The Golden Hour of Casualty Care: Rapid Handoff to Surgical Team is Associated With Improved Survival in War-injured US Service Members.

OBJECTIVE: To examine time from injury to initiation of surgical care and association with survival in US military casualties. BACKGROUND: Although the advantage of trauma care within the "golden hour" after an injury is generally accepted, evidence is scarce. METHODS: This retrospective, population-based cohort study included US military casualties injured in Afghanistan and Iraq, January 2007 to December 2015, alive at initial request for evacuation with maximum abbreviated injury scale scores ≥2 and documented 30-day survival status after injury. Interventions: (1) handoff alive to the surgical team, and (2) initiation of first surgery were analyzed as time-dependent covariates (elapsed time from injury) using sequential Cox proportional hazards regression to assess how intervention timing might affect mortality. Covariates included age, injury year, and injury severity. RESULTS: Among 5269 patients (median age, 24 years; 97% males; and 68% battle-injured), 728 died within 30 days of injury, 68% within 1 hour, and 90% within 4 hours. Only handoffs within 1 hour of injury and the resultant timely initiation of emergency surgery (adjusted also for prior advanced resuscitative interventions) were significantly associated with reduced 24-hour mortality compared with more delayed surgical care (adjusted hazard ratios: 0.34; 95% CI: 0.14-0.82; P = 0.02; and 0.40; 95% CI: 0.20-0.81; P = 0.01, respectively). In-hospital waits for surgery (mean: 1.1 hours; 95% CI; 1.0-1.2) scarcely contributed ( P = 0.67). CONCLUSIONS: Rapid handoff to the surgical team within 1 hour of injury may reduce mortality by 66% in US military casualties. In the subgroup of casualties with indications for emergency surgery, rapid handoff with timely surgical intervention may reduce mortality by 60%. To inform future research and trauma system planning, findings are pivotal.

Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials.

OBJECTIVE: To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia. BACKGROUND: A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators. METHODS: An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability. CONCLUSIONS: For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes.

A Pilot Trial of Platelets Stored Cold versus at Room Temperature for Complex Cardiothoracic Surgery.

BACKGROUND: This pilot trial focused on feasibility and safety to provide preliminary data to evaluate the hemostatic potential of cold-stored platelets (2° to 6°C) compared with standard room temperature-stored platelets (20° to 24°C) in adult patients undergoing complex cardiothoracic surgery. This study aimed to assess feasibility and to provide information for future pivotal trials. METHODS: A single center two-stage exploratory pilot study was performed on adult patients undergoing elective or semiurgent complex cardiothoracic surgery. In stage I, a two-armed randomized trial, platelets stored up to 7 days in the cold were compared with those stored at room temperature. In the subsequent single-arm stage II, cold storage time was extended to 8 to 14 days. The primary outcome was clinical effect measured by chest drain output. Secondary outcomes were platelet function measured by multiple electrode impedance aggregometry, total blood usage, immediate and long-term (28 days) adverse events, length of stay in intensive care, and mortality. RESULTS: In stage I, the median chest drain output was 720 ml (quartiles 485 to 1,170, n = 25) in patients transfused with room temperature-stored platelets and 645 ml (quartiles 460 to 800, n = 25) in patients transfused with cold-stored platelets. No significant difference was observed. The difference in medians between the room temperature- and cold-stored up to 7 days arm was 75 ml (95% CI, -220, 425). In stage II, the median chest drain output was 690 ml (500 to 1,880, n = 15). The difference in medians between the room temperature arm and the nonconcurrent cold-stored 8 to 14 days arm was 30 ml (95% CI, -1,040, 355). Platelet aggregation in vitro increased after transfusion in both the room temperature- and cold-stored platelet study arms. Total blood usage, number of adverse events, length of stay in intensive care, and mortality were comparable among patients receiving cold-stored and room temperature-stored platelets. CONCLUSIONS: This pilot trial supports the feasibility of platelets stored cold for up to 14 days and provides critical guidance for future pivotal trials in high-risk cardiothoracic bleeding patients.

Association of time to craniectomy with survival in patients with severe combat-related brain injury.

OBJECTIVEIn combat and austere environments, evacuation to a location with neurosurgery capability is challenging. A planning target in terms of time to neurosurgery is paramount to inform prepositioning of neurosurgical and transport resources to support a population at risk. This study sought to examine the association of wait time to craniectomy with mortality in patients with severe combat-related brain injury who received decompressive craniectomy.METHODSPatients with combat-related brain injury sustained between 2005 and 2015 who underwent craniectomy at deployed surgical facilities were identified from the Department of Defense Trauma Registry and Joint Trauma System Role 2 Registry. Eligible patients survived transport to a hospital capable of diagnosing the need for craniectomy and performing surgery. Statistical analyses included unadjusted comparisons of postoperative mortality by elapsed time from injury to start of craniectomy, and Cox proportional hazards modeling adjusting for potential confounders. Time from injury to craniectomy was divided into quintiles, and explored in Cox models as a binary variable comparing early versus delayed craniectomy with cutoffs determined by the maximum value of each quintile (quintile 1 vs 2-5, quintiles 1-2 vs 3-5, etc.). Covariates included location of the facility at which the craniectomy was performed (limited-resource role 2 facility vs neurosurgically capable role 3 facility), use of head CT scan, US military status, age, head Abbreviated Injury Scale score, Injury Severity Score, and injury year. To reduce immortal time bias, time from injury to hospital arrival was included as a covariate, entry into the survival analysis cohort was defined as hospital arrival time, and early versus delayed craniectomy was modeled as a time-dependent covariate. Follow-up for survival ended at death, hospital discharge, or hospital day 16, whichever occurred first.RESULTSOf 486 patients identified as having undergone craniectomy, 213 (44%) had complete date/time values. Unadjusted postoperative mortality was 23% for quintile 1 (n = 43, time from injury to start of craniectomy 30-152 minutes); 7% for quintile 2 (n = 42, 154-210 minutes); 7% for quintile 3 (n = 43, 212-320 minutes); 19% for quintile 4 (n = 42, 325-639 minutes); and 14% for quintile 5 (n = 43, 665-3885 minutes). In Cox models adjusted for potential confounders and immortal time bias, postoperative mortality was significantly lower when time to craniectomy was within 5.33 hours of injury (quintiles 1-3) relative to longer delays (quintiles 4-5), with an adjusted hazard ratio of 0.28, 95% CI 0.10-0.76 (p = 0.012).CONCLUSIONSPostoperative mortality was significantly lower when craniectomy was initiated within 5.33 hours of injury. Further research to optimize craniectomy timing and mitigate delays is needed. Functional outcomes should also be evaluated.

Association of Prehospital Blood Product Transfusion During Medical Evacuation of Combat Casualties in Afghanistan With Acute and 30-Day Survival.

IMPORTANCE: Prehospital blood product transfusion in trauma care remains controversial due to poor-quality evidence and cost. Sequential expansion of blood transfusion capability after 2012 to deployed military medical evacuation (MEDEVAC) units enabled a concurrent cohort study to focus on the timing as well as the location of the initial transfusion. OBJECTIVE: To examine the association of prehospital transfusion and time to initial transfusion with injury survival. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of US military combat casualties in Afghanistan between April 1, 2012, and August 7, 2015. Eligible patients were rescued alive by MEDEVAC from point of injury with either (1) a traumatic limb amputation at or above the knee or elbow or (2) shock defined as a systolic blood pressure of less than 90 mm Hg or a heart rate greater than 120 beats per minute. EXPOSURES: Initiation of prehospital transfusion and time from MEDEVAC rescue to first transfusion, regardless of location (ie, prior to or during hospitalization). Transfusion recipients were compared with nonrecipients (unexposed) for whom transfusion was delayed or not given. MAIN OUTCOMES AND MEASURES: Mortality at 24 hours and 30 days after MEDEVAC rescue were coprimary outcomes. To balance injury severity, nonrecipients of prehospital transfusion were frequency matched to recipients by mechanism of injury, prehospital shock, severity of limb amputation, head injury, and torso hemorrhage. Cox regression was stratified by matched groups and also adjusted for age, injury year, transport team, tourniquet use, and time to MEDEVAC rescue. RESULTS: Of 502 patients (median age, 25 years [interquartile range, 22 to 29 years]; 98% male), 3 of 55 prehospital transfusion recipients (5%) and 85 of 447 nonrecipients (19%) died within 24 hours of MEDEVAC rescue (between-group difference, -14% [95% CI, -21% to -6%]; P = .01). By day 30, 6 recipients (11%) and 102 nonrecipients (23%) died (between-group difference, -12% [95% CI, -21% to -2%]; P = .04). For the 386 patients without missing covariate data among the 400 patients within the matched groups, the adjusted hazard ratio for mortality associated with prehospital transfusion was 0.26 (95% CI, 0.08 to 0.84, P = .02) over 24 hours (3 deaths among 54 recipients vs 67 deaths among 332 matched nonrecipients) and 0.39 (95% CI, 0.16 to 0.92, P = .03) over 30 days (6 vs 76 deaths, respectively). Time to initial transfusion, regardless of location (prehospital or during hospitalization), was associated with reduced 24-hour mortality only up to 15 minutes after MEDEVAC rescue (median, 36 minutes after injury; adjusted hazard ratio, 0.17 [95% CI, 0.04 to 0.73], P = .02; there were 2 deaths among 62 recipients vs 68 deaths among 324 delayed transfusion recipients or nonrecipients). CONCLUSIONS AND RELEVANCE: Among medically evacuated US military combat causalities in Afghanistan, blood product transfusion prehospital or within minutes of injury was associated with greater 24-hour and 30-day survival than delayed transfusion or no transfusion. The findings support prehospital transfusion in this setting.

A joint latent class analysis for adjusting survival bias with application to a trauma transfusion study.

There is no clear classification rule to rapidly identify trauma patients who are severely hemorrhaging and may need substantial blood transfusions. Massive transfusion (MT), defined as the transfusion of at least 10 units of red blood cells within 24 h of hospital admission, has served as a conventional surrogate that has been used to develop early predictive algorithms and establish criteria for ordering an MT protocol from the blood bank. However, the conventional MT rule is a poor proxy, because it is likely to misclassify many severely hemorrhaging trauma patients as they could die before receiving the 10th red blood cells transfusion. In this article, we propose to use a latent class model to obtain a more accurate and complete metric in the presence of early death. Our new approach incorporates baseline patient information from the time of hospital admission, by combining respective models for survival time and usage of blood products transfused within the framework of latent class analysis. To account for statistical challenges, caused by induced dependent censoring inherent in 24-h sums of transfusions, we propose to estimate an improved standard via a pseudo-likelihood function using an expectation-maximization algorithm with the inverse weighting principle. We evaluated the performance of our new standard in simulation studies and compared with the conventional MT definition using actual patient data from the Prospective Observational Multicenter Major Trauma Transfusion study. Copyright © 2015 John Wiley & Sons, Ltd.

Cardiovascular Disease Risk Factors in Hispanic Adolescents in South Texas.

OBJECTIVES: Despite a national crisis of increased prevalence of obesity and type 2 diabetes mellitus in adolescents, especially among Hispanics, there is a paucity of data on health indicators among farmworker adolescents and their peers. The main aim of this study was to estimate the prevalence of cardiovascular disease risk factors in a population of Hispanic adolescent students in south Texas. The study also aimed to compare the prevalence of these risk factors between students enrolled in the Migrant Education Program (MEP) and other students, and between boys and girls. METHODS: In partnership with the Weslaco (Texas) Independent School District and the Migrant Education Department, a cohort study was conducted from 2007 to 2010 to estimate the prevalence of overall obesity (body mass index ≥85th percentile for age and sex), abdominal obesity (waist circumference ≥75th percentile for age, sex, and ethnicity), acanthosis nigricans (AN), and high blood pressure (HBP; ≥90th percentile for age, height, and sex or systolic/diastolic BP ≥120/80 mm Hg) among MEP students compared with other students from two south Texas high schools. Multilevel logistic regression was used to assess the relation between sex and our main outcomes of interest while accounting for within-school nesting of participants. RESULTS: Among 628 sampled students, 508 (80.9%) completed the consent procedure and participated in the study. Of these, 257 were MEP students and 251 were non-MEP peers. Approximately 96.7% of participants were Hispanic and 50.0% were boys. Analyses of data across the years comparing MEP students and non-MEP students show an average prevalence of 44.8% versus 47.7% for overall obesity, 43.2% versus 43.7% for abdominal obesity, 24.7% versus 24.7% for AN, and 29.2% versus 32.8% for HBP. Across recruitment and follow-up years, the prevalence of overall obesity, abdominal obesity, and HBP was 1.3 to 1.5, 1.2 to 1.8, and 2.9 to 4.6 times higher in boys than in girls, respectively. In contrast, the prevalence of AN varied little by sex. CONCLUSIONS: The high prevalence of cardiovascular risk factors in both groups suggests a compelling need for comprehensive, culturally targeted interventions to prevent future cardiovascular diseases in these high-risk Hispanic adolescents, especially among boys. There were not, however, substantial differences between MEP students and other students. These findings also support the feasibility of conducting future epidemiologic studies among adolescent farmworkers and their families, as well as culturally appropriate school or community-based interventions.

Prehospital Transfusion of Plasma and Red Blood Cells in Trauma Patients.

Abstract Objective. Earlier use of plasma and red blood cells (RBCs) has been associated with improved survival in trauma patients with substantial hemorrhage. We hypothesized that prehospital transfusion (PHT) of thawed plasma and/or RBCs would result in improved patient coagulation status on admission and survival. Methods. Adult trauma patient records were reviewed for patient demographics, shock, coagulopathy, outcomes, and blood product utilization from September 2011 to April 2013. Patients arrived by either ground or two different helicopter companies. All patients transfused with blood products (either pre- or in-hospital) were included in the study. One helicopter system (LifeFlight, LF) had thawed plasma and RBCs while the other air (OA) and ground transport systems used only crystalloid resuscitation. Patients receiving PHT were compared with all other patients meeting entry criteria to the study cohort. All comparisons were adjusted in multilevel regression models. Results. A total of 8,536 adult trauma patients were admitted during the 20-month study period, of which 1,677 met inclusion criteria. They represented the most severely injured patients (ISS = 24 and mortality = 26%). There were 792 patients transported by ground, 716 by LF, and 169 on OA. Of the LF patients, 137 (19%) received prehospital transfusion. There were 942 units (244 RBCs and 698 plasma) placed on LF helicopters, with 1.9% wastage. PHT was associated with improved acid-base status on hospital admission, decreased use of blood products over 24 hours, a reduction in the risk of death in the sickest patients over the first 6 hours after admission, and negligible blood products wastage. In this small single-center pilot study, there were no differences in 24-hour (odds ratio 0.57, p = 0.117) or 30-day mortality (odds ratio 0.71, p = 0.441) between LF and OA. Conclusions. Prehospital plasma and RBC transfusion was associated with improved early outcomes, negligible blood products wastage, but not an overall survival advantage. Similar to the data published from the ongoing war, improved early outcomes are associated with placing blood products prehospital, allowing earlier infusion of life-saving products to critically injured patients.

Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial.

IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS: No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE: Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01545232.

Acute occupational injury among adolescent farmworkers from South Texas.

PURPOSE: This combined cross-sectional/cohort study addressed research gaps by estimating the rate of non-fatal occupational injury and identifying potential determinants among a population of adolescent farmworkers who are largely Hispanic and migrant. METHODS: The cohort included 410 farmworkers (aged 13-19 years) attending high school in South Texas along the border with Mexico. Data collection involved a self-administered, Web-based survey that solicited information on demographics, farm work variables including person-time at risk, occupational injury, health status and health risk behaviours. Cox regression was used to identify potential risk factors for non-fatal injury events experienced during a 9-month recall period. RESULTS: Depending on the definition of injury, the rate of non-fatal injury ranged from 27.0-73.6/100 full time equivalents. Variables with an increased and statistically significant HR in an adjusted Cox model included: age groups <15 years-old (5.82) and 16 years-old (4.47), usually sleeping <8 h during the week (2.10), feeling tense, stressed or anxious sometimes/often (2.25), not watching TV (2.65), working around ditches (2.01) and detasseling (2.70). CONCLUSIONS: The high observed rates of non-fatal injury combined with the potential negative consequences and cost of these injuries signifies a compelling need for injury prevention efforts targeting adolescent, Hispanic, farmworkers.

Finding the bleeding edge: 24-hour mortality by unit of blood product transfused in combat casualties from 2002-2020.

BACKGROUND: Transfusion studies in civilian trauma patients have tried to identify a general futility threshold. We hypothesized that in combat settings there is no general threshold where blood product transfusion becomes unbeneficial to survival in hemorrhaging patients. We sought to assess the relationship between the number of units of blood products transfused and 24-hour mortality in combat casualties. METHODS: A retrospective analysis of the Department of Defense Trauma Registry supplemented with data from the Armed Forces Medical Examiner. Combat casualties who received at least one unit of blood product at US military medical treatment facilities (MTFs) in combat settings (2002-2020) were included. The main intervention was the total units of any blood product transfused, which was measured from the point of injury until 24 hours after admission from the first deployed MTF. The primary outcome was discharge status (alive, dead) at 24 hours from time of injury. RESULTS: Of 11,746 patients included, the median age was 24 years, and most patients were male (94.2%) with penetrating injury (84.7%). The median injury severity score was 17 and 783 (6.7%) patients died by 24 hours. Median units of blood products transfused was 8. Most blood products transfused were red blood cells (50.2%), followed by plasma (41.1%), platelets (5.5%), and whole blood (3.2%). Among the 10 patients who received the most units of blood product (164 units to 290 units), 7 survived to 24 hours. The maximum amount of total blood products transfused to a patient who survived was 276 units. Of the 58 patients who received over 100 units of blood product, 20.7% died by 24 hours. CONCLUSION: While civilian trauma studies suggest the possibility of futility with ultra-massive transfusion, we report that the majority (79.3%) of combat casualties who received transfusions greater than 100 units survived to 24 hours. These results do not support a threshold for futility of blood product transfusion. Further analysis as to predictors for mortality will help in situations of blood product and resource constraints. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Determining resuscitation outcomes in combat casualties: Design of the Deployed Hemostatic Emergency Resuscitation of Traumatic Exsanguinating Shock (Deployed HEROES) study.

BACKGROUND: During the course of the recent conflicts, the recommendations for resuscitation practices have evolved, but there has been no comprehensive comparative effectiveness study of these resuscitation strategies. The objective of this study was to describe the development and study design of the Deployed Hemostatic Emergency Resuscitation of Traumatic Exsanguinating Shock (Deployed HEROES) study-the first comprehensive analysis of military resuscitation practices in the deployed environment from October 2001 to October 2019. METHODS: This retrospective cohort study uses the Department of Defense Trauma Registry, Armed Services Blood Program database, and Military Trauma Mortality Review, while abstractors will use Theater Medical Data Store and Web Interface Patient Records to collect transfusion timing data. This study includes patients, who received blood products or died before receiving blood, treated at US military medical treatment facilities. The primary endpoints are survival at 6 hours, 24 hours, and 30 days postinjury. Secondary outcomes include infection, renal dysfunction, pulmonary dysfunction, and thromboembolic event. Exposure will be defined by blood product transfusion. Study groups will be frequency matched. Cox proportional hazards will compare patients who received warm fresh whole blood, low titer type-O whole blood, or only component therapy, while using adjustment for type of blood product transfused as a time-dependent covariate. Multilevel mixed-effects logistic regression will determine the effect of incompatible plasma in low titer type-O whole blood. RESULTS: An analysis plan for the Deployed HEROES study was developed with the aim of minimizing bias. CONCLUSION: This study will inform the optimal resuscitation strategies, which will potentially have a substantial impact on combat mortality. If whole blood is found to be the optimal transfusion strategy, this finding will be crucial in future operating environments involving dispersed medical assets. These results will provide critical information necessary for combat casualty care guidelines. LEVEL OF EVIDENCE: Prognostic and epidemiological; Level III.

Whole blood at the tip of the spear: A retrospective cohort analysis of warm fresh whole blood resuscitation versus component therapy in severely injured combat casualties.

BACKGROUND: Death from uncontrolled hemorrhage occurs rapidly, particularly among combat casualties. The US military has used warm fresh whole blood during combat operations owing to clinical and operational exigencies, but published outcomes data are limited. We compared early mortality between casualties who received warm fresh whole blood versus no warm fresh whole blood. METHODS: Casualties injured in Afghanistan from 2008 to 2014 who received ≥2 red blood cell containing units were reviewed using records from the Joint Trauma System Role 2 Database. The primary outcome was 6-hour mortality. Patients who received red blood cells solely from component therapy were categorized as the non-warm fresh whole blood group. Non- warm fresh whole blood patients were frequency-matched to warm fresh whole blood patients on identical strata by injury type, patient affiliation, tourniquet use, prehospital transfusion, and average hourly unit red blood cell transfusion rates, creating clinically unique strata. Multilevel mixed effects logistic regression adjusted for the matching, immortal time bias, and other covariates. RESULTS: The 1,105 study patients (221 warm fresh whole blood, 884 non-warm fresh whole blood) were classified into 29 unique clinical strata. The adjusted odds ratio of 6-hour mortality was 0.27 (95% confidence interval 0.13-0.58) for the warm fresh whole blood versus non-warm fresh whole blood group. The reduction in mortality increased in magnitude (odds ratio = 0.15, P = .024) among the subgroup of 422 patients with complete data allowing adjustment for seven additional covariates. There was a dose-dependent effect of warm fresh whole blood, with patients receiving higher warm fresh whole blood dose (>33% of red blood cell-containing units) having significantly lower mortality versus the non-warm fresh whole blood group. CONCLUSION: Warm fresh whole blood resuscitation was associated with a significant reduction in 6-hour mortality versus non-warm fresh whole blood in combat casualties, with a dose-dependent effect. These findings support warm fresh whole blood use for hemorrhage control as well as expanded study in military and civilian trauma settings.

The epidemiology and outcomes of prolonged trauma care (EpiC) study: methodology of a prospective multicenter observational study in the Western Cape of South Africa.

BACKGROUND: Deaths due to injuries exceed 4.4 million annually, with over 90% occurring in low-and middle-income countries. A key contributor to high trauma mortality is prolonged trauma-to-treatment time. Earlier receipt of medical care following an injury is critical to better patient outcomes. Trauma epidemiological studies can identify gaps and opportunities to help strengthen emergency care systems globally, especially in lower income countries, and among military personnel wounded in combat. This paper describes the methodology of the "Epidemiology and Outcomes of Prolonged Trauma Care (EpiC)" study, which aims to investigate how the delivery of resuscitative interventions and their timeliness impacts the morbidity and mortality outcomes of patients with critical injuries in South Africa. METHODS: The EpiC study is a prospective, multicenter cohort study that will be implemented over a 6-year period in the Western Cape, South Africa. Data collected will link pre- and in-hospital care with mortuary reports through standardized clinical chart abstraction and will provide longitudinal documentation of the patient's clinical course after injury. The study will enroll an anticipated sample of 14,400 injured adults. Survival and regression analysis will be used to assess the effects of critical early resuscitative interventions (airway, breathing, circulatory, and neurologic) and trauma-to-treatment time on the primary 7-day mortality outcome and secondary mortality (24-h, 30-day) and morbidity outcomes (need for operative interventions, secondary infections, and organ failure). DISCUSSION: This study is the first effort in the Western Cape of South Africa to build a standardized, high-quality, multicenter epidemiologic trauma dataset that links pre- and in-hospital care with mortuary data. In high-income countries and the U.S. military, the introduction of trauma databases and registries has led to interventions that significantly reduce post-injury death and disability. The EpiC study will describe epidemiology trends over time, and it will enable assessments of how trauma care and system processes directly impact trauma outcomes to ultimately improve the overall emergency care system. TRIAL REGISTRATION: Not applicable as this study is not a clinical trial.

Increasing low risk prostate cancer incidence in United States Air Force servicemen and selection of treatments.

PURPOSE: Periodic Health Assessments have been mandated for United States Air Force servicemen since the mid 1990s. Thus, we determined whether United States Air Force prostate cancer incidence rates increased thereafter and how these tumors segregate into low and intermediate/high risk categories. We also identified treatment choices. MATERIALS AND METHODS: We queried the Department of Defense Automated Central Tumor Registry for prostate cancer diagnosed in United States Air Force servicemen between 1991 and 2008 to determine incidence rates, disease risk category and treatments. RESULTS: Age adjusted rates in white active duty servicemen diagnosed for the most recent period of 2005 to 2008 increased 3-fold relative to the rate in the earliest period of 1991 to 1994. A similar trend was evident in black servicemen. Relative to the Surveillance, Epidemiology and End Results population prostate cancer rates in active duty United States Air Force men between 1995 and 2008 were significantly increased for the 2 racial groups. A significantly greater proportion of active duty servicemen than retirees (62% vs 40%) presented with low risk disease, defined as prostate specific antigen less than 10 ng/ml, Gleason sum less than 7 and clinical stage T1a-T2a. Of those with low risk disease significantly more active duty servicemen elected curative surgery than retirees (93% vs 53%). CONCLUSIONS: Prostate cancer incidence rates in United States Air Force servicemen have increased with time, exceeding rates in the Surveillance, Epidemiology and End Results population. While most cases are characterized as low risk, aggressive management is elected.

Evaluation metrics for biostatistical and epidemiological collaborations.

Increasing demands for evidence-based medicine and for the translation of biomedical research into individual and public health benefit have been accompanied by the proliferation of special units that offer expertise in biostatistics, epidemiology, and research design (BERD) within academic health centers. Objective metrics that can be used to evaluate, track, and improve the performance of these BERD units are critical to their successful establishment and sustainable future. To develop a set of reliable but versatile metrics that can be adapted easily to different environments and evolving needs, we consulted with members of BERD units from the consortium of academic health centers funded by the Clinical and Translational Science Award Program of the National Institutes of Health. Through a systematic process of consensus building and document drafting, we formulated metrics that covered the three identified domains of BERD practices: the development and maintenance of collaborations with clinical and translational science investigators, the application of BERD-related methods to clinical and translational research, and the discovery of novel BERD-related methodologies. In this article, we describe the set of metrics and advocate their use for evaluating BERD practices. The routine application, comparison of findings across diverse BERD units, and ongoing refinement of the metrics will identify trends, facilitate meaningful changes, and ultimately enhance the contribution of BERD activities to biomedical research.

Variations between level I trauma centers in 24-hour mortality in severely injured patients requiring a massive transfusion.

BACKGROUND: Significant differences in outcomes have been demonstrated between Level I trauma centers. Usually these differences are ascribed to regional or administrative differences, although the influence of variation in clinical practice is rarely considered. This study was undertaken to determine whether differences in early mortality of patients receiving a massive transfusion (MT, ≥ 10 units pf RBCs within 24 hours of admission) persist after adjustment for patient and transfusion practice differences. We hypothesized differences among centers in 24-hour mortality could predominantly be accounted for by differences in transfusion practices as well as patient characteristics. METHODS: Data were retrospectively collected over a 1-year period from 15 Level I centers on patients receiving an MT. A purposeful variable selection strategy was used to build the final multivariable logistic model to assess differences between centers in 24-hour mortality. Adjusted odds ratios for each center were calculated. RESULTS: : There were 550 patients evaluated, but only 443 patients had complete data for the set of variables included in the final model. Unadjusted mortality varied considerably across centers, ranging from 10% to 75%. Multivariable logistic regression identified injury severity score (ISS), abbreviated injury scale (AIS) of the chest, admission base deficit, admission heart rate, and total units of RBC transfused, as well as ratios of plasma:RBC and platelet:RBC to be associated with 24-hour mortality. After adjusting for severity of injury and transfusion, treatment variables between center differences were no longer significant. CONCLUSIONS: In the defined population of patients receiving an MT, between-center differences in 24-hour mortality may be accounted for by severity of injury as well as transfusion practices.