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The American Journal of Emergency... May 2024Traumatic brain injury (TBI) results in 2.5 million emergency department (ED) visits per year in the US, with mild traumatic brain injury (mTBI) accounting for 90% of... (Review)
Review
INTRODUCTION
Traumatic brain injury (TBI) results in 2.5 million emergency department (ED) visits per year in the US, with mild traumatic brain injury (mTBI) accounting for 90% of cases. There is considerable evidence that many experience chronic symptoms months to years later. This population is rarely represented in interventional studies. Management of adult mTBI in the ED has remained unchanged, without consensus of therapeutic options. The aim of this review was to synthesize existing literature of patient-centered ED treatments for adults who sustain an mTBI, and to identify practices that may offer promise.
METHODS
A systematic review was conducted using the PubMed and Cochrane databases, while following PRISMA guidelines. Studies describing pediatric patients, moderate to severe TBI, or interventions outside the ED were excluded. Two reviewers independently performed title and abstract screening. A third blinded reviewer resolved discrepancies. The Mixed Methods Appraisal Tool (MMAT) was employed to assess the methodological quality of the studies.
RESULTS
Our search strategy generated 1002 unique titles. 95 articles were selected for full-text screening. The 26 articles chosen for full analysis were grouped into one of the following intervention categories: (1) predictive models for Post-Concussion Syndrome (PCS), (2) discharge instructions, (3) pharmaceutical treatment, (4) clinical protocols, and (5) functional assessment. Studies that implemented a predictive PCS model successfully identified patients at highest risk for PCS. Trials implementing discharge related interventions found the use of video discharge instructions, encouragement of daily light exercise or bed rest, and text messaging did not significantly reduce mTBI symptoms. The use of electronic clinical practice guidelines (eCPG) and longer leaves of absence from work following injury reduced symptoms. Ondansetron was shown to reduce nausea in mTBI patients. Studies implementing ED Observation Units found significant declines in inpatient admissions and length of hospital stay. The use of tablet-based tasks was found to be superior to many standard cognitive assessments.
CONCLUSION
Validated instruments are available to aid clinicians in identifying patients at risk for PCS or serious cognitive impairment. EDOU management and evidence-based modifications to discharge instructions may improve mTBI outcomes. Additional research is needed to establish the therapeutic value of medications and lifestyle changes for the treatment of mTBI in the ED.
Topics: Adult; Humans; Child; Brain Concussion; Post-Concussion Syndrome; Brain Injuries, Traumatic; Emergency Service, Hospital; Patient-Centered Care
PubMed: 38460465
DOI: 10.1016/j.ajem.2024.02.038 -
Neurotherapeutics : the Journal of the... Oct 2023The use of animal models in pre-clinical research has significantly broadened our understanding of the pathologies that underlie traumatic brain injury (TBI)-induced... (Review)
Review
The use of animal models in pre-clinical research has significantly broadened our understanding of the pathologies that underlie traumatic brain injury (TBI)-induced damage and deficits. However, despite numerous pre-clinical studies reporting the identification of promising neurotherapeutics, translation of these therapies to clinical application has so far eluded the TBI research field. A concerted effort to address this lack of translatability is long overdue. Given the inherent heterogeneity of TBI and the replication crisis that continues to plague biomedical research, this is a complex task that will require a multifaceted approach centered around rigor and reproducibility. Here, we discuss the role of three primary focus areas for better aligning pre-clinical research with clinical TBI management. These focus areas are (1) reporting and standardization of protocols, (2) replication of prior knowledge including the confirmation of expected pharmacodynamics, and (3) the broad application of open science through inter-center collaboration and data sharing. We further discuss current efforts that are establishing the core framework needed for successfully addressing the translatability crisis of TBI.
Topics: Animals; Reproducibility of Results; Brain Injuries, Traumatic; Brain Injuries; Biomedical Research
PubMed: 37525025
DOI: 10.1007/s13311-023-01400-5 -
Scientific Reports Aug 2023The ability to model physiological systems through 3D neural in-vitro systems may enable new treatments for various diseases while lowering the need for challenging...
The ability to model physiological systems through 3D neural in-vitro systems may enable new treatments for various diseases while lowering the need for challenging animal and human testing. Creating such an environment, and even more impactful, one that mimics human brain tissue under mechanical stimulation, would be extremely useful to study a range of human-specific biological processes and conditions related to brain trauma. One approach is to use human cerebral organoids (hCOs) in-vitro models. hCOs recreate key cytoarchitectural features of the human brain, distinguishing themselves from more traditional 2D cultures and organ-on-a-chip models, as well as in-vivo animal models. Here, we propose a novel approach to emulate mild and moderate traumatic brain injury (TBI) using hCOs that undergo strain rates indicative of TBI. We subjected the hCOs to mild (2 s[Formula: see text]) and moderate (14 s[Formula: see text]) loading conditions, examined the mechanotransduction response, and investigated downstream genomic effects and regulatory pathways. The revealed pathways of note were cell death and metabolic and biosynthetic pathways implicating genes such as CARD9, ENO1, and FOXP3, respectively. Additionally, we show a steeper ascent in calcium signaling as we imposed higher loading conditions on the organoids. The elucidation of neural response to mechanical stimulation in reliable human cerebral organoid models gives insights into a better understanding of TBI in humans.
Topics: Animals; Humans; Mechanotransduction, Cellular; Brain Injuries, Traumatic; Brain Injuries; Nervous System Physiological Phenomena; Brain
PubMed: 37598247
DOI: 10.1038/s41598-023-40431-y -
MedEdPORTAL : the Journal of Teaching... 2024Pediatric trauma has long been one of the primary contributors to pediatric mortality. There are multiple cases in the literature involving cyanide (CN) toxicity, carbon...
INTRODUCTION
Pediatric trauma has long been one of the primary contributors to pediatric mortality. There are multiple cases in the literature involving cyanide (CN) toxicity, carbon monoxide (CO) toxicity, and smoke inhalation with thermal injury, but none in combination with mechanical trauma.
METHODS
In this 45-minute simulation case, emergency medicine residents and fellows were asked to manage a pediatric patient with multiple life-threatening traumatic and metabolic concerns after being extracted from a van accident with a resulting fire. Providers were expected to identify and manage the patient's airway, burns, hemoperitoneum, and CO and CN toxicities.
RESULTS
Forty learners participated in this simulation, the majority of whom had little prior clinical experience managing the concepts highlighted in it. All agreed or strongly agreed that the case was relevant to their work. After participation, learner confidence in the ability to manage each of the learning objectives was high. One hundred percent of learners felt confident or very confident in managing CO toxicity and completing primary and secondary surveys, while 97% were similarly confident in identifying smoke inhalation injury, preparing for a difficult airway, and managing CN toxicity.
DISCUSSION
This case was a well-received teaching tool for the management of pediatric trauma and metabolic derangements related to fire injuries. While this specific case represents a rare clinical experience, it is within the scope of expected knowledge for emergency medicine providers and offers the opportunity to practice managing multisystem trauma.
Topics: Humans; Child; Fires; Emergency Medicine; Smoke Inhalation Injury; Multiple Trauma
PubMed: 38414645
DOI: 10.15766/mep_2374-8265.11383 -
Journal of Neurotrauma Aug 2023After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience...
Prognostic Models for Global Functional Outcome and Post-Concussion Symptoms Following Mild Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study.
After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3-week post-concussion and mental health symptoms. Predictors were selected based on Akaike's Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.
Topics: Humans; Brain Concussion; Post-Concussion Syndrome; Prognosis; Brain Injuries, Traumatic; Biomarkers
PubMed: 37078144
DOI: 10.1089/neu.2022.0320 -
Scientific Reports Sep 2023Previously, we showed that Satureja Khuzestanica Jamzad essential oil (SKEO) and its major component, carvacrol (CAR), 5-isopropyl-2-methylphenol, has anti-inflammatory,...
Previously, we showed that Satureja Khuzestanica Jamzad essential oil (SKEO) and its major component, carvacrol (CAR), 5-isopropyl-2-methylphenol, has anti-inflammatory, anti-apoptotic, and anti-edematous properties after experimental traumatic brain injury (TBI) in rats. CAR, predominantly found in Lamiaceae family (Satureja and Oregano), is lipophilic, allowing diffusion across the blood-brain barrier (BBB). These experiments test the hypothesis that acute treatment with CAR after TBI can attenuate oxidative stress and BBB permeability associated with CAR's anti-edematous traits. Rats were divided into six groups and injured using Marmarou weight drop: Sham, TBI, TBI + Vehicle, TBI + CAR (100 and 200 mg/kg) and CAR200-naive treated rats. Intraperitoneal injection of vehicle or CAR was administered thirty minutes after TBI induction. 24 h post-injury, brain edema, BBB permeability, BBB-related protein levels, and oxidative capacity were measured. Data showed CAR 200 mg/kg treatment decreased brain edema and prevented BBB permeability. CAR200 decreased malondialdehyde (MDA) and reactive oxygen species (ROS) and increased superoxide dismutase (SOD) and total antioxidative capacity (T-AOC), indicating the mechanism of BBB protection is, in part, through antioxidant activity. Also, CAR 200 mg/kg treatment suppressed matrix metalloproteinase-9 (MMP-9) expression and increased ZO-1, occludin, and claudin-5 levels. These data indicate that CAR can promote antioxidant activity and decrease post-injury BBB permeability, further supporting CAR as a potential early therapeutic intervention that is inexpensive and more readily available worldwide. However, more experiments are required to determine CAR's long-term impact on TBI pathophysiology.
Topics: Animals; Rats; Blood-Brain Barrier; Antioxidants; Brain Injuries, Diffuse; Brain Injuries, Traumatic; Brain Injuries; Brain Edema; Excipients
PubMed: 37666857
DOI: 10.1038/s41598-023-40915-x -
Annual Review of Pharmacology and... Jan 2024Seizures and other forms of neurovolatility are emerging as druggable prodromal mechanisms that link traumatic brain injury (TBI) to the progression of later dementias.... (Review)
Review
Seizures and other forms of neurovolatility are emerging as druggable prodromal mechanisms that link traumatic brain injury (TBI) to the progression of later dementias. TBI neurotrauma has both acute and long-term impacts on health, and TBI is a leading risk factor for dementias, including chronic traumatic encephalopathy and Alzheimer's disease. Treatment of TBI already considers acute management of posttraumatic seizures and epilepsy, and impressive efforts have optimized regimens of antiepileptic drugs (AEDs) toward that goal. Here we consider that expanding these management strategies could determine which AED regimens best prevent dementia progression in TBI patients. Challenges with this prophylactic strategy include the potential consequences of prolonged AED treatment and that a large subset of patients are refractory to available AEDs. Addressing these challenges is warranted because the management of seizure activity following TBI offers a rare opportunity to prevent the onset or progression of devastating dementias.
Topics: Humans; Anticonvulsants; Epilepsy, Post-Traumatic; Brain Injuries, Traumatic; Seizures; Dementia
PubMed: 37788493
DOI: 10.1146/annurev-pharmtox-051921-013930 -
Scientific Reports Jun 2023Upon detecting a crash impact, the vehicle restraint system locks the driver in place. However, external factors such as speeding, crash mechanisms, roadway attributes,...
Upon detecting a crash impact, the vehicle restraint system locks the driver in place. However, external factors such as speeding, crash mechanisms, roadway attributes, vehicle type, and the surrounding environment typically contribute to the driver being jostled within the vehicle. As a result, it is crucial to model unrestrained and restrained drivers separately to reveal the true impact of the restraint system and other factors on driver injury severities. This paper aims to explore the differences in factors affecting injury severity for seatbelt-restrained and unrestrained drivers involved in speeding-related crashes while accounting for temporal instability in the investigation. Utilizing crash data from Thailand between 2012 and 2017, mixed logit models with heterogeneity in means and variances were employed to account for multi-layered unobserved heterogeneity. For restrained drivers, the risk of fatal or severe crashes was positively associated with factors such as male drivers, alcohol influence, flush/barrier median roadways, sloped roadways, vans, running off the roadway without roadside guardrails, and nighttime on unlit or lit roads. For unrestrained drivers, the likelihood of fatal or severe injuries increased in crashes involving older drivers, alcohol influence, raised or depressed median roadways, four-lane roadways, passenger cars, running off the roadway without roadside guardrails, and crashes occurring in rainy conditions. The out-of-sample prediction simulation results are particularly significant, as they show the maximum safety benefits achievable solely by using a vehicle's seatbelt system. Likelihood ratio test and predictive comparison findings highlight the considerable combined impact of temporal instability and the non-transferability of restrained and unrestrained driver injury severities across the periods studied. This finding also demonstrates a potential reduction in severe and fatal injury rates by simply replicating restrained driver conditions. The findings should be of value to policymakers, decision-makers, and highway engineers when developing potential countermeasures to improve driver safety and reduce the frequency of severe and fatal speeding-related single-vehicle crashes.
Topics: Humans; Male; Accidents, Traffic; Automobile Driving; Logistic Models; Motor Vehicles; Probability; Seat Belts; Wounds and Injuries
PubMed: 37328518
DOI: 10.1038/s41598-023-36906-7 -
JAMA Network Open Oct 2023Racial and ethnic disparities in pain management have been characterized in many hospital-based settings. Painful traumatic injuries are a common reason for 911... (Comparative Study)
Comparative Study
IMPORTANCE
Racial and ethnic disparities in pain management have been characterized in many hospital-based settings. Painful traumatic injuries are a common reason for 911 activations of the EMS (emergency medical services) system.
OBJECTIVE
To evaluate whether, among patients treated by EMS with traumatic injuries, race and ethnicity are associated with either disparate recording of pain scores or disparate administration of analgesia when a high pain score is recorded.
DESIGN, SETTINGS, AND PARTICIPANTS
This cohort study included interactions from 2019 to 2021 for US patients ages 14 to 99 years who had experienced painful acute traumatic injuries and were treated and transported by an advanced life support unit following the activation of the 911 EMS system. The data were analyzed in January 2023.
EXPOSURES
Acute painful traumatic injuries including burns.
MAIN OUTCOMES AND MEASURES
Outcomes were the recording of a pain score and the administration of a nonoral opioid or ketamine.
RESULTS
The study cohort included 4 781 396 EMS activations for acute traumatic injury, with a median (IQR) patient age of 59 (35-78) years (2 497 053 female [52.2%]; 31 266 American Indian or Alaskan Native [0.7%]; 59 713 Asian [1.2%]; 742 931 Black [15.5%], 411 934 Hispanic or Latino [8.6%], 10 747 Native Hawaiian or other Pacific Islander [0.2%]; 2 764 499 White [57.8%]; 16 161 multiple races [0.3%]). The analysis showed that race and ethnicity was associated with the likelihood of having a pain score recorded. Compared with White patients, American Indian and Alaskan Native patients had the lowest adjusted odds ratio (AOR) of having a pain score recorded (AOR, 0.74; 95% CI, 0.71-0.76). Among patients for whom a high pain score was recorded (between 7 and 10 out of 10), Black patients were about half as likely to receive opioid or ketamine analgesia as White patients (AOR, 0.53; 95% CI, 0.52-0.54) despite having a pain score recorded almost as frequently as White patients.
CONCLUSIONS AND RELEVANCE
In this nationwide study of patients treated by EMS for acute traumatic injuries, patients from racial or ethnic minority groups were less likely to have a pain score recorded, with Native American and Alaskan Natives the least likely to have a pain score recorded. Among patients with a high pain score, patients from racial and ethnic minority groups were also significantly less likely to receive opioid or ketamine analgesia treatment, with Black patients having the lowest adjusted odds of receiving these treatments.
Topics: Aged; Female; Humans; Middle Aged; Analgesia; Analgesics, Opioid; Black or African American; Cohort Studies; Emergency Medical Services; Ethnicity; Healthcare Disparities; Ketamine; Minority Groups; Pain; Pain Management; Wounds and Injuries; Male; Adult; Adolescent; Young Adult; Aged, 80 and over; United States; Asian; White; American Indian or Alaska Native; Hispanic or Latino; Native Hawaiian or Other Pacific Islander
PubMed: 37847499
DOI: 10.1001/jamanetworkopen.2023.38070 -
Accident; Analysis and Prevention Sep 2023Automated Driving System (ADS) fleets are currently being deployed in several dense-urban operational design domains within the United States. In these dense-urban...
OBJECTIVE
Automated Driving System (ADS) fleets are currently being deployed in several dense-urban operational design domains within the United States. In these dense-urban areas, pedestrians have historically comprised a significant portion, and sometimes the majority, of injury and fatal collisions. An expanded understanding of the injury risk in collision events involving pedestrians and human-driven vehicles can inform continued ADS development and safety benefits evaluation. There is no current systematic investigation of United States pedestrian collisions, so this study used reconstruction data from the German In-Depth Accident Study (GIDAS) to develop mechanistic injury risk models for pedestrians involved in collisions with vehicles.
DATA SOURCE
The study queried the GIDAS database for cases from 1999 to 2021 involving passenger vehicle or heavy vehicle collisions with pedestrians.
METHODS
We describe the injury patterns and frequencies for passenger vehicle-to-pedestrian and heavy vehicle-to-pedestrian collisions, where heavy vehicles included heavy trucks and buses. Injury risk functions were developed at the AIS2+, 3+, 4+ and 5+ levels for pedestrians involved in frontal collisions with passenger vehicles and separately for frontal collisions with heavy vehicles. Model predictors included mechanistic factors of collision speed, pedestrian age, sex, pedestrian height relative to vehicle bumper height, and vehicle acceleration before impact. Children (≤17 y.o.) and elderly (≥65 y.o.) pedestrians were included. We further conducted weighted and imputed analyses to understand the effects of missing data elements and of weighting towards the overall population of German pedestrian crashes.
RESULTS
We identified 3,112 pedestrians involved in collisions with passenger vehicles, where 2,524 of those collisions were frontal vehicle strikes. Furthermore, we determined 154 pedestrians involved in collisions with heavy vehicles, where 87 of those identified collisions were frontal vehicle strikes. Children were found to be at higher risk of injury compared to young adults, and the highest risk of serious injuries (AIS 3+) existed for the oldest pedestrians in the dataset. Collisions with heavy vehicles were more likely to produce serious (AIS 3+) injuries at low speeds than collisions with passenger vehicles. Injury mechanisms differed between collisions with passenger vehicles and with heavy vehicles. The initial engagement caused 36% of pedestrians' most-severe injuries in passenger vehicle collisions, compared with 23% in heavy vehicles collisions. Conversely, the vehicle underside caused 6% of the most-severe injuries in passenger vehicle collisions and 20% in heavy vehicles collisions.
SIGNIFICANCE
U.S. pedestrian fatalities have risen 59% since their recent recorded low in 2009. It is imperative that we understand and describe injury risk so that we can target effective strategies for injury and fatality reduction. This study builds on previous analyses by including the most modern vehicles, including children and elderly pedestrians, incorporating additional mechanistic predictors, broadening the scope of included crashes, and using multiple imputation and weighting to better estimate these effects relative to the entire population of German pedestrian collisions. This study is the first to investigate the risk of injury to pedestrians in collisions with heavy vehicles based on field data.
Topics: Child; Young Adult; Humans; Aged; Accidents, Traffic; Pedestrians; Motor Vehicles; Wounds and Injuries
PubMed: 37320981
DOI: 10.1016/j.aap.2023.107139