Neighborhood Disadvantage and Clinical Outcome Following Concussion in Adolescents.

Whether social determinants of health are associated with clinical outcome following concussion among adolescents is not well established. The present study examined whether neighborhood-level determinants are associated with clinical recovery time following concussion in adolescents. Participants included adolescent student athletes (n = 130; mean age = 16.6, standard deviation = 1.2; 60.8% boys, 39.2% girls) who attended one of nine selected high schools in Maine, USA. The Area of Deprivation Index (ADI), an indicator of neighborhood disadvantage was used to group high schools as either high or low in neighborhood disadvantage. Athletic trainers entered injury and recovery dates into an online surveillance application between September 2014 and January 2020. Chi-squared analyses and Kaplan-Meier survival analyses were used to compare the groups on two clinical outcomes: days to return to school and days to return to sports. Results of chi-squared tests did not reveal between-group differences in return to school at 21 or 28 days. However, groups differed in the percentage of adolescents who had returned to sports by 21 days (greater neighborhood disadvantage, 62.5%, lesser neighborhood disadvantage 82.0%, χ2 = 4.96, p = 0.03, odds ratio [OR] = 2.73, 95% confidence interval [CI], 1.11-6.74) and 28 days (greater neighborhood disadvantage, 78.6%, lesser neighborhood disadvantage 94.0%, χ2 = 5.18, p = 0.02, OR = 4.27, 95% CI, 1.13-16.16) following concussion. A larger proportion of adolescents attending schools located in areas of greater neighborhood disadvantage took more than 21 and 28 days to return to sports. These results indicate an association between a multi-faceted proxy indicator of neighborhood disadvantage and clinical outcome following concussion. Further research is needed to better characterize factors underlying group differences in time to return to sports and the interactions between neighborhood disadvantage and other correlates of clinical recovery following concussion.

A Common Data Element-Based Adjudication Process for mTBI Clinical Profiles: A Targeted Multidomain Clinical Trial Preliminary Study.

INTRODUCTION: The primary purpose of this study was to examine the prevalence and percent agreement of clinician-identified mild traumatic brain injury (mTBI) clinical profiles and cutoff scores for selected Federal Interagency Traumatic Brain Injury Research common data elements (CDEs). A secondary purpose was to investigate the predictive value of established CDE assessments in determining clinical profiles in adults with mTBI. MATERIALS AND METHODS: Seventy-one (23 males; 48 females) participants (M = 29.00, SD = 7.60, range 18-48 years) within 1-5 months (M = 24.20, SD = 25.30, range 8-154 days) of mTBI completed a clinical interview/exam and a multidomain assessment conducted by a licensed clinician with specialized training in concussion, and this information was used to identify mTBI clinical profile(s). A researcher administered CDE assessments to all participants, and scores exceeding CDE cutoffs were used to identify an mTBI clinical profile. The clinician- and CDE-identified clinical profiles were submitted to a multidisciplinary team for adjudication. The prevalence and percent agreement between clinician- and CDE-identified clinical profiles was documented, and a series of logistic regressions with adjusted odds ratios were performed to identify which CDE assessments best predicted clinician-identified mTBI clinical profiles. RESULTS: Migraine/headache, vestibular, and anxiety/mood mTBI clinical profiles exhibited the highest prevalence and overall percent agreement among CDE and clinician approaches. Participants exceeding cutoff scores for the Global Severity Index and Headache Impact Test-6 assessments were 3.90 and 8.81 times more likely to have anxiety/mood and migraine/headache profiles, respectively. The Vestibular/Ocular Motor Screening vestibular items and the Pittsburgh Sleep Quality Index total score were predictive of clinician-identified vestibular and sleep profiles, respectively. CONCLUSIONS: The CDEs from migraine/headache, vestibular, and anxiety/mood domains, and to a lesser extent the sleep modifier, may be clinically useful for identifying patients with these profiles following mTBI. However, CDEs for cognitive and ocular may have more limited clinical value for identifying mTBI profiles.

Targeted multidomain intervention for complex mTBI: protocol for a multisite randomized controlled trial in military-age civilians.

Background: Mild traumatic brain injury (mTBI) affects ~18,000 military personnel each year, and although most will recover in 3-4 weeks, many experience persisting symptoms and impairment lasting months or longer. Current standard of care for U.S. military personnel with complex mTBI involves initial (<48 h) prescribed rest, followed by behavioral (e.g., physical activity, sleep regulation, stress reduction, hydration, nutrition), and symptom-guided management. There is growing agreement that mTBI involves different clinical profiles or subtypes that require a comprehensive multidomain evaluation and adjudication process, as well as a targeted approach to treatment. However, there is a lack of research examining the effectiveness of this approach to assessing and treating mTBI. This multisite randomized controlled trial (RCT) will determine the effectiveness of a targeted multidomain (T-MD) intervention (anxiety/mood, cognitive, migraine, ocular, vestibular; and sleep, autonomic) compared to usual care (behavioral management) in military-aged civilians with complex mTBI. Methods: This study employs a single-blinded, two-group repeated measures design. The RCT will enroll up to 250 military-aged civilians (18-49 yrs) with a diagnosed complex mTBI within 8 days to 6 months of injury from two concussion specialty clinics. The two study arms are a T-MD intervention and a usual care, behavioral management control group. All participants will complete a comprehensive, multidomain clinical evaluation at their first clinical visit. Information gathered from this evaluation will be used to adjudicate mTBI clinical profiles. Participants will then be randomized to either the 4-week T-MD or control arm. The T-MD group will receive targeted interventions that correspond to the patient's clinical profile (s) and the control group will receive behavioral management strategies. Primary outcomes for this study are changes from enrollment to post-intervention on the Neurobehavioral Symptom Inventory (NSI), Patient Global Impression of Change (PGIC), and functional near-infrared spectroscopy (fNIRS). Time to return to activity (RTA), and healthcare utilization costs will also be assessed. Discussion: Study findings may inform a more effective approach to treat complex mTBI in military personnel and civilians, reduce morbidity, and accelerate safe return-to-duty/activity. Ethics and dissemination: The study is approved by the University of Pittsburgh Institutional Review board and registered at clinicaltrials.gov. Dissemination plans include peer-reviewed publications and presentations at professional meetings. Clinical Trial Registration: www.clinicaltrials.gov, identifier: NCT04549532.

Symptom Provocation Following Post-concussion Computerized Neurocognitive Testing and Its Relationship to Other Clinical Measures of Concussion.

OBJECTIVE: The objective of this study was to document the prevalence of post-computerized neurocognitive test (post-CNT) increases in symptoms in athletes with sport-related concussion, and to examine the effect of post-CNT symptom increases on concussion neurocognitive and vestibular/ocular motor clinical outcomes. METHODS: This was a retrospective analysis of medical records from a concussion specialty clinic. Two hundred and three athletes (M = 16.48 ± 1.97 years; 44% [90/203] female) completed a clinical visit for concussion within 30 days of injury (M = 7.73 ± 5.54 days). Computerized neurocognitive testing (the Immediate Post-concussion Assessment and Cognitive Testing: ImPACT), the Post-Concussion Symptom Scale (PCSS), and the Vestibular Ocular Motor Screening (VOMS) were the main outcome measures for the current study. RESULTS: Sixty-nine percent (141/203) of the sample did not report significant increases in PCSS scores following post-concussion CNT and were classified into a No Provocation (NO PROV) group. Thirty-one percent (62/203) of participants did report a significant increase in symptoms following post-concussion CNT and were classified into a Provocation (PROV) group. Neurocognitive performance was similar between groups. However, the PROV group reported significantly higher scores on the VOMS symptom items than the NO PROV group. CONCLUSIONS: The majority of adolescent athletes can complete a post-concussion CNT without experiencing significant increases in concussion symptoms. Individuals that report symptom increases from completing a post-concussion CNT are more likely to exhibit increased vestibular/ocular motor symptoms. These findings underscore the relationship between the clinical findings from both CNT and vestibular/ocular motor measures following concussion.

Sex Differences on the Concussion Clinical Profiles Screening in Adolescents With Sport-Related Concussion.

CONTEXT: Sex differences influence symptom presentations after sport-related concussion and may be a risk factor for certain concussion clinical profiles. OBJECTIVE: To examine sex differences on the Concussion Clinical Profile Screen (CP Screen) in adolescents after sport-related concussion. DESIGN: Cross-sectional study. SETTING: A concussion specialty clinic. PATIENTS OR OTHER PARTICIPANTS: A total of 276 adolescent (age = 15.02 ± 1.43 years; girls = 152 [55%]) athletes with a recently diagnosed concussion (≤30 days). MAIN OUTCOME MEASURE(S): The 5 CP Screen profiles (anxiety mood, cognitive fatigue, migraine, vestibular, ocular) and 2 modifiers (neck, sleep), symptom total, and symptom severity scores were compared using a series of Mann-Whitney U tests between boys and girls. RESULTS: Girls (n = 152) scored higher than boys (n = 124) on the cognitive fatigue (U = 7160.50, z = -3.46, P = .001) and anxiety mood (U = 7059, z = -3.62, P < .001) factors but not on the migraine (U = 7768, z = -2.52, P = .01) factor. Girls also endorsed a greater number of symptoms (n = 124; U = 27233, z = -3.33, P = .001) and scored higher in symptom severity (U = 7049, z = -3.60, P < .001) than boys. CONCLUSIONS: Among adolescents, symptom endorsement on the CP Screen varied based on sex, and clinicians need to be aware of these differences, especially when evaluating postconcussion presentation in the absence of baseline data.

Exploring the effect of napping on sleep quality and duration in collegiate athletes.

Purpose: The purpose of this study was to extend research on napping and sleep behaviors in collegiate athletes, and to compare nappers and non-nappers on sleep quality and duration. Methods: Current varsity, club, and intramural athletes between 18-29 years completed the Short Napping Behavior Scale, Pittsburgh Quality Sleep Index, Generalized Anxiety Disorder-7, and the Patient Health Questionnaire-9. Results: Approximately 72% (129/179) reported napping. There were no significant differences in outcomes between nap frequency groups on sleep quality (Χ2(3)=4.97, p=.17) or duration (Χ2(3)=1.20, p=.75). Moreover, there was no significant differences for nap length groups on sleep quality (Χ2(3)=7.03, p=.07) or duration (Χ2(3)=1.32, p=.72). Furthermore, there were no significant differences for nap timing groups on sleep quality (Χ2(3)=1.54, p=.67) or duration (Χ2(3)=2.43, p=.49). Conclusion: In a sample of collegiate athletes, nap frequency, length, and timing were not associated with worse sleep quality or duration.

In-Person Versus Telehealth for Concussion Clinical Care in Adolescents: A Pilot Study of Therapeutic Alliance and Patient Satisfaction.

OBJECTIVE: To conduct a pilot study of caregiver ratings of therapeutic alliance and patient satisfaction outcomes between telehealth and in-person concussion clinical care in male and female adolescent athletes. SETTING: Outpatient neuropsychology concussion clinic. PARTICIPANTS: Fifteen patients (aged 15.40 ± 1.35 years; 33% female) with a concussion and their accompanying caregivers ( n = 15; 87% female) were randomly assigned to an in-person clinic visit and 15 patients (aged 15.13 ± 1.25 years; 40% female) with a concussion and their accompanying caregivers ( n = 15; 73% female) were randomly assigned to a telehealth clinic visit. DESIGN: A prospective, randomized design. MAIN MEASURES: Therapeutic alliance and patient satisfaction scores. RESULTS: Therapeutic alliance scores were not significantly different for patients in the in-person or telehealth setting, and caregiver therapeutic alliance scores were significantly higher for the in-person condition than for the telehealth condition. There were no significant differences between in-person and telehealth session satisfaction scores for patients on depth, smoothness, positivity, arousal, and bad-good outcomes. Patient and caregiver satisfaction with the clinical setting was high (ie, General Endorsement). CONCLUSION: Telehealth is feasible for assessing and interpreting clinical concussion examination, interview, and neurocognitive findings, which are perceived by patients and their caregivers to be comparable with in-person care. Positive satisfaction scores also serve to reinforce the need for healthcare providers to seek ways to actively engage with patients and their caregivers through elements of communicative skills such as active listening, building patient rapport, encouraging patient autonomy, and providing an adequate amount of time for interaction and questions. Telehealth for concussion care is increasing in implementation across health systems, and demand is likely to grow in light of the current COVID-19 pandemic and advances in telehealth delivery.

Using change scores on the vestibular ocular motor screening (VOMS) tool to identify concussion in adolescents.

OBJECTIVE: To develop clinical cutoffs using change scores for the VOMS individual items and an overall VOMS change score that identified concussion in adolescent athletes. METHODS: Change score clinical cutoffs were calculated from a sample of adolescents (13-18 years) with SRC (n = 147) and a sample of uninjured adolescents CONTROL (n = 147). Receiver operating characteristic (ROC) curves, with area under the curve (AUC), based on Youden's J statistic were used to identify optimal cutoffs for identifying SRC from CONTROLS using VOMS individual item change scores, an overall VOMS change scores, and NPC distance (cm). RESULTS: AUC values for VOMS item change scores ranged from .55 to .71. Optimal change score cutoffs were ≥1 for VOMS items and ≥3 for overall VOMS change score. The optimal cutoff for NPC distance was ≥3 cm. A ROC analysis revealed a three-factor model (AUC = .76) for identifying SRC that included vertical vesibular ocular reflex (VVOR), visual motion sensitivity (VMS), and NPC distance items. The AUC (.73) for the overall VOMS change score was higher than any individual VOMS AUC values. CONCLUSIONS: This study supports an alternate scoring approach and clinical interpretation of VOMS items involving change scores that account for pretest symptoms.

Comparing Patient- and Clinician-Administered Near Point of Convergence After Concussion.

OBJECTIVE: (1) To compare patient- and clinician-administered measurements of near point of convergence (NPC) distance including the percentage of patients exceeding clinical cutoffs among concussed adolescents and (2) to assess the reliability of patient- and clinician-measured NPC distances. METHODS: A total of 762 patients (mean = 15.51, SD = 3.09 y) within 30 days of concussion participated. The NPC distance was measured consecutively with the patient and clinician controlling the fixation target. The differences between patient (PT) and clinician (CLIN) measurements and cases exceeding cutoffs (ie, ≥5 cm) were examined with a series of t tests and chi-square tests, respectively. Intraclass correlation coefficients and unbiased estimate of reliability were performed. RESULTS: The NPC measurements were similar, t(761) = -.26, P = .79, between the PT (mean = 3.52, SD = 3.77 cm) and CLIN (mean = 3.54, SD = 3.97 cm) conditions. The number of measurements that exceeded cutoffs was similar among the PT (2.5%; 19/762) and CLIN conditions (3%; 23/762) (P = .10), and the number of measurements classified as abnormal/invalid was also similar among the PT (2.5%; 19/762) and CLIN conditions (3%; 23/762) (P = .10). There was excellent reliability between the methods (intraclass correlation coefficients = .85, unbiased estimate of reliability = .92). CONCLUSION: The findings support the application of this assessment in clinical settings where the clinician may not have direct contact with their patient and rely on the patient (eg, telehealth).

The relationship between accelerometer-measured sleep and next day ecological momentary assessment symptom report during sport-related concussion recovery.

OBJECTIVES: Research examining sleep and concussion symptoms following sport-related concussion (SRC) is limited by retrospective self-report rather than objective data from wearable technology and real-time symptom report. The purpose of this study is to use actigraphy and ecological momentary assessment (EMA) to examine the relationship between sleep parameters and next day symptoms. METHODS: Seventeen athletes (47.1%F) aged 12-19 (15.35+/-2.09) years (<72 hours post-SRC) wore Actigraph GT3x+ to measure nighttime sleep and completed post-concussion symptom scales (PCSS) three times via mobile EMA, resulting in a range of 91-177 observations for each outcome. Generalized linear mixed models, utilizing independent variables of sleep efficiency (SE%: ratio of awake time to sleep time) and total sleep time (TST) examined the associations between nightly sleep and symptoms next-day and throughout recovery. RESULTS: SE% (IRR .97, 95%CI: .95, .99, P= .009) and TST (IRR .91, 95%CI: .84, .999, P = .047) were negatively associated with next day night symptoms. The negative relationship between SE% and the cognitive-migraine-fatigue (CMF) factor was significant for next day/night symptoms (P = .01), while TST was associated with symptom severity for the affective symptom factor (P = .015). Sleep was negatively associated with total symptoms and afternoon symptoms in Week 1 and total, morning, afternoon, and night symptoms in Week 2 (ps=.001-.021) of recovery. CONCLUSION: Sleep was negatively associated with symptoms the next day, especially late in the day and among CMF and emotional symptoms. The relationship between sleep and symptom burden was strongest in the subacute stage of concussion recovery, highlighting the potential importance of sleep intervention post-injury.

Sport Concussion Assessment Tool Symptom Inventory: Healthy and Acute Postconcussion Symptom Factor Structures.

CONTEXT: Previous researchers have examined factor structures for common concussion symptom inventories. However, they failed to discriminate between the acute (<72 hours) and subacute (3 days-3 months) periods after concussion. The Sport Concussion Assessment Tool (SCAT) is an acute assessment that, when compared with other concussion symptom inventories, includes or excludes symptoms that may result in different symptom factors. OBJECTIVE: The primary purpose was to investigate the symptom factor structure of the 22-item SCAT symptom inventory in healthy, uninjured and acutely concussed high school and collegiate athletes. The secondary purpose was to document the frequency of the unique SCAT symptom inventory items. DESIGN: Case series. SETTING: High school and college. PATIENTS OR OTHER PARTICIPANTS: A total of 1334 healthy, uninjured and 200 acutely concussed high school and collegiate athletes. MAIN OUTCOME MEASURE(S): Healthy, uninjured participants completed the SCAT symptom inventory at a single assessment. Participants in the acutely concussed sample completed the SCAT symptom inventory within 72 hours after concussion. Two separate exploratory factor analyses (EFAs) using a principal component analysis and varimax extraction method were conducted. RESULTS: A 3-factor solution accounted for 48.1% of the total variance for the healthy, uninjured sample: cognitive-fatigue (eg, feeling "in a fog" and "don't feel right"), migraine (eg, neck pain and headache), and affective (eg, more emotional and sadness) symptom factors. A 3-factor solution accounted for 55.0% of the variance for the acutely concussed sample: migraine-fatigue (eg, headache and "pressure in the head"), affective (eg, sadness and more emotional), and cognitive-ocular (eg, difficulty remembering and balance problems) symptom factors. CONCLUSIONS: The inclusion of unique SCAT symptom inventory items did not alter the symptom factor structure for the healthy, uninjured sample. For the acutely concussed sample, all but 1 unique SCAT symptom inventory item (neck pain) loaded onto a factor.

Identification and functional prediction of mitochondrial complex III and IV mutations associated with glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor in adults, with a dismal prognosis. Treatment is hampered by GBM's unique biology, including differential cell response to therapy. Although several mitochondrial abnormalities have been identified, how mitochondrial DNA (mtDNA) mutations contribute to GBM biology and therapeutic response remains poorly described. We sought to determine the spectrum of functional complex III and IV mtDNA mutations in GBM. METHODS: The complete mitochondrial genomes of 10 GBM cell lines were obtained using next-generation sequencing and combined with another set obtained from 32 GBM tissues. Three-dimensional structural mapping and analysis of all the nonsynonymous mutations identified in complex III and IV proteins was then performed to investigate functional importance. RESULTS: Over 200 mutations were identified in the mtDNAs, including a significant proportion with very low mutational loads. Twenty-five were nonsynonymous mutations in complex III and IV, 9 of which were predicted to be functional and affect mitochondrial respiratory chain activity. Most of the functional candidates were GBM specific and not found in the general population, and 2 were present in the germ-line. Patient-specific maps reveal that 43% of tumors carry at least one functional candidate. CONCLUSIONS: We reveal that the spectrum of GBM-associated mtDNA mutations is wider than previously thought, as well as novel structural-functional links between specific mtDNA mutations, abnormal mitochondria, and the biology of GBM. These results could provide tangible new prognostic indicators as well as targets with which to guide the development of patient-specific mitochondrially mediated chemotherapeutic approaches.