Dataset Information

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

ABSTRACT: 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?

SUBMITTER: Pattinson CL

PROVIDER: S-EPMC7453307 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Pattinson Cassandra L CL Meier Timothy B TB Guedes Vivian A VA Lai Chen C Devoto Christina C Haight Thaddeus T Broglio Steven P SP McAllister Thomas T Giza Christopher C Huber Daniel D Harezlak Jaroslaw J Cameron Kenneth K McGinty Gerald G Jackson Jonathan J Guskiewicz Kevin K Mihalik Jason J Brooks Alison A Duma Stefan S Rowson Steven S Nelson Lindsay D LD Pasquina Paul P McCrea Michael M Gill Jessica M JM

JAMA network open 20200803 8

<h4>Importance</h4>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.<h4>Objective</h4>To examine whether plasma biomarkers can differentiate collegiate athletes who RTS in less than 14 days or 14 days or more following SRC.<h4>Design, setting, and participants</h4>This multicenter prospective diagnostic stud ...[more]

PMID: 32852552

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Project description:CONTEXT:? Without a true criterion standard assessment, the sport-related concussion (SRC) diagnosis remains subjective. Inertial balance sensors have been proposed to improve acute SRC assessment, but few researchers have studied their clinical utility. OBJECTIVE:? To determine if group differences exist when using objective measures of balance in a sample of collegiate athletes with recent SRCs and participants serving as the control group and to calculate sensitivity and specificity to determine the diagnostic utility of the inertial balance sensor for acute SRC injuries. DESIGN:? Cross-sectional cohort study. SETTING:? Multicenter clinical trial. PATIENTS OR OTHER PARTICIPANTS:? We enrolled 48 participants with SRC (age = 20.62 ± 1.52 years, height = 179.76 ± 10.00 cm, mass = 83.92 ± 23.22 kg) and 45 control participants (age = 20.85 ± 1.42 years, height = 177.02 ± 9.59 cm, mass = 74.61 ± 14.92 kg) at 7 clinical sites in the United States. All were varsity or club collegiate athletes, and all participants with SRC were tested within 72 hours of SRC. MAIN OUTCOME MEASURE(S):? Balance performance was assessed using an inertial balance sensor. Two measures (root mean square sway and 95% ellipse sway area) were analyzed to represent a range of general balance measures. Balance assessments were conducted in double-legged, single-legged, and tandem stances. RESULTS:? A main effect for group was associated with the root mean square sway measure ( F1,91 = 11.75, P = .001), with the SRC group demonstrating balance deficits compared with the control group. We observed group differences in the 95% ellipse sway area measure for the double-legged ( F1,91 = 11.59, P = .001), single-legged ( F1,91 = 6.91, P = .01), and tandem ( F1,91 = 7.54, P = .007) stances. Sensitivity was greatest using a cutoff value of 0.5 standard deviations (54% [specificity = 71%]), whereas specificity was greatest using a cutoff value of 2 standard deviations (98% [sensitivity = 33%]). CONCLUSIONS:? Inertial balance sensors may be useful tools for objectively measuring balance during acute SRC evaluation. However, low sensitivity suggests that they may be best used in conjunction with other assessments to form a comprehensive screening that may improve sensitivity.

Project description:ObjectiveTo examine the progression of collegiate student athletes through five stages of a return-to-activity protocol following sport-related concussion (SRC).MethodsIn a multisite prospective cohort study, we identified the frequency of initial 24-48 hours physical and cognitive rest, and the sequence of (1) symptom resolution and return to (2) exertion activity, (3) limited sport, (4) full sport and (5) full academics. In resulting profiles we estimated the likelihood of return to full sport ≤14 days or prolonged >28 days and tested for variability based on timing of the stages.ResultsAmong 1715 athletes with SRC (31.6% females), 67.9% had 24-48 hours initial physical and cognitive rest. The median was 6 days to return to full academics, 8 days to symptom resolution and 9 days to exertion. Three profiles emerged; all had the same sport-specific return progression, but varied in the relative timing of full academics. In unadjusted analyses, full academics as the first stage corresponded to the longest time to return to full sport, and initiating exertion the same day as symptom resolution resulted in the shortest time. In adjusted regression analyses, athletes initiating full academics while still symptomatic were 21.5% less likely (95% CI -27.4% to -15.5%) to return to full sport ≤14 days and, analogously, 19.1% more likely (95% CI 13.4% to 24.7%) to have prolonged return >28 days. While additionally controlling for initial rest, sex, symptom count and concussion history, the likelihood of prolonged return >28 days was 37.0% (95% CI 25.2% to 48.8%) in athletes initiating exertion considerably before symptoms resolved (ie, 7+ days), but only 3.6% (95% CI -1.4% to 8.6%) in athletes initiating exertion shortly before achieving symptom resolution (ie, 3-4 days).ConclusionWe found evidence that sequential progressions were consistent with current recommendations including brief initial rest, and the initiation and relative timing of each stage impacted the final return-to-sport outcome.

Project description:Importance: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.

Project description:ContextMandated concussion education has aimed to improve student-athlete knowledge; however, some collegiate student-athletes continue to not disclose concussion. Concussion knowledge may not be the only factor influencing reporting, as student-athlete sex, sport, and pressure from external stakeholders (eg, coaches, teammates, fans, parents or family) have all been documented as influencing collegiate concussion-reporting behavior.ObjectiveTo examine factors associated with concussion nondisclosure in collegiate student-athletes.DesignCross-sectional study.SettingFour National Collegiate Athletic Association Division I and two Division II universities.Patients or other participantsA total of 1125 collegiate student-athletes completed the survey, and 741 provided viable responses and were included for data analysis.Main outcome measure(s)We used a 10- to 15-minute electronic or paper-and-pencil survey that asked about personal and sport demographics, diagnosed concussions and nondisclosed concussion history, concussion knowledge, and level of agreement regarding pressure to play after a head impact experienced during collegiate sport participation. Significant univariable factors were entered into a multivariable logistic regression analysis.ResultsSex (P = .005), sport-risk type (P < .001), diagnosed concussion history (P < .001), concussion knowledge (P = .017), and pressure from coaches (P < .001), teammates (P < .001), fans (P = .024), and parents or family (P = .003) were factors associated with concussion nondisclosure in individual univariable logistic regressions. After we conducted multivariable analyses, male sex (P = .001), high concussion-risk sport participation (P = .048), diagnosed concussion history (P < .001), increased concussion knowledge (P = .013), and experiencing pressure from coaches to continue playing after sustaining a hit to the head (P = .002) were factors associated with concussion nondisclosure in collegiate student-athletes.ConclusionsOur results suggest that concussion-education programs should go beyond the identification of signs and symptoms to include the dangers of continuing to play, long-term consequences, and transparency about concussion protocols. Comprehensive concussion-education programs should involve coaches and athletes to improve the reporting culture.

Project description:ContextConcussions are a global public health concern, and education on the importance of self-reporting may not reach all athletes to the same degree around the world.ObjectiveTo determine if differences were present in the concussion awareness, understanding, and -reporting behaviors of collegiate athletes' in 3 countries with varied degrees of concussion publicity.DesignCross-sectional survey.SettingCollegiate sports medicine clinics.Patients or other participantsCollegiate athletes in the United States (n = 964; high publicity), Ireland (n = 302; moderate publicity), and Jordan (n = 129; low publicity). The degree of concussion publicity was categorized based on the extent of national public health awareness initiatives, care guidelines, research publications, and mass media coverage.Main outcome measure(s)Participants completed a 10- to 15-minute survey on concussion awareness, understanding, and -reporting behaviors. The main outcome measures were concussion education (awareness; 21 options; select all sources of concussion information), concussion knowledge (understanding; maximum score of 49), and diagnosed/nondisclosed concussion history (reporting behaviors; self-report yes/no items).ResultsA higher proportion of Jordanian athletes reported never having received concussion information previously (73.6%) than Irish (24.2%) or US athletes (9.4%). Knowledge differed among countries (P < .0001, η2 = .28), with US athletes displaying higher total knowledge scores (40.9 ± 4.5) than Jordanian (35.1 ± 5.6) and Irish (32.1 ± 3.5) athletes. Greater percentages of Irish and US athletes reported a history of a diagnosed concussion (31.8% and 29.6%, respectively) and history of concussion nondisclosure (25.2% and 15.5%, respectively) than Jordanian athletes (2.3% and 0.0% for history of a diagnosed concussion and history of concussion nondisclosure, respectively).ConclusionsIn the United States, where concussion publicity is high, formal legislation exists, and sports medicine resources and concussion awareness and understanding were increased. More culturally appropriate concussion initiatives are needed globally to ensure that athletes around the world can identify concussive injuries and understand the dangers of continued sport participation while concussed.

Project description:ObjectiveTo describe variability in concussion biomarker concentrations collected from serum in a sample of healthy collegiate athletes, as well as report reliability metrics in a subsample of female athletes.MethodsIn this observational cohort study, β-amyloid peptide 42 (Aβ42), total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule associated protein 2, and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) serum concentrations were measured in 415 (61% male, 40% white, aged 19.0 ± 1.2 years) nonconcussed collegiate athletes without recent exposure to head impacts. Standardized normative distributions are reported for each biomarker. We evaluated main effects (analyses of variance) of sex and race, reporting demographic-specific normative metrics when appropriate. In a subset of 31 female participants, test-retest reliability (Pearson r) and reliable change indices (80%, 90%, and 95% confidence intervals) across a 6- to 12-month interval are reported for Aβ42, total tau, S100B, and UCH-L1.ResultsMales exhibited higher UCH-L1 (p < 0.001, Cohen d = 0.75) and S100B (p < 0.001, d = 0.56) than females, while females had higher CNPase (p < 0.001, d = 0.43). Regarding race, black participants had higher baseline levels of UCH-L1 (p < 0.001, d = 0.61) and S100B (p < 0.001, d = 1.1) than white participants. Conversely, white participants had higher baseline levels of Aβ42 (p = 0.005, d = 0.28) and CNPase (p < 0.001, d = 0.46). Test-retest reliability was generally poor, ranging from -0.02 to 0.40, and Aβ42 significantly increased from time 1 to time 2.ConclusionHealthy collegiate athletes express concussion-related serum biomarkers in variable concentrations. Accounting for demographic factors such as sex and race is essential. Evidence suggested poor reliability for serum biomarkers; however, understanding how other factors influence biomarker expression, as well as knowledge of reliable change metrics, may improve clinical interpretation and future study designs.

Project description:BACKGROUND:Timely removal from activity after concussion symptoms remains problematic despite heightened awareness. Previous studies indicated potential adverse effects of continuing to participate in physical activity immediately after sustaining a concussion. Hypothesis/Purpose: The purpose was to determine the effect of timing of removal from play after concussion on clinical outcomes. It was hypothesized that immediate removal from activity after sport-related concussion (SRC) would be associated with less time missed from sport, a shorter symptomatic period, and better outcomes on acute clinical measures. STUDY DESIGN:Cohort study; Level of evidence, 3. METHODS:Data were reported from the National Collegiate Athletic Association and Department of Defense Grand Alliance: Concussion Awareness, Research, and Education (CARE) Consortium. Participants with 506 diagnosed SRCs from 18 sports and 25 institutions and military service academies were analyzed and classified as either immediate removal from activity (I-RFA) or delayed removal from activity (D-RFA). Outcomes of interest included time missed from sport attributed to their SRC, symptom duration, and clinical assessment scores. RESULTS:There were 322 participants (63.6%) characterized as D-RFA. I-RFA status was associated with significantly less time missed from sport ( R2 change = .022-.024, P < .001 to P = .001) and shorter symptom duration ( R2 change = .044-.046, P < .001 [all imputations]) while controlling for other SRC recovery modifiers. These athletes missed approximately 3 fewer days from sport participation. I-RFA athletes had significantly less severe acute SRC symptoms and were at lower risk of recovery taking ?14 days (relative risk = .614, P < .001, small-medium effect size) and ?21 days (relative risk = .534, P = .010, small effect size). CONCLUSION:I-RFA is a protective factor associated with less severe acute symptoms and shorter recovery after SRC. Conveying this message to athletes, coaches, and others involved in the care of athletes may promote timely injury reporting.

Dataset Information

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

Publications

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

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