Factors Influencing Time to Return to Learn Among NCAA Student-Athletes Enrolled in the Concussion Assessment, Research, and Education (CARE) Study.

PURPOSE: The aim was to describe the demographic and post-injury factors that influence time to return to learn (RTL) among student-athletes enrolled in the Concussion Assessment, Research and Education (CARE) Consortium. METHODS: A total of 47,860 student-athletes enrolled in the National Collegiate Athletic Association-Department of Defense (NCAA-DoD) CARE Consortium study from 2014 to 2020, with 1485 sport-related concussions (SRCs) analyzed in the present dataset. Demographic and post-injury characteristics were calculated using descriptive statistics, followed by Kaplan-Meier estimates to examine median time to return to normal academic performance (i.e., RTL) by sex (male, female), baseline psychiatric conditions (depression, anxiety) and/or learning disorder, NCAA division (I, II, III), SRC history (0, 1, 2, 3+), NCAA sport category (contact, limited contact, non-contact sport), and median difference in baseline/post-injury symptom severity scores (< 21, ≥ 21). Further, a multivariable zero-inflated negative binomial (ZINB) regression model was used to examine their association with RTL. RESULTS: Overall, time to RTL (mean = 4.96 ± 8.24 days, median = 3.0 [interquartile range = 0.0, 6.0] days) was found to be influenced by several factors resulting in earlier trajectories. Notably, nearly 25% of the sample demonstrated immediate RTL (i.e., 0 days). Among student-athletes who did not immediately RTL, males demonstrated a decreased rate in RTL (rate = 0.79; 95% CI 0.66-0.96) compared to females. Further, student-athletes with a ≥ 21 change in symptom severity score (post-injury baseline) demonstrated a higher rate of RTL (rate = 1.47; 95% CI 1.21-1.79) compared to student-athletes with a symptom severity change score < 21. Lastly, male student-athletes demonstrated two times higher odds (odds ratio = 1.95; 95% CI 1.02-3.73) of immediate RTL compared to female student-athletes. No other covariates were associated with time to RTL. CONCLUSION: Collectively, the present findings suggest a rapid return to the classroom following concussion. Specifically, males demonstrated higher odds of time to RTL, whereas those with greater differences in symptom severity resulted in a higher rate of time to RTL among those who did not immediately RTL. Ultimately, these findings support prior work emphasizing an individualized approach to SRC management.

Gene Expression Alterations in Peripheral Blood Following Sport-Related Concussion in a Prospective Cohort of Collegiate Athletes: A Concussion Assessment, Research and Education (CARE) Consortium Study.

BACKGROUND: Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury. OBJECTIVE: The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery. METHODS: We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline. RESULTS: Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. CONCLUSIONS: Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.

Beyond acute concussion assessment to office management: a systematic review informing the development of a Sport Concussion Office Assessment Tool (SCOAT6) for adults and children.

OBJECTIVES: To systematically review the scientific literature regarding the assessment of sport-related concussion (SRC) in the subacute phase (3-30 days) and provide recommendations for developing a Sport Concussion Office Assessment Tool (SCOAT6). DATA SOURCES: MEDLINE, Embase, PsycINFO, Cochrane CENTRAL, CINAHL, SPORTDiscus and Web of Science searched from 2001 to 2022. Data extracted included study design, population, definition of SRC diagnosis, outcome measure(s) and results. ELIGIBILITY CRITERIA: (1) Original research, cohort studies, case-control studies, diagnostic accuracy and case series with samples >10; (2) SRC; (3) screening/technology that assessed SRC in the subacute period and (4) low risk of bias (ROB). ROB was performed using adapted Scottish Intercollegiate Guidelines Network criteria. Quality of evidence was evaluated using the Strength of Recommendation Taxonomy classification. RESULTS: Of 9913 studies screened, 127 met inclusion, assessing 12 overlapping domains. Results were summarised narratively. Studies of acceptable (81) or high (2) quality were used to inform the SCOAT6, finding sufficient evidence for including the assessment of autonomic function, dual gait, vestibular ocular motor screening (VOMS) and mental health screening. CONCLUSION: Current SRC tools have limited utility beyond 72 hours. Incorporation of a multimodal clinical assessment in the subacute phase of SRC may include symptom evaluation, orthostatic hypotension screen, verbal neurocognitive tests, cervical spine evaluation, neurological screen, Modified Balance Error Scoring System, single/dual task tandem gait, modified VOMS and provocative exercise tests. Screens for sleep disturbance, anxiety and depression are recommended. Studies to evaluate the psychometric properties, clinical feasibility in different environments and time frames are needed. PROSPERO REGISTRATION NUMBER: CRD42020154787.

Premorbid Risk Factors and Acute Injury Characteristics of Sport-Related Concussion Across the National Collegiate Athletic Association: Findings from the Concussion Assessment, Research, and Education (CARE) Consortium.

BACKGROUND: Previous sport-related concussion research highlights post-injury characteristics that influence recovery trajectories; however, there is limited information regarding premorbid factors that affect sport-related concussion risk. OBJECTIVE: We aimed to (a) compare premorbid demographic factors among a large cohort of collegiate student athletes who did or did not sustain a sport-related concussion and (b) assess differences in acute injury characteristics based on biological sex and contact level. METHODS: We conducted a cohort study of university student athletes from 22 sports enrolled in the Concussion Assessment, Research, and Education (CARE) Consortium study from 2014 to 2021 (n = 1804 student athletes with sport-related concussions; n = 21,702 student athletes without sport-related concussions). RESULTS: Statistical analyses indicated student athletes who self-identified as Black (odds ratio [OR] = 1.61; 95% confidence interval [CI] = 1.42, 1.81) or multiracial (OR = 1.32; 95% CI 1.10, 1.59) demonstrated greater odds of experiencing sport-related concussions than White-identifying student athletes. Additional findings suggest male athletes (OR = 1.47; 95% CI 1.20, 1.81) and contact sport student athletes (OR = 1.40; 95% CI 1.16, 1.70) may be at increased odds for sport-related concussions if they were previously diagnosed with attention deficit hyperactive disorder. Notable post-injury characteristics across sexes included differences in the incident loss of consciousness (male: 5.9%, female: 2.6%; p < 0.001), post-traumatic amnesia (male: 13.6%, female: 5.1%; p < 0.001), and retrograde amnesia (male: 6.8%, female: 2.8%; p < 0.001). A greater proportion of contact-sport student athletes experienced an altered mental status (52.7%) than limited contact (36.2%) and non-contact (48.6%) [p < 0.001]. Last, student athletes participating at lower contact levels were more likely to have a longer delay in removal from activity following injury (contact: 73.6 ± 322.2 min; limited contact: 139.1 ± 560.0 min; non-contact: 461.4 ± 1870.8 min; p = 0.005). CONCLUSIONS: The present study provides contemporary pre- and post-sport-related concussion injury characteristics using a considerably sized cohort of collegiate student athletes. These findings support previous work suggesting sport-related concussion results in complex individualized clinical presentations, which may influence management strategies.

Similar Concussion Rates in Spring Football and Preseason: Findings From the Concussion Assessment, Research and Education Consortium.

CONTEXT: Increasing attention has been directed toward identifying aspects of football participation for targeted policy change that reduces the concussion risk. Prior researchers evaluated concussion risks during the preseason and regular seasons, leaving the spring season largely unexplored. DESIGN: In this nationally representative observational investigation of 19 National Collegiate Athletic Association Division I collegiate football programs, we assessed concussion rates and head impact exposures during the preseason, regular season, and spring practices from 2014 to 2019. All participating programs recorded the incidence of concussions, and a subset (n = 6) also measured head impact exposures. RESULTS: Analyses by time of year and session type indicated that concussion rates and head impact exposures during all practice sessions and contact practices were higher in the spring and preseason than those in the regular season (P < .05). Concussion rates during the spring season and preseason were statistically similar. CONCLUSIONS: We identified comparable concussion risks in the spring season and preseason, highlighting the need for targeted policy interventions to protect athlete health and safety.

Linking Rivermead Post Concussion Symptoms Questionnaire (RPQ) and Sport Concussion Assessment Tool (SCAT) scores with item response theory.

OBJECTIVE: Despite the public health burden of traumatic brain injury (TBI) across broader society, most TBI studies have been isolated to a distinct subpopulation. The TBI research literature is fragmented further because often studies of distinct populations have used different assessment procedures and instruments. Addressing calls to harmonize the literature will require tools to link data collected from different instruments that measure the same construct, such as civilian mild traumatic brain injury (mTBI) and sports concussion symptom inventories. METHOD: We used item response theory (IRT) to link scores from the Rivermead Post Concussion Symptoms Questionnaire (RPQ) and the Sport Concussion Assessment Tool (SCAT) symptom checklist, widely used instruments for assessing civilian and sport-related mTBI symptoms, respectively. The sample included data from n = 397 patients who suffered a sports-related concussion, civilian mTBI, orthopedic injury control, or non-athlete control and completed the SCAT and/or RPQ. RESULTS: The results of several analyses supported sufficient unidimensionality to treat the RPQ + SCAT combined item set as measuring a single construct. Fixed-parameter IRT was used to create a cross-walk table that maps RPQ total scores to SCAT symptom severity scores. Linked and observed scores were highly correlated (r = .92). Standard errors of the IRT scores were slightly higher for civilian mTBI patients and orthopedic controls, particularly for RPQ scores linked from the SCAT. CONCLUSION: By linking the RPQ to the SCAT we facilitated efforts to effectively combine samples and harmonize data relating to mTBI.

Feasibility and Utility of a Flexible Outcome Assessment Battery for Longitudinal Traumatic Brain Injury Research: A TRACK-TBI Study.

The effects of traumatic brain injury (TBI) are difficult to measure in longitudinal cohort studies, because disparate pre-injury characteristics and injury mechanisms produce variable impairment profiles and recovery trajectories. In preparation for the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, which followed patients with injuries ranging from uncomplicated mild TBI to coma, we designed a multi-dimensional Flexible outcome Assessment Battery (FAB). The FAB relies on a decision-making algorithm that assigns participants to a Comprehensive (CAB) or Abbreviated Assessment Battery (AAB) and guides test selection across all phases of recovery. To assess feasibility of the FAB, we calculated the proportion of participants followed at 2 weeks (2w) and at 3, 6, and 12 months (3m, 6m, 12m) post-injury who completed the FAB and received valid scores. We evaluated utility of the FAB by examining differences in 6m and 12m Glasgow Outcome Scale-Extended (GOSE) scores between participant subgroups derived from the FAB-enabled versus traditional approach to outcome assessment applied at 2w. Among participants followed at 2w (n = 2094), 3m (n = 1871), 6m (n = 1736), and 12m (n = 1607) post-injury, 95-99% received valid completion scores on the FAB, in full or in part, either in person or by telephone. Level of function assessed by the FAB-enabled approach at 2w was associated with 6m and 12m GOSE scores (proportional odds p < 0.001). These findings suggest that the participant classification methodology afforded by the FAB may enable more effective data collection to improve detection of natural history changes and TBI treatment effects.

Optimizing Concussion Care Seeking: The Influence of Previous Concussion Diagnosis Status on Baseline Assessment Outcomes.

BACKGROUND: The prevalence of unreported concussions is high, and undiagnosed concussions can lead to worse postconcussion outcomes. It is not clear how those with a history of undiagnosed concussion perform on subsequent standard concussion baseline assessments. PURPOSE: To determine if previous concussion diagnosis status was associated with outcomes on the standard baseline concussion assessment battery. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Concussion Assessment, Research, and Education (CARE) Consortium participants (N = 29,934) self-reported concussion history with diagnosis status and completed standard baseline concussion assessments, including assessments for symptoms, mental status, balance, and neurocognition. Multiple linear regression models were used to estimate mean differences and 95% CIs among concussion history groups (no concussion history [n = 23,037; 77.0%], all previous concussions diagnosed [n = 5315; 17.8%], ≥1 previous concussions undiagnosed [n = 1582; 5.3%]) at baseline for all outcomes except symptom severity and Brief Symptom Inventory-18 (BSI-18) score, in which negative binomial models were used to calculate incidence rate ratios (IRRs). All models were adjusted for sex, race, ethnicity, sport contact level, and concussion count. Mean differences with 95% CIs excluding 0.00 and at least a small effect size (≥0.20), and those IRRs with 95% CIs excluding 1.00 and at least a small association (IRR, ≥1.10) were considered significant. RESULTS: The ≥1 previous concussions undiagnosed group reported significantly greater symptom severity scores (IRR, ≥1.38) and BSI-18 (IRR, ≥1.31) scores relative to the no concussion history and all previous concussions diagnosed groups. The ≥1 previous concussions undiagnosed group performed significantly worse on 6 neurocognitive assessments while performing better on only 2 compared with the no concussion history and all previous concussions diagnosed groups. There were no between-group differences on mental status or balance assessments. CONCLUSION: An undiagnosed concussion history was associated with worse clinical indicators at future baseline assessments. Individuals reporting ≥1 previous undiagnosed concussions exhibited worse baseline clinical indicators. This may suggest that concussion-related harm may be exacerbated when injuries are not diagnosed.

Utility of VOMS, SCAT3, and ImPACT Baseline Evaluations for Acute Concussion Identification in Collegiate Athletes: Findings From the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium.

BACKGROUND: The Vestibular/Ocular-Motor Screening (VOMS) is a valuable component of acute (<72 hours) sports-related concussion (SRC) assessments and is increasingly used with the Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) instrument and the third edition of the Sport Concussion Assessment Tool (SCAT3). Research has suggested that VOMS acute postinjury scores are useful in identifying acute concussion. However, the utility of preseason baseline measurements to improve diagnostic accuracy remains ambiguous. To this end, there is a need to determine how reliable VOMS baseline assessments are across years and whether incorporating individuals' baseline performance improves diagnostic yield for acute concussions. PURPOSE: To analyze VOMS, SCAT3, and ImPACT to evaluate the test-retest reliability of consecutive-year preseason baseline assessments to directly compare the diagnostic utility of these tools when incorporating baseline assessments versus using postinjury data alone to identify acute SRC. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Preseason and postinjury VOMS, SCAT3, ImPACT Post-Concussion Symptom Scale (PCSS), and ImPACT composite scores were analyzed for 3958 preseason (47.7% female) and 496 acute (≤48 hours) SRC (37.5% female) collegiate athlete evaluations in the National Collegiate Athletic Association-Department of Defense Concussion Assessment Research and Education Consortium. Descriptive statistics, Kolmogorov-Smirnov significance, and Cohen d effect size were calculated. Consecutive-year baseline reliability was evaluated for a subset of 447 athlete encounters using Pearson r, Cohen κ, Cohen d, and 2-way mixed intraclass correlation coefficients (ICCs). Wilcoxon signed rank tests were used to determine the statistical significance between population performances, and the 90% reliable change index (RCI) was calculated from the test-retest results. Preseason to postinjury change scores were then calculated from each tool's RCI. Finally, receiver operating characteristic (ROC) curve analyses were conducted, and DeLong method was used to compare the area under the curve (AUC) of raw postinjury scores versus change scores from preseason baseline assessments. Potential effects of sex, medical history (learning disorders or attention-deficit/hyperactivity disorder), and outlier data were also explored. RESULTS: Effect sizes were large, and overall predictive utilities were clinically useful for postinjury VOMS Total (d = 2.44; AUC = 0.85), the SCAT3 Symptom Evaluation total severity score (d = 1.74; AUC = 0.82), and the ImPACT PCSS total severity score (d = 1.67; AUC = 0.80). Comparatively, effect sizes were small and predictive utilities were poor for Standardized Assessment of Concussion (SAC), modified Balance Error Scoring System (mBESS), and all ImPACT composites (d = 0.11-0.46; AUC = 0.48-0.59). Preseason baseline test-retest reliability was poor to moderate (r = 0.23-0.52; κ = 0.32-0.36; ICC = 0.36-0.68) for all assessments except ImPACT Visual Motion Sensitivity (r = 0.73; ICC = 0.85). Incorporating baseline scores for VOMS Total, SCAT3 (Symptom Evaluation, SAC, mBESS), ImPACT PCSS, or ImPACT composites did not significantly improve AUCs. CONCLUSION: VOMS Total and symptom severity (SCAT3, PCSS) total scores had large effect sizes and clinically useful AUCs for identifying acute concussion. However, all tools demonstrated high within-patient test-retest variability, resulting in poor reliability. The findings in this sample of collegiate athletes suggest that incorporating baseline assessments does not significantly increase diagnostic yield for acute concussion.

Neurodevelopmental Disorders and Risk of Concussion: Findings from the National Collegiate Athletic Association Department of Defense Grand Alliance Concussion Assessment, Research, and Education (NCAA-DOD CARE) Consortium (2014-2017).

Evidence suggests neurodevelopmental disorders (NDs) may be associated with an increased incidence of concussion, but no studies have cross-sectionally and longitudinally assessed the associations of NDs and sex with concussion in collegiate athletes. We sought to assess the odds and relative risk (RR) of concussion in athletes self-reporting a diagnosis of attention deficit/hyperactivity disorder (ADHD), learning disability (LD), and ADHD+LD. Data from the Concussion Assessment, Research and Education (CARE) Consortium (2014-2017) were used to evaluate the likelihood of concussion for male and female athletes with ADHD, LD, and ADHD+LD, relative to controls. Odds ratios (ORs) of concussion history prior to enrollment and relative risk ratios for incurring a concussion following enrollment, with and without concussion history were calculated for all groups. Athletes with self-reported diagnosis of ADHD, LD, and ADHD+LD were more likely to report a single concussion (OR range = 1.528 to 1.828) and multiple concussions (OR range = 1.849 to 2.365) prior to enrollment in the CARE Consortium, irrespective of sex compared with control athletes. While enrolled in CARE, male athletes with ADHD, LD, and ADHD+LD had greater risk of incurring a concussion (RR range = 1.369 to 2.243) than controls, irrespective of concussion history. Male athletes with ADHD+LD with concussion history (RR = 2.221) and without concussion history (RR = 1.835) had greater risk of incurring a concussion than controls. These results suggest NDs may be associated with increased odds of single and multiple concussions, irrespective of sex. However, when we accounted for concussion history, it appears only male athletes with ADHD+LD had greater risk than respective controls. There were no significant differences between females and males with ADHD, LD, or ADHD+LD for either odds of concussion history or risk for incurring concussion.

Optimizing Order of Administration for Concussion Baseline Assessment Among NCAA Student-Athletes and Military Cadets.

BACKGROUND: Concussion pre-injury (i.e., baseline) assessments serve as a benchmark comparison point in the event an individual sustains a concussion and allows clinicians to compare to post-injury measures. However, baseline assessments must reflect the individual's true and most optimized performance to serve as a useful comparison. Mental fatigue and motivation throughout baseline testing may alter individual assessment performance, indicating an order of administration (OoA) may play an influential role in assessment outcomes. OBJECTIVE: To examine the influence concussion baseline battery OoA has on symptom, postural stability, cognitive screening, and computerized neurocognitive test outcomes. METHODS: We employed a retrospective observational cohort study to examine healthy collegiate student-athletes and military cadets (n = 2898, 19.0 ± 1.4 years, 66.1% male, 75.6% white, 54.4% Division-I) baseline assessment performance on the Sport Concussion Assessment Tool (SCAT; total symptom number and severity), Balance Error Scoring System (BESS; total error scores), Standardized Assessment of Concussion (SAC; total score), and Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) domain scores (verbal and visual memory, visual-motor speed, reaction time). Assessments were binned to beginning, middle, or end tertiles based upon OoA. We used one-way ANOVAs with Tukey post-hoc t tests, 95% confidence intervals (CI), and Cohen's d effect sizes for significant models (α = 0.05). RESULTS: SCAT total symptom number (mean difference = 2.23; 95% CI 1.76-2.70; d = 0.49, p < 0.001) and severity (mean difference = 5.58; 95% CI 4.42-6.74; d = 0.50; p < 0.001) were lower when completed at the end of baseline testing compared to the middle. Total BESS errors were 1.06 lower when completed at the middle relative to the end (95% CI 0.43-1.69; d = 0.17; p = 0.001). Total SAC scores were better at the beginning relative to middle (mean difference = 0.58; 95% CI 0.25-0.90; d = 0.33; p < 0.001) and end (mean difference = 0.44; 95% CI 0.16-0.73; d = 0.24; p = 0.001). Verbal memory, visual memory, and reaction time performance were highest at the beginning (p ≤ 0.002), while visual-motor speed performance was highest at the middle (p = 0.001). CONCLUSION: Completing baseline assessments in the order of (1) ImPACT, (2) SAC, (3) BESS, and (4) SCAT symptom checklist may improve performance across assessments collectively. Clinicians and researchers should consider completing baseline assessments in this order when possible to potentially aid in optimizing concussion baseline assessment performance and maximize post-concussion comparisons.

Discriminative Validity of Vestibular Ocular Motor Screening in Identifying Concussion Among Collegiate Athletes: A National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education Consortium Study.

BACKGROUND: Vestibular and ocular motor screening tools, such as the Vestibular/Ocular Motor Screening (VOMS), are recognized as important components of a multifaceted evaluation of sport-related concussion. Previous research has supported the predictive utility of the VOMS in identifying concussion, but researchers have yet to examine the predictive utility of the VOMS among collegiate athletes in the first few days after injury. PURPOSE: To determine the discriminative validity of individual VOMS item scores and an overall VOMS score for identifying collegiate athletes with an acute sport-related concussion (≤72 hours) from healthy controls matched by age, sex, and concussion history. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Participants (N = 570) aged 17 to 25 years were included from 8 institutions of the National Collegiate Athletic Association-Department of Defense CARE Consortium (Concussion Assessment, Research, and Education): 285 athletes who were concussed (per current consensus guidelines) and 285 healthy controls matched by age, sex, and concussion history. Participants completed the VOMS within 3 days of injury (concussion) or during preseason (ie, baseline; control). Symptoms are totaled for each VOMS item for an item score (maximum, 40) and totaled across items for an overall score (maximum, 280), and distance (centimeters) for near point of convergence (NPC) is averaged across 3 trials. Receiver operating characteristic analysis of the area under the curve (AUC) was performed on cutoff scores using Youden index (J) for each VOMS item, overall VOMS score, and NPC distance average. A logistic regression was conducted to identify which VOMS scores identified concussed status. RESULTS: A symptom score ≥1 on each VOMS item and horizontal vestibular/ocular reflex ≥2 significantly discriminated concussion from control (AUC, 0.89-0.90). NPC distance did not significantly identify concussion from control (AUC, 0.51). The VOMS overall score had the highest accuracy (AUC, 0.91) for identifying sport-related concussion from control. Among the individual items, vertical saccades ≥1 and horizontal vestibular/ocular reflex ≥2 best discriminated concussion from control. CONCLUSION: The findings indicate that individual VOMS items and overall VOMS scores are useful in identifying concussion in collegiate athletes within 3 days of injury. Clinicians can use the cutoffs from this study to help identify concussion in collegiate athletes.

Assessment of Blood Biomarker Profile After Acute Concussion During Combative Training Among US Military Cadets: A Prospective Study From the NCAA and US Department of Defense CARE Consortium.

Importance: Validation of protein biomarkers for concussion diagnosis and management in military combative training is important, as these injuries occur outside of traditional health care settings and are generally difficult to diagnose. Objective: To investigate acute blood protein levels in military cadets after combative training-associated concussions. Design, Setting, and Participants: This multicenter prospective case-control study was part of a larger cohort study conducted by the National Collegiate Athletic Association and the US Department of Defense Concussion Assessment Research and Education (CARE) Consortium from February 20, 2015, to May 31, 2018. The study was performed among cadets from 2 CARE Consortium Advanced Research Core sites: the US Military Academy at West Point and the US Air Force Academy. Cadets who incurred concussions during combative training (concussion group) were compared with cadets who participated in the same combative training exercises but did not incur concussions (contact-control group). Clinical measures and blood sample collection occurred at baseline, the acute postinjury point (<6 hours), the 24- to 48-hour postinjury point, the asymptomatic postinjury point (defined as the point at which the cadet reported being asymptomatic and began the return-to-activity protocol), and 7 days after return to activity. Biomarker levels and estimated mean differences in biomarker levels were natural log (ln) transformed to decrease the skewness of their distributions. Data were collected from August 1, 2016, to May 31, 2018, and analyses were conducted from March 1, 2019, to January 14, 2020. Exposure: Concussion incurred during combative training. Main Outcomes and Measures: Proteins examined included glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, neurofilament light chain, and tau. Quantification was conducted using a multiplex assay (Simoa; Quanterix Corp). Clinical measures included the Sport Concussion Assessment Tool-Third Edition symptom severity evaluation, the Standardized Assessment of Concussion, the Balance Error Scoring System, and the 18-item Brief Symptom Inventory. Results: Among 103 military service academy cadets, 67 cadets incurred concussions during combative training, and 36 matched cadets who engaged in the same training exercises did not incur concussions. The mean (SD) age of cadets in the concussion group was 18.6 (1.3) years, and 40 cadets (59.7%) were male. The mean (SD) age of matched cadets in the contact-control group was 19.5 (1.3) years, and 25 cadets (69.4%) were male. Compared with cadets in the contact-control group, those in the concussion group had significant increases in glial fibrillary acidic protein (mean difference in ln values, 0.34; 95% CI, 0.18-0.50; P < .001) and ubiquitin C-terminal hydrolase-L1 (mean difference in ln values, 0.97; 95% CI, 0.44-1.50; P < .001) levels at the acute postinjury point. The glial fibrillary acidic protein level remained high in the concussion group compared with the contact-control group at the 24- to 48-hour postinjury point (mean difference in ln values, 0.22; 95% CI, 0.06-0.38; P = .007) and the asymptomatic postinjury point (mean difference in ln values, 0.21; 95% CI, 0.05-0.36; P = .01). The area under the curve for all biomarkers combined, which was used to differentiate cadets in the concussion and contact-control groups, was 0.80 (95% CI, 0.68-0.93; P < .001) at the acute postinjury point. Conclusions and Relevance: This study's findings indicate that blood biomarkers have potential for use as research tools to better understand the pathobiological changes associated with concussion and to assist with injury identification and recovery from combative training-associated concussions among military service academy cadets. These results extend the previous findings of studies of collegiate athletes with sport-associated concussions.

Opportunities for Prevention of Concussion and Repetitive Head Impact Exposure in College Football Players: A Concussion Assessment, Research, and Education (CARE) Consortium Study.

Importance: Concussion ranks among the most common injuries in football. Beyond the risks of concussion are growing concerns that repetitive head impact exposure (HIE) may increase risk for long-term neurologic health problems in football players. Objective: To investigate the pattern of concussion incidence and HIE across the football season in collegiate football players. Design, Setting, and Participants: In this observational cohort study conducted from 2015 to 2019 across 6 Division I National Collegiate Athletic Association (NCAA) football programs participating in the Concussion Assessment, Research, and Education (CARE) Consortium, a total of 658 collegiate football players were instrumented with the Head Impact Telemetry (HIT) System (46.5% of 1416 eligible football players enrolled in the CARE Advanced Research Core). Players were prioritized for instrumentation with the HIT System based on their level of participation (ie, starters prioritized over reserves). Exposure: Participation in collegiate football games and practices from 2015 to 2019. Main Outcomes and Measures: Incidence of diagnosed concussion and HIE from the HIT System. Results: Across 5 seasons, 528 684 head impacts recorded from 658 players (all male, mean age [SD], 19.02 [1.25] years) instrumented with the HIT System during football practices or games met quality standards for analysis. Players sustained a median of 415 (interquartile range [IQR], 190-727) recorded head impacts (ie, impacts) per season. Sixty-eight players sustained a diagnosed concussion. In total, 48.5% of concussions (n = 33) occurred during preseason training, despite preseason representing only 20.8% of the football season (0.059 preseason vs 0.016 regular-season concussions per team per day; mean difference, 0.042; 95% CI, 0.020-0.060; P = .001). Total HIE in the preseason occurred at twice the proportion of the regular season (324.9 vs 162.4 impacts per team per day; mean difference, 162.6; 95% CI, 110.9-214.3; P < .001). Every season, HIE per athlete was highest in August (preseason) (median, 146.0 impacts; IQR, 63.0-247.8) and lowest in November (median, 80.0 impacts; IQR, 35.0-148.0). Over 5 seasons, 72% of concussions (n = 49) (game proportion, 0.28; 95% CI, 0.18-0.40; P < .001) and 66.9% of HIE (262.4 practices vs 137.2 games impacts per player; mean difference, 125.3; 95% CI, 110.0-140.6; P < .001) occurred in practice. Even within the regular season, total HIE in practices (median, 175.0 impacts per player per season; IQR, 76.0-340.5) was 84.2% higher than in games (median, 95.0 impacts per player per season; IQR, 32.0-206.0). Conclusions and Relevance: Concussion incidence and HIE among college football players are disproportionately higher in the preseason than regular season, and most concussions and HIE occur during football practices, not games. These data point to a powerful opportunity for policy, education, and other prevention strategies to make the greatest overall reduction in concussion incidence and HIE in college football, particularly during preseason training and football practices throughout the season, without major modification to game play. Strategies to prevent concussion and HIE have important implications to protecting the safety and health of football players at all competitive levels.

Health-promoting behaviours and concussion history are associated with cognitive function, mood-related symptoms and emotional-behavioural dyscontrol in former NFL players: an NFL-LONG Study.

OBJECTIVES: To examine the relationships among self-reported sport-related concussion (SRC) history and current health-promoting behaviours (exercise frequency, diet quality and sleep duration) with self-reported measures of brain health (cognitive function, symptoms of depression and anxiety and emotional-behavioural dyscontrol) in former NFL players. METHODS: In this cross-sectional study, a questionnaire was sent to former NFL players. Respondents reported SRC history (categorical: 0; 1-2; 3-5; 6-9; 10+ concussions), number of moderate-to-vigorous aerobic and resistance exercise sessions per week, diet quality (Rapid Eating Assessment for Participants-Shortened) and average nightly sleep duration. Outcomes were Patient-Reported Outcomes Measurement Information System Cognitive Function, Depression, and Anxiety, and Neuro-QoL Emotional-Behavioral Dyscontrol domain T-scores. Multivariable linear regression models were fit for each outcome with SRC history, exercise frequency, diet quality and sleep duration as explanatory variables alongside select covariates. RESULTS: Multivariable regression models (n=1784) explained approximately 33%-38% of the variance in each outcome. For all outcomes, SRC history (0.144≤|ß|≤0.217) was associated with poorer functioning, while exercise frequency (0.064≤|ß|≤0.088) and diet quality (0.057≤|ß|≤0.086) were associated with better functioning. Sleeping under 6 hours per night (0.061≤|ß|≤0.093) was associated with worse depressive symptoms, anxiety and emotional-behavioural dyscontrol. CONCLUSION: Several variables appear to be associated with mood and perceived cognitive function in former NFL players. SRC history is non-modifiable in former athletes; however, the effects of increasing postplaying career exercise frequency, making dietary improvements, and obtaining adequate sleep represent important potential opportunities for preventative and therapeutic interventions.