National characteristics of emergency medical services responses in the United States.

OBJECTIVE: Despite its long history and current prominence in U.S. communities, only limited data describe the national characteristics of emergency medical services (EMS) care in the United States. We sought to characterize out-of-hospital EMS care in the United States. METHODS: We conducted an analysis of the 2010 National Emergency Medical Services Information System (NEMSIS) research data set, encompassing EMS emergency response data from 29 states. From these data, we estimated the national number and incidence of EMS responses. We also characterized EMS responses and the patients receiving care. RESULTS: There were 7,563,843 submitted EMS responses, corresponding to an estimated national incidence of 17.4 million EMS emergency responses per year (56 per 1,000 person-years). The EMS response incidence varied by U.S. Census region (South 137.4 per 1,000 population per year, Northeast 85.2, West 39.7, and Midwest 33.3). The use of lights and sirens varied across Census regions (Northeast 90.3%, South 76.7%, West 68.8%, and Midwest 67.5%). The percentage of responses resulting in patient contact varied across Census regions (range 78.4% to 95.7%). The EMS time intervals were similar between Census regions; response median 5 minutes (interquartile range [IQR] 3-9), scene 14 minutes (10-20), and transport 11 minutes (7-19). Underserved populations (the elderly, minorities, rural residents, and the uninsured) were large users of EMS resources. CONCLUSION: These data highlight the breadth and diversity of EMS demand and care in the United States.

HLA class I - associated immunodominance affects CTL responsiveness to an ESO recombinant protein tumor antigen vaccine.

PURPOSE: Vaccination with full-length human tumor antigens aims at inducing or increasing antitumor immune responses, including CD8 CTL in cancer patients across the HLA barrier. We have recently reported that vaccination with a recombinant tumor-specific NY-ESO-1 (ESO) protein, administered with Montanide and CpG resulted in the induction of specific integrated antibody and CD4 T cell responses in all vaccinated patients examined, and significant CTL responses in half of them. Vaccine-induced CTL mostly recognized a single immunodominant region (ESO 81-110). The purpose of the present study was to identify genetic factor(s) distinguishing CTL responders from nonresponders. EXPERIMENTAL DESIGN: We determined the HLA class I alleles expressed by CTL responders and nonresponders using high-resolution molecular typing. Using short overlapping peptides spanning the ESO immunodominant CTL region and HLA class I/ESO peptide tetramers, we determined the epitopes recognized by the majority of vaccine-induced CTL. RESULTS: CTL induced by vaccination with ESO protein mostly recognized distinct but closely overlapping epitopes restricted by a few frequently expressed HLA-B35 and HLA-Cw3 alleles. All CTL responders expressed at least one of the identified alleles, whereas none of the nonresponders expressed them. CONCLUSIONS: Expression of HLA-B35 and HLA-Cw3 is associated with the induction of immunodominant CTL responses following vaccination with recombinant ESO protein. Because recombinant tumor-specific proteins are presently among the most promising candidate anticancer vaccines, our findings indicate that the monitoring of cancer vaccine trials should systematically include the assessment of HLA association with responsiveness.

Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa).

Outcome after cardiac arrest and cardiopulmonary resuscitation is dependent on critical interventions, particularly early defibrillation, effective chest compressions, and advanced life support. Utstein-style definitions and reporting templates have been used extensively in published studies of cardiac arrest, which has led to greater understanding of the elements of resuscitation practice and progress toward international consensus on science and resuscitation guidelines. Despite the development of Utstein templates to standardize research reports of cardiac arrest, international registries have yet to be developed. In April 2002, a task force of the International Liaison Committee on Resuscitation (ILCOR) met in Melbourne, Australia, to review worldwide experience with the Utstein definitions and reporting templates. The task force revised the core reporting template and definitions by consensus. Care was taken to build on previous definitions, changing data elements and operational definitions only on the basis of published data and experience derived from those registries that have used Utstein-style reporting. Attention was focused on decreasing the complexity of the existing templates and addressing logistical difficulties in collecting specific core and supplementary (ie, essential and desirable) data elements recommended by previous Utstein consensus conferences. Inconsistencies in terminology between in-hospital and out-of-hospital Utstein templates were also addressed. The task force produced a reporting tool for essential data that can be used for both quality improvement (registries) and research reports and that should be applicable to both adults and children. The revised and simplified template includes practical and succinct operational definitions. It is anticipated that the revised template will enable better and more accurate completion of all reports of cardiac arrest and resuscitation attempts. Problems with data definition, collection, linkage, confidentiality, management, and registry implementation are acknowledged and potential solutions offered. Uniform collection and tracking of registry data should enable better continuous quality improvement within every hospital, emergency medical services system, and community.

Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa).

Outcome following cardiac arrest and cardiopulmonary resuscitation is dependent on critical interventions, particularly early defibrillation, effective chest compressions, and advanced life support. Utstein-style definitions and reporting templates have been used extensively in published studies of cardiac arrest, which has led to greater understanding of the elements of resuscitation practice and progress toward international consensus on science and resuscitation guidelines. Despite the development of Utstein templates to standardize research reports of cardiac arrest, international registries have yet to be developed. In April 2002 a task force of ILCOR met in Melbourne, Australia, to review worldwide experience with the Utstein definitions and reporting templates. The task force revised the core reporting template and definitions by consensus. Care was taken to build on previous definitions, changing data elements and operational definitions only on the basis of published data and experience derived from those registries that have used Utstein-style reporting. Attention was focused on decreasing the complexity of the existing templates and addressing logistical difficulties in collecting specific core and supplementary (i.e., essential and desirable) data elements recommended by previous Utstein consensus conference. Inconsistencies in terminology between in-hospital and out-of-hospital Utstein templates were also addressed. The task force produced a reporting tool for essential data that can be used for both quality improvement (registries) and research reports and that should be applicable to both adults and children. The revised and simplified template includes practical and succinct operational definitions. It is anticipated that the revised template will enable better and more accurate completion of all reports of cardiac arrest and resuscitation attempts. Problems with data definition, collection, linkage, confidentiality, management, and registry implementation are acknowledged and potential solutions offered. Uniform collection and tracking of registry data should enable better continuous quality improvement within every hospital, EMS system, and community.

Out-of-hospital airway management in the United States.

OBJECTIVE: Prior studies describe airway management by single EMS agencies, regions or states. We sought to characterize out-of-hospital airway management interventions, outcomes and complications across the United States. METHODS: Using the 2008 National Emergency Medical Services Information System (NEMSIS) Public-Release Data Set containing data from 16 states, we identified patients receiving advanced airway management, including endotracheal intubation (ETI), alternate airways (Combitube, Laryngeal Mask Airway (LMA), King LT, Esophageal-Obturator Airway (EOA)), and cricothyroidotomy (needle and open). We examined airway management success and complications in the full cohort and in key subsets (cardiac arrest, non-arrest medical, non-arrest injury, children <10 and 10-19 years, rapid-sequence intubation (RSI), population setting and US census region). We analyzed the data using descriptive statistics. RESULTS: Among 4,383,768 EMS activations, there were 10,356 ETI, 2246 alternate airways, and 88 cricothyroidotomies. ETI success rates were: overall 6482/8418 (77.0%; 95% CI: 76.1-77.9%), cardiac arrest 3494/4482 (78.0%), non-arrest medical 616/846 (72.8%), non-arrest injury 417/505 (82.6%), children <10 years 295/397 (74.3%), children 10-19 years 228/289 (78.9%), adult 5829/7552 (77.2%), and rapid-sequence intubation 289/355 (81.4%). ETI success was success was lowest in the South US census region. Alternate airway success was 1564/1794 (87.2%). Major complications included: bleeding 84 (7.0 per 1000 interventions), vomiting 80 (6.7 per 1000) and esophageal intubation 12 (1.0 per 1000). CONCLUSIONS: In this study characterizing out-of-hospital airway management across the United States, we observed low out-of-hospital ETI success rates. These data may guide national efforts to improve the quality of out-of-hospital airway management.

Vaccination with a recombinant protein encoding the tumor-specific antigen NY-ESO-1 elicits an A2/157-165-specific CTL repertoire structurally distinct and of reduced tumor reactivity than that elicited by spontaneous immune responses to NY-ESO-1-expressing Tumors.

In a recent vaccination trial assessing the immunogenicity of an NY-ESO-1 (ESO) recombinant protein administered with Montanide and CpG, we have obtained evidence that this vaccine induces specific cytolytic T lymphocytes (CTL) in half of the patients. Most vaccine-induced CTLs were directed against epitopes located in the central part of the protein, between amino acids 81 and 110. This immunodominant region, however, is distinct from another ESO CTL region, 157-165, that is a frequent target of spontaneous CTL responses in A2+ patients bearing ESO tumors. In this study, we have investigated the CTL responses to ESO 157-165 in A2+ patients vaccinated with the recombinant protein. Our data indicate that after vaccination with the protein, CTL responses to ESO 157-165 are induced in some, but not all, A2+ patients. ESO 157-165-specific CTLs induced by vaccination with the ESO protein were functionally heterogeneous in terms of tumor recognition and often displayed decreased tumor reactivity as compared with ESO 157-165-specific CTLs isolated from patients with spontaneous immune responses to ESO. Remarkably, protein-induced CTLs used T-cell receptors similar to those previously isolated from patients vaccinated with synthetic ESO peptides (Vbeta4.1) and distinct from those used by highly tumor-reactive CTLs isolated from patients with spontaneous immune responses (Vbeta1.1, Vbeta8.1, and Vbeta13.1). Together, these results demonstrate that vaccination with the ESO protein elicits a repertoire of ESO 157-165-specific CTLs bearing T-cell receptors that are structurally distinct from those of CTLs found in spontaneous immune responses to the antigen and that are heterogeneous in terms of tumor reactivity, being often poorly tumor reactive.

Vaccination with recombinant NY-ESO-1 protein elicits immunodominant HLA-DR52b-restricted CD4+ T cell responses with a conserved T cell receptor repertoire.

PURPOSE: ESO is a tumor-specific antigen with wide expression in human tumors of different histologic types and remarkable spontaneous immunogenicity. We have previously shown that specific T(H)1 and antibody responses can be elicited in patients with no detectable preexisting immune responses by vaccination with rESO administered with Montanide ISA-51 and CpG ODN 7909. The purpose of the present study was to characterize vaccine-induced ESO-specific CD4(+) T cell responses. EXPERIMENTAL DESIGN: We generated CD4(+) T cell clones from patient C2, who had the highest CD4(+) T cell response to the vaccine, and analyzed their fine specificity and HLA class II restriction to determine the recognized epitope. We then assessed the response to the identified epitope in all vaccinated patients expressing the corresponding HLA class II allele. RESULTS: We found that ESO-specific CD4(+) T cell clones from patient C2 recognize peptide ESO(119-143) (core region 123-137) presented by HLA-DR52b (HLA-DRB3*0202), a MHC class II allele expressed by about half of Caucasians. Importantly, following vaccination, all patients expressing DR52b developed significant responses to the identified epitope, accounting for, on average, half of the total CD4(+) T cell responses to the 119-143 immunodominant region. In addition, analysis of ESO-specific DR52b-restricted CD4(+) T cells at the clonal level revealed significant conservation of T cell receptor usage among different individuals. CONCLUSIONS: The identification of a DR52b-restricted epitope from ESO that is immunodominant in the context of vaccine-elicited immune responses is instrumental for the immunologic monitoring of vaccination trials targeting this important tumor antigen.

Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming.

The use of recombinant tumor antigen proteins is a realistic approach for the development of generic cancer vaccines, but the potential of this type of vaccines to induce specific CD8(+) T cell responses, through in vivo cross-priming, has remained unclear. In this article, we report that repeated vaccination of cancer patients with recombinant NY-ESO-1 protein, Montanide ISA-51, and CpG ODN 7909, a potent stimulator of B cells and T helper type 1 (Th1)-type immunity, resulted in the early induction of specific integrated CD4(+) Th cells and antibody responses in most vaccinated patients, followed by the development of later CD8(+) T cell responses in a fraction of them. The correlation between antibody and T cell responses, together with the ability of vaccine-induced antibodies to promote in vitro cross-presentation of NY-ESO-1 by dendritic cells to vaccine-induced CD8(+) T cells, indicated that elicitation of NY-ESO-1-specific CD8(+) T cell responses by cross-priming in vivo was associated with the induction of adequate levels of specific antibodies. Together, our data provide clear evidence of in vivo cross-priming of specific cytotoxic T lymphocytes by a recombinant tumor antigen vaccine, underline the importance of specific antibody induction for the cross-priming to occur, and support the use of this type of formulation for the further development of efficient cancer vaccines.

Emergency medical services information systems and a future EMS national database.

Since the early 1970s, various publications and legislation have contributed to the development of emergency medical services (EMS) information systems and databases. Yet, even today, EMS systems vary in their ability to collect patient and systems data and to put these data to use. In addition, no means currently exists to easily link disparate EMS databases to allow analysis at local, state, and national levels. For this reason, the National Association of State EMS Directors is working with its federal partners at the National Highway Traffic Safety Administration (NHTSA) and the Trauma and EMS program of the Health Resources and Services Administration's (HRSA's) Maternal and Child Health Bureau to develop a national EMS database. Such a database would be useful in developing nationwide EMS training curricula, evaluating patient and EMS system outcomes, facilitating research efforts, determining national fee schedules and reimbursement rates, and providing valuable information on other issues related to EMS care.

Alternative cardiopulmonary resuscitation devices.

Cardiopulmonary resuscitation (CPR) involving manual external chest compression combined with artificial respiration was first described in 1960 by Kouwenhoven et al. (Kouwenhoven W, Jude JR, Knickerbocker GG. Closed-chest cardiac massage. JAMA. 1960; 173:1064-7). In the four decades since then, there have been no widely accepted alternatives for this technique. Even with the subsequent worldwide adoption of CPR and other advanced cardiac life support measures, long-term survival after prehospital cardiac arrest is still typically only 5%, to 10%. The performance of CPR must therefore be improved to increase the rate of long-term survival. Currently under development are new, alternative techniques such as interposed abdominal compression (IAC), active compression-decompression (ACD), pneumatic and nonpneumatic circumferential chest compression, and minimally invasive cardiac massage. Many of these newer techniques, compared with standard manual CPR, appear to provide superior vital organ blood flow and increased blood pressure. To date, only IAC (in-hospital only) and ACD have been shown to improve long-term survival in clinical studies. Circumferential chest compression and minimally invasive cardiac massage, on the other hand, have not yet been adequately tested in large clinical trials. Despite the difficulty and expense in studying these CPR techniques, additional research is necessary to evaluate their effectiveness in improving survival after sudden cardiac arrest.

Performance measurements in emergency medical services.

With the strong encouragement of leading health care agencies, business principles are being implemented throughout health care, including emergency medical services (EMS). The reason is simple--quality of care can be enhanced by incorporating the management concepts of continuous quality improvement (CQI). The CQI process couples carefully identified, measurable performance indicators with information systems to monitor, analyze, and trend data. Benchmarking outcomes with other EMS systems allows the identification of "best practices" and the evolution of standards. Emergency medical services professionals must actively participate with the broader health care community in creating performance measurements to ensure that high-quality care is delivered consistently.