Out-of-hospital fluid resuscitation occurred in less than one third of patients with severe sepsis, and routinely measured out-of-hospital variables were associated with greater serum lactate and SOFA in the ED., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This article summarizes the discussions of the emergency medical services (EMS) breakout session at the June 2010 Academic Emergency Medicine consensus conference "Beyond Regionalization: Integrated Networks of Emergency Care." The group focused on prehospital issues such as the identification of patients by EMS personnel, protocol-driven destination selection, bypassing closer nondesignated centers to transport patients directly to more distant designated specialty centers, and the modes of transport to be used as they relate to the regionalization of emergency care. It is our hope that the proposed research agenda will be advanced in a way that begins to rigorously approach the unanswered research questions and that these answers, in turn, will lead to an evidence-based, cohesive, comprehensive, and more uniform set of guidelines that govern the delivery and practice of prehospital emergency care., (2010 by the Society for Academic Emergency Medicine.)

Objective: To study the association between time to antibiotic administration and survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department., Design: Single-center cohort study., Setting: The emergency department of an academic tertiary care center from 2005 through 2006., Patients: Two hundred sixty-one patients undergoing early goal-directed therapy., Interventions: None., Measurements and Main Results: Effects of different time cutoffs from triage to antibiotic administration, qualification for early goal-directed therapy to antibiotic administration, triage to appropriate antibiotic administration, and qualification for early goal-directed therapy to appropriate antibiotic administration on in-hospital mortality were examined. The mean age of the 261 patients was 59 +/- 16 yrs; 41% were female. In-hospital mortality was 31%. Median time from triage to antibiotics was 119 mins (interquartile range, 76-192 mins) and from qualification to antibiotics was 42 mins (interquartile range, 0-93 mins). There was no significant association between time from triage or time from qualification for early goal-directed therapy to antibiotics and mortality when assessed at different hourly cutoffs. When analyzed for time from triage to appropriate antibiotics, there was a significant association at the <1 hr (mortality 19.5 vs. 33.2%; odds ratio, 0.30 [95% confidence interval, 0.11-0.83]; p = .02) time cutoff; similarly, for time from qualification for early goal-directed therapy to appropriate antibiotics, a significant association was seen at the < or =1 hr (mortality 25.0 vs. 38.5%; odds ratio, 0.50 [95% confidence interval, 0.27-0.92]; p = .03) time cutoff., Conclusions: Elapsed times from triage and qualification for early goal-directed therapy to administration of appropriate antimicrobials are primary determinants of mortality in patients with severe sepsis and septic shock treated with early goal-directed therapy.

Background: Early identification and treatment of patients with severe sepsis improves outcome, yet the role of out-of-hospital intravenous (IV) fluid is unknown., Objective: To determine if the delivery of out-of-hospital fluid in patients with severe sepsis is associated with reduced time to achievement of goal-oriented resuscitation in the emergency department (ED)., Methods: We performed a secondary data analysis of a retrospective cohort study in a metropolitan, tertiary care, university-based medical center supported by a two-tiered system of out-of-hospital emergency medical services (EMS) providers. We studied the association between delivery of out-of-hospital fluid by advanced life support (ALS) providers and the achievement of resuscitation endpoints (central venous pressure [CVP] > or =8 mmHg, mean arterial pressure [MAP] > or =65 mmHg, and central venous oxygen saturation [ScvO(2)] > or =70%) within six hours after triage during early goal-directed therapy (EGDT) in the ED., Results: Twenty five (48%) of 52 patients transported by ALS with severe sepsis received out-of-hospital fluid. Data for age, gender, source of sepsis, and presence of comorbidities were similar between patients who did and did not receive out-of-hospital fluid. Patients receiving out-of-hospital fluid had lower out-of-hospital mean (+/- standard deviation) systolic blood pressure (95 +/- 40 mmHg vs. 117 +/- 29 mmHg; p = 0.03) and higher median (interquartile range) Sequential Organ Failure Assessment (SOFA) scores in the ED (7 [5-8] vs. 4 [4-6]; p = 0.01) than patients not receiving out-of-hospital fluid. Despite greater severity of illness, patients receiving out-of-hospital fluid approached but did not attain a statistically significant increase in the likelihood of achieving MAP > or =65 mmHg within six hours after ED triage (70% vs. 44%, p = 0.09). On average, patients receiving out-of-hospital fluid received twice the fluid volume within one hour after ED triage (1.1 L [1.0-2.0 L] vs. 0.6 L [0.3-1.0 L]; p = 0.01). No difference in achievement of goal CVP (72% vs. 60%; p = 0.6) or goal ScvO(2) (54% vs. 36%; p = 0.25) was observed between groups., Conclusions: Less than half of patients with severe sepsis transported by ALS received out-of-hospital fluid. Patients receiving out-of-hospital IV access and fluids approached but did not attain a statistically significant increase in the likelihood of achieving goal MAP during EGDT. These preliminary findings require additional investigation to evaluate the optimal role of out-of-hospital resuscitation in treating patients with severe sepsis.

Objectives: Prior data demonstrated that a urine dipstick used alone was a sensitive predictor of abnormal creatinine, but not sufficiently enough to forego screening of serum creatinine prior to administration of contrast for diagnostic studies. The authors hypothesized that a brief historical questionnaire coupled with a urine dipstick would have high sensitivity for renal dysfunction, potentially eliminating the need for a serum creatinine prior to contrast administration., Methods: This was a prospective study of a convenience sample of patients at two academic tertiary-care emergency departments (EDs) during 2006-2007. Subjects included patients who had both a serum creatinine result reported by the laboratory and a urine dipstick result reported in the medical record. Data included triage vital signs, basic demographic data, 14 medical history items, dipstick urinalysis, and serum creatinine results. The main outcome measure was an abnormal serum creatinine, defined as greater than 1.5 mg/dL., Results: Complete data sets were collected on 1,354 patient visits. Of these, there were 161 (12%) with a serum creatinine of >1.5 mg/dL. Logistic regression analysis identified the following independent predictors associated with elevated creatinine: age greater than 60 years, known renal insufficiency, diabetes, hypertension, diuretic use, vomiting, and proteinuria. Nearly all patients with abnormal creatinine (98%) had at least one of these seven predictors. A decision tool combining these predictors would have identified 158 of 161 patients with an abnormal creatinine (sensitivity, 98.1%; 95% confidence interval [CI] = 95.8% to 99.9%) and a specificity of 21.2% (95% CI = 18.8% to 23.2%)., Conclusions: The absence of six historical factors and absence of proteinuria can be safely used to identify patients who are unlikely to have an abnormal creatinine.

Objectives: We sought to review findings from recent literature on the postresuscitation care of cardiac arrest patients using therapeutic hypothermia as part of nontrial treatment., Design: Literature review., Setting: Hospital-based environment., Subjects: Patients initially resuscitated from cardiac arrest who underwent hypothermia induction as a treatment regimen or historical control patients who did not receive hypothermia therapy., Measurement: : We compiled protocol methodology from the various studies, as well as survival-to-hospital discharge and neurological outcomes., Main Results: Although varied in their protocols and outcome reporting, results from published investigations confirmed the findings from landmark randomized controlled trials, in that the use of therapeutic hypothermia increased survival with an odds ratio of 2.5 (95% confidence interval, 1.8-3.3) and favorable outcome with an odds ratio of 2.5 (95% confidence interval, 1.9-3.4)., Conclusions: The survival and neurological outcomes benefit from therapeutic hypothermia are robust when compared over a wide range of studies of actual implementation.

Background: Comatose survivors of out-of-hospital cardiac arrest (OHCA) have high in-hospital mortality due to a complex pathophysiology that includes cardiovascular dysfunction, inflammation, coagulopathy, brain injury and persistence of the precipitating pathology. Therapeutic hypothermia (TH) is the only intervention that has been shown to improve outcomes in this patient population. Due to the similarities between the post-cardiac arrest state and severe sepsis, it has been postulated that early goal-directed hemodyamic optimization (EGDHO) combined with TH would improve outcome of comatose cardiac arrest survivors., Objective: We examined the feasibility of establishing an integrated post-cardiac arrest resuscitation (PCAR) algorithm combining TH and EGDHO within 6h of emergency department (ED) presentation., Methods: In May, 2005 we began prospectively identifying comatose (Glasgow Motor Score<6) survivors of OHCA treated with our PCAR protocol. The PCAR patients were compared to matched historic controls from a cardiac arrest database maintained at our institution., Results: Between May, 2005 and January, 2008, 18/20 (90%) eligible patients were enrolled in the PCAR protocol. They were compared to historic controls from 2001 to 2005, during which time 18 patients met inclusion criteria for the PCAR protocol. Mean time from initiation of TH to target temperature (33 degrees C) was 2.8h (range 0.8-23.2; SD=h); 78% (14/18) had interventions based upon EGDHO parameters; 72% (13/18) of patients achieved their EGDHO goals within 6h of return of spontaneous circulation (ROSC). Mortality for historic controls who qualified for the PCAR protocol was 78% (14/18); mortality for those treated with the PCAR protocol was 50% (9/18) (p=0.15)., Conclusions: In patients with ROSC after OHCA, EGDHO and TH can be implemented simultaneously.

Purpose: We sought to generate national estimates for post-cardiac arrest mortality, to assess trends, and to identify hospital factors associated with survival., Methods: We used a national sample of US hospitals to identify patients resuscitated after cardiac arrest from 2000 to 2004 to describe the association between hospital factors (teaching status, location, size) and mortality, length of stay, and hospital charges. Analyses were performed using logistic regression., Results: A total of 109,739 patients were identified. In-hospital mortality was 70.6%. A 2% decrease in unadjusted mortality from 71.6% in 2000 to 69.6% in 2004 (OR 0.96, P < 0.001) was observed. Mortality was lower at teaching hospitals (OR 0.58, P = 0.001), urban hospitals (OR 0.63, P = 0.004), and large hospitals (OR 0.55, P < 0.001)., Conclusion: Mortality after in-hospital cardiac arrest decreased over 5 years. Mortality was lower at urban, teaching, and large hospitals. There are implications for dissemination of best practices or regionalization of post-cardiac arrest care.

Over the past several years, the implementation of therapeutic hypothermia has provided an exciting opportunity toward improving survival from out-of-hospital cardiac arrest. There are compelling data to support the prompt use of therapeutic hypothermia for initial survivors from out-of-hospital cardiac arrest, but animal data have suggested that initiation of therapeutic hypothermia during the intra-arrest period may significantly improve outcomes even further. In the first feasibility study in humans, Bruel and colleagues report on the implementation of this intra-arrest approach among patients suffering out-of-hospital cardiac arrest, an exciting prospect that is discussed in the present commentary.

Study Objective: We examine the validity of the emergency department (ED) occupancy rate as a measure of crowding by comparing it to the Emergency Department Work Index Score (EDWIN), a previously validated scale., Methods: A multicenter validation study was conducted according to ED visit data from 6 academic EDs for a 3-month period in 2005. Hourly ED occupancy rate (ie, total number of patients in ED divided by total number of licensed beds) and EDWIN scores were calculated. The correlation between the scales was determined and their validity evaluated by their ability to discriminate between hours when 1 or more patients left without being seen and hours when the ED was on ambulance diversion, using area under the curve (AUC) statistics estimated from the bootstrap method., Results: We calculated the ED occupancy rate and EDWIN for 2,208 consecutive hours at each of the 6 EDs. The overall correlation between the 2 scales was 0.58 (95% confidence interval [CI] 0.56 to 0.60). The ED occupancy rate (AUC=0.73; 95% CI 0.65 to 0.80) and the EDWIN (AUC=0.65; 95% CI 0.58 to 0.72) did not differ significantly in correctly identifying hours when patients left without being seen. The ED occupancy rate (AUC=0.78; 95% CI 0.75 to 0.80) and the EDWIN (AUC=0.70; 95% CI 0.59 to 0.81) performed similarly for ED diversion hours., Conclusion: The ED occupancy rate and the EDWIN classified leaving without being seen and ambulance diversion hours with moderate accuracy. Although the ED occupancy rate is not ideal, its simplicity makes real-time assessment of crowding feasible for more EDs nationwide.

Study Objective: Despite creatinine clearance (CrCl) being a better estimate of renal function, serum creatinine (Cr) is more commonly used to screen for renal insufficiency in patients scheduled for an enhanced abdominal computed tomography (CT) in an attempt to reduce the likelihood of contrast-induced nephropathy (CIN). Our objective was to determine the incidence of renal insufficiency (a CrCl <60 mL/min) among patients who have serum Cr below 1.5 mg/dL (the most commonly accepted Cr cutoff for the administration of intravenous contrast). This study was conducted in a population of emergency department patients with acute abdominal pain being considered for CT scan., Methods: We performed post hoc analysis of a prospective cross-sectional study that enrolled nongravid adults with acute nontraumatic abdominal pain. Patients on dialysis were excluded. The data that we collected included demographics, history, duration/description of pain, patient reported weight, laboratory data, imaging studies, and final diagnosis. Creatinine clearance values (< or >60 mL/min) were compared to Cr values of 1.0, 1.2, 1.5, and 1.8 mg/dL to determine the percentage of patients at risk for nephropathy after contrast injection at each Cr cutoff. Descriptive statistics were used with 95% confidence intervals (CIs)., Results: Seven hundred sixty-five patients were enrolled; 59% (451/765) had an abdominal CT scan. Of 108 patients with CrCl less than 60 mL/min, 59 patients had a Cr less than 1.8 mg/dL (55%; 95% CI, 45%-64%); 43 had a Cr less than 1.5 mg/dL, the most commonly accepted Cr cutoff for contrast administration (40%; 95% CI, 31%-50%); 21 patients had a Cr less than 1.2 mg/dL (19%; 95% CI, 12%-28%); and 10 had a Cr less than 1.0 mg/dL (9%; 95% CI, 5%-16%)., Conclusion: The most commonly used Cr cutoff (1.5 mg/dL) for contrast administration fails to identify 40% of the patients at risk for CIN. Future studies should address whether using CrCl rather than serum Cr decreases the incidence of contrast-induced nephropathy.

Purpose: To define the toxicity profile and the recommended phase II doses of 9-aminocamptothecin (9-AC) administered as a weekly 120-h infusion., Methods: 9-AC was administered over 120 h weekly to 55 adult cancer patients with solid tumors over doses ranging from 0.41 to 0.77 mg/m2 per day in a phase I and pharmacologic study. 9-AC formulated in dimethylacetamide/polyethylene glycol (DMA) was administered on a 3 of 4-week schedule, and the newer colloidal dispersion (CD) formulation was given on a 2 of 3-week schedule., Results: Overall, 193 courses of therapy were administered over 122 dose levels. On the 3 of 4-week schedule, 9-AC DMA infused at > or = 0.6 mg/m2 per day for 120 h weekly produced dose-limiting neutropenia, thrombocytopenia, and diarrhea, or resulted in 1-2-week treatment delays. Shortening treatments to 2 of 3 weeks resulted in dose-limiting neutropenia and fatigue at infusion rates > 0.72 mg/m2 per day. The ratio of 9-AC lactone to total (carboxylate + lactone) drug plasma concentrations at steady-state was 0.15 +/- 0.07. Clinical toxicities and drug pharmacokinetics were not substantially different between the DMA and CD formulations. One objective response was observed in a patient with bladder cancer and minor responses were observed in patients with lung and colon cancers. Plasma area under the concentration versus time curve for 9-AC lactone modestly correlated with the degree of thrombocytopenia (r=0.51) using a sigmoid Emax pharmacodynamic model., Conclusion: The recommended phase II dose for the 9-AC DMA formulation is 0.48 mg/m2 per h over 120 h for 3 of 4 weeks and for the 9-AC CD formulation is 0.6 mg/m2 per day over 120 h for 2 of 3 weeks. Both regimens were well tolerated and feasible to administer.

Purpose: We conducted a phase I and pharmacologic study of a weekly 96-hour infusion of irinotecan to determine the maximum-tolerated dose, define the toxicity profile, and characterize the clinical pharmacology of irinotecan and its metabolites., Patients and Methods: In 26 adult patients with solid tumors, the duration and dose rate of infusion were escalated in new patients until toxicity was observed., Results: In 11 patients who were treated with irinotecan at 12.5 mg/m(2)/d for 4 days weekly for 2 of 3 weeks, dose-limiting grade 3 diarrhea occurred in three patients and grade 3 thrombocytopenia occurred in two patients. The recommended phase II dose is 10 mg/m(2)/d for 4 days given weekly for 2 of 3 weeks. At this dose, the steady-state plasma concentration (Css) of total SN-38 (the active metabolite of irinotecan) was 6.42 +/- 1.10 nmol/L, and the Css of total irinotecan was 28.60 +/- 17.78 nmol/L. No patient experienced grade 3 or 4 neutropenia during any cycle. All other toxicities were mild to moderate. The systemic exposure to SN-38 relative to irinotecan was greater than anticipated, with a molar ratio of the area under the concentration curve (AUC) of SN-38 to irinotecan of 0.24 +/- 0.08. One objective response lasting 12 months in duration was observed in a patient with metastatic colon cancer., Conclusion: The recommended phase II dose of irinotecan of 10 mg/m(2)/d for 4 days weekly for 2 of 3 weeks was extremely well tolerated. Further efficacy testing of this pharmacologic strategy of administering intermittent low doses of irinotecan is warranted.

Purpose: To investigate the pharmacokinetics and pharmacodynamics of 9-aminocamptothecin (9-AC) infused over 72 hours at doses of 5 to 74 micrograms/m2/h., Patients and Methods: 9-AC lactone and total (lactone plus carboxylate) plasma concentrations were measured in 44 patients with solid tumors using a high-performance liquid chromatography (HPLC) assay. Fifteen patients underwent extended pharmacokinetic sampling to determine the distribution and elimination kinetics of 9-AC., Results: At steady-state, 8.7% +/- 4.7% (mean +/- SD) of the total drug circulated in plasma as the active 9-AC lactone. Clearance of 9-AC lactone was uniform (24.5 +/- 7.3 L/h/m2) over the entire dose range examined; however, total 9-AC clearance was nonlinear and increased at higher dose levels. In 15 patients treated at dose levels > or = 47 micrograms/m2/h, the volume of distribution at steady-state for 9-AC lactone was 195 +/- 114 L/m2 and for total 9-AC it was 23.6 +/- 10.6 L/m2. The elimination half-life was 4.47 +/- 0.53 hours for 9-AC lactone and 8.38 +/- 2.10 hours for total 9-AC. In pharmacodynamic studies, dose-limiting neutropenia correlated with steady-state lactone concentrations (Css) R2 = .77) and drug dose (R2 = .71)., Conclusion: Plasma 9-AC concentrations rapidly declined to low levels following the end of a 72-hour infusion and the mean fraction of total 9-AC circulating in plasma as the active lactone was less than 10%. The pharmacokinetics of 9-AC may have a great impact on its clinical activity and should be considered in the design of future clinical trials of this topoisomerase I inhibitor.