Differences in State Traumatic Brain Injury-Related Deaths, by Principal Mechanism of Injury, Intent, and Percentage of Population Living in Rural Areas - United States, 2016-2018.

Traumatic brain injuries (TBIs) have contributed to approximately one million deaths in the United States over the last 2 decades (1). CDC analyzed National Vital Statistics System (NVSS) mortality data for a 3-year period (2016-2018) to examine numbers and rates of TBI-related deaths, the percentage difference between each state's rate and the overall U.S. TBI-related death rate, leading causes of TBI, and the association between TBI and a state's level of rurality. During 2016-2018, a total of 181,227 TBI-related deaths (17.3 per 100,000 population per year) occurred in the United States. The percentage difference between state TBI-related death rates and the overall U.S. rate during this period ranged from 46.2% below to 101.2% above the overall rate. By state, the lowest rate was in New Jersey (9.3 per 100,000 population per year); the states with the highest rates were Alaska (34.8), Wyoming (32.6), and Montana (29.5). States in the South and those with a higher proportion of residents living in rural areas had higher rates, whereas states in the Northeast and those with a lower proportion of residents living in rural areas had lower TBI-related death rates. In 43 states, suicide was the leading cause of TBI-related deaths; in other states, unintentional falls or unintentional motor vehicle crashes were responsible for the highest numbers and rates of TBI-related deaths. Consistent with previous studies (2), differences in TBI incidence and outcomes were observed across U.S. states; therefore, states can use these findings to develop and implement evidence-based prevention strategies, based on their leading causes of TBI-related deaths. Expanding evidence-based prevention strategies that address TBI-related deaths is warranted, especially among states with high rates due to suicide, unintentional falls, and motor vehicle crashes.

Cost-effectiveness of immediate total-body CT in patients with severe trauma (REACT-2 trial).

BACKGROUND: The effect of immediate total-body CT (iTBCT) on health economic aspects in patients with severe trauma is an underreported issue. This study determined the cost-effectiveness of iTBCT compared with conventional radiological imaging with selective CT (standard work-up (STWU)) during the initial trauma evaluation. METHODS: In this multicentre RCT, adult patients with a high suspicion of severe injury were randomized in-hospital to iTBCT or STWU. Hospital healthcare costs were determined for the first 6 months after the injury. The probability of iTBCT being cost-effective was calculated for various levels of willingness-to-pay per extra patient alive. RESULTS: A total of 928 Dutch patients with complete clinical follow-up were included. Mean costs of hospital care were €25 809 (95 per cent bias-corrected and accelerated (bca) c.i. €22 617 to €29 137) for the iTBCT group and €26 155 (€23 050 to €29 344) for the STWU group, a difference per patient in favour of iTBCT of €346 (€4987 to €4328) (P = 0.876). Proportions of patients alive at 6 months were not different. The proportion of patients alive without serious morbidity was 61.6 per cent in the iTBCT group versus 66.7 per cent in the STWU group (difference -5.1 per cent; P = 0.104). The probability of iTBCT being cost-effective in keeping patients alive remained below 0.56 for the whole group, but was higher in patients with multiple trauma (0.8-0.9) and in those with traumatic brain injury (more than 0.9). CONCLUSION: Economically, from a hospital healthcare provider perspective, iTBCT should be the diagnostic strategy of first choice in patients with multiple trauma or traumatic brain injury.

Traumatismo cranioencefálico no Brasil: análise epidemiológica / Cranioencephalic traumatism in Brazil: epidemiological analysis

Introdução: O traumatismo cranioencefálico (TCE) é definido por agressão de ordem traumática, que pode ser classificado como leve, moderado e grave, pela Escala de Coma de Glasgow (ECG). No Brasil, o traumatismo tem grande importância pela alta incidência e morbimortalidade. Objetivo: Analisar o perfil epidemiológico dos pacientes internados devido à TCE no Brasil. Método: Trata-se de estudo descritivo, cujos dados foram obtidos através de abordagem documental do Departamento de Informática do Sistema Único de Saúde (DATASUS). Para o estudo epidemiológico foram utilizados dados da prevalência da morbidade no Brasil, no período de 2010 a 2019. Resultados: O número de internações foi predominante no sexo masculino (76,23%), na faixa etária entre 20 e 29 anos (17,65%); em relação à permanência hospitalar, foi obtido uma média de 6,2 dias de internação; os índices de mortalidade foram maiores no sexo masculino (10,06%), assim como o valor gasto com os pacientes, com 81,39% para esse sexo. Conclusão: A partir do presente estudo foi possível observar que no Brasil os jovens do sexo masculino, vítimas de TCE, são os que mais internam e geram custos à saúde, permitindo evidenciar essa parcela populacional como grupo de risco. Os pacientes, vítimas de TCE, tem prognóstico relacionado a fatores como a idade, gravidade do trauma, tipo de lesão, dentre outros fatores que possam estar associados. Desse modo, torna-se fundamental a análise do perfil epidemiológico do TCE para uma melhor intervenção, buscando cuidados constantes, evitando-se complicações, permitindo uma conduta mais adequada e resolutiva e, consequentemente, um melhor prognóstico

Introduction: The traumatic brain injury is defined by traumatic aggression, which can be classified as mild, moderate and severe, by the Glasgow Coma Scale. In Brazil, trauma is of great importance due to its high incidence and morbidity and mortality. Objective: To analyze the epidemiological profile of hospitalized patients due to traumatic brain injury in Brazil. Method: This is a descriptive study, whose data were obtained through a documentary approach by the Department of Informatics of the Unified Health System. For the epidemiological study, data on the prevalence of morbidity in Brazil, from 2010 to 2019 were used. Results: The number of hospitalizations was predominant in the male gender (76.23%) and in the age group between 20 and 29 years old (17.65%); in relation to hospital stay, an average of 6.2 days was obtained; mortality rates were higher in males (10.06%); and the amount spent on patients, were significantly higher in males (81.39%). Conclusion: The present study made it possible to observe that, in Brazil, young men are the ones who intern the most and generate health costs through the traumatic brain injury, allowing to show this population as a risk group. Patients, victims of this injury, have a prognosis related to factors such as age, trauma severity, type of injury, among other factors that may be associated, it is essential to analyze the epidemiological profile for intervention seeking constant care to avoid complications , allow appropriate and resolutive conduct and consequently seek a better prognosis

Functional outcome, in-hospital healthcare consumption and in-hospital costs for hospitalised traumatic brain injury patients: a Dutch prospective multicentre study.

BACKGROUND: The high occurrence and acute and chronic sequelae of traumatic brain injury (TBI) cause major healthcare and socioeconomic challenges. This study aimed to describe outcome, in-hospital healthcare consumption and in-hospital costs of patients with TBI. METHODS: We used data from hospitalised TBI patients that were included in the prospective observational CENTER-TBI study in three Dutch Level I Trauma Centres from 2015 to 2017. Clinical data was completed with data on in-hospital healthcare consumption and costs. TBI severity was classified using the Glasgow Coma Score (GCS). Patient outcome was measured by in-hospital mortality and Glasgow Outcome Score-Extended (GOSE) at 6 months. In-hospital costs were calculated following the Dutch guidelines for cost calculation. RESULTS: A total of 486 TBI patients were included. Mean age was 56.1 ± 22.4 years and mean GCS was 12.7 ± 3.8. Six-month mortality (4.2%-66.7%), unfavourable outcome (GOSE ≤ 4) (14.6%-80.4%) and full recovery (GOSE = 8) (32.5%-5.9%) rates varied from patients with mild TBI (GCS13-15) to very severe TBI (GCS3-5). Length of stay (8 ± 13 days) and in-hospital costs (€11,920) were substantial and increased with higher TBI severity, presence of intracranial abnormalities, extracranial injury and surgical intervention. Costs were primarily driven by admission (66%) and surgery (13%). CONCLUSION: In-hospital mortality and unfavourable outcome rates were rather high, but many patients also achieved full recovery. Hospitalised TBI patients show substantial in-hospital healthcare consumption and costs, even in patients with mild TBI. Because these costs are likely to be an underestimation of the actual total costs, more research is required to investigate the actual costs-effectiveness of TBI care.

Estimating prognosis for traumatic brain injury patients in a low-resource setting: how do providers compare to the CRASH risk calculator?

OBJECTIVE: Traumatic brain injury (TBI), a burgeoning global health concern, is one condition that could benefit from prognostic modeling. Risk stratification of TBI patients on presentation to a health facility can support the prudent use of limited resources. The CRASH (Corticosteroid Randomisation After Significant Head Injury) model is a well-established prognostic model developed to augment complex decision-making. The authors' current study objective was to better understand in-hospital decision-making for TBI patients and determine whether data from the CRASH risk calculator influenced provider assessment of prognosis. METHODS: The authors performed a choice experiment using a simulated TBI case. All participant doctors received the same case, which included a patient history, vitals, and physical examination findings. Half the participants also received the CRASH risk score. Participants were asked to estimate the patient prognosis and decide the best next treatment step. The authors recruited a convenience sample of 28 doctors involved in TBI care at both a regional and a national referral hospital in Uganda. RESULTS: For the simulated case, the CRASH risk scores for 14-day mortality and an unfavorable outcome at 6 months were 51.4% (95% CI 42.8%, 59.8%) and 89.8% (95% CI 86.0%, 92.6%), respectively. Overall, participants were overoptimistic when estimating the patient prognosis. Risk estimates by doctors provided with the CRASH risk score were closer to that score than estimates made by doctors in the control group; this effect was more pronounced for inexperienced doctors. Surgery was selected as the best next step by 86% of respondents. CONCLUSIONS: This study was a novel assessment of a TBI prognostic model's influence on provider estimation of risk in a low-resource setting. Exposure to CRASH risk score data reduced overoptimistic prognostication by doctors, particularly among inexperienced providers.

Factors affecting mortality after traumatic brain injury in a resource-poor setting.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of long-term disability and economic loss to society. The aim of this study was to assess the factors affecting mortality after TBI in a resource-poor setting. METHODS: Chart review was performed for randomly selected patients who presented with TBI between 2013 and 2017 at St Mary's Hospital, Lacor, northern Uganda. Data collected included demographic details, time from injury to presentation, and vital signs on arrival. In-hospital management and mortality were recorded. Severe head injury was defined as a Glasgow Coma Scale score below 9. RESULTS: A total of 194 patient charts were reviewed. Median age at time of injury was 27 (i.q.r. 2-68) years. The majority of patients were male (M : F ratio 4·9 : 1). Some 30·9 per cent of patients had severe head injury, and an associated skull fracture was observed in 8·8 per cent. Treatment was mainly conservative in 94·8 per cent of patients; three patients (1·5 per cent) had burr-holes, four (2·1 per cent) had a craniotomy, and three (1·5 per cent) had skull fracture elevation. The mortality rate was 33·0 per cent; 46 (72 per cent) of the 64 patients who died had severe head injury. Of the ten surgically treated patients, seven died, including all three patients who had a burr-hole. In multivariable analysis, factors associated with mortality were mean arterial pressure (P = 0·012), referral status (P = 0·001), respiratory distress (P = 0·040), severe head injury (P = 0·011) and pupil reactivity (P = 0·011). CONCLUSION: TBI in a resource-poor setting remains a major challenge and affects mainly young males. Decisions concerning surgical intervention are compromised by the lack of both CT and intracranial pressure monitoring, with consequent poor outcomes.

ANTECEDENTES: La lesión cerebral traumática (traumatic brain injury, TBI) es un insulto al cerebro causado por una fuerza física externa que produce un estado de conciencia disminuido o alterado, lo que resulta en un deterioro de las capacidades cognitivas o del funcionamiento físico. Es una causa importante de discapacidad a largo plazo y pérdida económica para la sociedad. El objetivo de este estudio fue evaluar los factores que afectan a la mortalidad después de una TBI en un entorno de escasos recursos. MÉTODOS: Se realizó la revisión de historias clínicas de pacientes seleccionados al azar que habían presentado una TBI entre 2013 y 2017 en el Hospital St. Mary's, un hospital privado sin ánimo de lucro ubicado en el distrito de Gulu, Lacor, en el norte de Uganda. Se recogieron datos de las características demográficas, intervalo de tiempo entre la lesión y la atención médica, y signos vitales a la llegada al hospital. Se registró también el manejo hospitalario y la mortalidad. El traumatismo craneal grave se definió como aquel con una escala de coma de Glasgow (Glasgow Coma Scale, GCS) por debajo de 9. RESULTADOS: Se revisaron 194 historias clínicas de pacientes. La mediana de edad en el momento del traumatismo fue de 27 (rango intercuartílico de 2 a 68) años. La mayoría eran varones con una relación varón:mujer de 4,9:1. En el 38,1% de los casos los traumatismos craneales fueron calificados como graves y se observó una fractura de cráneo asociada en el 8,8% de los pacientes. Los tratamientos ofrecidos fueron principalmente conservadores en el 94,9%; tres pacientes (1,6%) precisaron trépanos, en cuatro pacientes (2,1%) se realizó una craneotomía y otros tres pacientes (1,6%) precisaron elevación de una fractura craneal con hundimiento. La mortalidad fue del 33,0%; El 71,9% de ellos tenían un traumatismo craneal grave. Entre los pacientes tratados quirúrgicamente, siete (70%) murieron, incluidos los tres pacientes en los que se realizó un trépano. Los factores asociados con la mortalidad en el análisis multivariable fueron la presión arterial media (P < 0,05), el estado en el traslado (P < 0,05), la dificultad respiratoria (P = 0,040), el traumatismo craneal grave (P = 0,012) y la reactividad pupilar (P = 0,011). CONCLUSIÓN: El TBI en un entorno con pocos cursos continúa siendo un desafío importante, afectando principalmente a varones jóvenes. Las decisiones relativas a la intervención quirúrgica y el momento de su práctica están seriamente comprometidas por la falta de disponibilidad de tomografía computarizada (TAC) y monitorización de la presión intracraneal, lo que conlleva unos pobres resultados.

The delayed detection of an acute neurological worsening increases traumatic brain injury lethality / [La detección tardía del deterioro neurológico agudo incrementa la letalidad por trauma craneoencefálico.]

Introduction: Traumatic brain injury is a leading worldwide cause of death and disability in young people. Severity classification is based on the Glasgow Coma Scale. However, the neurological worsening in an acute setting does not always correspond to the initial severity suggesting an underestimation of the real magnitude of the injury. Objective: To study the correlation between the initial severity according to the Glasgow Coma Scale and the patient outcome in the context of different clinical and tomography variables. Materials and methods: We analyzed a retrospective cohort of 490 patients with closed traumatic brain injury requiring a stay in the intensive care unit of two third-level hospitals in Barranquilla. The risk was estimated by calculating the OR (95% CI). The significance level was established at an alpha value of 0.05. Results: Forty-one percent of all patients required orotracheal intubation; 51.2% were initially classified with moderate trauma and 6,0% as mild. The delay in the aggressive management of the traumas affected mainly those patients with traumas classified as moderate in whom lethality increased to 100% when there was delay in the detection of the neurological worsening and in the establishment of the aggressive treatment beyond 4 to 8 hours while the lethality in patients who received this treatment within the first hour reduced to <20%. Conclusions: The risk of lethality in traumatic brain injury increases with the delayed detection of neurological worsening in an acute setting, especially when aggressive management is performed after the first hour post-trauma.

Introducción. El trauma craneoencefálico es una de las principales causas de muerte y discapacidad en adultos jóvenes. Su gravedad se define según la escala de coma de Glasgow. Sin embargo, el deterioro neurológico agudo no siempre concuerda con la gravedad inicial indicada por la escala, lo que implica una subestimación de la magnitud real de la lesión. Objetivo. Estudiar la correlación entre la gravedad inicial del trauma craneoencefálico según la escala de coma de Glasgow y la condición final del paciente, en el contexto de diferentes variables clínicas y de los hallazgos de la tomografía. Materiales y métodos. Se analizó una cohorte retrospectiva de 490 pacientes con trauma craneoencefálico cerrado que requirieron atención en la unidad de cuidados intensivos de dos centros de tercer nivel de Barranquilla. La estimación del riesgo se estableció con la razón de momios (odds ratio, OR) y un intervalo de confianza (IC) del 95 %. Se utilizó un alfa de 0,05 como nivel de significación. Resultados. El 41,0 % de los pacientes requirió intubación endotraqueal; el 51,2 % había presentado traumas inicialmente clasificados como moderados y, el 6,0 %, como leves. El retraso en la implementación de un tratamiento agresivo afectó principalmente a aquellos con trauma craneoencefálico moderado, en quienes la letalidad aumentó al 100 % cuando no se detectó a tiempo el deterioro neurológico y, por lo tanto, el tratamiento agresivo se demoró más de 4 a 8 horas. Por el contrario, la letalidad fue de menos de 20 % cuando se brindó el tratamiento agresivo en el curso de la primera hora después del trauma. Conclusiones. El riesgo de letalidad del trauma craneoencefálico aumentó cuando el deterioro neurológico se detectó tardíamente y el tratamiento agresivo se inició después de transcurrida la primera hora a partir del trauma.

Older Patients With Severe Traumatic Brain Injury: National Variability in Palliative Care.

BACKGROUND: Older patients with traumatic brain injury (TBI) have higher mortality and morbidity than their younger counterparts. Palliative care (PC) is recommended for all patients with a serious or life-limiting illness. However, its adoption for trauma patients has been variable across the nation. The goal of this study was to assess PC utilization and intensity of care in older patients with severe TBI. We hypothesized that PC is underutilized despite its positive effects. MATERIALS AND METHODS: The National Inpatient Sample database (2009-2013) was queried for patients aged ≥55 y with International Classification of Diseases, Ninth Revision codes for TBI with loss of consciousness ≥24 h. Outcome measures included PC rate, in-hospital mortality, discharge disposition, length of stay (LOS), and intensity of care represented by craniotomy and or craniectomy, ventilator use, tracheostomy, and percutaneous endoscopic gastrostomy. RESULTS: Of 5733 patients, 78% died in hospital with a median LOS of 1 d, and 85% of the survivors were discharged to facilities. The overall PC rate was 35%. Almost 40% of deaths received PC, with nearly half within 48 h of admission. PC was used in 26% who had neurosurgical procedures, compared with 35% who were nonoperatively managed (P = 0.003). PC was associated with less intensity of care in the entire population. For survivors, those with PC had significantly shorter LOS, compared with those without PC. CONCLUSIONS: Despite high mortality, only one-third of older patients with severe TBI received PC. PC was associated with decreased use of life support and lower intensity of care. Significant efforts need to be made to bridge this quality gap and improve PC in this high-risk population.

Signal Information Prediction of Mortality Identifies Unique Patient Subsets after Severe Traumatic Brain Injury: A Decision-Tree Analysis Approach.

Nonlinear physiological signal features that reveal information content and causal flow have recently been shown to be predictors of mortality after severe traumatic brain injury (TBI). The extent to which these features interact together, and with traditional measures to describe patients in a clinically meaningful way remains unclear. In this study, we incorporated basic demographics (age and initial Glasgow Coma Scale [GCS]) with linear and non-linear signal information based features (approximate entropy [ApEn], and multivariate conditional Granger causality [GC]) to evaluate their relative contributions to mortality using cardio-cerebral monitoring data from 171 severe TBI patients admitted to a single neurocritical care center over a 10 year period. Beyond linear modelling, we employed a decision tree analysis approach to define a predictive hierarchy of features. We found ApEn (p = 0.009) and GC (p = 0.004) based features to be independent predictors of mortality at a time when mean intracranial pressure (ICP) was not. Our combined model with both signal information-based features performed the strongest (area under curve = 0.86 vs. 0.77 for linear features only). Although low "intracranial" complexity (ApEn-ICP) outranked both age and GCS as crucial drivers of mortality (fivefold increase in mortality where ApEn-ICP <1.56, 36.2% vs. 7.8%), decision tree analysis revealed clear subsets of patient populations using all three predictors. Patients with lower ApEn-ICP who were >60 years of age died, whereas those with higher ApEn-ICP and GCS ≥5 all survived. Yet, even with low initial intracranial complexity, as long as patients maintained robust GC and "extracranial" complexity (ApEn of mean arterial pressure), they all survived. Incorporating traditional linear and novel, non-linear signal information features, particularly in a framework such as decision trees, may provide better insight into "health" status. However, caution is required when interpreting these results in a clinical setting prior to external validation.

PATHway to success: Implementation of a multiprofessional acute trauma health care team decreased length of stay and cost in patients with neurological injury requiring tracheostomy.

BACKGROUND: The aim of this study was to determine whether the implementation of a dedicated multiprofessional acute trauma health care (mPATH) team would decrease length of stay without adversely impacting outcomes of patients with severe traumatic brain and spinal cord injuries. The mPATH team was comprised of a physical, occupational, speech, and respiratory therapist, nurse navigator, social worker, advanced care provider, and physician who performed rounds on the subset of trauma patients with these injuries from the intensive care unit to discharge. METHODS: Following the formation and implementation of the mPATH team at our Level I trauma center, a retrospective cohort study was performed comparing patients in the year immediately prior to the introduction of the mPATH team (n = 60) to those in the first full year following implementation (n = 70). Demographics were collected for both groups. Inclusion criteria were Glasgow Coma Scale score less than 8 on postinjury Day 2, all paraplegic and quadriplegic patients, and patients older than 55 years with central cord syndrome who underwent tracheostomy. The primary endpoint was length of stay; secondary endpoints were time to tracheostomy, days to evaluation by occupational, physical, and speech therapy, 30-day readmission, and 30-day mortality. RESULTS: The median time to evaluation by occupational, physical, and speech therapy was universally decreased. Injury Severity Score was 27 in both cohorts. Time to tracheostomy and length of stay were both decreased. Thirty-day readmission and mortality rates remained unchanged. A cost savings of US $11,238 per index hospitalization was observed. CONCLUSION: In the year following the initiation of the mPATH team, we observed earlier time to occupational, physical, and speech therapist evaluation, decreased length of stay, and cost savings in severe traumatic brain and spinal cord injury patients requiring tracheostomy compared with our historical control. These benefits were observed without adversely impacting 30-day readmission or mortality. LEVEL OF EVIDENCE: Therapeutic/care management, Level III.

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial.

BACKGROUND: Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI. METHODS: This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277). RESULTS: Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86-1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80-1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64-0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91-1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74-1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90-1·33]). INTERPRETATION: Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury. FUNDING: National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme). TRANSLATIONS: For the Arabic, Chinese, French, Hindi, Japanese, Spanish and Urdu translations of the abstract see Supplementary Material.

Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study.

BACKGROUND: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. METHODS: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). FINDINGS: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]). INTERPRETATION: Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes. FUNDING: European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

Injury-specific variables improve risk adjustment and hospital quality assessment in severe traumatic brain injury.

BACKGROUND: Hospital benchmarking is essential to quality improvement, but its usefulness depends on the ability of statistical models to adequately control for inter-hospital differences in patient mix. We explored whether the addition of injury-specific clinical variables to the current American College of Surgeons-Trauma Quality Improvement Program (TQIP) algorithm would improve model fit. METHODS: We analyzed a prospective registry containing all adult patients who presented to a regional consortium of 14 trauma centers between 2010 and 2011 with severe traumatic brain injury (TBI). We used hierarchical logistic regression and stepwise forward selection to develop two novel risk-adjustment models. We then tested our novel models against the current TQIP model and ranked hospitals by their risk-adjusted mortality rates under each model to determine how model selection affects quality benchmarking. RESULTS: Seven hundred thirty-four patients met inclusion criteria. Stepwise selection resulted in two distinct models: one that added three TBI-specific variables (pupil reactivity, cerebral edema, loss of basal cisterns) to the model specification currently used by TQIP and another that combined two TBI-specific variables (pupil reactivity, cerebral edema) with a three-variable subset of TQIP (age, Abbreviated Injury Scale score for the head region, Glasgow Coma Scale motor score). Both novel models outperformed TQIP. Although rankings remained largely unchanged across model configurations, several hospitals moved across quality terciles. CONCLUSION: The inclusion of injury-specific variables improves risk adjustment for patients with severe TBI. Trauma Quality Improvement Program should consider replacing several of its general patient characteristics with injury-specific clinical predictors to increase efficiency, reduce the risk of overfitting, and improve the accuracy of hospital benchmarking. LEVEL OF EVIDENCE: Prognostic and epidemiological, level II.

Fatal traumatic brain injuries during 13 years of successive alcohol tax increases in Finland - a nationwide population-based registry study.

We sought to investigate how increases in alcohol taxation and changes in alcohol consumption were associated with the incidence rate of fatal traumatic brain injuries (TBI) in Finland during the years 2004-2016. Nationwide, mandatory cause of death database covering all deaths in Finland was searched for all deaths related to TBIs (ICD-10: S06.X) in persons ≥16 years of age during 2004-2016. Study period included 28,657,870 person-years and 325,514 deaths of which 12,110 were TBI-related. Occurrence rates were standardized to European 2013 standard population. Data for alcohol consumption were obtained from the National Institute for Health and Welfare and for alcohol taxation from Ministry of Finance, Finland. Standardized incidence rate of TBI-related death was 22.0 (95% CI 21.61-22.38) per 100,000 person-years. Overall alcohol consumption decreased on average by 1.2% annually. Concurrently, the overall incidence rate of fatal TBIs decreased by 4.1% annually (by 4.3% in men and 2.4% in women). There was an association between overall alcohol consumption and TBI-related mortality rate (p < 0.001). Tax-rate increases of all beverage types were associated with decreased incidence rate of TBI-related death in men (p < 0.001), in women (p < 0.036) and overall (p < 0.001). In this population-based study, we report that during 13 years of successive alcohol tax increases, overall alcohol consumption has decreased in parallel with a reduction in the incidence rate of fatal TBIs in Finland.

Cost-Effectiveness of Erythropoietin in Traumatic Brain Injury: A Multinational Trial-Based Economic Analysis.

The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data from the EPO-TBI trial to evaluate the cost-effectiveness of EPO in patients with moderate or severe TBI from the healthcare payers' perspective. We addressed the issue of transferability in multi-national trials by estimating costs and effects for specific geographical regions of the study (Australia/New Zealand, Europe, and Saudi Arabia). Unadjusted mean quality-adjusted life-years (QALYs; 95% confidence interval [CI]) at 6 months were 0.027 (0.020-0.034; p < 0.001) higher in the EPO group, with an adjusted QALY increment of 0.014 (0.000-0.028; p = 0.04). Mean unadjusted costs (95% CI) were $US5668 (-9191 to -2144; p = 0.002) lower in the treatment group; controlling for baseline IMPACT-TBI score and regional heterogeneity reduced this difference to $2377 (-12,446 to 7693; p = 0.64). For a willingness-to-pay threshold of $US50,000 per QALY, 71.8% of replications were considered cost-effective. Therefore, we did not find evidence that EPO was significantly cost-effective in the treatment of moderate or severe TBI at 6-month follow-up.

Socioeconomic Status Affects Outcomes After Severity-Stratified Traumatic Brain Injury.

BACKGROUND: Socioeconomic status (SES) and race have been shown to increase the incidence of being afflicted by a traumatic brain injury (TBI) resulting in worse posthospitalization outcomes. The goal of this study was to determine the effect disparities have on in-hospital mortality, discharge to inpatient rehabilitation, hospital length of stay (LOS), and TBI procedures performed stratified by severity of TBI. METHODS: This was a retrospective cohort study of patients with closed head injuries using the National Trauma Data Bank (2012-2015). Multivariate logistic/linear regression models were created to determine the impact of race and insurance status in groups graded by head Abbreviated Injury Scale (AIS). RESULTS: We analyzed 131,461 TBI patients from NTDB. Uninsured patients experienced greater mortality at an AIS of 5 (odds ratio [OR] = 1.052, P = 0.001). Uninsured patients had a decreased likelihood of being discharged to inpatient rehabilitation with an increasing AIS beginning from an AIS of 2 (OR = 0.987, P = 0.008) to an AIS of 5 (OR = 0.879, P < 0.001). Black patients had an increased LOS as their AIS increased from an AIS of 2 (0.153 d, P < 0.001) to 5 (0.984 d, P < 0.001) with the largest discrepancy in LOS occurring at an AIS of 5. CONCLUSIONS: Disparities in race and SES are associated with differences in mortality, LOS, and discharge to inpatient rehabilitation. Patients with more severe TBI have the greatest divergence in treatment and outcome when stratified by race and ethnicity as well as SES.

Risk of Mortality in Individuals with Hip Fracture and Traumatic Brain Injury.

OBJECTIVES: To estimate the prevalence of diagnosed traumatic brain injury (TBI) in individuals hospitalized with hip fracture and examine its association with all-cause mortality. DESIGN: Nested cohort study. SETTING: National sample of Medicare beneficiaries from 2006 to 2010. PARTICIPANTS: Beneficiaries aged 65 and older hospitalized with hip fracture. MEASUREMENTS: TBI at the time of hip fracture was defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The main outcome was all-cause mortality during follow-up. RESULTS: Prevalence of TBI in individuals with hip fracture was 2.7%. Absolute risk of mortality attributable to TBI in individuals with hip fracture was 15/100 person-years. TBI was significantly associated with risk of death in multivariable analysis (hazard ratio=1.24, 95% confidence interval=1.14-1.35). CONCLUSION: TBI was associated with greater risk of mortality in individuals with hip fracture. Practitioners should consider evaluating for presence of TBI in this vulnerable population. J Am Geriatr Soc 67:124-127, 2019.

Long-term survival and five year hospital resource usage following traumatic brain injury in Scotland from 1997 to 2015: A population-based retrospective cohort study.

BACKGROUND: It is unclear if traumatic brain injury (TBI) results in excess mortality compared with head injury without injury to neural structures (HI). Because TBI populations exhibit significant demographic differences from uninjured populations, to determine the effect of TBI on survival, it is essential that a similarly injured control population be used. We aimed to determine if survival and hospital resource usage differ following TBI compared with HI. METHODS: This retrospective population-based cohort study included all 25 319 patients admitted to a Scottish NHS hospital from 1997 to 2015 with TBI. Participants were identified using previously validated ICD-10 based definitions. For comparison, a control group of all 194 049 HI cases was also identified. Our main outcome measures were hazards of all-cause mortality for patients with TBI, compared with those with HI, over the 18-year follow-up period; and odds of mortality at one month post-injury. Number of days spent as inpatients and number of outpatient attendances per surviving month post-injury were used as measures of resource utilisation. RESULTS: The adjusted odds ratio for mortality in the first month post-injury for TBI, compared with HI, was 7.12 (95% confidence interval [CI] 6.73-7.52; p < 0.001). For the remaining 18-year study period, the hazards of morality after TBI were 0.93 (CI 0.90-0.96; p < 0.001). During the five-year post-injury period, brain injury was associated with 2.15 (CI 2.10-2.20; p < 0.001) more days spent as inpatient and 1.09 times more outpatient attendances (CI 1.07-1.11; p < 0.001) compared with HI. CONCLUSIONS: Although initial mortality following TBI is high, survivors of the first month post-injury can achieve comparable long-term survival to HI. However, this is associated with, and may require, increased utilisation of hospital services in the TBI group.

Therapeutic hypothermia to reduce intracranial pressure after traumatic brain injury: the Eurotherm3235 RCT.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability and death in young adults worldwide. It results in around 1 million hospital admissions annually in the European Union (EU), causes a majority of the 50,000 deaths from road traffic accidents and leaves a further ≈10,000 people severely disabled. OBJECTIVE: The Eurotherm3235 Trial was a pragmatic trial examining the effectiveness of hypothermia (32-35 °C) to reduce raised intracranial pressure (ICP) following severe TBI and reduce morbidity and mortality 6 months after TBI. DESIGN: An international, multicentre, randomised controlled trial. SETTING: Specialist neurological critical care units. PARTICIPANTS: We included adult participants following TBI. Eligible patients had ICP monitoring in place with an ICP of > 20 mmHg despite first-line treatments. Participants were randomised to receive standard care with the addition of hypothermia (32-35 °C) or standard care alone. Online randomisation and the use of an electronic case report form (CRF) ensured concealment of random treatment allocation. It was not possible to blind local investigators to allocation as it was obvious which participants were receiving hypothermia. We collected information on how well the participant had recovered 6 months after injury. This information was provided either by the participant themself (if they were able) and/or a person close to them by completing the Glasgow Outcome Scale - Extended (GOSE) questionnaire. Telephone follow-up was carried out by a blinded independent clinician. INTERVENTIONS: The primary intervention to reduce ICP in the hypothermia group after randomisation was induction of hypothermia. Core temperature was initially reduced to 35 °C and decreased incrementally to a lower limit of 32 °C if necessary to maintain ICP at < 20 mmHg. Rewarming began after 48 hours if ICP remained controlled. Participants in the standard-care group received usual care at that centre, but without hypothermia. MAIN OUTCOME MEASURES: The primary outcome measure was the GOSE [range 1 (dead) to 8 (upper good recovery)] at 6 months after the injury as assessed by an independent collaborator, blind to the intervention. A priori subgroup analysis tested the relationship between minimisation factors including being aged < 45 years, having a post-resuscitation Glasgow Coma Scale (GCS) motor score of < 2 on admission, having a time from injury of < 12 hours and patient outcome. RESULTS: We enrolled 387 patients from 47 centres in 18 countries. The trial was closed to recruitment following concerns raised by the Data and Safety Monitoring Committee in October 2014. On an intention-to-treat basis, 195 participants were randomised to hypothermia treatment and 192 to standard care. Regarding participant outcome, there was a higher mortality rate and poorer functional recovery at 6 months in the hypothermia group. The adjusted common odds ratio (OR) for the primary statistical analysis of the GOSE was 1.54 [95% confidence interval (CI) 1.03 to 2.31]; when the GOSE was dichotomised the OR was 1.74 (95% CI 1.09 to 2.77). Both results favoured standard care alone. In this pragmatic study, we did not collect data on adverse events. Data on serious adverse events (SAEs) were collected but were subject to reporting bias, with most SAEs being reported in the hypothermia group. CONCLUSIONS: In participants following TBI and with an ICP of > 20 mmHg, titrated therapeutic hypothermia successfully reduced ICP but led to a higher mortality rate and worse functional outcome. LIMITATIONS: Inability to blind treatment allocation as it was obvious which participants were randomised to the hypothermia group; there was biased recording of SAEs in the hypothermia group. We now believe that more adequately powered clinical trials of common therapies used to reduce ICP, such as hypertonic therapy, barbiturates and hyperventilation, are required to assess their potential benefits and risks to patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN34555414. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 45. See the NIHR Journals Library website for further project information. The European Society of Intensive Care Medicine supported the pilot phase of this trial.

Increased hospice enrollment and decreased neurosurgical interventions without changes in mortality for older Medicare patients with moderate to severe traumatic brain injury.

BACKGROUND: Hospice improves quality and value of end of life care (EOLC), and enrollment has increased for older patients dying from chronic medical conditions. It remains unknown if the same is true for older patients who die after moderate to severe traumatic brain injury (msTBI). METHODS: Subjects included Medicare beneficiaries (≥65 years) who were hospitalized for msTBI from 2005 to 2011. Outcomes included intensity and quality of EOLC for decedents within 30 days of admission, and 30-day mortality for the entire cohort. Logistic regression was used to analyze the association between year of admission, mortality, and EOLC. RESULTS: Among 50,342 older adults, 30-day mortality was 61.2%. Mortality was unchanged over the study period (aOR 0.93 [0.87-1.00], p = 0.06). Additionally, 30-day non-survivors had greater odds of hospice enrollment, lower odds of undergoing neurosurgery, but greater odds of gastrostomy. CONCLUSION: Between 2005 and 2011, hospice enrollment increased, but there was no change in 30-day mortality.