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.

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.

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.

Differences in sport-related concussion for female and male athletes in comparable collegiate sports: a study from the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium.

OBJECTIVES: To examine sex differences in sport-related concussion (SRC) across comparable sports. METHODS: Prospective cohort of collegiate athletes enrolled between 2014 and 2017 in the Concussion Assessment, Research and Education Consortium study. RESULTS: Among 1071 concussions (females=615; 57.4%), there was no difference in recovery (median days to full return to play) (females=13.5 (IQR 9.0, 23.1) vs males=11.8 (IQR 8.1, 19.0), p=0.96). In subgroup analyses, female recovery was longer in contact (females=12.7 days (IQR 8.8, 21.4) vs males=11.0 days (IQR 7.9, 16.2), p=0.0021), while male recovery was longer in limited contact sports (males=16.9 days (IQR 9.7, 101.7) vs females=13.8 days (IQR 9.1, 22.0), p<0.0001). There was no overall difference in recovery among Division I schools (females=13.7 (IQR 9.0, 23.1) vs males=12.2 (IQR 8.2 19.7), p=0.5), but females had longer recovery at the Division II/III levels (females=13.0 (IQR 9.2, 22.7) vs males=10.6 (IQR 8.1, 13.9), p=0.0048). CONCLUSION: Overall, no difference in recovery between sexes across comparable women's and men's sports in this collegiate cohort was found. However, females in contact and males in limited contact sports experienced longer recovery times, while females had longer recovery times at the Division II/III level. These disparate outcomes indicate that, while intrinsic biological sex differences in concussion recovery may exist, important, modifiable extrinsic factors may play a role in concussion outcomes.

Progress and Future Directions of the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium and Mind Matters Challenge at the US Service Academies.

Despite the significant impact that concussion has on military service members, significant gaps remain in our understanding of the optimal diagnostic, management, and return to activity/duty criteria to mitigate the consequences of concussion. In response to these significant knowledge gaps, the US Department of Defense (DoD) and the National Collegiate Athletic Association (NCAA) partnered to form the NCAA-DoD Grand Alliance in 2014. The NCAA-DoD CARE Consortium was established with the aim of creating a national multisite research network to study the clinical and neurobiological natural history of concussion in NCAA athletes and military Service Academy cadets and midshipmen. In addition to the data collected for the larger CARE Consortium effort, the service academies have pursued military-specific lines of research relevant to operational and medical readiness associated with concussion. The purpose of this article is to describe the structure of the NCAA-DoD Grand Alliance efforts at the service academies, as well as discuss military-specific research objectives and provide an overview of progress to date. A secondary objective is to discuss the challenges associated with conducting large-scale studies in the Service Academy environment and highlight future directions for concussion research endeavors across the CARE Service Academy sites.

Bifactor Model of the Sport Concussion Assessment Tool Symptom Checklist: Replication and Invariance Across Time in the CARE Consortium Sample.

BACKGROUND: Identifying separate dimensions of concussion symptoms may inform a precision medicine approach to treatment. It was previously reported that a bifactor model identified distinct acute postconcussion symptom dimensions. PURPOSE: To replicate previous findings of a bifactor structure of concussion symptoms in the Concussion Assessment Research and Education (CARE) Consortium sample, examine measurement invariance from pre- to postinjury, and evaluate whether factors are associated with other clinical and biomarker measures. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2. METHODS: Collegiate athletes were prospectively evaluated using the Sport Concussion Assessment Tool-3 (SCAT-3) during preseason (N = 31,557); 2789 were followed at <6 hours and 24 to 48 hours after concussion. Item-level SCAT-3 ratings were analyzed using exploratory and confirmatory factor analyses. Bifactor and higher-order models were compared for their fit and interpretability. Measurement invariance tested the stability of the identified factor structure across time. The association between factors and criterion measures (clinical and blood-based markers of concussion severity, symptom duration) was evaluated. RESULTS: The optimal structure for each time point was a 7-factor bifactor model: a General factor, on which all items loaded, and 6 specific factors-Vestibulo-ocular, Headache, Sensory, Fatigue, Cognitive, and Emotional. The model manifested strict invariance across the 2 postinjury time points but only configural invariance from baseline to postinjury. From <6 to 24-48 hours, some dimensions increased in severity (Sensory, Fatigue, Emotional), while others decreased (General, Headache, Vestibulo-ocular). The factors correlated with differing clinical and biomarker criterion measures and showed differing patterns of association with symptom duration at different time points. CONCLUSION: Bifactor modeling supported the predominant unidimensionality of concussion symptoms while revealing multidimensional properties, including a large dominant General factor and 6 independent factors: Headache, Vestibulo-ocular, Sensory, Cognitive, Fatigue, and Emotional. Unlike the widely used SCAT-3 symptom severity score, which declines gradually after injury, the bifactor model revealed separable symptom dimensions that have distinct trajectories in the acute postinjury period and different patterns of association with other markers of injury severity and outcome. CLINICAL RELEVANCE: The SCAT-3 total score remains a valuable, robust index of overall concussion symptom severity, and the specific factors identified may inform management strategies. Because some symptom dimensions continue to worsen in the first 24 to 48 hours after injury (ie, Sensory, Fatigue, Emotional), routine follow-up in this time frame may be valuable to ensure that symptoms are managed effectively.

Plasma Biomarker Concentrations Associated With Return to Sport Following Sport-Related Concussion in Collegiate Athletes-A Concussion Assessment, Research, and Education (CARE) Consortium Study.

Importance: Identifying plasma biomarkers associated with the amount of time an athlete may need before they return to sport (RTS) following a sport-related concussion (SRC) is important because it may help to improve the health and safety of athletes. Objective: To examine whether plasma biomarkers can differentiate collegiate athletes who RTS in less than 14 days or 14 days or more following SRC. Design, Setting, and Participants: This multicenter prospective diagnostic study, conducted by the National Collegiate Athletics Association-Department of Defense Concussion Assessment, Research, and Education Consortium, included 127 male and female athletes who had sustained an SRC while enrolled at 6 Concussion Assessment, Research, and Education Consortium Advanced Research Core sites as well as 2 partial-Advanced Research Core military service academies. Data were collected between February 2015 and May 2018. Athletes with SRC completed clinical testing and blood collection at preseason (baseline), postinjury (0-21 hours), 24 to 48 hours postinjury, time of symptom resolution, and 7 days after unrestricted RTS. Main Outcomes and Measures: A total of 3 plasma biomarkers (ie, total tau protein, glial fibrillary acidic protein [GFAP], and neurofilament light chain protein [Nf-L]) were measured using an ultrasensitive single molecule array technology and were included in the final analysis. RTS was examined between athletes who took less than 14 days vs those who took 14 days or more to RTS following SRC. Linear mixed models were used to identify significant interactions between period by RTS group. Area under the receiver operating characteristic curve analyses were conducted to examine whether these plasma biomarkers could discriminate between RTS groups. Results: The 127 participants had a mean (SD) age of 18.9 (1.3) years, and 97 (76.4%) were men; 65 (51.2%) took less than 14 days to RTS, and 62 (48.8%) took 14 days or more to RTS. Linear mixed models identified significant associations for both mean (SE) plasma total tau (24-48 hours postinjury, <14 days RTS vs ≥14 days RTS: -0.65 [0.12] pg/mL vs -0.14 [0.14] pg/mL; P = .008) and GFAP (postinjury, 14 days RTS vs ≥14 days RTS: 4.72 [0.12] pg/mL vs 4.39 [0.11] pg/mL; P = .04). Total tau at the time of symptom resolution had acceptable discrimination power (area under the receiver operating characteristic curve, 0.75; 95% CI, 0.63-0.86; P < .001). We also examined a combined plasma biomarker panel that incorporated Nf-L, GFAP, and total tau at each period to discriminate RTS groups. Although the analyses did reach significance at each time period when combined, results indicated that they were poor at distinguishing the groups (area under the receiver operating characteristic curve, <0.7). Conclusions and Relevance: The findings of this study suggest that measures of total tau and GFAP may identify athletes who will require more time to RTS. However, further research is needed to improve our ability to determine recovery following an SRC.

Exploring Baseline Concussion-Assessment Performance in Adapted Wheelchair Sport Athletes.

CONTEXT: With growing awareness of and advocacy for including individuals with disabilities in sport, implementation of concussion-assessment and -management strategies is warranted. Limited research is available on concussion assessment in adapted wheelchair sport athletes. OBJECTIVE: To examine baseline symptom reporting, computerized neurocognitive testing, and a modified balance scoring system in adapted athletes. A secondary objective was to provide preliminary normative data for this population. DESIGN: Cross-sectional study. SETTING: University athletic training room and computer laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-one athletes (age = 22.1 ± 3.0 years) from 1 institution's collegiate adapted athletics program. MAIN OUTCOME MEASURE(S): Athletes completed baseline Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and the Wheelchair Error Scoring System (WESS) before the start of their respective seasons. Symptom reporting variables consisted of total symptoms, symptom severity scores, and baseline symptom factors (eg, vestibular-somatic, sleep arousal, cognitive-sensory, and affective). We analyzed ImPACT composite scores of verbal memory, visual memory, visual motor processing speed, and reaction time and impulse control to determine neurocognitive function. Balance performance was quantified using the WESS condition and overall errors. RESULTS: Compared with normative reference values, 17 (81%) of adapted athletes reported greater symptoms and 20 (95%) performed at or below average on at least 1 neurocognitive composite score. Mean errors on the WESS were 3.14 ± 2.9, with 81% committing ≥1 error. Sex differences were not present for symptoms, neurocognitive testing, or balance measures. CONCLUSIONS: Our findings provide context for baseline performance in adapted athletes and help to further develop the WESS as an assessment of balance in these athletes.

Optimizing Components of the Sport Concussion Assessment Tool for Acute Concussion Assessment.

BACKGROUND: The Sport Concussion Assessment Tool (SCAT) could be improved by identifying critical subsets that maximize diagnostic accuracy and eliminate low information elements. OBJECTIVE: To identify optimal SCAT subsets for acute concussion assessment. METHODS: Using Concussion Assessment, Research, and Education (CARE) Consortium data, we compared student-athletes' and cadets' preinjury baselines (n = 2178) with postinjury assessments within 6 h (n = 1456) and 24 to 48 h (n = 2394) by considering demographics, symptoms, Standard Assessment of Concussion (SAC), and Balance Error Scoring System (BESS) scores. We divided data into training/testing (60%/40%) sets. Using training data, we integrated logistic regression with an engineering methodology-mixed integer programming-to optimize models with ≤4, 8, 12, and 16 variables (Opt-k). We also created models including only raw scores (Opt-RS-k) and symptom, SAC, and BESS composite scores (summary scores). We evaluated models using testing data. RESULTS: At <6 h and 24 to 48 h, most Opt-k and Opt-RS-k models included the following symptoms: do not feel right, headache, dizziness, sensitivity to noise, and whether physical or mental activity worsens symptoms. Opt-k models included SAC concentration and delayed recall change scores. Opt-k models had lower Brier scores (BS) and greater area under the curve (AUC) (<6 h: BS = 0.072-0.089, AUC = 0.95-0.96; 24-48 h: BS = 0.085-0.093, AUC = 0.94-0.95) than Opt-RS-k (<6 h: BS = 0.082-0.087, AUC = 0.93-0.95; 24-48 h: BS = 0.095-0.099, AUC = 0.92-0.93) and summary score models (<6 h: BS = 0.14, AUC = 0.89; 24-48 h: BS = 0.15, AUC = 0.87). CONCLUSION: We identified SCAT subsets that accurately assess acute concussion and improve administration time over the complete battery, highlighting the importance of eliminating "noisy" elements. These findings can direct clinicians to the SCAT components that are most sensitive to acute concussion.

Investigating the Range of Symptom Endorsement at Initiation of a Graduated Return-to-Play Protocol After Concussion and Duration of the Protocol: A Study From the National Collegiate Athletic Association-Department of Defense Concussion, Assessment, Research, and Education (CARE) Consortium.

BACKGROUND: Organizations recommend that athletes should be asymptomatic or symptom-limited before initiating a graduated return-to-play (GRTP) protocol after sports-related concussion, although asymptomatic or symptom-limited is not well-defined. HYPOTHESES: (1) There will be a range (ie, beyond zero as indicator of "symptom-free") in symptom severity endorsement when athletes are deemed ready to initiate a GRTP protocol. (2) Baseline symptom severity scores and demographic/preinjury medical history factors influence symptom severity scores at the commencement of the GRTP protocol. (3) Greater symptom severity scores at GRTP protocol initiation will result in longer protocol duration. (4) Symptom severity scores will not differ between those who did and did not sustain a repeat injury within 90 days of their initial injury. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Across 30 universities, athletes (N = 1531) completed assessments at baseline and before beginning the GRTP protocol, as determined by local medical staff. Symptom severity scores were recorded with the symptom checklist of the Sport Concussion Assessment Tool-3rd Edition. Nonparametric comparisons were used to examine the effect of medical, demographic, and injury factors on symptom endorsement at GRTP protocol initiation, as well as differences in symptom severity scores between those who did and did not sustain a repeat injury within 90 days. A Cox regression was used to examine the association between symptom severity scores at GRTP protocol initiation and protocol duration. RESULTS: Symptom severity scores at the time when the GRTP protocol was initiated were as follows: 0 to 5 (n = 1378; 90.0%), 6 to 10 (n = 76; 5.0%), 11 to 20 (n = 42; 3.0%), and ≥21 (n = 35; 2.0%). Demographic (sex and age), medical (psychiatric disorders, attention-deficit/hyperactivity disorder, learning disorder), and other factors (baseline symptom endorsement and sleep) were significantly associated with higher symptom severity scores at the GRTP initiation (P < .05). The 4 GRTP initiation time point symptom severity score groups did not significantly differ in total time to unrestricted RTP, χ2(3) = 1.4; P = .73. When days until the initiation of the GRTP protocol was included as a covariate, symptom severity scores between 11 and 20 (P = .02; hazard ratio = 1.44; 95% CI, 1.06-1.96) and ≥21 (P < .001; hazard ratio = 1.88; 95% CI, 1.34-2.63) were significantly associated with a longer GRTP protocol duration as compared with symptom severity scores between 0 and 5. Symptom severity scores at GRTP initiation did not significantly differ between those who sustained a repeat injury within 90 days and those who did not (U = 29,893.5; P = .75). CONCLUSION: A range of symptom severity endorsement was observed at GRTP protocol initiation, with higher endorsement among those with higher baseline symptom endorsement and select demographic and medical history factors. Findings suggest that initiation of a GRTP protocol before an absolute absence of all symptoms is not associated with longer progression of the GRTP protocol, although symptom severity scores >10 were associated with longer duration of a GRTP protocol. Results can be utilized to guide clinicians toward optimal GRTP initiation (ie, balancing active recovery with avoidance of premature return to activity).

Academic aptitude mediates the relationship between socioeconomic status and race in predicting ImPACT scores in college athletes.

Objective: To evaluate the influences of sociodemographic factors, estimated head impact exposure, and academic aptitude on ImPACT scores in college athletes.Methods: Data were reported on 18,886 participants (58% male) from the NCAA/DoD CARE Consortium. Race, SES, concussion history, estimated repetitive head impact exposure (eRHIE), and academic aptitude (SAT or ACT score) were our predictors of interest. Cognition was measured using ImPACT composite scores. We evaluated the mediating effects of academic aptitude on sociodemographic predictors and eRHIE on ImPACT scores. We then evaluated a football-only subsample and added age of first exposure to football (AFE) to the model. Males, females, and football players were analyzed separately using structural equation modeling.Results: Academic aptitude was associated with Black/African American race, SES, and each of the ImPACT composite scores. There were significant indirect effects of Black/African American race and SES on all ImPACT composite scores. Academic aptitude fully mediated SES effects and either fully or partially mediated race effects. Contrary to expectation, greater concussion history and eRHIE predicted better ImPACT scores.Conclusions: Academic aptitude, a stable indicator of premorbid cognitive function, consistently and most strongly predicted baseline ImPACT scores in collegiate student-athletes. Concussion and eRHIE history demonstrated a small positive, but non-significant, relationship with cognitive scores at the time of college athletic participation. This study suggests that attempts to characterize cognitive ability across the lifespan must consider premorbid functioning and sociodemographic variables.

King-Devick Test Reliability in National Collegiate Athletic Association Athletes: A National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research and Education Report.

CONTEXT: The King-Devick (KD) test has received considerable attention in the literature as an emerging concussion assessment. However, important test psychometric properties remain to be addressed in large-scale independent studies. OBJECTIVE: To assess (1) test-retest reliability between trials, (2) test-retest reliability between years 1 and 2, and (3) reliability of the 2 administration modes. DESIGN: Cross-sectional study. SETTING: Collegiate athletic training facilities. PATIENTS OR OTHER PARTICIPANTS: A total of 3248 intercollegiate student-athletes participated in year 1 (male = 55.3%, age = 20.2 ± 2.3 years, height = 1.78 ± 0.11 m, weight = 80.7 ± 21.0 kg) and 833 participated in both years. MAIN OUTCOME MEASURE(S): Time, in seconds, to complete the KD error free. The KD test reliability was assessed between trials and between annual tests over 2 years and stratified by test modality (spiral-bound cards [n = 566] and tablet [n = 264]). RESULTS: The KD test was reliable between trials (trial 1 = 43.2 ± 8.3 seconds, trial 2 = 40.8 ± 7.8 seconds; intraclass correlation coefficient [ICC] (2,1) = 0.888, P < .001), between years (year 1 = 40.8 ± 7.4 seconds, year 2 = 38.7 ± 7.7 seconds; ICC [2,1] = 0.827, P < .001), and for both spiral-bound cards (ICC [2,1] = 0.834, P < .001) and tablets (ICC [2,1] = 0.827, P < .001). The mean change between trials for a single test was -2.4 ± 3.8 seconds. Although most athletes improved from year 1 to year 2, 27.1% (226 of 883) of participants demonstrated worse (slower) KD times (3.2 ± 3.9 seconds) in year 2. CONCLUSIONS: The KD test was reliable between trials and years and when stratified by modality. A small improvement of 2 seconds was identified with annual retesting, likely due to a practice effect; however, 27% of athletes displayed slowed performance from year 1 to year 2. These results suggest that the KD assessment was a reliable test with modest learning effects over time and that the assessment modality did not adversely affect baseline reliability.