Using Decision Tree Methodology to Predict Employment After Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: To build decision tree prediction models for long-term employment outcomes of individuals after moderate to severe closed traumatic brain injury (TBI) and assess model accuracy in an independent sample. SETTING: TBI Model Systems Centers. PARTICIPANTS: TBI Model Systems National Database participants injured between January 1997 and January 2017 with moderate to severe closed TBI. Sample sizes were 7867 (year 1 postinjury), 6783 (year 2 postinjury), and 4927 (year 5 postinjury). DESIGN: Cross-sectional analyses using flexible classification tree methodology and validation using an independent subset of TBI Model Systems National Database participants. MAIN MEASURES: Competitive employment at 1, 2, and 5 years postinjury. RESULTS: In the final employment prediction models, posttraumatic amnesia duration was the most important predictor of employment in each outcome year. Additional variables consistently contributing were age, preinjury education, productivity, and occupational category. Generally, individuals spending fewer days in posttraumatic amnesia, who were competitively employed preinjury, and more highly educated had better outcomes. Predictability in test data sets ranged from a C-statistic of 0.72 (year 5; confidence interval: 0.68-0.76) to 0.77 (year 1; confidence interval: 0.74-0.80). CONCLUSION: An easy-to-use decision tree tool was created to provide prognostic information on long-term competitive employment outcomes in individuals with moderate to severe closed TBI. Length of posttraumatic amnesia, a clinical marker of injury severity, and preinjury education and employment status were the most important predictors.

Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery: A TRACK-TBI Study.

Importance: Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders. Objective: To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI. Design, Setting, and Participants: This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023. Exposure: Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI]). Main Outcomes and Measures: The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury. Results: A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI). Conclusions and Relevance: This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT).

CONTEXT: Traumatic brain injury (TBI) is a serious public health problem in the United States, yet no treatment is currently available to improve outcome after TBI. Approved for use in TBI in 59 countries, citicoline is an endogenous substance offering potential neuroprotective properties as well as facilitated neurorepair post injury. OBJECTIVE: To determine the ability of citicoline to positively affect functional and cognitive status in persons with complicated mild, moderate, and severe TBI. DESIGN, SETTING, AND PATIENTS: The Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind randomized clinical trial conducted between July 20, 2007, and February 4, 2011, among 1213 patients at 8 US level 1 trauma centers to investigate effects of citicoline vs placebo in patients with TBI classified as complicated mild, moderate, or severe. INTERVENTION: Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. MAIN OUTCOME MEASURES: Functional and cognitive status, assessed at 90 days using the TBI-Clinical Trials Network Core Battery. A global statistical test was used to analyze the 9 scales of the core battery. Secondary outcomes were functional and cognitive improvement, assessed at 30, 90, and 180 days, and examination of the long-term maintenance of treatment effects. RESULTS: Rates of favorable improvement for the Glasgow Outcome Scale-Extended were 35.4% in the citicoline group and 35.6% in the placebo group. For all other scales the rate of improvement ranged from 37.3% to 86.5% in the citicoline group and from 42.7% to 84.0% in the placebo group. The citicoline and placebo groups did not differ significantly at the 90-day evaluation (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]). CONCLUSION: Among patients with traumatic brain injury, the use of citicoline compared with placebo for 90 days did not result in improvement in functional and cognitive status. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00545662.

Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury: Findings From the TRACK-TBI Study.

Importance: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. Objective: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. Design, Setting, and Participants: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. Exposures: TBI. Main Outcomes and Measures: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Results: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34). Conclusions and Relevance: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

Importance: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. Objective: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. Design, Setting, and Participants: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. Exposures: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. Main Outcomes and Measures: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). Results: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02). Conclusions and Relevance: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury: A TRACK-TBI Study With External Validation in CENTER-TBI.

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. Conclusions and Relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.

Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study.

Importance: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. Objective: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. Design, Setting, and Participants: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. Exposures: Moderate or severe TBI. Main Outcomes and Measures: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. Results: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. Conclusions and Relevance: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.

Association of Posttraumatic Epilepsy With 1-Year Outcomes After Traumatic Brain Injury.

Importance: Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known. Objective: To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort. Design, Setting, and Participants: This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018. Patients with TBI, extracranial orthopedic injuries (orthopedic controls), and individuals without reported injuries (eg, friends and family of participants; hereafter friend controls) were prospectively followed for 12 months. Data were analyzed from January 2020 to April 2021. Exposure: Demographic, imaging, and clinical information was collected according to TBI Common Data Elements. Incidence of self-reported PTE was assessed using the National Institute of Neurological Disorders and Stroke Epilepsy Screening Questionnaire (NINDS-ESQ). Main Outcomes and Measures: Primary outcomes included Glasgow Outcome Scale Extended, Rivermead Cognitive Metric (RCM; derived from the Rivermead Post Concussion Symptoms Questionnaire), and the Brief Symptom Inventory-18 (BSI). Results: Of 3296 participants identified as part of the study, 3044 met inclusion criteria, and 1885 participants (mean [SD] age, 41.3 [17.1] years; 1241 [65.8%] men and 644 [34.2%] women) had follow-up information at 12 months, including 1493 patients with TBI; 182 orthopedic controls, 210 uninjured friend controls; 41 patients with TBI (2.8%) and no controls had positive screening results for PTE. Compared with a negative screening result for PTE, having a positive screening result for PTE was associated with presenting Glasgow Coma Scale score (8.1 [4.8] vs.13.5 [3.3]; P < .001) as well as with anomalous acute head imaging findings (risk ratio, 6.42 [95% CI, 2.71-15.22]). After controlling for age, initial Glasgow Coma Scale score, and imaging findings, compared with patients with TBI and without PTE, patients with TBI and with positive PTE screening results had significantly lower Glasgow Outcome Scale Extended scores (mean [SD], 6.1 [1.7] vs 4.7 [1.5]; P < .001), higher BSI scores (mean [SD], 50.2 [10.7] vs 58.6 [10.8]; P = .02), and higher RCM scores (mean [SD], 3.1 [2.6] vs 5.3 [1.9]; P = .002) at 12 months. Conclusions and Relevance: In this cohort study, the incidence of self-reported PTE after TBI was found to be 2.8% and was independently associated with unfavorable outcomes. These findings highlight the need for effective antiepileptogenic therapies after TBI.

Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study.

IMPORTANCE: Most traumatic brain injuries (TBIs) are classified as mild (mTBI) based on admission Glasgow Coma Scale (GCS) scores of 13 to 15. The prevalence of persistent functional limitations for these patients is unclear. OBJECTIVES: To characterize the natural history of recovery of daily function following mTBI vs peripheral orthopedic traumatic injury in the first 12 months postinjury using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, and, using clinical computed tomographic (CT) scans, examine whether the presence (CT+) or absence (CT-) of acute intracranial findings in the mTBI group was associated with outcomes. DESIGN, SETTING, AND PARTICIPANTS: TRACK-TBI, a cohort study of patients with mTBI presenting to US level I trauma centers, enrolled patients from February 26, 2014, to August 8, 2018, and followed up for 12 months. A total of 1453 patients at 11 level I trauma center emergency departments or inpatient units met inclusion criteria (ie, mTBI [n = 1154] or peripheral orthopedic traumatic injury [n = 299]) and were enrolled within 24 hours of injury; mTBI participants had admission GCS scores of 13 to 15 and clinical head CT scans. Patients with peripheral orthopedic trauma injury served as the control (OTC) group. EXPOSURES: Participants with mTBI or OTC. MAIN OUTCOMES AND MEASURES: The Glasgow Outcome Scale Extended (GOSE) scale score, reflecting injury-related functional limitations across broad life domains at 2 weeks and 3, 6, and 12 months postinjury was the primary outcome. The possible score range of the GOSE score is 1 (dead) to 8 (upper good recovery), with a score less than 8 indicating some degree of functional impairment. RESULTS: Of the 1453 participants, 953 (65.6%) were men; mean (SD) age was 40.9 (17.1) years in the mTBI group and 40.9 (15.4) years in the OTC group. Most participants (mTBI, 87%; OTC, 93%) reported functional limitations (GOSE <8) at 2 weeks postinjury. At 12 months, the percentage of mTBI participants reporting functional limitations was 53% (95% CI, 49%-56%) vs 38% (95% CI, 30%-45%) for OTCs. A higher percentage of CT+ patients reported impairment (61%) compared with the mTBI CT- group (49%; relative risk [RR], 1.24; 95% CI, 1.08-1.43) and a higher percentage in the mTBI CT-group compared with the OTC group (RR, 1.28; 95% CI, 1.02-1.60). CONCLUSIONS AND RELEVANCE: Most patients with mTBI presenting to US level I trauma centers report persistent, injury-related life difficulties at 1 year postinjury, suggesting the need for more systematic follow-up of patients with mTBI to provide treatments and reduce the risk of chronic problems after mTBI.

Making Football Safer: Assessing the Current National Football League Policy on the Type of Helmets Allowed on the Playing Field.

In an effort to reduce concussions in football, a helmet safety-rating system was developed in 2011 that rated helmets based on their ability to reduce g-forces experienced by the head across a range of impact forces measured on the playing field. Although this was considered a major step in making the game safer, the National Football League (NFL) continues to allow players the right to choose what helmet to wear during play. This prompted us to ask: What helmets do NFL players wear and does this helmet policy make the game safer? Accordingly, we identified the helmets worn by nearly 1000 players on Week 13 of the 2015-2016 season and Week 1 of the 2016-2017 season. Using stop-motion footage, we found that players wore a wide range of helmets with varying safety ratings influenced in part by the player's position and age. Moreover, players wearing lower safety-rated helmets were more likely to receive a concussion than those wearing higher safety-rated helmets. Interestingly, many players suffering a concussion in 2015 did not switch to a higher safety-rated helmet in 2016. Using a helmet-to-helmet impactor, we found that the g-forces experienced in the highest safety-rated helmets were roughly 30% less than that for the lowest safety-rated helmets. These results suggest that the current NFL helmet policy puts players at increased risk of receiving a concussion as many players are wearing low safety-rated helmets, which transmits more energy to the brain than higher safety-rated helmets, following collision. Thus, to reduce concussions, the NFL should mandate that players only wear helmets that receive the highest safety rating.

Predicting Long-Term Global Outcome after Traumatic Brain Injury: Development of a Practical Prognostic Tool Using the Traumatic Brain Injury Model Systems National Database.

For patients surviving serious traumatic brain injury (TBI), families and other stakeholders often desire information on long-term functional prognosis, but accurate and easy-to-use clinical tools are lacking. We aimed to build utilitarian decision trees from commonly collected clinical variables to predict Glasgow Outcome Scale (GOS) functional levels at 1, 2, and 5 years after moderate-to-severe closed TBI. Flexible classification tree statistical modeling was used on prospectively collected data from the TBI-Model Systems (TBIMS) inception cohort study. Enrollments occurred at 17 designated, or previously designated, TBIMS inpatient rehabilitation facilities. Analysis included all participants with nonpenetrating TBI injured between January 1997 and January 2017. Sample sizes were 10,125 (year-1), 8,821 (year-2), and 6,165 (year-5) after cross-sectional exclusions (death, vegetative state, insufficient post-injury time, and unavailable outcome). In our final models, post-traumatic amnesia (PTA) duration consistently dominated branching hierarchy and was the lone injury characteristic significantly contributing to GOS predictability. Lower-order variables that added predictability were age, pre-morbid education, productivity, and occupational category. Generally, patient outcomes improved with shorter PTA, younger age, greater pre-morbid productivity, and higher pre-morbid vocational or educational achievement. Across all prognostic groups, the best and worst good recovery rates were 65.7% and 10.9%, respectively, and the best and worst severe disability rates were 3.9% and 64.1%. Predictability in test data sets ranged from C-statistic of 0.691 (year-1; confidence interval [CI], 0.675, 0.711) to 0.731 (year-2; CI, 0.724, 0.738). In conclusion, we developed a clinically useful tool to provide prognostic information on long-term functional outcomes for adult survivors of moderate and severe closed TBI. Predictive accuracy for GOS level was demonstrated in an independent test sample. Length of PTA, a clinical marker of injury severity, was by far the most critical outcome determinant.

Assessment of Follow-up Care After Emergency Department Presentation for Mild Traumatic Brain Injury and Concussion: Results From the TRACK-TBI Study.

Importance: Mild traumatic brain injury (mTBI) affects millions of Americans each year. Lack of consistent clinical practice raises concern that many patients with mTBI may not receive adequate follow-up care. Objective: To characterize the provision of follow-up care to patients with mTBI during the first 3 months after injury. Design, Setting, and Participants: This cohort study used data on patients with mTBI enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study between February 26, 2014, and August 25, 2016. We examined site-specific variations in follow-up care, the types of clinicians seen by patients receiving follow-up care, and patient and injury characteristics associated with a higher likelihood of receiving follow-up care. The TRACK-TBI study is a prospective, multicenter, longitudinal observational study of patients with TBI presenting to the emergency department of 1 of 11 level I US trauma centers. Study data included patients with head trauma who underwent a computed tomography (CT) scan within 24 hours of injury, had a Glasgow Coma Scale score of 13 to 15, were aged 17 years or older, and completed follow-up care surveys at 2 weeks and 3 months after injury (N = 831). Main Outcomes and Measures: Follow-up care was defined as hospitals providing TBI educational material at discharge, hospitals calling patients to follow up, and patients seeing a physician or other medical practitioner within 3 months after the injury. Unfavorable outcomes were assessed with the Rivermead Post Concussion Symptoms Questionnaire. Results: Of 831 patients (289 [35%] female; 483 [58%] non-Hispanic white; mean [SD] age, 40.3 [16.9] years), less than half self-reported receiving TBI educational material at discharge (353 patients [42%]) or seeing a physician or other health care practitioner within 3 months after injury (367 patients [44%]). Follow-up care varied by study site; adjusting for patient characteristics, the provision of educational material varied from 19% to 72% across sites. Of 236 patients with a positive finding on a CT scan, 92 (39%) had not seen a medical practitioner 3 months after the injury. Adjusting for injury severity and demographics, patient admission to the hospital ward or intensive care unit, patient income, and insurance status were not associated with the probability of seeing a medical practitioner. Among the patients with 3 or more moderate to severe postconcussive symptoms, only 145 of 279 (52%) reported having seen a medical practitioner by 3 months. Conclusions and Relevance: There are gaps in follow-up care for patients with mTBI after hospital discharge, even those with a positive finding on CT or who continue to experience postconcussive symptoms.

Nutritional Supplementation with Chlorella pyrenoidosa Lowers Serum Methylmalonic Acid in Vegans and Vegetarians with a Suspected Vitamin B12 Deficiency.

Since vitamin B12 occurs in substantial amounts only in foods derived from animals, vegetarians and particularly vegans are at risk of developing deficiencies of this essential vitamin. The chlorella used for this study is a commercially available whole-food supplement, which is believed to contain the physiologically active form of the vitamin. This exploratory open-label study was performed to determine if adding 9 g of Chlorella pyrenoidosa daily could help mitigate a vitamin B12 deficiency in vegetarians and vegans. Seventeen vegan or vegetarian adults (26-57 years of age) with a known vitamin B12 deficiency, as evidenced by a baseline serum methylmalonic acid (MMA) level above 270 nmol/L at screening, but who otherwise appeared healthy were enrolled in the study. Each participant added 9 g of C. pyrenoidosa to their daily diet for 60 ± 5 days and their serum MMA, vitamin B12, homocysteine (Hcy) levels as well as mean corpuscular volume (MCV), hemoglobin (Hgb), and hematocrit (Hct) were measured at 30 and 60 days from baseline. After 30 and 60 days, the serum MMA level fell significantly (P < .05) by an average ∼34%. Fifteen of the 17 (88%) subjects showed at least a 10% drop in MMA. At the same time, Hcy trended downward and serum vitamin B12 trended upward, while MCV, Hgb, and Hct appeared unchanged. The results of this work suggest that the vitamin B12 in chlorella is bioavailable and such dietary supplementation is a natural way for vegetarians and vegans to get the vitamin B12 they need.

Altered white matter in cocaine-dependent subjects with traumatic brain injury: A diffusion tensor imaging study.

BACKGROUND: Diffusion tensor imaging (DTI) is a useful technique for non-invasively investigating the microstructural organization of white matter (WM), and the most consistent DTI finding regarding cocaine-related WM alterations is in the corpus callosum (CC). WM injury has also been observed in subjects with traumatic brain injury (TBI), including in the CC. METHODS: We used DTI to test if the WM microstructure is relatively more impaired in cocaine-dependent subjects who had suffered a mild TBI (mTBI). Fractional anisotropy (FA), which reflects the degree of alignment of cellular structures within fiber tracts and their structural integrity, was compared across cocaine-dependent subjects with mTBI (COCTBI group, n = 9), matched cocaine-dependent subjects without TBI (COC group, n = 12), and matched healthy controls (CTL group, n = 12). RESULTS: The COCTBI group had significantly lower FA in the genu, body, and splenium of CC, than the CTL group whenever the education was controlled or not. The COC group had significantly lower FA in the left and right anterior corona radiata than the CTL group only when the education was controlled. There was no significant difference in FA between the COC and COCTBI groups. CONCLUSION: Cocaine dependence (or mTBI) related WM impairments in the CC were not detectable in this small subject sample. The significant finding in the CC suggests that the concurrence of cocaine dependence and mTBI might result in more severe damage to the CC, which could even be detected in small sample size.

Contrasting effects of interleukin-2 secretion by rat glioma cells contingent upon anatomical location: accelerated tumorigenesis in the central nervous system and complete rejection in the periphery.

Rat T9.F glioma cells were transduced with the interleukin (IL)-2 gene. Clone T9.F/IL2/#12 secreted a high level of IL-2 (15 ng/10(6) cells/48 h). Enhanced tumor progression and reduced survival was observed when T9.F/IL2/#12 cells were implanted intracranially. Subcutaneous injection of T9.F/IL2/#12 cells induced a palpable nodule, which regressed in approximately 15 days, resulting in tumor-specific protection. Lymphocytes from T9.F/IL2/#12 primed rats specifically respond to T9.F antigens but lacked cytotoxicity towards T9.F cells. Intracranial T9.F/IL2/#12 tumors were markedly infiltrated by CD4(+) and CD8(+) T cells, natural killer (NK)-T cells and myeloid progenitor cells, whereas subcutaneous T9.F/IL2/#12 tumors contained an elevated level of NK cells.

Outcome measures for clinical trials in neurotrauma.

Under the auspices of the American Brain Injury Consortium and the Joint Section of Neurotrauma and Critical Care of the American Association of Neurological Surgeons, the authors have reviewed and formulated opinions based on the evidence on protocol design and the outcome measures used for clinical trials in patients with a severe or moderate traumatic brain injury (TBI). First, in view of the heterogeneity of the population under study, the authors suggest that block randomization and stratification should always be used in the design of neurotrauma trials. Second, although the Glasgow Outcome Scale (GOS) remains the most widely used and accepted instrument for TBI trials, the authors believe the eight-point expanded scale that has recently been designed will ultimately provide greater discrimination, and narrower categories and will ultimately prove superior for detecting more subtle changes in outcome. Furthermore, the authors recommend, in view of the profound cognitive impairment in survivors of TBI, that neuropsychological tests be explored further as an adjunct to the GOS. Future research should focus on the development of more sensitive and specific surrogate outcome measures such as magnetic resonance imaging, neurochemical, neuropsychological, and quality of life measures in order to detect a neuroprotective effect in patients with TBI.

Nutritional supplementation with Chlorella pyrenoidosa for mild to moderate hypertension.

Pharmacological treatment of hypertension reduces the risk of cardiovascular disease; however, randomized, controlled clinical trials and population studies have also shown that abnormally high blood pressure (BP) can be lowered with diet modification and exercise. The objective of this pilot study was to determine whether daily dietary supplementation with 10 g Chlorella tablets and 100 ml Chlorella extract for 2 months would reduce BP in subjects with a mean sitting diastolic BP (SiDBP) between 90 and 115 mm Hg. Thirty-three people were enrolled and underwent a 4-week washout period from all antihypertensive medications, during which they consumed placebo. At completion of this washout/placebo period, 24 subjects were considered evaluable (i.e., had a SiDBP between 90 and 115 mm Hg) and were continued in the study. After 1 or 2 months of dietary Chlorella supplementation, the average heart rate, sitting systolic BP, and SiDBP changed only slightly; after 2 months of Chlorella consumption, the group's mean SiDBP was 96.5 +/- 6.6. However, a heterogenous response pattern to Chlorella existed, with 25% (6/24) of the subjects achieving their BP goal (SiDBP less than 90 mm Hg). Furthermore, the BP of nonresponders did not increase significantly above washout values. Quality-of-life questionnaires indicated an overall perception that health had significantly improved in conjunction with Chlorella consumption. The results indicate that, for some subjects with mild to moderate hypertension, a daily dietary supplement of Chlorella reduced or kept stable their SiDBP.

The effect of oral care on intracranial pressure in critically ill adults.

A major goal in the care of patients with neurological problems is to prevent or minimize episodes of increased intracranial pressure (ICP). Elevations in ICP in response to nursing interventions have been acknowledged since the 1960s when ICP monitoring was first introduced in the clinical setting. Until recently, few studies have specifically examined the effect of oral care on ICP, and oral care and other hygiene measures were combined or not specified, prohibiting a direct interpretation of the influence of oral care alone on ICP. The purpose of this study was to describe the relationship between routine oral care interventions and the changes in ICP specifically focusing on the effect of intensity and duration of this intervention. Twenty-three patients with a clinical condition requiring ICP monitoring were enrolled over a 12-month period. Oral care provided by neuroscience intensive care nurses was observed and videotaped. Characteristics of the intervention were documented including products used, patient positioning, and duration of the intervention. A 1-5 subjective scale was used to score intensity of oral care. Wrist actigraphy data were collected from the nurses to provide an objective measure of intensity. Patient physiologic data were collected at 12-second epochs 5 minutes before, during, and 5 minutes after oral care. The mixed-effect repeated measures analysis of variance model indicated that there was a statistically significant increase in ICP in response to oral care (p = .0031). There was, however, no clinically significant effect on ICP. This study provides evidence that oral care is safe to perform in patients in the absence of preexisting elevated ICP.

The citicoline brain injury treatment (COBRIT) trial: design and methods.

Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established. Citicoline, a naturally occurring endogenous compound, offers the potential of neuroprotection, neurorecovery, and neurofacilitation to enhance recovery after TBI. Citicoline has a favorable side-effect profile in humans and several meta-analyses suggest a benefit of citicoline treatment in stroke and dementia. COBRIT is a randomized, double-blind, placebo-controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate, and severe TBI. In all, 1292 patients will be recruited over an estimated 32 months from eight clinical sites with random assignment to citicoline (1000 mg twice a day) or placebo (twice a day), administered enterally or orally. Functional outcomes are assessed at 30, 90, and 180 days after the day of randomization. The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global test procedure at 90 days. The measures comprise the following core battery: the California Verbal Learning Test II; the Controlled Oral Word Association Test; Digit Span; Extended Glasgow Outcome Scale; the Processing Speed Index; Stroop Test part 1 and Stroop Test part 2; and Trail Making Test parts A and B. Secondary outcomes include survival, toxicity, and rate of recovery.