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Item Assessment of Blood Biomarker Profile After Acute Concussion During Combative Training Among US Military Cadets(JAMA, 2021-02) Giza, Christopher C.; McCrea, Michael; Huber, Daniel; Cameron, Kenneth L.; Houston, Megan N.; Jackson, Jonathan C.; McGinty, Gerald; Pasquina, Paul; Broglio, Steven P.; Brooks, Alison; DiFiori, John; Duma, Stefan; Harezlak, Jaroslaw; Goldman, Joshua; Guskiewicz, Kevin; McAllister, Thomas W.; McArthur, David; Meier, Timothy B.; Mihalik, Jason P.; Nelson, Lindsay D.; Rowson, Steven; Gill, Jessica; Foroud, Tatiana; Katz, Barry; Saykin, Andrew; Campbell, Darren E.; Svoboda, Steven; Psychiatry, School of MedicineImportance: 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.Item Association of Alzheimer’s disease polygenic risk score with concussion severity and recovery metrics(Wiley, 2025-01-09) Dybing, Kaitlyn M.; McAllister, Thomas W.; Wu, Yu-Chien; McDonald, Brenna C.; McCrea, Michael A.; Broglio, Steven P.; Pasquina, Paul F.; Brooks, M. Alison; Mihalik, Jason P.; Guskiewicz, Kevin M.; Giza, Christopher C.; Goldman, Joshua; Duma, Stefan; Rowson, Steve; Svoboda, Steven; Cameron, Kenneth L.; Houston, Megan N.; Campbell, Darren E.; McGinty, Gerald; Jackson, Jonathan; Risacher, Shannon L.; Saykin, Andrew J.; Nudelman, Kelly N.; Radiology and Imaging Sciences, School of MedicineBackground: Shared genetic risk between Alzheimer’s disease (AD) and concussion may help explain the association between concussion and elevated risk for dementia. However, there has been little investigation into whether AD risk genes also associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate associations between AD genetic risk and concussion severity/recovery in the NCAA‐DoD Grand Alliance CARE Consortium (CARE) dataset. Method: There were 1,917 injuries in the dataset upon project initiation. After removing repeated injuries, related participants, and those without genetic/outcome data, we had 931 participants. Outcomes were number of days to return to play (RTP) as a recovery measure, and four severity measures (scores on SAC and BESS, SCAT symptom severity and total number of symptoms). We calculated PRS using a published score (de Rojas et al., 2021) and performed a linear regression (MLR) of RTP by PRS in normal (<24 days) and long (>24 days) RTP subgroups. We then compared severity measures by PRS using MLR. Next, we used t‐tests to examine outcomes by APOE genotype in military and civilian subgroups. We also performed chi‐squared tests of RTP category (normal vs. long) by APOE genotype. Finally, we analyzed outcomes by PRS in European or African genetic ancestry subgroups using MLR. Result: Higher PRS was associated with longer injury to RTP interval in the normal RTP (<24 days) subgroup (estimate = 0.0412, SE = 0.182, p = 0.0237). 1 SD increase in PRS resulted in a 0.412 day (9.89 hours) increase to the interval. This may be clinically meaningful in the collegiate athlete environment. We did not identify any other significant differences. Conclusion: Our preliminary results provide limited evidence for an impact of AD PRS on concussion recovery, though the pattern was inconsistent and its clinical significance is uncertain. Future studies should attempt to replicate these findings in larger samples with longer follow‐up using PRS calculated from multiple/diverse populations, which will be especially relevant for diverse datasets like CARE.Item Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium(JAMA Network, 2020-01-03) McCrea, Michael; Broglio, Steven P.; McAllister, Thomas W.; Gill, Jessica; Giza, Christopher C.; Huber, Daniel L.; Harezlak, Jaroslaw; Cameron, Kenneth L.; Houston, Megan N.; McGinty, Gerald; Jackson, Jonathan C.; Guskiewicz, Kevin; Mihalik, Jason; Brooks, M. Alison; Duma, Stephan; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; Meier, Timothy B.; CARE Consortium Investigators; Foroud, Tatiana; Katz, Barry P.; Saykin, Andrew J.; Campbell, Darren E.; Svoboda, Steven J.; Goldman, Joshua; DiFiori, Jon; Psychiatry, School of MedicineImportance: There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective: To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants: This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures: Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results: A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance: The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.Item Bifactor Model of the Sport Concussion Assessment Tool Symptom Checklist: Replication and Invariance Across Time in the CARE Consortium Sample(Sage, 2020-09) Brett, Benjamin L.; Kramer, Mark D.; McCrea, Michael A.; Broglio, Steven P.; McAllister, Thomas; Nelson, Lindsay D.; Hazzard, Joseph B., Jr.; Kelly, Louise A.; Ortega, Justus; Port, Nicholas; Pasquina, Paul F.; Jackson, Jonathan; Cameron, Kenneth L.; Houston, Megan N.; Goldman, Joshua T.; Giza, Christopher; Buckley, Thomas; Clugston, James R.; Schmidt, Julianne D.; Feigenbaum, Luis A.; Eckner, James T.; Master, Christina L.; Collins, Michael W.; Kontos, Anthony P.; Chrisman, Sara P.D.; Duma, Stefan M.; Miles, Christopher M.; Susmarski, Adam; Psychiatry, School of MedicineBackground: 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.Item A cohort study to identify and evaluate concussion risk factors across multiple injury settings: findings from the CARE Consortium(Biomed Central, 2019-01-14) Van Pelt, Kathryn L.; Allred, Dain; Cameron, Kenneth L.; Campbell, Darren E.; D’Lauro, Christopher J.; He, Xuming; Houston, Megan N.; Johnson, Brian R.; Kelly, Tim F.; McGinty, Gerald; Meehan, Sean; O’Donnell, Patrick G.; Peck, Karen Y.; Svoboda, Steven J.; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P.; Medicine, School of MedicineBACKGROUND: Concussion, or mild traumatic brain injury, is a major public health concern affecting 42 million individuals globally each year. However, little is known regarding concussion risk factors across all concussion settings as most concussion research has focused on only sport-related or military-related concussive injuries. METHODS: The current study is part of the Concussion, Assessment, Research, and Education (CARE) Consortium, a multi-site investigation on the natural history of concussion. Cadets at three participating service academies completed annual baseline assessments, which included demographics, medical history, and concussion history, along with the Sport Concussion Assessment Tool (SCAT) symptom checklist and Brief Symptom Inventory (BSI-18). Clinical and research staff recorded the date and injury setting at time of concussion. Generalized mixed models estimated concussion risk with service academy as a random effect. Since concussion was a rare event, the odds ratios were assumed to approximate relative risk. RESULTS: Beginning in 2014, 10,604 (n = 2421, 22.83% female) cadets enrolled over 3 years. A total of 738 (6.96%) cadets experienced a concussion, 301 (2.84%) concussed cadets were female. Female sex and previous concussion were the most consistent estimators of concussion risk across all concussion settings. Compared to males, females had 2.02 (95% CI: 1.70-2.40) times the risk of a concussion regardless of injury setting, and greater relative risk when the concussion occurred during sport (Odds Ratio (OR): 1.38 95% CI: 1.07-1.78). Previous concussion was associated with 1.98 (95% CI: 1.65-2.37) times increased risk for any incident concussion, and the magnitude was relatively stable across all concussion settings (OR: 1.73 to 2.01). Freshman status was also associated with increased overall concussion risk, but was driven by increased risk for academy training-related concussions (OR: 8.17 95% CI: 5.87-11.37). Medical history of headaches in the past 3 months, diagnosed ADD/ADHD, and BSI-18 Somatization symptoms increased overall concussion risk. CONCLUSIONS: Various demographic and medical history factors are associated with increased concussion risk. While certain factors (e.g. sex and previous concussion) are consistently associated with increased concussion risk, regardless of concussion injury setting, other factors significantly influence concussion risk within specific injury settings. Further research is required to determine whether these risk factors may aid in concussion risk reduction or prevention.Item Concussion-Recovery Trajectories Among Tactical Athletes: Results From the CARE Consortium(Allen Press, 2020-07) Van Pelt, Kathryn L.; Allred, C. Dain; Brodeur, Rachel; Cameron, Kenneth L.; Campbell, Darren E.; D’Lauro, Christopher J.; He, Xuming; Houston, Megan N.; Johnson, Brian R.; Kelly, Tim F.; McGinty, Gerald; Meehan, Sean K.; O’Donnell, Patrick G.; Peck, Karen Y.; Svoboda, Steven J.; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P.; Psychiatry, School of MedicineContext: Assessments of the duration of concussion recovery have primarily been limited to sport-related concussions and male contact sports. Furthermore, whereas durations of symptoms and return-to-activity (RTA) protocols encompass total recovery, the trajectory of each duration has not been examined separately. Objective: To identify individual (eg, demographics, medical history), initial concussion injury (eg, symptoms), and external (eg, site) factors associated with symptom duration and RTA-protocol duration after concussion. Design: Cohort study. Setting: Three US military service academies. Patients or other participants: A total of 10 604 cadets at participating US military service academies enrolled in the study and completed a baseline evaluation and up to 5 postinjury evaluations. A total of 726 cadets (451 men, 275 women) sustained concussions during the study period. Main outcome measure(s): Number of days from injury (1) until the participant became asymptomatic and (2) to complete the RTA protocol. Results: Varsity athlete cadets took less time than nonvarsity cadets to become asymptomatic (hazard ratio [HR] = 1.75, 95% confidence interval = 1.38, 2.23). Cadets who reported less symptom severity on the Sport Concussion Assessment Tool, third edition (SCAT3), within 48 hours of concussion had 1.45 to 3.77 times shorter symptom-recovery durations than those with more symptom severity. Similar to symptom duration, varsity status was associated with a shorter RTA-protocol duration (HR = 1.74, 95% confidence interval = 1.34, 2.25), and less symptom severity on the SCAT3 was associated with a shorter RTA-protocol duration (HR range = 1.31 to 1.47). The academy that the cadet attended was associated with the RTA-protocol duration (P < .05). Conclusions: The initial total number of symptoms reported and varsity athlete status were strongly associated with symptom and RTA-protocol durations. These findings suggested that external (varsity status and academy) and injury (symptom burden) factors influenced the time until RTA.Item Descriptive Analysis of a Baseline Concussion Battery Among U.S. Service Academy Members: Results from the Concussion Assessment, Research, and Education (CARE) Consortium(Oxford, 2018-11) O'Connor, Kathryn L.; Allred, C. Dain; Cameron, Kenneth L.; Campbell, Darren E.; D'Lauro, Christopher J.; Houston, Megan N.; Johnson, Brian R.; Kelly, Tim F.; McGinty, Gerald; O'Donnell, Patrick G.; Peck, Karen Y.; Svoboda, Steven J.; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P.; Psychiatry, School of MedicineIntroduction The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. Materials and Methods All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Results Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p’s < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen’s d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. Conclusion The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels.Item Detailed description of Division I ice hockey concussions: Findings from the NCAA and Department of Defense CARE Consortium(Elsevier, 2021-03) Van Pelt, Kathryn L.; Caccese, Jaclyn B.; Eckner, James T.; Putukian, Margot; Brooks, M. Alison; Cameron, Kenneth L.; Houston, Megan N.; Posner, Matthew A.; Jackson, Jonathan C.; McGinty, Gerald T.; Hillis, Cameron J.; McAllister, Thomas W.; McCrea, Michael A.; Broglio, Steven P.; Buckley, Thomas A.; Psychiatry, School of MedicineObjective: Since concussion is the most common injury in ice hockey, the objective of the current study was to elucidate risk factors, specific mechanisms, and clinical presentations of concussion in men's and women's ice hockey. Methods: Ice hockey players from 5 institutions participating in the Concussion Assessment, Research, and Education Consortium were eligible for the current study. Participants who sustained a concussion outside of this sport were excluded. There were 332 (250 males, 82 females) athletes who participated in ice hockey, and 47 (36 males, 11 females) who sustained a concussion. Results: Previous concussion (odds ratio (OR) = 2.00; 95% confidence interval (95% CI): 1.02‒3.91) was associated with increased incident concussion odds, while wearing a mouthguard was protective against incident concussion (OR = 0.43; 95%CI: 0.22‒0.85). Overall, concussion mechanisms did not significantly differ between sexes. There were specific differences in how concussions presented clinically across male and female ice hockey players, however. Females (9.09%) were less likely than males (41.67%) to have a delayed symptom onset (p = 0.045). Additionally, females took significantly longer to reach asymptomatic (p = 0.015) and return-to-play clearance (p = 0.005). Within the first 2 weeks post-concussion, 86.11% of males reached asymptomatic, while only 45.50% of females reached the same phase of recovery. Most males (91.67%) were cleared for return to play within 3 weeks of their concussion, compared to less than half (45.50%) of females. Conclusion: The current study proposes possible risk factors, mechanisms, and clinical profiles to be validated in future concussions studies with larger female sample sizes. Understanding specific risk factors, concussion mechanisms, and clinical profiles of concussion in collegiate ice hockey may generate ideas for future concussion prevention or intervention studies.Item Opportunities for Prevention of Concussion and Repetitive Head Impact Exposure in College Football Players: A Concussion Assessment, Research, and Education (CARE) Consortium Study(American Medical Association, 2021) McCrea, Michael A.; Shah, Alok; Duma, Stefan; Rowson, Steven; Harezlak, Jaroslaw; McAllister, Thomas W.; Broglio, Steven P.; Giza, Christopher C.; Goldman, Joshua; Cameron, Kenneth L.; Houston, Megan N.; McGinty, Gerald; Jackson, Jonathan C.; Guskiewicz, Kevin; Mihalik, Jason P.; Brooks, M. Alison; Pasquina, Paul; Stemper, Brian D.; Psychiatry, School of MedicineImportance: 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.Item Progress and Future Directions of the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium and Mind Matters Challenge at the US Service Academies(Frontiers, 2020-09-24) Houston, Megan N.; O'Donovan, Kevin J.; Trump, Jesse R.; Brodeur, Rachel M.; McGinty, Gerald T.; Wickiser, J. Kenneth; D'Lauro, Christopher J.; Jackson, Jonathan C.; Svoboda, Steven J.; Susmarski, Adam J.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Pasquina, Paul; Cameron, Kenneth L.; Psychiatry, School of MedicineDespite 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.