Risk of motor vehicle collision associated with cannabis and alcohol use among patients presenting for emergency care.

BACKGROUND: The objective of this study was to examine the relationship between cannabis and alcohol use and occurrence of motor vehicle collision (MVC) among patients in the emergency department (ED). METHODS: This was a cross-sectional study of visits to EDs in Denver, CO, Portland, OR, and Sacramento, CA by drivers who were involved in MVCs and presented with injuries (cases) and non-injured drivers (controls) who presented for medical care. We obtained blood samples and measured delta-9-THC and its metabolites. Alcohol levels were determined by breathalyzer or samples taken in the course of clinical care. Participants completed a research-assistant-administered interview consisting of questions about drug and alcohol use prior to their visit, context of use, and past-year drug and alcohol use. Multiple logistic regression was used to estimate the association between MVC and cannabis/alcohol use, adjusted for demographic characteristics. We then stratified participants based on levels of cannabis use and calculated the odds of MVC across these levels, first using self-report and then using blood levels for delta-9-THC in separate models. We conducted a case-crossover analysis, using 7-day look-back data to allow each participant to serve as their own control. Sensitivity analyses examined the influence of usual use patterns and driving in a closed (car, truck, van) versus open (motorcycle, motorbike, all-terrain vehicle) vehicle. RESULTS: Cannabis alone was not associated with higher odds of MVC, while acute alcohol use alone, and combined use of alcohol and cannabis were both independently associated with higher odds of MVC. Stratifying by level of self-reported or measured cannabis use, higher levels were not associated with higher odds for MVC, with or without co-use of alcohol; in fact, high self-reported acute cannabis use was associated with lower odds of MVC (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.05-0.65). In the case-crossover analysis, alcohol use alone or in combination with cannabis was associated with higher odds of MVC, while cannabis use alone was again associated with decreased odds of MVC. CONCLUSIONS: Alcohol use alone or in conjunction with cannabis was consistently associated with higer odds for MVC. However, the relationship between measured levels of cannabis and MVC was not as clear. Emphasis on actual driving behaviors and clinical signs of intoxication to determine driving under the influence has the strongest rationale.

How effective is extracorporeal life support for patients with out-of-hospital cardiac arrest initiated at the emergency department? A systematic review and meta-analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is commonly initiated for adults experiencing cardiac arrest within the cardiac catheterization lab or the intensive care unit. However, the potential benefit of ECPR for these patients in the emergency department (ED) remains undocumented. This study aims to assess the benefit of ECPR initiated in the ED for patients with out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a systematic review and meta-analysis of studies comparing ECPR initiated in the ED versus conventional CPR. Relevant articles were identified by searching several databases including PubMed, EMBASE, Web of Science, and Cochrane collaborations up to July 31, 2022. Pooled estimates were calculated using the inverse variance heterogeneity method, while heterogeneity was evaluated using Q and I2 statistics. The risk of bias in included studies was evaluated using validated bias assessment tools. The primary outcome was a favorable neurological outcome at hospital discharge, and the secondary outcome was survival to hospital discharge or 30-day survival. Sensitivity analyses were performed to explore the benefits of ED-initiated ECPR in studies utilizing propensity score (PPS) analysis. Publication bias was assessed using Doi plots and the Luis Furuya-Kanamori (LFK) index. RESULTS: The meta-analysis included a total of eight studies comprising 51,173 patients. ED-initiated ECPR may not be associated with a significant increase in favorable neurological outcomes (odds ratio [OR] 1.43, 95% confidence interval [CI] 0.30-6.70, I2 = 96%). However, this intervention may be linked to improved survival to hospital discharge (OR 3.34, 95% CI 2.23-5.01, I2 = 17%). Notably, when analyzing only PPS data, ED-initiated ECPR demonstrated efficacy for both favorable neurological outcomes (OR 1.89, 95% CI 1.26-2.83, I2 = 21%) and survival to hospital discharge (OR 3.37, 95% CI 1.52-7.49, I2 = 57%). Publication bias was detected for primary (LFK index 2.50) and secondary (LFK index 2.14) outcomes. CONCLUSION: The results of this study indicate that ED-initiated ECPR may not offer significant benefits in terms of favorable neurological outcomes for OHCA patients. However, it may be associated with increased survival to hospital discharge. Future studies should prioritize randomized trials with larger sample sizes and strive for homogeneity in patient populations to obtain more robust evidence in this area.

Impact of Race and Ethnicity on Emergency Medical Services Administration of Opioid Pain Medications for Injured Children.

BACKGROUND: Treatment with analgesics for injured children is often not provided or delayed during prehospital transport. OBJECTIVE: Our aim was to evaluate racial and ethnic disparities with the use of opioids during transport of injured children. METHODS: We conducted a prospective study of injured children transported to 1 of 10 emergency departments from July 2019 to April 2020. Emergency medical services (EMS) providers were surveyed about prehospital pain interventions during transport. Our primary outcome was the use of opioids. We performed multivariate regression analyses to evaluate the association of patient demographic characteristics (race, ethnicity, age, and gender), presence of a fracture, EMS provider type (Advanced Life Support [ALS] or non-ALS) and experience (years), and study site with the use of opioids. RESULTS: We enrolled 465 patients; 19% received opioids during transport. The adjusted odds ratios (AORs) for Black race and Hispanic ethnicity were 0.5 (95% CI 0.2-1.2) and 0.4 (95% CI 0.2-1.3), respectively. The presence of a fracture (AOR 17.0), ALS provider (AOR 5.6), older patient age (AOR 1.1 for each year), EMS provider experience (AOR 1.1 for each year), and site were associated with receiving opioids. CONCLUSIONS: There were no statistically significant associations between race or ethnicity and use of opioids for injured children. The presence of a fracture, ALS provider, older patient age, EMS provider experience, and site were associated with receiving opioids.

How Epinephrine Administration Interval Impacts the Outcomes of Resuscitation during Adult Cardiac Arrest: A Systematic Review and Meta-Analysis.

Current guidelines for treating cardiac arrest recommend administering 1 mg of epinephrine every 3−5 min. However, this interval is based solely on expert opinion. We aimed to investigate the impact of the epinephrine administration interval (EAI) on resuscitation outcomes in adults with cardiac arrest. We systematically reviewed the PubMed, EMBASE, and Scopus databases. We included studies comparing different EAIs in adult cardiac arrest patients with reported neurological outcomes. Pooled estimates were calculated using the IVhet meta-analysis, and the heterogeneities were assessed using Q and I2 statistics. We evaluated the study risk of bias and overall quality using validated bias assessment tools. Three studies were included. All were classified as "good quality" studies. Only two reported the primary outcome. Compared with a recommended EAI of 3−5 min, a favorable neurological outcome was not significantly different in patients with the other frequencies: for <3 min, odds ratio (OR) 1.93 (95% CI: 0.82−4.54); for >5 min, OR 1.01 (95% CI: 0.55−1.87). For survival to hospital discharge, administering epinephrine for less than 3 min was not associated with a good outcome (OR 1.66, 95% CI: 0.89−3.10). Moreover, EAI of >5 min did not pose a benefit (OR 0.87, 95% CI: 0.68−1.11). Our review showed that EAI during CPR was not associated with better hospital outcomes. Further clinical trials are necessary to determine the optimal dosing interval for epinephrine in adults with cardiac arrest.

Pediatric traumatic hemorrhagic shock consensus conference recommendations.

ABSTRACT: Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.

Tranexamic acid in pediatric hemorrhagic trauma.

ABSTRACT: There is strong evidence in adult literature that tranexamic acid (TXA) given within 3 hours from injury is associated with improved outcomes. The evidence for TXA use in injured children is limited to retrospective studies and one prospective observational trial. Two studies in combat settings and one prospective civilian US study have found association with improved mortality. These studies indicate the need for a randomized controlled trial to evaluate the efficacy of TXA in injured children and to clarify appropriate timing, dose and patient selection. Additional research is also necessary to evaluate trauma-induced coagulopathy in children. Recent studies have identified three distinct fibrinolytic phenotypes following trauma (hyperfibrinolysis, physiologic fibrinolysis, and fibrinolytic shutdown), which can be identified with viscohemostatic assays. Whether viscohemostatic assays can appropriately identify children who may benefit or be harmed by TXA is also unknown.

Pediatric traumatic hemorrhagic shock consensus conference research priorities.

BACKGROUND: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock. METHODS: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were informed by a systematic review of topics in this area and a discussion of these areas in the consensus conference. Research priorities were synthesized along themes and prioritized by anonymous voting. RESULTS: Eleven research priorities that warrant additional investigation were identified by the consensus committee. Areas of proposed study included well-designed clinical trials and evaluations, including increasing the speed and accuracy of identifying and treating hemorrhagic shock, defining the role of whole blood and tranexamic acid use, and assessment of the utility and appropriate use of viscoelastic techniques during early resuscitation. The committee recommended the need to standardize essential definitions, data elements, and data collection to facilitate research in this area. CONCLUSION: Research gaps remain in many areas related to the care of hemorrhagic shock after pediatric injury. Addressing these gaps is needed to develop improved evidence-based recommendations for the care of pediatric trauma patients in hemorrhagic shock.

A systematic review and meta-analysis of clinical signs, symptoms, and imaging findings in patients with suspected renal colic.

Study Objective: The objective of this study was to conduct a systematic review and meta-analysis of the diagnostic accuracy of the clinical signs, symptoms, laboratory investigations, and imaging modalities commonly used in patients with clinically suspected renal colic. Methods: We conducted this systematic review and meta-analysis according to an a priori, registered protocol (PROSPERO CRD42017055153). A literature search was performed using MEDLINE and EMBASE from inception to July 2, 2020. We assessed the risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2, calculated likelihood ratios (LRs), and applied a random-effects model for meta-analysis. Results: Among 7641 references screened, 76 were included in the systematic review and 53 were included in the meta-analyis. The overall pooled prevalence for ureteral stones was 63% (95% confidence interval [CI], 58%-67%). No individual demographic feature, symptom, or sign when present had an LR+ ≥2.0 for identifying ureterolithiasis. A (Sex, Timing and Origin of pain, race, presence or absence of Nausea, and Erythrocytes) STONE score ≥10 increased (sensitivity 0.49, specificity 0.91, LR 5.3 [95% CI, 4.1-6.7]) and a STONE score <6 reduced the likelihood of ureteral stones (sensitivity 0.94, specificity 0.43, LR 0.15 [95% CI, 0.10-0.22]). Standard-dose (sensitivity 0.96, specificity 0.94, LR+ 16 [95% CI, 11-23], LR- 0.05 [95% CI, 0.03-0.07]) and low-dose computed tomography (CT) scanning (sensitivity 0.93, specificity 0.94, LR+ 17 [95% CI, 8.8-31], LR- 0.08 [95% CI, 0.03-0.19]) were the most useful imaging techniques for identifying patients with or without ureteral stones. Conclusions: Individual signs, symptoms, or the presence of microscopic hematuria do not substantially impact the likelihood of ureteral stones in patients with clinically suspected renal colic. The STONE score at high and low thresholds and a modified STONE score at a high threshold may sufficiently guide physicians' decisions to obtain imaging. Low-dose, non-contrast CT imaging provides superior diagnostic accuracy compared with all other imaging index tests that are comparable with standard CT imaging. Limitations of the evidence include methodological shortcomings and considerable heterogeneity of the included studies.

Increased identification of cannabis use among drivers involved in motor vehicle collisions using an expanded cannabis inventory.

OBJECTIVES: The objectives of this study were to implement and examine the potential capture rate of a novel instrument, the Expanded Cannabis Inventory, in a population of emergency department (ED) patients presenting after motor vehicle collisions (MVC). METHODS: Study participants who presented to the ED after MVC were recruited from three hospitals in cannabis-legal states (Denver, CO; Portland, OR; and Sacramento, CA). Research assistants (RAs) administered the Expanded Cannabis Inventory, which includes a wide variety of products that have become readily available in states where cannabis is legal, in addition to assessments related to patient demographic characteristics, general health, cannabis attitudes, and dependency measures. RAs also obtained blood samples for delta-9-THC and metabolites. RESULTS: Among 692 participants who provided responses to questions about cannabis use, 292 (42%) reported past-year use. Seventy-eight (27%) of those identified as using cannabis were only captured due to items in the expanded instrument. These patients were more likely to be White and were more likely to perceive daily use to be of high risk. Fewer had Cannabis Use Disorder Inventory Test (CUDIT) scores consistent with hazardous cannabis use. However, more of the patients only captured by the expanded instrument had high measured blood levels of delta-9-THC on samples obtained in the ED. CONCLUSIONS: Changing cannabis use patterns must be reflected in our measurements for clinical practice, research, and surveillance. Instruments that are the current standard in clinical practice capture limited data and may no longer perform well enough to identify a complete cohort or to provide insight into the health behaviors of patients.

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): a pilot randomized trial.

BACKGROUND: The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage; however, the drug has not been evaluated in a trial in injured children. We evaluated the feasibility of a large-scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries. METHODS: Severely injured children (0 up to 18th birthday) were randomized into a double-blind randomized trial of 1) TXA 15 mg/kg bolus dose, followed by 2 mg/kg/hr infusion over 8 hours, 2) TXA 30 mg/kg bolus dose, followed by 4 mg/kg/hr infusion over 8 hours, or 3) normal saline placebo bolus and infusion. The trial was conducted at 4 pediatric Level I trauma centers in the United States between June 2018 and March 2020. We enrolled patients under federal exception from informed consent (EFIC) procedures when parents were unable to provide informed consent. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The target enrollment rate was at least 1.25 patients per site per month. RESULTS: A total of 31 patients were randomized with a mean age of 10.7 years (standard deviation [SD] 5.0 years) and 22 (71%) patients were male. The mean time from injury to randomization was 2.4 hours (SD 0.6 hours). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. The enrollment rate using EFIC was 1.34 patients per site per month. All eligible enrolled patients received study intervention (9 patients TXA 15 mg/kg bolus dose, 10 patients TXA 30 mg/kg bolus dose, and 12 patients placebo) and had the primary outcome measured. No statistically significant differences in any of the clinical outcomes were identified. CONCLUSION: Based on enrollment rate, protocol adherence, and measurement of the primary outcome in this pilot trial, we confirmed the feasibility of conducting a large-scale, randomized trial evaluating the efficacy of TXA in severely injured children with hemorrhagic brain and/or torso injuries using EFIC.

Effectiveness and safety of tranexamic acid in pediatric trauma: A systematic review and meta-analysis.

OBJECTIVE: Trauma is the leading cause of childhood death in the United States. Our goal was to determine the effectiveness of tranexamic acid (TXA) in improving survival in pediatric trauma. METHODS: MEDLINE (OVID), Embase (OVID), Cochrane Central Register databases, CINAHL (EBSCO), Web of Science (Clarivate Analytics), and grey literature sources were searched for publications reporting survival and safety outcomes in children receiving TXA in acute trauma, with no language restrictions, published until February 11, 2021. Two independent researchers assessed studies for eligibility, bias, and quality. Data on the study setting, injury type, participants, design, interventions, TXA dosing and outcomes were extracted. The primary outcome was survival in children who received TXA following trauma. Forest plots of effect estimates were constructed for each study. Heterogeneity was assessed and data were pooled by meta-analysis using a random-effects model. RESULTS: Fourteen articles met inclusion criteria - six single-institution and eight multicentre retrospective cohort studies. Overall, TXA use was not associated with increased survival in pediatric trauma (adjusted odds ratio [aOR]: 0.61, 95% CI: 0.30-1.22) after adjustment for patient-level variables, such as injury severity. Increased survival was documented in the subset of children experiencing trauma in combat settings (aOR for mortality: 0.31, 95% CI: 0.14-0.68). There were no differences in the odds of thromboembolic events (OR 1.15, 95% CI: 0.46-2.87) in children who received TXA versus not. CONCLUSIONS: The utility of TXA in children with trauma is unclear. Guidelines supporting TXA use in pediatric trauma may not be based on the available evidence of its use in this context. Rigorous trials measuring survival and other meaningful outcomes and exploring optimal TXA dosing are urgently needed. Study Registration (PROSPERO): CRD42020157683.

Cost-effectiveness of patient observation on cranial CT use with minor head trauma.

OBJECTIVE: To evaluate the cost-effectiveness of planned observation on cranial CT use in children with minor head trauma. DESIGN: Planned secondary analysis of a multicentre prospective observation study. SETTING: Australia and New Zealand. PATIENTS: An analytic cohort of 18 471 children aged <18 years with Glasgow Coma Scale scores 14-15 presenting <24 hours after blunt head trauma stratified by the Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) risk categories. INTERVENTION: A plan for observation and immediate CT scan were documented after the initial assessment. The planned observation group included those with planned observation and no immediate plan for CT. MAIN OUTCOME MEASURES: Taking an Australian public-funded healthcare perspective, we estimated the cost-effectiveness of planned observation on the adjusted mean costs per child and CT use reduction by net benefit regression analysis using ordinary least squares with robust SEs and bootstrapping. All costs presented in 2018 euros. RESULTS: Planned observation in 4945 (27%) children was cost-saving of €85 (95% CI -120 to -51) with 10.4% lower CT use (95% CI 9.6 to 11.2). This strategy was cost-saving for the PECARN high-risk (-€757 (95% CI -961 to -554)) and intermediate-risk (-€52 (95% CI -99 to -4.3)) categories, with 43% (95% CI 39 to 47) and 11% (95% CI 9.6 to 12.4) lower CT use, respectively. The very low-risk category incurred more cost of €86 (95% CI 67 to 104) with planned observation and 0.05% lower CT use (95% CI -0.61 to 0.71). CONCLUSION: Planned ED observation in selected children with minor head trauma is cost-effective for reducing CT use for the PECARN intermediate-risk and high-risk categories. TRIAL REGISTRATION NUMBER: ACTRN12614000463673.

Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of eight experts developed expert-based statements for plasma and platelet transfusions in critically ill neonates and children with severe trauma, traumatic brain injury, and/or intracranial hemorrhage. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement and six expert consensus statements. CONCLUSIONS: The lack of evidence precludes proposing recommendations on monitoring of the coagulation system and on plasma and platelets transfusion in critically ill pediatric patients with severe trauma, severe traumatic brain injury, or nontraumatic intracranial hemorrhage.

Discriminatory Capacity of the Physical Domain Versus the Full-Scale Pediatric Quality of Life Inventory With Traumatic Brain Injury Severity in Children.

ABSTRACT: A previous study demonstrated that the Pediatric Quality of Life Inventory, a health-related quality-of-life instrument consisting of physical and psychosocial domain scores, reliably differentiates between children with varying severities of traumatic brain injuries (N = 729) 3, 12, and 24 mos after injury. However, the Pediatric Quality of Life Inventory physical domain score alone may simplify evaluation outcomes in physical rehabilitation and clinical research when comparing different trauma interventions. Therefore, we performed a secondary analysis to evaluate and compare the discriminative capacity of traumatic brain injury severity for changes in the overall Pediatric Quality of Life Inventory or the Pediatric Quality of Life Inventory physical domain score alone. We used linear mixed models to assess the change of outcome scores from baseline compared with arm-injury controls. Somers' D was calculated to compare discriminatory capacity with injury severity as a predictor of change in Pediatric Quality of Life Inventory outcome scores. We found that traumatic brain injury severity in children can be differentiated by the Pediatric Quality of Life Inventory physical domain score alone. However, at all follow-up time points, traumatic brain injury severity had higher discriminatory capacity for changes in the overall Pediatric Quality of Life Inventory. Our results suggest that the overall Pediatric Quality of Life Inventory should be used preferentially in children with traumatic brain injuries, although further investigation of the physical domain is warranted in conditions where physical injuries may predominate.

A Novel Use of NEMSIS to Create a PECARN-Specific EMS Patient Registry.

Background: Research networks need access to EMS data to conduct pilot studies and determine feasibility of prospective studies. Combining data across EMS agencies is complicated and costly. Leveraging the National EMS Information System (NEMSIS) to extract select agencies' data may be an efficient and cost-effective method of providing network-level data. Objective: Describe the process of creating a Pediatric Emergency Care Applied Research Network (PECARN) specific NEMSIS data set and determine if these data were nationally representative. Methods: We established data use agreements (DUAs) with EMS agencies participating in PECARN to allow for agency identification through NEMSIS. Using 2019 NEMSIS version 3.4.0 data for EMS events with patients 18 years old and younger, we compared PECARN NEMSIS data to national NEMSIS data. Analyzed variables were selected for their ability to characterize events. No statistical analyses were utilized due to the large sample, instead, differences of ±5% were deemed clinically meaningful. Results: DUAs were established for 19 EMS agencies, creating a PECARN data set with 305,188 EMS activations of which 17,478 (5.7%) were pediatric. Of the pediatric activations, 17,140 (98.1%) were initiated through 9-1-1 and 9,487 (55.4%) resulted in transport by the documenting agency. The national data included 36,288,405 EMS activations of which 2,152,849 (5.9%) were pediatric. Of the pediatric activations 1,704,141 (79.2%) were initiated through 9-1-1 and 1,055,504 (61.9%) were transported by the documenting agency. Age and gender distributions were similar between the two groups, but the PECARN-specific data under-represents Black and Latinx patients. Comparison of EMS provider primary impressions revealed that three of the five most common were similar with injury being the most prevalent for both data sets along with mental/behavioral health and seizure. Conclusion: We demonstrated that NEMSIS can be leveraged to create network specific data sets. PECARN's EMS data were similar to the national data, though racial/ethnic minorities and some primary impressions may be under-represented. Additionally, more EMS activations in PECARN study areas originated through 9-1-1 but fewer were transported by the documenting agency. This is likely related to the type of participating agencies, their ALS response level, and the diversity of the communities they serve.

Effect of age on the efficacy of tranexamic acid: An analysis of heterogeneity of treatment effect within the CRASH-2 dataset.

BACKGROUND: Trauma is a major cause of morbidity and mortality in older adults and will become more common as the population ages. Tranexamic acid (TXA) is a lysine analogue frequently used in the setting of significant trauma with hemorrhage. The aim of this study is to investigate the heterogeneity of treatment effect of TXA as it relates to patient age during trauma care. METHODS: We included patients from the CRASH-2 trial who were randomized within 3 h of injury. Patients were stratified into age groups <26 years, 26 to 35 years, 36 to 45 years, 46 to 55 years, and >55 years. Multiple logistic regression models were utilized to evaluate adjusted odds ratios (OR) with 95% confidence intervals (CI) for mortality. Heterogeneity of treatment effect was evaluated using Akaike and Bayesian information criteria to determine the optimum logistic regression model after which a Wald Chi-square test was utilized to evaluate statistical significance. RESULTS: On univariate analysis, TXA administration decreased mortality within the <26 years cohort (decrease of 2.1%, 95% CI 0.2 to 4.0), 46 to 55 years cohort (decrease 6.7%, 95% CI 2.7 to 10.7), and >55 years cohort (decrease of 5.3%, 95% CI 0.4 to 10.3). On adjusted analysis, when compared to the 36 to 45 years cohort, the <26 year cohort experienced a decreased mortality (OR 0.72, 95% CI 0.62 to 0.85) whereas the >55 year cohort experienced increased mortality (OR 1.8, 95% CI 1.5 to 2.2). Assessment for heterogeneity of treatment effect of TXA administration between groups approached but did not reach statistical significance (p = 0.11). CONCLUSIONS: Mortality related to trauma increases with age, however, there does not appear to be heterogeneity of treatment effect for TXA administration among different age groups.

The design of a Bayesian adaptive clinical trial of tranexamic acid in severely injured children.

BACKGROUND: Trauma is the leading cause of death and disability in children in the USA. Tranexamic acid (TXA) reduces the blood transfusion requirements in adults and children during surgery. Several studies have evaluated TXA in adults with hemorrhagic trauma, but no randomized controlled trials have occurred in children with trauma. We propose a Bayesian adaptive clinical trial to investigate TXA in children with brain and/or torso hemorrhagic trauma. METHODS/DESIGN: We designed a double-blind, Bayesian adaptive clinical trial that will enroll up to 2000 patients. We extend the traditional Emax dose-response model to incorporate a hierarchical structure so multiple doses of TXA can be evaluated in different injury populations (isolated head injury, isolated torso injury, or both head and torso injury). Up to 3 doses of TXA (15 mg/kg, 30 mg/kg, and 45 mg/kg bolus doses) will be compared to placebo. Equal allocation between placebo, 15 mg/kg, and 30 mg/kg will be used for an initial period within each injury group. Depending on the dose-response curve, the 45 mg/kg arm may open in an injury group if there is a trend towards increasing efficacy based on the observed relationship using the data from the lower doses. Response-adaptive randomization allows each injury group to differ in allocation proportions of TXA so an optimal dose can be identified for each injury group. Frequent interim stopping periods are included to evaluate efficacy and futility. The statistical design is evaluated through extensive simulations to determine the operating characteristics in several plausible scenarios. This trial achieves adequate power in each injury group. DISCUSSION: This trial design evaluating TXA in pediatric hemorrhagic trauma allows for three separate injury populations to be analyzed and compared within a single study framework. Individual conclusions regarding optimal dosing of TXA can be made within each injury group. Identifying the optimal dose of TXA, if any, for various injury types in childhood may reduce death and disability.

Cost-effectiveness of field trauma triage among injured children transported by emergency medical services.

BACKGROUND: A pediatric field triage strategy that meets the national policy benchmark of ≥95% sensitivity would likely improve health outcomes but increase heath care costs. Our objective was to compare the cost-effectiveness of current pediatric field triage practices to an alternative field triage strategy that meets the national policy benchmark of ≥95% sensitivity. STUDY DESIGN: We developed a decision-analysis Markov model to compare the outcomes and costs of the two strategies. We used a prospectively collected cohort of 3507 (probability weighted, unweighted n = 2832) injured children transported by 44 emergency medical services (EMS) agencies to 28 trauma and non-trauma centers in the Northwestern United States from 1/1/2011 to 12/31/2011 to derive the alternative field triage strategy and to populate model probability and cost inputs for both strategies. We compared the two strategies by calculating quality adjusted life years (QALYs) and health care costs over a time horizon from the time of injury until death. We set an incremental cost-effectiveness ratio threshold of less than $100,000 per QALY for the alternative field triage to be a cost-effective strategy. RESULTS: Current pediatric field triage practices had a sensitivity of 87.4% (95% confidence interval [CI] 71.9 to 95.0%) and a specificity of 82.3% (95% CI 81.0 to 83.5%) and the alternative field triage strategy had a sensitivity of 97.3% (95% CI 82.6 to 99.6%) and a specificity of 46.1% (95% CI 43.8 to 48.4%). The alternative field triage strategy would cost $476,396 per QALY gained compared to current pediatric field triage practices and thus would not be a cost-effective strategy. Sensitivity analyses demonstrated similar findings. CONCLUSION: Current field triage practices do not meet national policy benchmarks for sensitivity. However, an alternative field triage strategy that meets the national policy benchmark of ≥95% sensitivity is not a cost-effective strategy.

Recommended Primary Outcomes for Clinical Trials Evaluating Hemostatic Agents in Patients With Intracranial Hemorrhage: A Consensus Statement.

Importance: In patients with acute spontaneous or traumatic intracranial hemorrhage, early hemostasis is thought to be critical to minimize ongoing bleeding. However, research evaluating hemostatic therapies has been hampered by a lack of standardized clinical trial outcome measures. Objective: To identify appropriate primary outcomes for phase 2 and 3 clinical trials of therapies aimed at reducing acute intracranial bleeding. Evidence Review: A comprehensive review of all previous clinical trials of hemostatic therapy for intracranial bleeding was performed, and studies measuring the frequency, risk factors, and association of intracranial bleeding with outcome of hemorrhage growth were included. Findings: A hierarchy of 3 outcome measures is recommended, with the first choice being a global patient-centered clinical outcome scale measured 30 to 180 days after the event; the second, a combined clinical and radiographic end point associating hemorrhage expansion with a poor patient-centered outcome at 24 hours or later; and the third, a radiographic measure of hemorrhage expansion at 24 hours alone. Additional recommendations stress the importance of separating various subtypes of bleeding when possible, early treatment within a standardized treatment window, and the routine use of computerized planimetry comparing continuous measures of absolute and relative hemorrhage growth as either a primary or secondary end point. Conclusions and Relevance: Standardization of outcome measures in studies of intracranial bleeding and hemostatic therapy will support comparative effectiveness research and meta-analysis, with the goal of accelerating the translation of research into clinical practice. The 3 outcome measures proposed in this consensus statement could help this process.

Enrollment with and without exception from informed consent in a pilot trial of tranexamic acid in children with hemorrhagic injuries.

BACKGROUND: Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time-sensitive, life-threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries. METHODS: We conducted a four-center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC. RESULTS: We enrolled one of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, seven (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months. CONCLUSIONS: In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.