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Background: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear., Methods: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months., Results: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively., Conclusions: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.)., (Copyright © 2024 Massachusetts Medical Society.)

Approximately 15 % of individuals who sustained a mild Traumatic Brain Injury (TBI) develop persistent post-concussion symptoms (PPCS). We hypothesized that blood biomarkers drawn in the Emergency Department (ED) could help predict PPCS. The main objective of this project was to measure the association between four biomarkers and PPCS at 90 days post mild TBI. We conducted a prospective cohort study in seven Canadian EDs. Patients aged ≥ 14 years presenting to the ED within 24 h of a mild TBI who were discharged were eligible. Clinical data and blood samples were collected in the ED, and a standardized questionnaire was administered 90 days later to assess the presence of symptoms. The following biomarkers were analyzed: S100B protein, Neuron Specific Enolase (NSE), cleaved-Tau (c-Tau) and Glial Fibrillary Acidic Protein (GFAP). The primary outcome measure was the presence of PPCS at 90 days after trauma. Relative risks and Areas Under the Curve (AUC) were computed. A total of 595 patients were included, and 13.8 % suffered from PPCS at 90 days. The relative risk of PPCS was 0.9 (95 % CI: 0.5-1.8) for S100B ≥ 20 pg/mL, 1.0 (95 % CI: 0.6-1.5) for NSE ≥ 200 pg/mL, 3.4 (95 % CI: 0.5-23.4) for GFAP ≥ 100 pg/mL, and 1.0 (95 % CI: 0.6-1.8) for C-Tau ≥ 1500 pg/mL. AUC were 0.50, 0.50, 0.51 and 0.54, respectively. Among mild TBI patients, S100B protein, NSE, c-Tau or GFAP do not seem to predict PPCS. Future research testing of other biomarkers is needed to determine their usefulness in predicting PPCS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None. J. Perry has a peer-reviewed mid-career salary support grant from the Heart and Stroke Foundation of Ontario. S. Berthelot and P. Archambault hold a career research award from the Fonds de recherche du Québec- Santé., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. A systematic search was conducted in MEDLINE ® , Embase, Cochrane CENTRAL, Web of Science, and Web sites of organizations publishing recommendations on pediatric injury care. We included CPGs developed in high-income countries from January 2012 to May 2023, with at least one recommendation targeting pediatric (≤ 19 years old) moderate-to-severe TBI populations. The quality of included clinical practice guidelines was assessed using the AGREE II tool. We synthesized evidence on recommendations using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We identified 15 CPGs of which 9 were rated moderate to high quality using AGREE II. We identified 90 recommendations, of which 40 (45%) were evidence based. Eleven of these were based on moderate to high quality evidence and were graded as moderate or strong by at least one guideline. These included transfer, imaging, intracranial pressure control, and discharge advice. We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones.

Purpose: Tracheostomy is a surgical procedure that is commonly performed in patients admitted to the intensive care unit (ICU). It is frequently required in patients with moderate to severe traumatic brain injury (TBI), a subset of patients with prolonged altered state of consciousness that may require a long period of mechanical respiratory assistance. While many clinicians favour the use of early tracheostomy in TBI patients, the evidence in favour of this practice remains scarce. The aims of our study were to evaluate the potential clinical benefits of tracheostomy versus prolonged endotracheal intubation, as well as whether the timing of the procedure may influence outcome in patients with moderate to severe TBI., Methods: We conducted a retrospective multicentre cohort study based on data from the provincial integrated trauma system of Quebec (Québec Trauma Registry). The study population was selected from adult trauma patients hospitalized between 2013 and 2019. We included patients 16 yr and older with moderate to severe TBI (Glasgow Coma Scale score < 13) who required mechanical ventilation for 96 hr or longer. Our primary outcome was 30-day mortality. Secondary outcomes included hospital and ICU mortality, six-month mortality, duration of mechanical ventilation, ventilator-associated pneumonia, ICU and hospital length of stay as well as orientation of patients upon discharge from the hospital. We used propensity score covariate adjustment. To overcome the effect of immortal time bias, an extended Cox shared frailty model was used to compare mortality between groups., Results: From 2013 to 2019, 26,923 patients with TBI were registered in the Québec Trauma Registry. A total of 983 patients who required prolonged endotracheal intubation for 96 hr or more were included in the study, 374 of whom underwent a tracheostomy and 609 of whom remained intubated. We observed a reduction in 30-day mortality (adjusted hazard ratio, 0.33; 95% confidence interval, 0.21 to 0.53) associated with tracheostomy compared with prolonged endotracheal intubation. This effect was also seen in the ICU as well as at six months. Tracheostomy, when compared with prolonged endotracheal intubation, was associated with an increase in the duration of mechanical respiratory assistance without any increase in the length of stay. No effect on mortality was observed when comparing early vs late tracheostomy procedures. An early procedure was associated with a reduction in the duration of mechanical respiratory support as well as hospital and ICU length of stay., Conclusion: In this multicentre cohort study, tracheostomy was associated with decreased mortality when compared with prolonged endotracheal intubation in patients with moderate to severe TBI. This effect does not appear to be modified by the timing of the procedure. Nevertheless, the generalization and application of these results remains limited by potential residual time-dependent indication bias., (© 2023. The Author(s).)

Background and importance Older adults are at higher risk of undertriage and mortality following a traumatic brain injury (TBI). Early identification and accurate triage of severe cases is therefore critical. However, the Glasgow Coma Scale (GCS) might lack sensitivity in older patients. Objective This study investigated the effect of age on the association between the GCS and TBI severity. Design, settings, and participants This multicentre retrospective cohort study (2003-2017) included TBI patients aged ≥16 years with an Abbreviated Injury Scale (AIS of 3, 4 or 5). Older adults were defined as aged 65 and over. Outcomes measure and analysis Median GCS score were compared between older and younger adults, within subgroups of similar AIS. Multivariable logistic regressions were computed to assess the association between age and mortality. The primary analysis comprised patients with isolated TBI, and secondary analysis included patients with multiple trauma. Main results A total of 12 562 patients were included, of which 9485 (76%) were isolated TBIs. Among those, older adults represented 52% ( n  = 4931). There were 22, 27 and 51% of older patients with an AIS-head of 3, 4 and 5 respectively compared to 32, 25 and 43% among younger adults. Within the different subgroups of patients, median GCS scores were higher in older adults: 15 (14-15) vs. 15 (13-15), 15 (14-15) vs. 14 (13-15), 15 (14-15) vs. 14 (8-15), for AIS-head 3, 4 and 5 respectively (all P  < 0.0001). Older adults had increased odds of mortality compared to their younger counterparts at all AIS-head levels: AIS-head = 3 [odds ratio (OR) = 2.9, 95% confidence interval (CI) 1.6-5.5], AIS-head = 4, (OR = 2.7, 95% CI 1.6-4.7) and AIS-head = 5 (OR = 2.6, 95% CI 1.9-3.6) TBI (all P  < 0.001). Similar results were found among patients with multiple trauma. Conclusions In this study, among TBI patients with similar AIS-head score, there was a significant higher median GCS in older patients compared to younger patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Traumatic brain injury (TBI) is the leading cause of mortality and long-term disability in young adults. Despite the high prevalence of anaemia and red blood cell transfusion in patients with TBI, the optimal haemoglobin (Hb) transfusion threshold is unknown. We undertook a randomised trial to evaluate whether a liberal transfusion strategy improves clinical outcomes compared with a restrictive strategy., Methods and Analysis: HEMO globin T ransfusion Threshold in Traumatic Brain I njury Optimizati ON is an international pragmatic randomised open label blinded-endpoint clinical trial. We will include 742 adult patients admitted to an intensive care unit (ICU) with an acute moderate or severe blunt TBI (Glasgow Coma Scale ≤12) and a Hb level ≤100 g/L. Patients are randomly allocated using a 1:1 ratio, stratified by site, to a liberal (triggered by Hb ≤100 g/L) or a restrictive (triggered by Hb ≤70 g/L) transfusion strategy applied from the time of randomisation to the decision to withdraw life-sustaining therapies, ICU discharge or death. Primary and secondary outcomes are assessed centrally by trained research personnel blinded to the intervention. The primary outcome is the Glasgow Outcome Scale extended at 6 months. Secondary outcomes include overall functional independence measure, overall quality of life (EuroQoL 5-Dimension 5-Level; EQ-5D-5L), TBI-specific quality of life (Quality of Life after Brain Injury; QOLIBRI), depression (Patient Health Questionnaire; PHQ-9) and mortality., Ethics and Dissemination: This trial is approved by the CHU de Québec-Université Laval research ethics board (MP-20-2018-3706) and ethic boards at all participating sites. Our results will be published and shared with relevant organisations and healthcare professionals., Trial Registration Number: NCT03260478., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The knowledge gap regarding acute care resource use for patients with traumatic brain injury (TBI) impedes efforts to improve the efficiency and quality of the care of these patients. Our objective was to evaluate interhospital variation in resource use for patients with TBI, identify determinants of high resource use and assess the association between hospital resource use and clinical outcomes., Methods: We conducted a multicentre retrospective cohort study including patients aged 16 years and older admitted to the inclusive trauma system of Quebec following TBI, between 2013 and 2016. We estimated resource use using activity-based costs. Clinical outcomes included mortality, complications and unplanned hospital readmission. Interhospital variation was evaluated using intraclass correlation coefficients (ICCs) with 95% confidence intervals (CIs). Correlations between hospital resource use and clinical outcomes were evaluated using correlation coefficients on weighted, risk-adjusted estimates with 95% CIs., Results: We included 6319 patients. We observed significant interhospital variation in resource use for patients discharged alive, which was not explained by patient case mix (ICC 0.052, 95% CI 0.043 to 0.061). Adjusted mean resource use for patients discharged to long-term care was more than twice that of patients discharged home. Hospitals with higher resource use tended to have a lower incidence of mortality ( r -0.347, 95% CI -0.559 to -0.087) and unplanned readmission ( r -0.249, 95% CI -0.481 to 0.020) but a higher incidence of complications ( r 0.491, 95% CI 0.255 to 0.666)., Conclusion: Resource use for TBI varies significantly among hospitals and may be associated with differences in mortality and morbidity. Negative associations with mortality and positive associations with complications should be interpreted with caution but suggest there may be a trade-off between adverse events and survival that should be evaluated further., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Objective: Evaluate interhospital variation in resource use for in-hospital injury deaths., Background: Significant variation in resource use for end-of-life care has been observed in the US for chronic diseases. However, there is an important knowledge gap on end-of-life resource use for trauma patients., Methods: We conducted a multicenter, retrospective cohort study of injury deaths following hospitalization in any of the 57 trauma centers in a Canadian trauma system (2013-2016). Resource use intensity was measured using activity-based costing (2016 $CAN) according to time of death (72 h, 3-14 d, ≥14 d). We used multilevel log-linear regression to model resource use and estimated interhospital variation using intraclass correlation coefficients (ICC)., Results: Our study population comprised 2044 injury deaths. Variation in resource use between hospitals was observed for all 3 time frames (ICC = 6.5%, 6.6%, and 5.9% for < 72 h, 3-14 d, and ≥14 d, respectively). Interhospital variation was stronger for allied health services (ICC = 18 to 26%), medical imaging (ICC = 4 to 10%), and the ICU (ICC = 5 to 6%) than other activity centers. We observed stronger interhospital variation for patients < 65 years of age (ICC = 11 to 34%) than those ≥65 (ICC = 5 to 6%) and for traumatic brain injury (ICC = 5 to 13%) than other injuries (ICC = 1 to 8%)., Conclusions: We observed variation in resource use intensity for injury deaths across trauma centers. Strongest variation was observed for younger patients and those with traumatic brain injury. Results may reflect variation in level of care decisions and the incidence of withdrawal of life-sustaining therapies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Despite numerous interventions and treatment options, the outcomes of traumatic brain injury (TBI) have improved little over the last 3 decades, which raises concern about the value of care in this patient population. We aimed to synthesize the evidence on 14 potentially low-value clinical practices in TBI care. Using umbrella review methodology, we identified systematic reviews evaluating the effectiveness of 14 potentially low-value practices in adults with acute TBI. We present data on methodological quality (Assessing the Methodological Quality of Systematic Reviews), reported effect sizes, and credibility of evidence (I to IV). The only clinical practice with evidence of benefit was therapeutic hypothermia (credibility of evidence II to IV). However, the most recent meta-analysis on hypothermia based on high-quality trials suggested harm (credibility of evidence IV). Meta-analyses on platelet transfusion for patients on antiplatelet therapy were all consistent with harm but were statistically non-significant. For the following practices, effect estimates were consistently close to the null: computed tomography (CT) in adults with mild TBI who are low-risk on a validated clinical decision rule; repeat CT in adults with mild TBI on anticoagulant therapy with no clinical deterioration; antibiotic prophylaxis for external ventricular drain placement; and decompressive craniectomy for refractory intracranial hypertension. We identified five clinical practices with evidence of lack of benefit or harm. However, evidence could not be considered to be strong for any clinical practice as effect measures were imprecise and heterogeneous, systematic reviews were often of low quality, and most included studies had a high risk of bias.

Introduction: Traumatic brain injury (TBI) leads to 50 000 deaths, 85 000 disabilities and costs $60 billion each year in the USA. Despite numerous interventions and treatment options, the outcomes of TBI have improved little over the last three decades. In a previous scoping review and expert consultation survey, we identified 13 potentially low-value clinical practices in acute TBI. The objective of this umbrella review is to synthesise the evidence on potentially low-value clinical practices in the care of acute TBI., Methods and Analysis: Using umbrella review methodology, we will search Cochrane Central Register of Controlled Trials, Embase, Epistemonikos, International Prospective Register of Systematic Reviews (PROSPERO) and PubMed to identify systematic reviews evaluating the effect of potential intrahospital low-value practices using tailored population, intervention, comparator, outcome and study design questions based on the results of a previous scoping review. We will present data on the methodological quality of these reviews (Assessing the Methodological Quality of Systematic Reviews-2), reported effect sizes and strength of evidence (Grading of Recommendations, Assessment, Development and Evaluation)., Ethics and Dissemination: Ethics approval is not required as original data will not be collected. Knowledge users from five healthcare quality organisations and clinical associations are involved in the design and conduct of the study. Results will be disseminated in a peer-reviewed journal, at international scientific meetings and to clinical, healthcare quality and patient-partner associations. This work will support the development of metrics to measure the use of low-value practices, inform policy makers on potential targets for deimplementation and in the long term reduce the use of low-value clinical practices in acute TBI care., Prospero Registration Number: CRD42019132428., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Restrictive transfusion strategies have been advocated in critically ill patients. Nevertheless, considerable uncertainty exists regarding optimal transfusion thresholds in traumatic brain injury (TBI) patients because the injured brain is susceptible to hypoxemic damage. We aimed to identify the determinants of red blood cell (RBC) transfusion and the perceived optimal transfusion thresholds in adult patients with moderate-to-severe TBI., Methods: We conducted an electronic, self-administered survey targeting critical care specialists and neurosurgeons from Canada, Australia, and the United Kingdom caring for TBI patients. The questionnaire was initially developed by a panel of experts using a structured process (domains/items generation and reduction). The questionnaire was validated for clinical sensibility, reliability, and content., Results: The response rate was 28.7% (218/760). When presented with the hypothetical scenario of a young adult TBI patient, a wide range of transfusion practices was observed, with 47 (95% confidence interval [CI], 41 to 54)% favouring RBC transfusion at a hemoglobin level of ≤ 70 g·L -1 in the acute phase of care, while 73 (95% CI, 67 to 79)% would use this trigger in the plateau phase of care. Multiple trauma, neuro-monitoring data, hemorrhagic shock, and planned surgery were the main factors that influenced the need for transfusion. The lack of clinical evidence and guidelines was responsible for uncertainty regarding RBC transfusion strategies in this patient population., Conclusion: In our survey about critically ill TBI patients, transfusion practice was found to be mainly influenced by the acuity of care, patient characteristics, and neuro-monitoring. Clinical equipoise regarding optimal transfusion strategy is believed to be mainly attributed to the lack of clear clinical evidence and guidelines. Appropriate randomized-controlled trials are required to determine the optimal transfusion strategies in TBI patients.

Background: Most deaths in critically ill patients with severe traumatic brain injury are associated with a decision to withdraw life-sustaining treatments. We aimed to identify the behavioural determinants that influence recommendations by critical care physicians to consider the withdrawal of life-sustaining treatments in this population., Methods: We conducted a descriptive qualitative study based on the Theoretical Domains Framework of critical care physicians caring for patients with severe traumatic brain injury across Canada. We stratified critical care physicians by regions and used a purposive sampling strategy. We conducted semistructured phone interviews using a piloted and pretested interview guide. We transcribed the interviews verbatim and verified the content for accuracy. We performed the analysis using a 3-step approach: coding, generation of specific beliefs and generation of specific themes., Results: We recruited 20 critical care physicians across 4 geographic regions. After reaching saturation, we identified 7 core themes across 4 Theoretical Domains Framework domains for factors relevant to the decision to withdraw life-sustaining treatments. Four factors (i.e., clinical triggers, social triggers, interaction with families and intentions with medical decisions) were identified before the decision is made and 3 were identified during the decision-making process (i.e., considerations, priorities and knowledge needs). We identified multiple themes reflecting internal ( n = 18, 8 Theoretical Domains Framework domains) and external ( n = 15, 6 Theoretical Domains Framework domains) influences on the decision to withdraw life-sustaining treatments., Interpretation: We identified several core themes and domains considered by critical care physicians in Canada in the decision to withdraw life-sustaining treatments in critically ill patients with severe traumatic brain injury. Future research should aim at identifying the factors influencing surrogate decision-makers in the decision to withdraw life-sustaining treatments in these patients., Competing Interests: Competing interests: None declared., (© 2019 Joule Inc. or its licensors or its licensors.)

Objectives: Biomarkers have been suggested as potential prognostic predictors following a moderate or severe traumatic brain injury but their prognostic accuracy is still uncertain. The objective of this systematic review is to assess the ability of the glial fibrillary acidic protein to predict prognosis in patients with moderate or severe traumatic brain injury., Data Sources: MEDLINE, Embase, CENTRAL, and BIOSIS electronic databases and conference abstracts, bibliographies of selected studies, and narrative reviews were searched., Study Selection: Pairs of reviewers identified eligible studies. Cohort studies including greater than or equal to four patients with moderate or severe traumatic brain injury and reporting glial fibrillary acidic protein levels according to the outcomes of interest, namely Glasgow Outcome Scale or Extended Glasgow Outcome Scale, and mortality, were eligible., Data Extraction: Pairs of reviewers independently extracted data from the selected studies using a standardized case report form. Mean levels were log-transformed, and their differences were pooled with random effect models. Results are presented as geometric mean ratios. Methodologic quality, risk of bias, and applicability concerns of the included studies were assessed., Data Synthesis: Seven-thousand seven-hundred sixty-five citations were retrieved of which 15 studies were included in the systematic review (n = 1,070), and nine were included in the meta-analysis (n = 701). We found significant associations between glial fibrillary acidic protein serum levels and Glasgow Outcome Scale score less than or equal to 3 or Extended Glasgow Outcome Scale score less than or equal to 4 (six studies: geometric mean ratio 4.98 [95% CI, 2.19-11.13]; I = 94%) and between mortality (seven studies: geometric mean ratio 8.13 [95% CI, 3.89-17.00]; I = 99%)., Conclusions: Serum glial fibrillary acidic protein levels were significantly higher in patients with an unfavorable prognosis. Glial fibrillary acidic protein has a potential for clinical bedside use in helping for prognostic assessment. Further research should focus on multimodal approaches including tissue biomarkers for prognostic evaluation in critically ill patients with traumatic brain injury.

Purpose: The intensity of care provided to critically ill patients has been shown to be associated with mortality. In patients with traumatic brain injury (TBI), specialized neurocritical care is often required, but whether it affects clinically significant outcomes is unknown. We aimed to determine the association of the intensity of care on mortality and the incidence of withdrawal of life-sustaining therapies in critically ill patients with severe TBI., Methods: We conducted a post hoc analysis of a multicentre retrospective cohort study of critically ill adult patients with severe TBI. We defined the intensity of care as a daily cumulative sum of interventions during the intensive care unit stay. Our outcome measures were all-cause hospital mortality and the incidence of withdrawal of life-sustaining therapies., Results: Seven hundred sixteen severe TBI patients were included in our study. Most were male (77%) with a mean (standard deviation) age of 42 (20.5) yr and a median [interquartile range] Glasgow Coma Scale score of 3 [3-6]. Our results showed an association between the intensity of care and mortality (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.63 to 0.74) and the incidence of withdrawal of life-sustaining therapy (HR, 0.73; 95% CI, 0.67 to 0.79)., Conclusion: In general, more intense care was associated with fewer deaths and a lower incidence of withdrawal of life-sustaining therapies in critically ill patients with severe TBI.

Background Most deaths following severe traumatic brain injury follow decisions to withdraw life-sustaining therapies. However, the incidence of the withdrawal of life-sustaining therapies and its potential impact on research data interpretation have been poorly characterized. The aim of this systematic review was to assess the reporting and the impact of withdrawal of life-sustaining therapies in randomized clinical trials of patients with severe traumatic brain injury. Methods We searched Medline, Embase, Cochrane Central, BIOSIS, and CINAHL databases and references of included trials. All randomized controlled trials published between January 2002 and August 2015 in the six highest impact journals in general medicine, critical care medicine, and neurocritical care (total of 18 journals) were considered for eligibility. Randomized controlled trials were included if they enrolled adult patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) and reported data on mortality. Our primary objective was to assess the proportion of trials reporting the withdrawal of life-sustaining therapies in a publication. Our secondary objectives were to describe the overall mortality rate, the proportion of deaths following the withdrawal of life-sustaining therapies, and to assess the impact of the withdrawal of life-sustaining therapies on trial results. Results From 5987 citations retrieved, we included 41 randomized trials (n = 16,364, ranging from 11 to 10,008 patients). Overall mortality was 23% (range = 3%-57%). Withdrawal of life-sustaining therapies was reported in 20% of trials (8/41, 932 patients in trials) and the crude number of deaths due to the withdrawal of life-sustaining therapies was reported in 17% of trials (7/41, 884 patients in trials). In these trials, 63% of deaths were associated with the withdrawal of life-sustaining therapies (105/168). An analysis carried out by imputing a 4% differential rate in instances of withdrawal of life-sustaining therapies between study groups yielded different results and conclusions in one third of the trials. Conclusion Data on the withdrawal of life-sustaining therapies are incompletely reported in randomized controlled trials of patients with severe traumatic brain injury. Given the high proportion of deaths due to the withdrawal of life-sustaining therapies in severe traumatic brain injury patients, and the potential of this medical decision to influence the results of clinical trials, instances of withdrawal of life-sustaining therapies should be systematically reported in clinical trials in this group of patients.

The aims of this study were to document the frequency of major and minor depressive episodes in the first year after traumatic brain injury (TBI), taking into account TBI severity and pre-morbid history of major depression, and to describe trajectories of depressive episodes. Participants were 227 adults who were hospitalized post-TBI (76% male; mean age = 41 years; 50% mild, 33% moderate, and 17% severe TBI). Major and minor depressive episodes were assessed with the Mini International Neuropsychiatric Interview at three time points (4, 8, and 12 months after TBI). Overall, 29% of participants had a major depressive episode in at least one of the three assessments, with fairly stable rates across assessments. Participants with mild TBI were more likely than those with moderate/severe TBI to be diagnosed with major depression, as were individuals with a positive pre-morbid history of depression compared to those without such history. In addition, 13% of participants had a minor depressive episode in at least one of the three assessments. Rates of minor depression significantly decreased from 4 to 8-12 months post-injury. Results also revealed a wide variety of trajectories of depressive episodes across assessments. Of note, 52% of major depression cases still fulfilled diagnostic criteria 4 months later, whereas 38% of minor depression cases deteriorated to major depression at the following assessment. These findings suggest that depression is highly prevalent after TBI, and monitoring of patients with subthreshold depressive symptoms is warranted in order to prevent the development of full-blown major depressive episodes.

Purpose: We aimed to evaluate the association between transfusion practices and clinical outcomes in patients with traumatic brain injury., Material and Methods: We conducted a retrospective cohort study of adult patients with moderate or severe traumatic brain injury admitted to the intensive care unit (ICU) of a level I trauma center between 2009 and 2013. The associations between hemoglobin (Hb) level, red blood cell (RBC) transfusion and clinical outcomes were estimated using robust Poisson models and proportional hazard models with time-dependent variables, adjusted for confounders., Results: We included 215 patients. Sixty-six patients (30.7%) were transfused during ICU stay. The median pre-transfusion Hb among transfused patients was 81g/L (IQR 67-100), while median nadir Hb among non-transfused patients was 110g/L (IQR 93-123). Poor outcomes were significantly more frequent in patients who were transfused (mortality risk ratio [RR]: 2.15 [95% CI 1.37-3.38] and hazard ratio: 3.06 [95% CI 1.57-5.97]; neurological complications RR: 3.40 [95% CI 1.35-8.56]; trauma complications RR: 1.65 [95% CI 1.31-2.08]; ICU length of stay geometric mean ratio: 1.42 [95% CI 1.06-1.92])., Conclusions: During ICU stay, transfused patients tended to have lower Hb levels and worse outcomes than patients who did not receive RBCs, after adjustment for confounders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Traumatic brain injury is a major cause of death and disability, yet many predictors of outcome are not precise enough to guide initial clinical decision-making. Although increasingly used in the early phase following traumatic brain injury, the prognostic utility of MRI remains uncertain. We thus undertook a systematic review and meta-analysis of studies evaluating the predictive value of acute MRI lesion patterns for discriminating clinical outcome in traumatic brain injury., Data Sources: MEDLINE, EMBASE, BIOSIS, and CENTRAL from inception to November 2015., Study Selection: Studies of adults who had MRI in the acute phase following moderate or severe traumatic brain injury. Our primary outcomes were all-cause mortality and the Glasgow Outcome Scale., Data Extraction: Two authors independently performed study selection and data extraction. We calculated pooled effect estimates with a random effects model, evaluated the risk of bias using a modified version of Quality in Prognostic Studies and determined the strength of evidence with the Grading of Recommendations, Assessment, Development, and Evaluation., Data Synthesis: We included 58 eligible studies, of which 27 (n = 1,652) contributed data to meta-analysis. Brainstem lesions were associated with all-cause mortality (risk ratio, 1.78; 95% CI, 1.01-3.15; I = 43%) and unfavorable Glasgow Outcome Scale (risk ratio, 2.49; 95% CI, 1.72-3.58; I = 81%) at greater than or equal to 6 months. Diffuse axonal injury patterns were associated with an increased risk of unfavorable Glasgow Outcome Scale (risk ratio, 2.46; 95% CI, 1.06-5.69; I = 74%). MRI scores based on lesion depth demonstrated increasing risk of unfavorable neurologic outcome as more caudal structures were affected. Most studies were at high risk of methodological bias., Conclusions: MRI following traumatic brain injury yields important prognostic information, with several lesion patterns significantly associated with long-term survival and neurologic outcome. Given the high risk of bias in the current body of literature, large well-controlled studies are necessary to better quantify the prognostic role of early MRI in moderate and severe traumatic brain injury.

Purpose: To evaluate the incidence, determinants and impact on outcome of in-hospital complications in adults with traumatic brain injury (TBI)., Materials and Methods: We conducted a multicenter cohort study of TBI patients admitted between 2007 and 2012 in an inclusive Canadian trauma system. Risk ratios of complications, odds ratios of mortality and geometric mean ratios of length of stay (LOS) were calculated using generalized linear models with adjustment for prognostic indicators and hospital cluster effects., Results: Of 12,887 patients, 3.2% had at least one neurological complication and 22.6% a non-neurological complication. Mechanical ventilation, head injury severity, blood transfusion and neurosurgical intervention had the strongest correlation with neurological complications. Mechanical ventilation, the Glasgow Coma Scale, blood transfusion and concomitant injuries had the strongest correlation with non-neurological complications. Neurological and non-neurological complications were associated with a 85% and 53% increase in the odds of mortality, and a 60% and two-fold increases in LOS, respectively., Conclusions: More than 20% of patients with TBI developed a complication. Many of these complications were associated with increased mortality and LOS. Results highlight the importance of prevention strategies adapted to treatment decisions and underline the need to improve knowledge on the underuse and overuse of clinical interventions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Severe traumatic brain injury is a significant cause of morbidity and mortality in young adults. Assessing long-term neurological outcome after such injury is difficult and often characterised by uncertainty. The objective of this feasibility study was to establish the feasibility of conducting a large, multicentre prospective study to develop a prognostic model of long-term neurological outcome in critically ill patients with severe traumatic brain injury., Design: A prospective cohort study., Setting: 9 Canadian intensive care units enrolled patients suffering from acute severe traumatic brain injury. Clinical, biological, radiological and electrophysiological data were systematically collected during the first week in the intensive care unit. Mortality and functional outcome (Glasgow Outcome Scale extended) were assessed on hospital discharge, and then 3, 6 and 12 months following injury., Outcomes: The compliance to protocolised test procedures was the primary outcome. Secondary outcomes were enrolment rate and compliance to follow-up., Results: We successfully enrolled 50 patients over a 12-month period. Most patients were male (80%), with a median age of 45 years (IQR 29.0-60.0), a median Injury Severity Score of 38 (IQR 25-50) and a Glasgow Coma Scale of 6 (IQR 3-7). Mortality was 38% (19/50) and most deaths occurred following a decision to withdraw life-sustaining therapies (18/19). The main reasons for non-enrolment were the time window for inclusion being after regular working hours (35%, n=23) and oversight (24%, n=16). Compliance with protocolised test procedures ranged from 92% to 100% and enrolment rate was 43%. No patients were lost to follow-up at 6 months and 2 were at 12 months., Conclusions: In this multicentre prospective feasibility study, we achieved feasibility objectives pertaining to compliance to test, enrolment and follow-up. We conclude that the TBI-Prognosis prospective multicentre study in severe traumatic brain injury patients in Canada is feasible., Competing Interests: Competing interestsNone declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Optimisation of healthcare practices in patients sustaining a traumatic brain injury is of major concern given the high incidence of death and long-term disabilities. Considering the brain's susceptibility to ischaemia, strategies to optimise oxygenation to brain are needed. While red blood cell (RBC) transfusion is one such strategy, specific RBC strategies are debated. We aimed to evaluate RBC transfusion frequency, determinants of transfusions and associated clinical outcomes., Methods: We conducted a retrospective multicentre cohort study using data from the National Trauma Registry of Canada. Patients admitted with moderate or severe traumatic brain injury to participating hospitals between April 2005 and March 2013 were eligible. Patient information on blood products, comorbidities, interventions and complications from the Discharge Abstract Database were linked to the National Trauma Registry data. Relative weights analyses evaluated the contribution of each determinant. We conducted multivariate robust Poisson regression to evaluate the association between potential determinants, mortality, complications, hospital-to-home discharge and RBC transfusion. We also used proportional hazard models to evaluate length of stay for time to discharge from ICU and hospital., Results: Among the 7062 patients with traumatic brain injury, 1991 patients received at least one RBC transfusion during their hospital stay. Female sex, anaemia, coagulopathy, sepsis, bleeding, hypovolemic shock, other comorbid illnesses, serious extracerebral trauma injuries were all significantly associated with RBC transfusion. Serious extracerebral injuries altogether explained 61% of the observed variation in RBC transfusion. Mortality (risk ratio (RR) 1.23 (95% CI 1.13 to 1.33)), trauma complications (RR 1.38 (95% CI 1.32 to 1.44)) and discharge elsewhere than home (RR 1.88 (95% CI 1.75 to 2.04)) were increased in patients who received RBC transfusion. Discharge from ICU and hospital were also delayed in transfused patients., Conclusions: RBC transfusion is common in patients with traumatic brain injury and associated with unfavourable outcomes. Trauma severity is an important determinant of RBC transfusion. Prospective studies are needed to further evaluate optimal transfusion strategies in traumatic brain injury., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The International Classification of Diseases (ICD) is the main classification system used for population-based traumatic brain injury (TBI) surveillance activities but does not contain direct information on injury severity. International Classification of Diseases-based injury severity measures can be empirically derived or mapped to the Abbreviated Injury Scale, but no single approach has been formally recommended for TBI., Objective: The aim of this study was to compare the accuracy of different ICD-based injury severity measures for predicting in-hospital mortality and intensive care unit (ICU) admission in TBI patients., Methods: We conducted a population-based retrospective cohort study. We identified all patients 16 years or older with a TBI diagnosis who received acute care between April 1, 2006, and March 31, 2013, from the Quebec Hospital Discharge Database. The accuracy of five ICD-based injury severity measures for predicting mortality and ICU admission was compared using measures of discrimination (area under the receiver operating characteristic curve [AUC]) and calibration (calibration plot and the Hosmer-Lemeshow goodness-of-fit statistic)., Results: Of 31,087 traumatic brain-injured patients in the study population, 9.0% died in hospital, and 34.4% were admitted to the ICU. Among ICD-based severity measures that were assessed, the multiplied derivative of ICD-based Injury Severity Score (ICISS-Multiplicative) demonstrated the best discriminative ability for predicting in-hospital mortality (AUC, 0.858; 95% confidence interval, 0.852-0.864) and ICU admissions (AUC, 0.813; 95% confidence interval, 0.808-0.818). Calibration assessments showed good agreement between observed and predicted in-hospital mortality for ICISS measures. All severity measures presented high agreement between observed and expected probabilities of ICU admission for all deciles of risk., Conclusions: The ICD-based injury severity measures can be used to accurately predict in-hospital mortality and ICU admission in TBI patients. The ICISS-Multiplicative generally outperformed other ICD-based injury severity measures and should be preferred to control for differences in baseline characteristics between TBI patients in surveillance activities or injury research when only ICD codes are available., Level of Evidence: Prognostic study, level III.

Background: Traumatic brain injury (TBI) is the leading cause of disability in children and young adults and costs CAD$3 billion annually in Canada. Stakeholders have expressed the urgent need to obtain information on resource use for TBI to improve the quality and efficiency of acute care in this patient population. We aimed to assess the components and determinants of hospital and ICU LOS for TBI admissions., Methods: We performed a retrospective multicenter cohort study on 11,199 adults admitted for TBI between 2007 and 2012 in an inclusive Canadian trauma system. Our primary outcome measure was index hospital LOS (admission to the hospital with the highest designation level). Index LOS was compared to total LOS (all consecutive admissions related to the injury). Expected LOS was calculated by matching TBI admissions to all-diagnosis hospital admissions by age, gender, and year of admission. LOS determinants were identified using multilevel linear regression., Results: Geometric mean total LOS was 1day longer than geometric mean index LOS (12.6 versus 11.7 days). Observed index and ICU LOS were respectively 4.2days and 2.5days longer than that expected according to all-diagnosis admissions. The six most important determinants of LOS were discharge destination, severity of concomitant injuries, extracranial complications, GCS, TBI severity, and mechanical ventilation, accounting for 80% of explained variation., Conclusions: Results of this multicenter retrospective cohort study suggest that hospital and ICU LOS for TBI admissions are 56% and 119% longer than expected according to all-diagnosis admissions, respectively. In addition, hospital LOS is underestimated when only the index visit is considered and is largely influenced by discharge destination and extracranial complications, suggesting that improvements could be achieved with better discharge planning and interventions targeting prevention of in-hospital complications. This study highlights the importance of considering TBI patients as a distinct population when allocating resources or planning quality improvement interventions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)