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Concussions are common among youth athletes and could disrupt critical neurodevelopment. This study examined the association between age of first concussion (AFC) and neurocognitive performance, psychological distress, postural stability, and symptoms commonly associated with concussion in healthy collegiate men and women student athletes.Participants included 4267 collegiate athletes from various contact, limited-contact, and non-contact sports (1818 women and 2449 men) who completed baseline assessments as part of the Concussion Assessment, Research and Education (CARE) Consortium. Psychological distress was assessed with the Brief Symptom Inventory 18; neurocognitive performance was assessed with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); symptoms commonly associated with concussion were assessed with the ImPACT Post-Concussion Symptom Scale; postural stability was assessed with the Balance Error Scoring System. Generalized linear models were used to examine the effects of AFC on clinical outcomes separately in men and women.Later AFC was associated with lower global (Exp(B) = 0.96, P = 0.001) and somatic (Exp(B) = 0.96, P = 0.002) psychological distress on the Brief Symptom Inventory 18 and faster ImPACT reaction time (B = - 0.003, P = 0.001) in women. AFC was not associated with any clinical outcomes in men.Younger AFC was associated with some differences in psychological distress and reaction time among women but not men; however, these results are likely not clinically meaningful. Sociodemographic disparities, pre-existing conditions, and sport type may impact clinical and cognitive outcomes in collegiate athletes more than concussion history. Future work should examine the relationship between AFC and lifespan-related outcomes.

Background: The Vestibular/Ocular-Motor Screening (VOMS) is a valuable component of acute (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.

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.

Few studies have analyzed the Sport Concussion Assessment Tool's (SCAT) utility among athletes whose concussion assessment is challenging. Using a previously published algorithm, we identified possible and probable concussions at

Context Nearly 44 million youth participate in organized youth sports programs in the United States each year. However, approximately 25% of parents have considered removing their children from sports due to the fear of concussion. Objective To determine which adult decision-making modifiers (eg, gender, educational attainment, career type) influenced support for youth contact-sports participation. Design Cross-sectional study. Setting Midwestern university and medical center. Patients or Other Participants Convenience sample of staff and faculty (N = 5761; 73.9% female) from 2017 to 2018. Main Outcome Measure(s) Support for youth contact-sports participation using multivariate binary logistic regression to calculate odds ratios and 95% CIs. Results The sample was split between adults with children (AWCs; n = 3465, age = 45.39 ± 13.27 years, 76.72% female) and adults without children (AWOCs; n = 2296, age = 30.84 ± 9.01 years, 70.26% female). Among AWCs, those who obtained a bachelor's degree or higher were more likely to support contact-sports participation. Females were more inclined to allow all contact sports, specifically football (odds ratio [OR] = 2.22; 95% CI = 1.64, 3.01) and ice hockey (OR = 1.98; 95% CI = 1.42, 2.78). Overall, previous adult sport participation, increasing number of children, and child gender were significant modifying variables in greater support of youth contact-sports participation among AWCs (P < .001). Among AWOCs, previous sport participation in football (OR = 3.27; 95% CI = 2.14, 4.87), ice hockey (OR = 4.26; 95% CI = 2.23, 8.17), or soccer (OR = 2.29; 95% CI = 1.48, 3.54) increased the likelihood of an adult supporting contact-sports participation. Lastly, all adults were less inclined to support a daughter participating in any contact sport than a son. Conclusions These results reveal adult- and child-specific variables that may influence youth contact-sports participation. These decisions may be developed through the lens of certain gender role beliefs and may lead adults to perceive certain sports as more appropriate for sons than daughters.

Highlights • Previous concussion was associated with 2 times increased odds of incident concussion, while wearing a mouthguard was protective against incident concussion, reducing odds by 57%. • Overall, concussion mechanisms did not significantly differ between sexes. • Females took significantly longer to reach asymptomatic and return-to-play clearance. 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 one-half (45.50%) of females., Objective 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., Graphical Abstract Image, graphical abstract

Purpose In patients with obesity, micronutrient deficiencies have been reported both before and after bariatric surgery (BS). Obesity is a chronic pro-inflammatory status, and inflammation increases the risk of micronutrient malnutrition. Our objective was to assess in pre-BS patients the prevalence of micronutrient deficiencies and their correlation with blood values of C-reactive protein (CRP). Methods Anthropometric data, instrumental examinations, and blood variables were centrally measured in the first 200 patients undergoing a pre-BS evaluation at the “Città della Salute e della Scienza” Hospital of Torino, starting from January 2018. Results At least one micronutrient deficiency was present in 85.5% of pre-BS patients. Vitamin D deficiency was the most prevalent (74.5%), followed by folate (33.5%), iron (32%), calcium (13%), vitamin B12 (10%), and albumin (5.5%) deficiency. CRP values were high (> 5 mg/L) in 65% of the patients. These individuals showed increased rate of iron, folate, vitamin B12 deficiency, and a higher number of micronutrient deficiencies. In a multiple logistic regression model, increased CRP levels were significantly associated with deficiencies of vitamin B12 (OR = 5.84; 95% CI 1.25–27.2; p = 0.024), folate (OR = 4.02; 1.87–8.66; p p = 0.01). Conclusions Micronutrient deficiencies are common in patients with severe obesity undergoing BS, especially when inflammation is present. In the presence of increased CRP values before surgery, it might be advisable to search for possible multiple micronutrient deficiencies.

ObjectiveTo study longitudinal recovery trajectories of white matter after sports-related concussion (SRC) by performing diffusion tensor imaging (DTI) on collegiate athletes who sustained SRC.MethodsCollegiate athletes (n = 219, 82 concussed athletes, 68 contact-sport controls, and 69 non–contact-sport controls) were included from the Concussion Assessment, Research and Education Consortium. The participants completed clinical assessments and DTI at 4 time points: 24 to 48 hours after injury, asymptomatic state, 7 days after return-to-play, and 6 months after injury. Tract-based spatial statistics was used to investigate group differences in DTI metrics and to identify white-matter areas with persistent abnormalities. Generalized linear mixed models were used to study longitudinal changes and associations between outcome measures and DTI metrics. Cox proportional hazards model was used to study effects of white-matter abnormalities on recovery time.ResultsIn the white matter of concussed athletes, DTI-derived mean diffusivity was significantly higher than in the controls at 24 to 48 hours after injury and beyond the point when the concussed athletes became asymptomatic. While the extent of affected white matter decreased over time, part of the corpus callosum had persistent group differences across all the time points. Furthermore, greater elevation of mean diffusivity at acute concussion was associated with worse clinical outcome measures (i.e., Brief Symptom Inventory scores and symptom severity scores) and prolonged recovery time. No significant differences in DTI metrics were observed between the contact-sport and non–contact-sport controls.ConclusionsChanges in white matter were evident after SRC at 6 months after injury but were not observed in contact-sport exposure. Furthermore, the persistent white-matter abnormalities were associated with clinical outcomes and delayed recovery time.

Context 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.

With morbidity and mortality related to opioid use continuing to increase, clinicians need to better understand the risk for opioid misuse in patient populations. Screening for opioid misuse risk has not been routinely adopted as a standard practice in clinical settings. A pilot study was performed to determine the feasibility of screening for future opioid misuse risk using the Opioid Risk Tool (ORT) in an ambulatory oncology clinic. Twelve patients in this sample scored in the moderate- to high-risk range for aberrant behavior, and 8 patients reported a personal history of substance abuse, indicating a need for opioid misuse risk screening in populations of patients with cancer. Because it is easy and quick to use, the ORT may be a feasible tool to incorporate into standard practice.

Continued participation after sport-related concussion (SRC) worsens outcomes, but it is unknown if duration of continued participation after SRC impacts recovery outcomes, and which athletes who continue to participate are at greatest risk for poor SRC outcomes. The purpose of this National Collegiate Athletic Association/Department of Defense (NCAA/DoD) Concussion Assessment, Research, and Education (CARE) Consortium study was to evaluate the association of estimated duration of continued participation after SRC with symptom severity and recovery time in collegiate athletes.Clinicians estimated if/how long athletes continued participation after SRC. Collegiate athletes who continued participation after suspected SRC (n = 195/373, 52.3%) completed the Graded Symptom Checklist to evaluate the severity of total symptoms and migraine/fatigue, cognitive/ocular, and affective symptom clusters. Linear regression analyzed the associations between estimated duration of continued participation, symptom severity, and recovery time. Binary logistic regression examined the association of estimated duration of continued participation with the odds of recovery ≥ 14 and ≥ 21 days. Statistical significance was p 0.05.Athletes who continued to participate did so for 27.9 ± 25.3 min (mean ± standard deviation; range 1-90 min). Longer estimated continued participation (1-90 min) was associated with greater symptom severity (β = 0.122, p = 0.02), affective (β = 0.171, p = 0.001) and migraine/fatigue symptoms (β = 0.104, p = 0.049), longer symptom duration (β = 0.193, p 0.001), and longer time missed (β = 0.156, p = 0.003). Longer estimated continued participation positively interacted with female sex (cognitive/ocular: female RLonger estimated duration of continued participation after SRC was associated with higher symptom severity, particularly affective and migraine/fatigue; longer symptom duration; and more time missed from sport. SRC outcomes in those who continue to play may be especially severe for female athletes, athletes with migraine history, and athletes with prior concussion(s). The findings can help clinicians and administrators to educate athletes on the importance of immediate removal following a suspected SRC.

Background: Current consensus and position statements recommend that concussed patients be asymptomatic upon the initiation of the graduated return to activity (RTA) protocol. However, a significant number of concussed patients are beginning their RTA protocols while endorsing symptoms. Purpose: To characterize symptom endorsement at the beginning of the RTA protocol and examine the association between symptom endorsement and RTA protocol duration in service academy cadets. Study Design: Cohort study; Level of evidence, 2. Methods: A prospective cohort study was conducted with cadets at 3 US service academies. Postconcussion symptom inventories were recorded upon the initiation of an RTA protocol. The Sport Concussion Assessment Tool Symptom Inventory was used to classify participants into 3 groups (0 symptoms, 1 symptom, and ≥2 symptoms) upon the initiation of the RTA protocol. The primary outcome of interest was RTA protocol duration. Kaplan-Meier survival estimates were calculated to estimate RTA protocol duration by symptom endorsement, sex, varsity status, academic break, and time to graduated RTA initiation. Univariate and multivariable Cox proportional hazards models were used to estimate the association between symptom endorsement at the initiation of the RTA protocol and RTA protocol duration (α < .05). Results: Data were analyzed from 966 concussed cadets (36% women). Headache (42%) and faintness/dizziness (44%) were the most commonly endorsed symptoms on the Sport Concussion Assessment Tool-Third Edition and the Brief Symptom Inventory-18, respectively. Univariate results revealed a significant association between endorsing ≥2 symptoms and RTA protocol duration. In the multivariable model, endorsing ≥2 symptoms maintained a statistically significant association with RTA protocol duration. Significant associations were observed between RTA protocol duration and nonvarsity status (27% longer), women (15% longer), academic breaks (70% longer), and time to the initiation of the RTA protocol (1.1% longer daily incremental increase) after controlling for covariates. Conclusion: Symptom endorsement at the initiation of an RTA protocol was associated with RTA protocol duration. Cadets who had returned to preinjury baseline symptom burden or improved from baseline symptom burden and endorsed ≥2 symptoms at the initiation of the RTA protocol took longer to RTA.

BackgroundHypercortisolism accounts for relevant morbidity and mortality and is often a diagnostic challenge for clinicians. A prompt diagnosis is necessary to treat Cushing’s syndrome as early as possible.ObjectiveThe aim of this study was to develop and validate a clinical model for the estimation of pre-test probability of hypercortisolism in an at-risk population.DesignWe conducted a retrospective multicenter case-control study, involving five Italian referral centers for Endocrinology (Turin, Messina, Naples, Padua and Rome). One hundred and fifty patients affected by Cushing’s syndrome and 300 patients in which hypercortisolism was excluded were enrolled. All patients were evaluated, according to current guidelines, for the suspicion of hypercortisolism.ResultsThe Cushing score was built by multivariable logistic regression, considering all main features associated with a clinical suspicion of hypercortisolism as possible predictors. A stepwise backward selection algorithm was used (final model AUC=0.873), then an internal validation was performed through ten-fold cross-validation. Final estimation of the model performance showed an average AUC=0.841, thus reassuring about a small overfitting effect. The retrieved score was structured on a 17.5-point scale: low-risk class (score value: ≤5.5, probability of disease=0.8%); intermediate-low-risk class (score value: 6-8.5, probability of disease=2.7%); intermediate-high-risk class (score value: 9-11.5, probability of disease=18.5%) and finally, high-risk class (score value: ≥12, probability of disease=72.5%).ConclusionsWe developed and internally validated a simple tool to determine pre-test probability of hypercortisolism, the Cushing score, that showed a remarkable predictive power for the discrimination between subjects with and without a final diagnosis of Cushing’s syndrome.

Context Preseason testing can be time intensive and cost prohibitive. Therefore, using normative data for postconcussion interpretation in lieu of preseason testing is desirable. Objective To establish the recovery trajectory for clinical reaction time (RTclin) and assess the usefulness of changes from baseline (comparison of postconcussion scores with individual baseline scores) and norm-based cutoff scores (comparison of postconcussion scores with a normative mean) for identifying impairments postconcussion. Design Case-control study. Setting Multisite clinical setting. Patients or Other Participants An overlapping sample of 99 participants (age = 19.0 ± 1.1 years) evaluated within 6 hours postconcussion, 176 participants (age = 18.9 ± 1.1 years) evaluated at 24 to 48 hours postconcussion, and 214 participants (age = 18.9 ± 1.1 years) evaluated once they were cleared to begin a return-to-play progression were included. Participants with concussion were compared with 942 control participants (age = 19.0 ± 1.0 years) who did not sustain a concussion during the study period but completed preseason baseline testing at 2 points separated by 1 year (years 1 and 2). Main Outcome Measure(s) At each time point, follow-up RTclin (ie, postconcussion or year 2) was compared with the individual year 1 preseason baseline RTclin and normative baseline data (ie, sex and sport specific). Receiver operating characteristic curves were calculated to compare the sensitivity and specificity of RTclin change from baseline and norm-based cutoff scores. Results Clinical reaction time performance declined within 6 hours (18 milliseconds, 9.2% slower than baseline). The decline persisted at 24 to 48 hours (15 milliseconds, 7.6% slower than baseline), but performance recovered by the time of return-to-play initiation. Within 6 hours, a change from baseline of 16 milliseconds maximized combined sensitivity (52%) and specificity (79%, area under the curve [AUC] = 0.702), whereas a norm-based cutoff score of 19 milliseconds maximized combined sensitivity (46%) and specificity (86%, AUC = 0.700). At 24 to 48 hours, a change from baseline of 2 milliseconds maximized combined sensitivity (64%) and specificity (61%, AUC = 0.666), whereas a norm-based cutoff score of 0 milliseconds maximized combined sensitivity (63%) and specificity (62%, AUC = 0.647). Conclusions Norm-based cutoff scores can be used for interpreting RTclin scores postconcussion in collegiate athletes when individual baseline data are not available, although low sensitivity and specificity limit the use of RTclin as a stand-alone test.

Sport-related concussion is recognized as a significant injury with variable recovery rates.This study defined the acute natural history of sport concussion in male and female collegiate athletes participating in a broad array of sports.We conducted a prospective, longitudinal investigation among collegiate student athletes (n = 34,709) from 30 academic institutions. Primary outcomes included the time (days) from injury until initiation of a return to participation (RTP) protocol and time from injury until medical clearance for unrestricted RTP.Concussed athletes (n = 1751, 19.2 years, 63.2% male) participating in 22 different sports began the RTP protocol in a median 6.4 (IQR 3.7-11.8) days. Time to initiate the RTP protocol was lengthened by less frequent post-injury assessments, greater initial post-injury symptom severity, limited contact sports participation, practice/training injuries, and three or more prior concussions. The median total RTP duration was 12.8 (IQR 8.7-20.1) days. Total RTP duration was shorter with ADHD medication usage, males, and greater assessment frequency; while greater initial post-injury symptom severity, practice-/training-related injuries, and three or more prior concussions had longer recoveries.Although median recovery times are consistent with previous guidelines, it was not until 1 month post-injury that a preponderance of collegiate athletes were cleared to begin the RTP protocol (92%) or cleared for unrestricted sport participation (85%). Intrinsic and extrinsic factors had a small effect, altering recovery trajectories by up to 2 days, suggesting a largely unified approach to post-injury monitoring and management across all athletes. These data represent a shift from previous classification parameters of normal clinical recovery.

Context Comprehensive assessments are recommended to evaluate sport-related concussion (SRC). The degree to which the King-Devick (KD) test adds novel information to an SRC evaluation is unknown. Objective To describe relationships at baseline among the KD and other SRC assessments and explore whether the KD provides unique information to a multimodal baseline concussion assessment. Design Cross-sectional study. Setting Five National Collegiate Athletic Association institutions participating in the Concussion Assessment, Research and Education (CARE) Consortium. Patients or Other Participants National Collegiate Athletic Association student-athletes (N = 2258, age = 20 ± 1.5 years, 53.0% male, 68.9% white) in 11 men's and 13 women's sports. Main Outcome Measure(s) Participants completed baseline assessments on the KD and (1) the Symptom Inventory of the Sport Concussion Assessment Tool–3rd edition, (2) the Brief Symptom Inventory-18, (3) the Balance Error Scoring System, (4) the Standardized Assessment of Concussion (SAC), (5) the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test battery, and (6) the Vestibular/Ocular Motor Screening tool during their first year in CARE. Correlation coefficients between the KD and the 6 other concussion assessments in isolation were determined. Assessments with ρ magnitude >0.1 were included in a multivariate linear regression analysis to evaluate their relative association with the KD. Results Scores for SAC concentration, ImPACT visual motor speed, and ImPACT reaction time were correlated with the KD (ρ = −0.216, −0.276, and 0.164, respectively) and were thus included in the regression model, which explained 16.8% of the variance in baseline KD time (P < .001, Cohen f2 = 0.20). Better SAC concentration score (β = −.174, P < .001), ImPACT visual motor speed (β = −.205, P < .001), and ImPACT reaction time (β = .056, P = .020) were associated with faster baseline KD performance, but the effect sizes were small. Conclusions Better performance on cognitive measures involving concentration, visual motor speed, and reaction time was weakly associated with better baseline KD performance. Symptoms, psychological distress, balance, and vestibular-oculomotor provocation were unrelated to KD performance at baseline. The findings indicate limited overlap at baseline among the CARE SRC assessments and the KD.

ContextThe 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.ObjectiveTo assess (1) test-retest reliability between trials, (2) test-retest reliability between years 1 and 2, and (3) reliability of the 2 administration modes.DesignCross-sectional study.SettingCollegiate athletic training facilities.Patients or Other ParticipantsA 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]).ResultsThe 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.ConclusionsThe 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.

Objective: Neuropsychological evaluations include hold tests like word-reading ability as estimates of premorbid intellect thought to be resilient to the effects of neurologic insult. We te...

Background: Sport-related concussions (SRCs) are associated with short-term disablement, characterized as increased concussion symptoms and lower health-related quality of life (HRQoL). However, there are limited longitudinal data detailing how an SRC affects disablement beyond short-term injury recovery. Purpose: To longitudinally assess the effect of SRCs on symptoms and HRQoL in high school athletes through the 12 months after injury. Study Design: Cohort study; Level of evidence, 2. Methods: The 125 participants included high school athletes who sustained an SRC (female patients, 36%; mean ± SD age, 15.9 ± 1.1 years). The Post-concussion Symptom Scale (PCSS) from the Sport Concussion Assessment Tool–3 and the Pediatric Quality of Life Inventory 4.0 (PedsQL) were completed at enrollment and repeated at 24 to 72 hours (onset) and at 7 days (D7) after the SRC; on the date of return to play (RTP); and at 3, 6, and 12 months (M12) after the SRC. Scores at each time point were compared with the athletes’ own baseline via linear mixed models for repeated measures, controlling for age, sex, and history of previous SRC and with patient as a random effect. Results: Relative to baseline, female patients reported higher PCSS symptom and severity scores at onset ( P < .001) and D7 ( P < .001), while scores were not higher ( P > .05) for RTP through M12. As compared with baseline, male patients reported higher PCSS scores at onset ( P < .001) and D7 ( P = .003) and severity scores at onset ( P < .001) and D7 ( P = .016), while the symptom and severity scores were not higher ( P > .05) at RTP through M12. Female participants reported lower PedsQL physical scores at onset ( P = .006), while scores were not lower ( P > .05) from D7 through M12. Female psychosocial scores were not lower ( P > .05) at any time after the SRC, while the total PedsQL score was lower at onset ( P = .05) but not from D7 through M12. Male physical scores were lower at onset ( P < .001) and D7 ( P = .001) but not lower ( P > .05) from RTP through M12. Male psychosocial and PedsQL scores were unchanged ( P > .05) from baseline at onset through M12. Conclusion: After an SRC, high school athletes reported initial disablement (increased symptoms and lower HRQoL) through their RTP. However, after RTP, no similar disablement was detected through 12 months after injury.

The aim of our study was to estimate the overall rate of first hospitalizations for diabetic foot (DF) regardless of the outcome in amputations, as well as the mortality rate with their determinants in the period 2012–2016 in Piedmont Region in Italy. The study included all the subjects registered in the Regional Diabetes Registry and alive as at January 1, 2012. DF cases were identified by record linkage with the regional hospital discharge database. Incident cases of diabetic foot were followed up for mortality. The 5-year rates were 1762, 324, and 343 × 100,000 patients for first hospitalization without amputations, with major amputations, and with minor amputations, respectively. Patients not undergoing amputations were more than 70% of the cohort. Patients with the more severe stages of diabetes and those with low education were at higher risk of each type of hospitalization. The risk of death during a mean follow-up of 2.5 years was about 16, 18, and 30% among patients without amputations, with major amputations, and with minor amputations, respectively. Males, insulin-treated patients, those affected with severe diabetes complications, particularly on dialysis, and those with lower levels of education were at higher risk. The heavier burden of DF on hospitalizations is due to cases without amputation, a condition that is seldom considered in the diabetes literature. The severity of diabetes, preexisting complications, and low educational levels are associated with both first hospitalization and subsequent survival at any level of severity of DF.

Kutcher and Giza suggested incorporating levels of certainty in concussion diagnosis decisions. These guidelines were based on clinical experience rather than objective data. Therefore, we combined data-driven optimization with predictive modeling to identify which athletes are unlikely to have concussion and to classify remaining athletes as having possible, probable, or definite concussion with diagnostic certainty. We developed and validated our framework using data from the Concussion Assessment, Research, and Education (CARE) Consortium. Acute concussions had assessments at6 h (

ObjectiveWe compared data from the National Collegiate Athletic Association (NCAA) Concussion Study (1999–2001) and the NCAA-Department of Defense Concussion Assessment, Research and Education (CARE) Consortium (2014–2017) to examine how clinical management, return to play (RTP) and risk of repeat concussion in collegiate football players have changed over the past 15 years.MethodsWe analysed data on reported duration of symptoms, symptom-free waiting period (SFWP), RTP and occurrence of within-season repeat concussion in collegiate football players with diagnosed concussion from the NCAA Study (n=184) and CARE (n=701).ResultsCARE athletes had significantly longer symptom duration (CARE median=5.92 days, IQR=3.02–9.98 days; NCAA median=2.00 days, IQR=1.00–4.00 days), SFWP (CARE median=6.00 days, IQR=3.49–9.00 days; NCAA median=0.98 days, IQR=0.00–4.00 days) and RTP (CARE median=12.23 days, IQR=8.04–18.92 days; NCAA median=3.00 days, IQR=1.00–8.00 days) than NCAA Study athletes (all pConclusionOur findings indicate that concussion in collegiate football is managed more conservatively than 15 years ago. These changes in clinical management appear to have reduced the risk of repetitive concussion during the critical period of cerebral vulnerability after sport-related concussion (SRC). These data support international guidelines recommending additional time for brain recovery before athletes RTP after SRC.

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. To examine the influence concussion baseline battery OoA has on symptom, postural stability, cognitive screening, and computerized neurocognitive test outcomes. 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). SCAT total symptom number (mean difference = 2.23; 95% CI 1.76–2.70; d = 0.49, p

Key Points Question Is concussion incurred during combative training associated with changes in blood levels of protein biomarkers for traumatic brain injury among military service academy cadets? Findings In this case-control study of 103 military service academy cadets in the US, the levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 biomarkers among cadets who incurred concussions during combative training indicated significant increases compared with baseline values and values found in matched cadets who participated in the same combative training exercises but did not incur concussions. Neurofilament light chain levels were significantly higher among cadets with concussions compared with those without concussions at less than 6 hours after injury to 7 days after return to activity. Meaning In this study, blood biomarkers delineated physiological changes after concussions that were incurred during military combative training, indicating patterns that were largely consistent with those reported in studies of sport-associated concussions., 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 (, This case-control study examines whether blood levels of protein biomarkers for traumatic brain injury change after concussions incurred during combative training exercises among US military service academy cadets.

ObjectiveSingle cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19.MethodsGBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered.ResultsIncidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002).ConclusionsThis study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.

Symptom resolution is a key marker in determining fitness for return to activity following concussion, but in some cases, distinguishing persistent symptoms due to concussion versus symptoms related to other factors can be challenging.To determine base rates of postconcussional syndrome (PCS) diagnostic categorization in healthy cadets and student athletes with no recent concussion.13,009 cadets and 21,006 student athletes completed baseline preseason testing. After inclusion/exclusion criteria were applied, the final sample included 12,039 cadets [9123 men (75.8%); 2916 women (24.2%)] and 18,548 student athletes [10,192 men (54.9%); 8356 women (45.1%)]. Participants completed the Sport Concussion Assessment Tool-3rd Edition (SCAT3) symptom evaluation as part of baseline preseason testing. The PCS diagnostic categorization was classified by the International Classification of Diseases, 10th Revision (ICD-10) symptom criteria for PCS.In the absence of recent concussion, subgroups of cadets (17.8% of men; 27.6% of women) and student athletes (11.4% of men; 20.0% of women) reported a cluster of symptoms that would meet the ICD-10 symptom criteria for PCS. Participants with insufficient sleep and/or preexisting conditions (e.g., mental health problems), freshmen cadets, and cadets at the U.S. Coast Guard Academy and at the U.S. Air Force Academy (freshmen were tested during basic cadet training) were more likely to report a cluster of symptoms that would meet the ICD-10 symptom criteria for PCS.The ICD-10 symptom criteria for PCS can be mimicked by preexisting conditions, insufficient sleep, and/or stress. Findings support person-specific assessment and management of symptoms following concussion.

ObjectivesTo examine sex differences in sport-related concussion (SRC) across comparable sports.MethodsProspective cohort of collegiate athletes enrolled between 2014 and 2017 in the Concussion Assessment, Research and Education Consortium study.ResultsAmong 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), pConclusionOverall, 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.

Sensation-seeking, or the need for novel and exciting experiences, is thought to play a role in sport-related concussion (SRC), yet much remains unknown regarding these relationships and, more importantly, how sensation-seeking influences SRC risk. The current study assessed sensation-seeking, sport contact level, and SRC history and incidence in a large sample of NCAA collegiate athletes. Data included a full study sample of 22,374 baseline evaluations and a sub-sample of 2037 incident SRC. Independent samples t-test, analysis of covariance, and hierarchical logistic regression were constructed to address study hypotheses. Results showed that (1) among participants without SRC, sensation-seeking scores were higher in athletes playing contact sports compared to those playing limited- or non-contact sports (p &lt, 0.001, R2 = 0.007, η2p = 0.003), (2) in the full study sample, a one-point increase in sensation-seeking scores resulted in a 21% greater risk of prior SRC (OR = 1.212, 95% CI: 1.154–1.272), and in the incident SRC sub-sample, a 28% greater risk of prior SRC (OR = 1.278, 95% CI: 1.104–1.480), (3) a one-point increase in sensation-seeking scores resulted in a 12% greater risk of incident SRC among the full study sample, and (4) sensation-seeking did not vary as a function of incident SRC (p = 0.281, η2p = 0.000). Our findings demonstrate the potential usefulness of considering sensation-seeking in SRC management.

Context Football is the most popular sport among US high school students and among the highest for sport-related concussion (SRC) incidence. Limited data detail how SRCs affect high school football players' psychosocial and health status beyond short-term injury recovery. Objective To longitudinally assess how SRCs affected symptoms, depression, and health-related quality of life (HRQoL) in high school football players up to 12 months after SRC. Design Prospective cohort study. Setting Thirty-one Wisconsin high schools. Patients or Other Participants A total of 1176 interscholastic football players (age = 16.0 ± 1.2 years). Main Outcome Measure(s) Participants completed the Post-concussion Symptom Scale (PCSS) from the Sport Concussion Assessment Tool 3 (SCAT3), Patient Health Questionnaire-9 (PHQ-9) for depression, and Pediatric Quality of Life Inventory 4.0 (PedsQL) for HRQoL at enrollment. Participants who sustained an SRC repeated each measure within 72 hours of their injury (onset) and at 7 days (D7), return to play (RTP), and 3 months (M3), 6 months (M6), and 12 months (M12) after SRC. Scores at each time point were compared with each participant's baseline using linear mixed models for repeated measures while controlling for age and previous SRC with participant as a random effect. Results Sixty-two participants sustained an SRC. Participants reported a higher number of PCSS symptoms, greater symptom severity, and lower PedsQL physical summary scores at onset and D7. From RTP through M12, PCSS symptoms, PCSS severity scores, PedsQL total scores, physical summary, and psychosocial summary were unchanged or improved relative to baseline. The PHQ-9 scores were not higher than baseline at any post-SRC interval. Conclusions High school football players in this study who sustained an SRC described no sustained adverse health outcomes (increased PCSS symptoms or symptom severity, increased depression symptoms, or lower HRQoL) after their RTP through M12 after injury.

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 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 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.

Key Points Question Are plasma biomarkers associated with a return-to-sport period of less than 14 days vs 14 days or more in male and female collegiate athletes following a sport-related concussion? Findings This diagnostic study, which included 127 collegiate athletes who had sustained a sports-related concussion, found that higher total tau concentrations 24 to 48 hours after injury and at the time of symptom resolution as well as lower glial fibrillary acidic protein levels acutely postinjury were associated with return-to-sport decisions. Meaning In this study, total tau and glial fibrillary acidic protein levels were associated with return to sport in male and female collegiate athletes following a sports-related concussion., This diagnostic study examines whether plasma biomarkers can differentiate collegiate athletes who return to sport in less than 14 days vs 14 days or more following a sports-related concussion., 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

ObjectivesTo determine the acute and early long-term associations of sport-related concussion (SRC) and subcortical and cortical structures in collegiate contact sport athletes.MethodsAthletes with a recent SRC (n=99) and matched contact (n=91) and non-contact sport controls (n=95) completed up to four neuroimaging sessions from 24 to 48 hours to 6 months postinjury. Subcortical volumes (amygdala, hippocampus, thalamus and dorsal striatum) and vertex-wise measurements of cortical thickness/volume were computed using FreeSurfer. Linear mixed-effects models examined the acute and longitudinal associations between concussion and structural metrics, controlling for intracranial volume (or mean thickness) and demographic variables (including prior concussions and sport exposure).ResultsThere were significant group-dependent changes in amygdala volumes across visits (p=0.041); this effect was driven by a trend for increased amygdala volume at 6 months relative to subacute visits in contact controls, with no differences in athletes with SRC. No differences were observed in any cortical metric (ie, thickness or volume) for primary or secondary analyses.ConclusionA single SRC had minimal associations with grey matter structure across a 6-month time frame.

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.

The absence of evidence-based guidelines make medical disqualification (MDQ) following concussion one of the most challenging decision-making processes faced by sports medicine professionals.We aimed to compare premorbid and postmorbid factors between student-athletes that were and were not medically disqualified from sport following a concussion.Among 1832 student-athletes diagnosed with concussion within the CARE Consortium, 53 (2.9%) were medically disqualified (MDQ +) and 1779 (97.1%) were not medically disqualified (MDQ-). We used contingency tables and descriptive statistics for an initial evaluation of a broad list of premorbid and postmorbid factors. For those factors showing association with MDQ status, we calculated odds ratios and 95% confidence intervals for the odds of being MDQ + in the presence of the identified factor.History of 2 (OR: 3.2, 95% CI 1.5, 6.9) or 3 + (OR: 7.4, 95% CI 3.4, 15.9) previous concussions; 1 + headaches in past 3 months (OR: 1.8, 95% CI 1.0, 3.2); immediate removal from play (OR: 2.4, 95% CI 1.2, 4.9); alcohol (OR: 2.6, 95% CI 1.2, 5.4), tobacco (OR: 3.3, 95% CI 1.1, 9.5), or marijuana use since injury (OR: 5.4, 95% CI 1.5, 19.0); as well as prolonged recovery due to mental health alterations (OR: 5.3, 95% CI 2.0, 14.1) or motivation/malingering (OR: 7.5, 95% CI 3.3, 17.0) increased odds of being MDQ + . The MDQ + group took longer to become asymptomatic relative to the MDQ- group (MDQ + : 23.5 days, 95% CI 15.8, 31.2; MDQ-: 10.6 days, 95% CI 9.5, 11.6; p 0.001).MDQ following concussion was relatively rare. We identified three patterns related to MDQ following concussion: (1) concussion and headache history were the only premorbid factors that differed (2) initial concussion presentation was more severe and more immediate in the MDQ + group, and (3) post-concussion recovery outcomes expressed the greatest differences between groups.

Context In the absence of baseline testing, normative data may be used to interpret postconcussion scores on the clinical reaction-time test (RTclin). However, to provide normative data, we must understand the performance factors associated with baseline testing. Objective To explore performance factors associated with baseline RTclin from among candidate variables representing demographics, medical and concussion history, self-reported symptoms, sleep, and sport-related features. Design Cross-sectional study. Setting Clinical setting (eg, athletic training room). Patients or Other Participants A total of 2584 National Collegiate Athletic Association student-athletes (n = 1206 females [47%], 1377 males [53%], and 1 unreported ( Main Outcome Measure(s) Potential performance factors were sex; race; ethnicity; dominant hand; sport type; number of prior concussions; presence of anxiety, learning disability, attention-deficit disorder or attention-deficit/hyperactivity disorder, depression, or migraine headache; self-reported sleep the night before the test; mass; height; age; total number of symptoms; and total symptom burden at baseline. The primary study outcome measure was mean baseline RTclin. Results The overall RTclin was 202.0 ± 25.0 milliseconds. Female sex (parameter estimate [B] = 8.6 milliseconds, P < .001, Cohen d = 0.54 relative to male sex), black or African American race (B = 5.3 milliseconds, P = .001, Cohen d = 0.08 relative to white race), and limited-contact (B = 4.2 milliseconds, P < .001, Cohen d = 0.30 relative to contact) or noncontact (B = 5.9 milliseconds, P < .001, Cohen d = 0.38 relative to contact) sport participation were associated with slower RTclin. Being taller was associated with a faster RTclin, although this association was weak (B = −0.7 milliseconds, P < .001). No other predictors were significant. When adjustments are made for sex and sport type, the following normative data may be considered (mean ± standard deviation): female, noncontact (211.5 ± 25.8 milliseconds), limited contact (212.1 ± 24.3 milliseconds), contact (203.7 ± 21.5 milliseconds); male, noncontact (199.4 ± 26.7 milliseconds), limited contact (196.3 ± 23.9 milliseconds), contact (195.0 ± 23.8 milliseconds). Conclusions Potentially clinically relevant differences existed in RTclin for sex and sport type. These results provide normative data adjusting for these performance factors.

To determine whether decreased sleep duration postconcussion influences days to asymptomatic and assessment of performance throughout recovery.Prospective.Institutional Clinical Research Laboratory.Four hundred twenty-three collegiate athletes were diagnosed with concussion.Multidimensional concussion assessment battery was conducted at baseline, within 24 to 48 hours, daily [2-4 days postinjury (PI); symptoms only], once asymptomatic, and after return-to-play. The battery included the following: 22-item symptom checklist, Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and computerized neurocognitive test [Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT)].We subtracted baseline sleep duration from 24 to 48 hours postconcussion sleep duration and categorized athletes into the following groups: shorter sleep (≤-1 hour), no change (-1 hour,+1 hour), and longer sleep (≥+1 hour). A 1-way analysis of variance (ANOVA) was conducted to compare days to asymptomatic and separate mixed-model ANOVAs to compare total symptom scores, SAC total scores, BESS total error scores, and ImPACT composite scores between sleep categories across time points (α = 0.05).Sleep groups did not differ in days to asymptomatic. The shorter sleep group had greater symptom severity than no sleep change and longer sleep groups at 24 to 48 hours (shorter: 39.1 ± 20.7; no change: 25.1 ± 18.4, P = 0.007; longer: 25.7 ± 21.8, P = 0.004), and at 2 to 4 days PI (shorter: 21.8 ± 21.8; no change: 10.5 ± 10.8, P = 0.013; longer: 11.9 ± 14.2, P = 0.007), but did not differ at other time points (ie, asymptomatic and return-to-play). Participants with shorter sleep exhibited slower ImPACT reaction times at 24 to 48 hours (shorter: 0.68 ± 0.14; no change: 0.61 ± 0.09, P = 0.016; and longer: 0.62 ± 0.12, P = 0.028) and asymptomatic time points (shorter: 0.62 ± 0.11; no change: 0.56 ± 0.05; P = 0.015).Postinjury sleep declines may be associated with symptom severity and worsened reaction time during initial stages of recovery or may be the result of the concussion itself. Clinicians should be aware of alterations in sleep duration and manage appropriately to mitigate initial symptom burden postconcussion.

Neuroblastoma is a sympathetic nervous system tumor, primarily presenting in children under 6 years of age. The long‐term prognosis for patients with high‐risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapy. This report provides an update to a phase II trial evaluating DFMO as maintenance therapy in HRNB. Event‐free survival (EFS) and overall survival (OS) of 81 subjects with HRNB treated with standard COG induction, consolidation and immunotherapy followed by 2 years of DFMO on the NMTRC003/003b Phase II trial were compared to a historical cohort of 76 HRNB patients treated at Beat Childhood Cancer Research Consortium (BCC) hospitals who were disease‐free after completion of standard upfront therapy and did not receive DFMO. The 2‐ and 5‐year EFS were 86.4% [95% confidence interval (CI) 79.3%‐94.2%] and 85.2% [77.8%‐93.3%] for the NMTRC003/003b subset vs 78.3% [69.5%‐88.3%] and 65.6% [55.5%‐77.5%] for the historical control group. The 2‐ and 5‐year OS were 98.8% [96.4‐100%] and 95.1% [90.5%‐99.9%] vs 94.4% [89.3%‐99.9%] and 81.6% [73.0%‐91.2%], respectively. DFMO maintenance for HRNB after completion of standard of care therapy was associated with improved EFS and OS relative to historical controls treated at the same institutions. These results support additional investigations into the potential role of DFMO in preventing relapse in HRNB., What's new? The long‐term prognosis for patients with high‐risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapy. This phase II clinical trial update is the first study to demonstrate statistically and clinically significant improvement in event‐free and overall survival in HRNB patients as a result of DFMO administration following standard upfront therapy relative to a closely matched historical control. The findings support DFMO maintenance as a novel strategy to prevent relapse in a high‐risk population for relapse following frontline treatment.

Sports medicine clinicians routinely use computerized neurocognitive testing in sport-related concussion management programs. Debates continue regarding the appropriateness of normative reference comparisons versus obtaining individual baseline assessments, particularly for populations with greater likelihood of having below- or above-average cognitive abilities. Improving normative reference methods could offer alternatives to perceived logistical and financial burdens imposed by universal baseline testing. To develop and validate the Concussion Assessment, Research, and Education (CARE) Consortium Multiple Variable Prediction (MVP) norms for the Immediate Postconcussion Assessment and Cognitive Testing (ImPACT). We developed the CARE-MVP norms for ImPACT composite scores using regression-based equations. Predictor variables included sex, race (white/Caucasian, black/African American, Asian, or Multiple Races), medical history [attention-deficit/hyperactivity disorder (ADHD), learning disorder (LD), prior concussion(s), prior psychiatric diagnosis], and an estimate of premorbid intellect (Wechsler Test of Adult Reading). CARE-MVP norms were first validated in an independent sample of healthy collegiate athletes by comparing predicted and actual baseline test scores using independent-samples t-tests and Cohen’s d effect sizes. We then evaluated base rates of low scores in athletes self-reporting ADHD/LD (vs. non-ADHD/LD) and black/African American race (vs. white/Caucasian) across multiple normative reference methods (Chi square, Cramer’s V effect size). Lastly, we validated the CARE-MVP norms in a concussed sample (dependent samples t test, Cohen’s d effect size). A total of 5233 collegiate athletes (18.8 ± 1.2 years, 70.5% white/Caucasian, 39.1% female) contributed to the CARE-MVP norms (development N = 2616; internal validation N = 2617). Race and WTAR score were the strongest and most consistent ImPACT score predictors. There were negligible mean differences between observed and predicted (CARE-MVP) baseline scores (Cohen’s d

Collegiate football players who started playing tackle football before age 12 years did not show worse neuropsychological test performance than those who started playing tackle football after age 12 years. It is unknown if beginning other contact sports, such as lacrosse, at a younger age is associated with worse neurocognitive performance, greater psychological distress, or worse postural stability in collegiate student athletes. The purpose of this study was to examine the association between estimated age of first exposure (eAFE) to repetitive head impacts (RHI) and these outcome measures in collegiate student athletes. 1891 female and 4448 male collision/contact (i.e., football, ice hockey, lacrosse, wrestling, soccer) and non-contact (i.e., golf, rifle, rowing/crew, swimming, tennis) sport athletes completed baseline testing, including the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Brief Symptom Inventory 18 (BSI-18), and Balance Error Scoring System (BESS). For women, the eAFE-by-sport interaction was associated with ImPACT Verbal Memory and Visual Memory, whereby earlier eAFE to contact sports was associated with higher composite scores (B = − 0.397, B = − 0.485, respectively). For men, the eAFE-by-sport interaction was associated with BSI-18 Depression and Global Severity Index and symptom severity scores, whereby earlier eAFE to football was associated with lower psychological distress and symptom severity [Depression, Exp(B) = 1.057; Global Severity Index, Exp(B) = 1.047; Symptom Severity, Exp(B) = 1.046]. Parameter estimates were small suggesting these results may have minimal practical relevance. Findings suggest that RHI during early adolescence is unrelated to brain health as measured by these specific outcome measures in collegiate student athletes.

Context In many US high schools, the athletic trainer (AT) has the responsibility to identify and manage athletes with concussions. Although the availability of ATs varies a great deal among schools, how the level of AT availability in high schools affects the reported incidence and management of sport-related concussions (SRCs) is unknown. Objective To determine how the presence of an AT affects the reporting and management of SRCs. Design Prospective cohort study. Patients or Other Participants A total of 2459 (female = 37.5%, age = 16.1 ± 1.2 years) athletes from 31 Wisconsin high schools were categorized as having low availability (LoAT), mid availability (MidAT), or high availability (HiAT) of ATs. Athletic trainers recorded the incidence, days lost from sport, and postconcussion management through return to sport. The incidence of SRC reporting among categories was examined using a multivariate Cox proportional hazards model. Fisher exact tests were used to determine if postconcussion management differed based on AT availability. Results The incidence of reported SRCs was lower for the LoAT schools (2.4%) compared with the MidAT (5.6%, hazard ratio = 2.59, P = .043) and HiAT (7.0%, hazard ratio = 3.33, P = .002) schools. The median time before the first AT interaction was longer for LoAT schools (24.0 hours) than for MidAT (0.5 hours, post hoc P = .012) and HiAT (0.2 hours, post hoc P = .023) schools. The number of post-SRC interactions was different in all groups (LoAT = 2 interactions, MidAT = 3, and HiAT = 4; all post hoc P values < .05). Days lost were greater for MidAT and HiAT (both 14 days lost) schools compared with LoAT schools (11.5 days lost, post hoc P = .231 and P = .029, respectively). Athletes at LoAT schools were less likely to undergo a return-to-play protocol (9/18 SRCs, 50.0%) than athletes at MidAT (44/47 SRCs, 93.6%; post hoc P = .001) or HiAT (64/64 SRCs, 100%; post hoc P < .001) schools. Conclusions The level of AT availability positively influenced the reported incidence of SRCs as well as postconcussion management activities in this sample of high schools.

The purpose of this study was to compare global and specific health-related quality of life (HRQOL) throughout concussion recovery between those with and without concussion history. Student-athletes diagnosed with concussion completed global (Short Form-12v2; SF-12) and specific (Hospital Anxiety and Depression Scale: HADS) HRQOL assessments at baseline, 24-48 h, asymptomatic, return-to-play, and 6-months post-injury. Baseline scores were compared to post-injury time points for SF-12 subscores (physical and mental; PCS-12, MCS-12) and HADS subscores (depression and anxiety; HADS-D, HADS-A). We conducted a 2 × 5 mixed model ANOVA for group (with and without concussion history) and time (four post-injury assessments compared to baseline). We did not observe interaction or main effects for group, except those with concussion history had worse HADS-D subscores than those without concussion history. PCS-12 subscores were worse at 24-48 h, asymptomatic, and return-to-play compared to baseline, but returned to baseline 6-months post-injury. MCS-12 subscores did not differ at any time points. HADS-D subscores worsened 24-48 h post-injury, but improved for additional assessments compared to baseline. HADS-A improved post-injury compared to baseline at asymptomatic, return-to-play, and 6-month assessments, but was similar to baseline 24-48 h post-injury. HRQOL physical aspects slightly worsened post-injury and restored to baseline after returning to play.

Recent evidence suggests that athletes are at a higher risk of lower-body injuries in the months and years following a concussion. However, little is known about how people modify their movements post-concussion. This study examined kinematics during a jump cut motion in young adults with a concussion history (n=9; 4 males, 5 females; 3.1years' post-injury) and 10 controls (6 males, 4 females). Peak center of mass and peak knee angles during the landing phase of a jump-cut maneuver were evaluated. Participants with a concussion history demonstrated decreased knee varus (left: Mconc=-0.5±1.0°, Mctrl=3.6±1.0°; right: Mconc=5.1±1.2°, Mctrl=7.8±1.12°) and external rotation (left: Mconc=2.5±1.6°, Mctrl=13.0±1.5°; right: Mconc=7.7±1.6°, Mctrl=12.8±1.5°) regardless of whether the cut was oriented towards to the left or right. The kinematic patterns demonstrated in individuals with a concussion history may be suggestive of increased knee injury risk. This study adds to the growing body of literature linking orthopedic injury in those no longer displaying the acute signs and symptoms of concussion.

Sport-related concussion (SRC) has become a major health problem, affecting millions of athletes each year. Despite the increasing occurrence and prevalence of SRC, its underlying mechanism and recovery course have yet to be fully elucidated. The National Collegiate Athletic Association–Department of Defense Grand Alliance: Concussion Assessment, Research and Education (CARE) Consortium is a large-scale, multisite study of the natural history of concussion across multiple sports. The Advanced Research Core (ARC) of CARE is focused on the advanced biomarker assessment of a reduced subject cohort. This paper reports findings from two ARC sites to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared relative CBF maps assessed in 24 concussed contact sport athletes obtained at 24–48 h after injury to those of a control group of 24 matched contact sport players. Significantly less CBF was detected in several brain regions in concussed athletes, while clinical assessments also indicated clinical symptom and performance impairments in SRC patients. Correlations were found between decreased CBF in acute SRC and clinical assessments, including Balance Error Scoring System total score and Immediate Post-Concussion Assessment and Cognitive Test memory composite and impulse control composite scores, as well as days from injury to asymptomatic. Although using different ASL MRI sequences, our preliminary results from two sites are consistent with previous reports and suggest that advanced ASL MRI methods might be useful for detecting acute neurobiological changes in acute SRC.

Gestational diabetes mellitus (GDM), a common pregnancy complication, is associated with an increased risk of maternal/perinatal outcomes. We performed a prospective observational explorative study in 41 GDM patients to evaluate their microbiota changes during pregnancy and the associations between the gut microbiota and variations in nutrient intakes, anthropometric and laboratory variables. GDM patients routinely received nutritional recommendations according to guidelines. The fecal microbiota (by 16S amplicon-based sequencing), was assessed at enrolment (24–28 weeks) and at 38 weeks of gestational age. At the study end, the microbiota α-diversity significantly increased (P Bacteroides. In multiple regression models, Faecalibacterium was significantly associated with fasting glucose; Collinsella (directly) and Blautia (inversely) with insulin, and with Homeostasis-Model Assessment Insulin-Resistance, while Sutterella with C-reactive protein levels. Consistent with this latter association, the predicted metagenomes showed a correlation between those taxa and inferred KEGG genes associated with lipopolysaccharide biosynthesis. A higher bacterial richness and strong correlations between pro-inflammatory taxa and metabolic/inflammatory variables were detected in GDM patients across pregnancy. Collectively these findings suggest that the development of strategies to modulate the gut microbiota might be a potentially useful tool to impact on maternal metabolic health.