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Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.

Consensus criteria for traumatic encephalopathy syndrome (TES) specify that at least one core clinical feature of cognitive impairment (CI; e.g., difficulties with memory, executive function) or neurobehavioral dysregulation (ND; e.g., explosiveness, rage, and mood lability) be present and not fully accounted for by other health disorders. Associations between self-reported symptoms that mirror the core clinical features of TES?and how they may be related to concomitant medical conditions?remain unclear. The purpose of this study was to evaluate the association of medical conditions and football exposures with TES clinical features (CI+/?, ND+/?) in 1741 former professional American-style football (ASF) players (age, 57.7???13.9 years; professional seasons, 6.6???3.9 years). Demographics (age, race/ethnicity, current body mass index, age of first football exposure, use of performance-enhancing drugs, position played, and past concussion symptoms), self-reported medical conditions (anxiety, depression, attention-deficit hyperactivity disorder [ADHD], sleep apnea, headache, stroke, hypertension, heart disease, high cholesterol, erectile dysfunction, and low testosterone) were collected. Of 1741 participants, 7.4% were CI+ and/or ND+ (n?=?129). Participants who were CI+ or ND+ were more likely to report one or more coexisting medical conditions than participants who did not report CI or ND (odds ratio [OR]?=?2.04; 95% confidence interval: 1.25?3.47; p?=?0.003). Separate general linear models for each medical condition that adjusted for demographics and football-related factors identified significant associations between ADHD, diabetes, erectile dysfunction, headaches, sleep apnea, anxiety, and low testosterone and CI+ and/or ND+ (ORs?=?1.8?6.0). Chi-square automatic interaction detection (CHAID) multi-variable decision tree models that incorporated medical conditions and football exposures accurately differentiated former players meeting either CI or ND clinical criteria from those meeting none (accuracy?=?91.2?96.6%). CHAID identified combinations of depression, headache, sleep apnea, ADHD, and upper quartiles of concussion symptom history as most predictive of CI+ and/or ND+ status. CI+ and/or ND+ players were more likely to report medical conditions known to cause cognitive symptoms. Concussion exposure and medical conditions significantly increased the likelihood that a former ASF player would demonstrate cognitive or neurobehavioral dysfunction. Clinicians engaged with this population should consider whether treatable coexisting condition(s) could account for some portion of the clinical picture associated with TES presentation.

Background The purpose of this study is to compare the prevalence of self‐reported cardiovascular conditions among individuals with moderate to severe traumatic brain injury (TBI) to a propensity‐matched control cohort. Methods and Results A cross‐sectional study described self‐reported cardiovascular conditions (hypertension, congestive heart failure [CHF], myocardial infarction [MI], and stroke) from participants who completed interviews between January 2015 and March 2020 in 2 harmonized large cohort studies, the TBI Model Systems and the National Health and Nutrition Examination Survey. Mixed‐effect logistic regression models were used to compare the prevalence of cardiovascular conditions after 1:1 propensity‐score matching based on age, sex, race, ethnicity, body mass index, education level, and smoking status. The final sample was 4690 matched pairs. Individuals with TBI were more likely to report hypertension (odds ratio [OR], 1.18 [95% CI, 1.08–1.28]) and stroke (OR, 1.70 [95% CI, 1.56–1.98]) but less likely to report CHF (OR, 0.81 [95% CI, 0.67–0.99]) or MI (OR, 0.66 [95% CI, 0.55–0.79]). There was no difference in rate of CHF or MI for those ≤50 years old; however, rates of CHF and MI were lower in the TBI group for individuals >50 years old. Over 65% of individuals who died before the first follow‐up interview at 1 year post‐TBI were >50 years old, and those >50 years old were more likely to die of heart disease than those ≤50 years old (17.6% versus 8.6%). Conclusions Individuals with moderate to severe TBI had an increased rate of self‐reported hypertension and stroke but lower rate of MI and CHF than uninjured adults, which may be due to survival bias.

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24?h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1?4/5?8); and incomplete versus full recovery (GOSE

OBJECTIVES:. We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate–severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN:. Retrospective cohort study. SETTING:. ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS:. Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate–severe TBI (Glasgow Coma Scale of

The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Phase 1 Cohort, enrolled 1375 TBI patients (GCS 3–15) presenting to one of 18 US Level I trauma centers within 24 h of injury who had an admission head CT; blood samples were collected, along with 122 orthopedic and 209 healthy controls. The TBI cohort consisted of 810 CT-negative (CT-) and 549 CT-positive (CT+) subjects. Of the CT- subjects who had MRIs, 121 were MRI-positive (MRI+) and 333 were MRI-negative (MRI-). UCH-L1 POC showed best diagnostic performance for CT + versus CT-, 0–8 h post-injury with an AUC of 0·779 [0·708–0.850] when compared to the 0–25 h interval, with an AUC of 0.684 [0.655–0.712]. NSE assay has an AUC of 0.695 [0.619–0.770] for the 0–8 h interval and 0.634 [0.603–0.665] for the 0–25 h interval. During the first 8 after injury, POC UCH-L1 outperforms NSE in identifying TBI patients with structural abnormalities on neuroimaging.

Introduction Social isolation has been found to be a significant risk factor for health outcomes, on par with traditional risk factors. This isolation is characterised by reduced social interactions, which can be detected acoustically. To accomplish this, we created a machine learning algorithm called SocialBit. SocialBit runs on a smartwatch and detects minutes of social interaction based on vocal features from ambient audio samples without natural language processing.Methods and analysis In this study, we aim to validate the accuracy of SocialBit in stroke survivors with varying speech, cognitive and physical deficits. Training and testing on persons with diverse neurological abilities allows SocialBit to be a universally accessible social sensor. We are recruiting 200 patients and following them for up to 8 days during hospitalisation and rehabilitation, while they wear a SocialBit-equipped smartwatch and engage in naturalistic daily interactions. Human observers tally the interactions via a video livestream (ground truth) to analyse the performance of SocialBit against it. We also examine the association of social interaction time with stroke characteristics and outcomes. If successful, SocialBit would be the first social sensor available on commercial devices for persons with diverse abilities.Ethics and dissemination This study has received ethical approval from the Institutional Review Board of Mass General Brigham (Protocol #2020P003739). The results of this study will be published in a peer-reviewed journal.

Abstract Social networks have broad effects on health and quality of life. Biopsychosocial factors may also modify the effects of brain trauma on clinical and pathological outcomes. However, social network characterization is missing in studies of contact sports athletes. Here, we characterized the personal social networks of former National Football League players compared to non-football US males. In 303 former football players and 269 US males, we found that network structure (e.g., network size) did not differ, but network composition (e.g., proportion of family versus friends) did differ. Football players had more men than women, and more friends than family in their networks compared to US males. Black players had more racially diverse networks than White players and US males. These results are unexpected because brain trauma and chronic illnesses typically cause diminished social relationships. We anticipate our study will inform more multi-dimensional study of, and treatment options for, contact sports athletes. For example, the strong allegiances of former athletes may be harnessed in the form of social network interventions after brain trauma. Because preserving health of contact sports athletes is a major goal, the study of social networks is critical to the design of future research and treatment trials.

Abstract The need to develop patient-specific interventions is apparent when one considers that clinical studies often report satisfactory motor gains only in a portion of participants. This observation provides the foundation for “precision rehabilitation”. Tracking and predicting outcomes defining the recovery trajectory is key in this context. Data collected using wearable sensors provide clinicians with the opportunity to do so with little burden on clinicians and patients. The approach proposed in this paper relies on machine learning-based algorithms to derive clinical score estimates from wearable sensor data collected during functional motor tasks. Sensor-based score estimates showed strong agreement with those generated by clinicians. Score estimates of upper-limb impairment severity and movement quality were marked by a coefficient of determination of 0.86 and 0.79, respectively. The application of the proposed approach to monitoring patients’ responsiveness to rehabilitation is expected to contribute to the development of patient-specific interventions, aiming to maximize motor gains.

Goal: The aim of the study herein reported was to review mobile health (mHealth) technologies and explore their use to monitor and mitigate the effects of the COVID-19 pandemic. Methods: A Task Force was assembled by recruiting individuals with expertise in electronic Patient-Reported Outcomes (ePRO), wearable sensors, and digital contact tracing technologies. Its members collected and discussed available information and summarized it in a series of reports. Results: The Task Force identified technologies that could be deployed in response to the COVID-19 pandemic and would likely be suitable for future pandemics. Criteria for their evaluation were agreed upon and applied to these systems. Conclusions: mHealth technologies are viable options to monitor COVID-19 patients and be used to predict symptom escalation for earlier intervention. These technologies could also be utilized to monitor individuals who are presumed non-infected and enable prediction of exposure to SARS-CoV-2, thus facilitating the prioritization of diagnostic testing.

We examined the association between the severity of acute concussion symptoms and time to return to school and to sports in National Collegiate Athletic Association (NCAA) Division III collegiate athletes. We hypothesized that students with the lowest burden of acute symptoms, measured in the first 72 h, would have the fastest return to school and sports and those with the highest burden of symptoms would have the slowest return to school and sports. This injury surveillance cohort included 808 athletes from 11 NCAA Division III colleges who sustained a concussion between 2014 and 2019. Athletic trainers documented time to return to school and to sports. Kruskal-Wallis tests with post-hoc planned comparison Mann-Whitney U tests were used to assess whether athletes took longer to return based on their acute symptom burden (Low, Medium, or High). Survival analysis (Kaplan Meier with log rank tests) was used to compare the recovery times based on acute symptom burden (censored at 28 days). Chi-square tests compared the proportion of those who had not yet returned to school or sports at various recovery benchmarks (i.e., 1 week, 10 days, 2 weeks, 3 weeks, 4 weeks) based on acute symptom burden. Women (median = 5 days) took slightly longer than men (median = 4 days) to return to school (p = 0.001; r = −0.11, small effect). Women and men did not differ on time to return to sports (p = 0.32, r = −0.04). A greater proportion with high acute symptoms remained out of school at 5 (odds ratio, OR = 4.53), 7 (OR = 4.98), and 10 (OR = 4.80) days compared to those with low acute symptoms. A greater proportion with high acute symptoms remained out of sports at 10 (OR = 4.11), 14 (OR = 3.46), and 21 (OR = 3.01) days compared to those with low acute symptoms. This study shows a strong association between having a high burden of acute post-concussion symptoms and having a slower return to school and sports in Division III collegiate athletes. Moreover, it also illustrates the converse: that those athletes with a low burden of acute symptoms have a faster return to school and sports.

BackgroundParticipation in American-style football (ASF), one of the most popular sports worldwide, has been associated with adverse health outcomes. However, prior clinical studies of former ASF players have been limited by reliance on subjective self-reported data, inadequate sample size, or focus on a single disease process in isolation.ObjectiveTo determine the burden of objective multi-system pathology and its relationship with subjective health complaints among former professional ASF players.MethodsThe In-Person Assessment is a case-control, multi-day, deep human phenotyping protocol designed to characterize and quantify pathology among former professional ASF players. Participants, recruited from an on-going large-scale longitudinal cohort study, will include 120 men who report either no health conditions, a single health condition, or multiple health conditions across the key domains of cardiometabolic disease, disordered sleep, chronic pain, and cognitive impairment. Data will be collected from validated questionnaires, structured interviews, physical examinations, multi-modality imaging, and functional assessments over a 3-day study period. A pilot study was conducted to assess feasibility and to obtain participant feedback which was used to shape the final protocol.ResultsThis study provides a comprehensive assessment of objective multi-system pathology and its relationship with subjective health complaints among former professional ASF players.ConclusionThe study will determine whether subjective health complaints among former professional ASF players are explained by objective explanatory pathology and will provide novel opportunities to examine the interrelatedness of co-morbidities. It is anticipated that this protocol will be applicable to other clinical and occupational populations.

Background: Ensuring the strength of the physician workforce is essential to optimizing patient care. Challenges that undermine the profession include inequities in advancement, high levels of burnout, reduced career duration, and elevated risk for mental health problems, including suicide. This narrative review explores whether physicians within four subpopulations represented in the workforce at levels lower than predicted from their numbers in the general population?women, racial and ethnic minorities in medicine, sexual and gender minorities, and people with disabilities?are at elevated risk for these problems, and if present, how these problems might be addressed to support patient care. In essence, the underlying question this narrative review explores is as follows: Do physician workforce disparities affect patient care? While numerous articles and high-profile reports have examined the relationship between workforce diversity and patient care, to our knowledge, this is the first review to examine the important relationship between diversity-related workforce disparities and patient care. Methods: Five databases (PubMed, the Cochrane Library of Systematic Reviews, EMBASE, Web of Knowledge, and EBSCO Discovery Service) were searched by a librarian. Additional resources were included by authors, as deemed relevant to the investigation. Results: The initial database searches identified 440 potentially relevant articles. Articles were categorized according to subtopics, including (1) underrepresented physicians and support for vulnerable patient populations; (2) factors that could exacerbate the projected physician deficit; (3) methods of addressing disparities among underrepresented physicians to support patient care; or (4) excluded (n=155). The authors identified another 220 potentially relevant articles. Of 505 potentially relevant articles, 199 (39.4%) were included in this review. Conclusions: This report demonstrates an important gap in the literature regarding the impact of physician workforce disparities and their effect on patient care. This is a critical public health issue and should be urgently addressed in future research and considered in clinical practice and policy decision-making.

Researchers operationalize persistent post-concussion symptoms in children and adolescents using varied definitions. Many pre-existing conditions, personal characteristics, and current health issues can affect symptom endorsement rates in the absence of, or in combination with, a recent concussion, and the use of varied definitions can lead to differences in conclusions about persistent symptoms and recovery across studies. This study examined how endorsement rates varied by 14 different operational definitions of persistent post-concussion symptoms for uninjured boys and girls with and without pre-existing or current health problems. This cross-sectional study included a large sample (age range: 11–18) of girls (n = 21,923) and boys (n = 26,556) without a recent concussion who completed the Post-Concussion Symptom Scale at preseason baseline. Endorsements rates varied substantially by definition, health history, and current health issues. The most lenient definition (i.e., a single mild symptom) was endorsed by most participants (54.5% of boys/65.3% of girls). A large portion of participants with pre-existing mental health problems (42.7% of boys/51.5% of girls), current moderate psychological distress (70.9% of boys/72.4% of girls), and insufficient sleep prior to testing (33.4% of boys/47.6% of girls) endorsed symptoms consistent with mild ICD-10 postconcussional syndrome; whereas participants with no current or prior health problems rarely met this definition (1.6% of boys/1.6% of girls). The results illustrate the tremendous variability in the case definitions of persistent symptoms and the importance of harmonizing definitions across future studies.

The objective of this study was to determine whether adolescents with attention-deficit/hyperactivity disorder (ADHD) have prolonged return to school and sports following concussion compared to those without ADHD and whether medication status or concussion history is associated with recovery time. We hypothesized that having ADHD would not be associated with longer recovery time. This prospective observational cohort study, conducted between 2014 and 2019, examined concussion recovery among school sponsored athletics throughout Maine, USA. The sample included 623 adolescents, aged 14–19 years (mean = 16.3, standard deviation = 1.3 years), 43.8% girls, and 90 (14.4%) reported having ADHD. Concussions were identified by certified athletic trainers. We computed days to return to school (full time without accommodations) and days to return to sports (completed return to play protocol) following concussion. Adolescents with ADHD [median days = 7, interquartile range (IQR) = 3–13, range = 0–45] did not take longer than those without ADHD (median days = 7, IQR = 3–13, range = 0–231) to return to school (U = 22,642.0, p = 0.81, r = 0.01; log rank: χ12 = 0.059, p = 0.81). Adolescents with ADHD (median days = 14, IQR = 10–20, range = 2–80) did not take longer than those without ADHD (median days = 15, IQR = 10–21, range = 1–210) to return to sports (U = 20,295.0, p = 0.38, r = 0.04; log rank: χ12 = 0.511, p = 0.48). Medication status and concussion history were not associated with longer recovery times. Adolescents with ADHD did not take longer to functionally recover following concussion. Recovery times did not differ based on whether adolescents with ADHD reported taking medication to treat their ADHD or whether they reported a prior history of concussion.

Objectives: To evaluate the prevalence of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in a population of former National Football League (NFL) players. Methods: Participants were 3913 former NFL players (participation in years 1960–2019) who completed either an online or mailed survey that included self-reported TKA and THA, year(s) of surgery and date of birth. The prevalence of TKA and THA was reported by age category and compared to published cohorts of athlete populations and general population of non-athletes in the USA. Results: 12.3% and 8.1% of sample reported TKA and THA, respectively. The prevalence of both TKA and THA was higher in former NFL players compared to US non-athletes across all ages. Prevalence of TKA was not statistically higher than in other former athlete cohorts but performed at younger ages. The prevalence of TKA and THA was higher than in other cohorts of former NFL players. Conclusion: Former NFL players had higher prevalence of arthroplasty than the general population, suggesting prior participation in American-style football may contribute to elevated risk for arthroplasty at younger ages. Understanding risk factors in style of play, lifestyle and other contributors is important to improve joint health of this population.

Introduction:. Opioid consumption for those in comprehensive inpatient rehabilitation units is high because of the complexity of their injuries. Notably, pain in rehabilitation leads to worsened clinical outcomes because of maladaptive behaviors and poor engagement during therapies. It is critical to developing evidence-based pharmacobehavioral interventions. Based on principles of classical conditioning, conditioning open-label placebo (COLP) is a promising approach for reducing opioid use in comprehensive inpatient rehabilitation, and this technique takes advantage of the possibility of association learning and opioid pharmacology to promote evoked placebo-driven analgesia. Objectives:. In this brief report, we evaluate the feasibility of COLP as a pharmacobehavioral intervention to decrease total opioid consumption in patients with pain hospitalized at Spaulding Rehabilitation Hospital. Methods:. Inpatients with spinal cord injury and polytrauma (n = 20) with moderate to severe pain were randomized to receive COLP (n = 10) or treatment-as-usual for 6 consecutive days. Opioid utilization was measured by morphine equivalents using the morphine equivalent dose conversion; pain severity was assessed using the numerical visual analog scale. Results:. Conditioning open-label placebo significantly reduced total opioid consumption by the end of the intervention period (P ≤ 0.001). Pain reduction was also significant for the COLP group (P = 0.005), whereas the treatment-as-usual group demonstrated a trend towards pain reduction (P = 0.05). Conclusions:. This study presents the first data in the use of a pharmacobehavioral intervention that capitalize on the benefits of open-label placebo and classical drug conditioning for opioid dose reduction in a population with moderate to severe pain exposed to intensive inpatient rehabilitation.

Objective: Pre-injury mental health problems are associated with greater symptom reporting following sport-related concussion. We applied a statistical and psychometric approach known as network analysis to examine the interrelationships among symptoms at baseline in adolescent student athletes with a history of mental health problems.Design: Cross-sectional study.Setting: High schools in Maine, USA.Participants: A cohort of 44,527 adolescent student athletes completed baseline preseason testing with ImPACT® between 2009 and 2015, and those with a history of mental health problems reporting at least one symptom were included (N = 2,412; 14–18 years-old, 60.1% girls).Independent Variables: Self-reported history of treatment for a psychiatric condition.Main Outcome Measures: Physical, cognitive, and emotional symptoms from the Post-Concussion Symptom Scale.Results: Student athletes reported high frequencies of emotional symptoms (nervousness: boys = 46.6%, girls = 58.3%; irritability: boys = 37.9%, girls = 46.9%; sadness: boys = 38.7%, girls = 53.2%), sleep/arousal-related symptoms (trouble falling asleep: boys = 50.4%, girls = 55.1%; sleeping less than usual: boys = 43.8%, girls = 45.2%; and fatigue: boys = 40.3%, girls = 45.2%), headaches (boys = 27.5%, girls = 41.8%), and inattention (boys = 47.8%, girls = 46.9%) before the start of the season. Although uncommonly endorsed, dizziness was the most central symptom (i.e., the symptom with the highest aggregate connectedness with different symptoms in the network), followed by feeling more emotional and feeling slowed down. Dizziness was related to physical and somatic symptoms (e.g., balance, headache, nausea, numbness/tingling) whereas increased emotionality was related to sadness, nervousness, and irritability. Feeling slowed down was connected to cognitive (e.g., fogginess, forgetfulness), and sensory symptoms (e.g., numbness/tingling, light sensitivity). There were no gender differences in the symptom network structure.Conclusions: We examined the interconnections between symptoms reported by student athletes with mental health problems at preseason baseline, identifying how physical, cognitive, and emotional symptoms interact and potentially reinforce each other in the absence of injury. These findings are a step toward informing more precise interventions for this subgroup of athletes if they are slow to recover following concussion.

The objective of this study was to evaluate concussion-like symptom reporting among uninjured adolescents with Attention-deficit/hyperactivity disorder (ADHD), stratified by several cooccurring conditions, and to examine the base rate and predictors of uninjured adolescents with ADHD meeting diagnostic criteria for the International Classification of Diseases, 10th Revision (ICD-10) post-concussional syndrome (PCS). Participants in this cross-sectional, observational study, were drawn from a cohort of 48,834 adolescent student athletes from Maine (ages 13–18) with no concussion in the past 6 months who completed a preseason, baseline testing program between 2009 and 2015. The final sample included 3,031 students with ADHD, 2,146 (70.8%) boys and 885 (29.2%) girls. They were 15.2 years old on average (SD = 1.3). Concussion-like symptom reporting was more common in girls than boys. Most students with ADHD reported one or more symptoms (69.3% of boys and 81.1% of girls). The presence of an additional, co-occurring condition or comorbidity was associated with increased symptom reporting. In the absence of a recent concussion, 28.8% percent of boys and 47.1% of girls with ADHD endorsed symptoms resembling an ICD-10 diagnosis of post-concussional syndrome (PCS). Adolescents with pre-existing conditions were even more likely to endorse symptoms that resembled PCS (28–47% of boys and 45–69% of girls). Prior treatment for a psychiatric condition was the strongest independent predictor for meeting PCS criteria in boys, followed by treatment for migraines and co-occurring learning disorder. For girls, the only independent predictor was prior treatment of a psychiatric condition. In uninjured adolescent student athletes, ADHD appears to mimic the post-concussion syndrome. Adolescents with ADHD commonly endorse concussion-like symptoms in the absence of a recent concussion. Demographic characteristics (sex) and the presence of co-occurring conditions are related to symptom reporting in adolescents with ADHD. Understanding factors associated with baseline symptom reporting, such as pre-existing ADHD, is important when evaluating youth who have persistent symptoms following concussion as well as making both return to school and return to athletics decisions.

IntroductionInhalation injuries carry significant acute care burden including prolonged ventilator days and length of stay. However, few studies have examined post-acute outcomes of inhalation injury survivors. This study compares the long-term outcomes of burn survivors with and without inhalation injury.MethodsData collected by the Burn Model System National Database from 1993 to 2019 were analyzed. Demographic and clinical characteristics for adult burn survivors with and without inhalation injury were examined. Outcomes included employment status, Short Form-12/Veterans Rand-12 Physical Composite Score (SF-12/VR-12 PCS), Short Form-12/Veterans Rand-12 Mental Composite Score (SF-12/VR-12 MCS), and Satisfaction With Life Scale (SWLS) at 24 months post-injury. Regression models were used to assess the impacts of sociodemographic and clinical covariates on long-term outcome measures. All models controlled for demographic and clinical characteristics.ResultsData from 1,871 individuals were analyzed (208 with inhalation injury; 1,663 without inhalation injury). The inhalation injury population had a median age of 40.1 years, 68.8% were male, and 69% were White, non-Hispanic. Individuals that sustained an inhalation injury had larger burn size, more operations, and longer lengths of hospital stay (pConclusionsBurn survivors with inhalation injury were significantly less likely to be employed at 24 months post-injury compared to survivors without inhalation injury. However, other health-related quality of life outcomes were similar between groups. This study suggests distinct long-term outcomes in adult burn survivors with inhalation injury which may inform future resource allocation and treatment paradigms.

Purpose: The purpose of this study was to examine cortical thickness and subcortical volumes in professional rugby players with an extensive history of concussions compared to control subjects. Method: Participants included 24 active and former professional rugby league players [Age M(SD) = 33.3(6.3); Range = 21–44] with an extensive history of concussion and 18 age- and education-matched controls with no history of neurotrauma or participation in contact sports. Participants underwent T1-weighted imaging and completed a neuropsychological battery, including two tests of memory. Whole brain cortical thickness analysis and structural volume analysis was performed using FreeSurfer version 6.0. Results: Professional rugby league players reported greater alcohol consumption (p

Objective: To identify reproducible sub-classes of traumatic brain injury (TBI) that correlate with patient outcomes.Methods: Two TBI datasets from the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System were utilized, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot and Citicoline Brain Injury Treatment Trial (COBRIT). Patients included in these analyses had closed head injuries with Glasgow Comas Scale (GCS) scores of 13–15 at arrival at the Emergency Department (ED). Sparse hiearchical clustering was applied to identify TBI sub-classes within each dataset. The reproducibility of the sub-classes was evaluated by investigating similarities in clinical variable profiles and patient outcomes in each sub-class between the two datasets, as well as by using a statistical metric called in-group proportion (IGP).Results: Seven TBI sub-classes were identified in the first dataset. There were between-class differences in patient outcomes at 90 days (Glasgow Outcome Scale Extended (GOSE): p < 0.001) and 180 days (Trail Making Test (TMT): p = 0.03). Four of seven sub-classes were reproducible in the second dataset with very high IGPs (94, 100, 99, 97%). Seven TBI sub-classes were also identified in the second dataset. There were significant between-class differences in patient outcomes at 180 days (GOSE: p = 0.024; Brief Symptom Inventory (BSI) p = 0.007; TMT: p < 0.001). Three of seven sub-classes were reproducible in the second dataset with very high IGPs (100% for all).Conclusions: Reproducible TBI sub-classes were identified across two independent datasets, suggesting that these sub-classes exist in a general population. Differences in patient outcomes according to sub-class assignment suggest that this sub-classification could be used to guide post-TBI prognosis.

BACKGROUND:The current classification of traumatic brain injury (TBI) into "mild", "moderate", or "severe" does not adequately account for the patient heterogeneity that still exists within each of these categories. The objective of this study was to identify "sub-groups" of mild TBI (mTBI) patients based on data available at the time of the initial post-TBI patient evaluation and to determine if the sub-grouping correlates with patient outcomes at 90 and 180 days post-TBI. METHODS:Data from patients in the TRACK-TBI Pilot dataset who had a Glasgow Coma Scale (GCS) score of 13 to 15 at arrival to the Emergency Department and a closed head injury were included. Considering 53 clinical variables that are typically available during the initial evaluation of the patient with mild TBI, sparse heirarchial clustering with cluster quality assessment was used to identify the optimal number of patient sub-groups. Patient sub-groups were then compared for ten outcomes measured at 90 or 180 days post-TBI. RESULTS:Amongst the 485 patients with mTBI, optimal clustering was based on the inclusion of 12 clinical variables that divided the patients into 5 mild TBI sub-groups. Clinical variables driving the sub-clustering included: gender, employment status, marital status, TBI due to falling, brain CT scan result, systolic blood pressure, diastolic blood pressure, administration of IV fluids in the Emergency Department, alcohol use, tobacco use, history of neurologic disease, and history of psychiatric disease. These 5 mild TBI sub-groups differed in their 90 day and 180 day outcomes within several domains including global outcomes, persistence of TBI-related symptoms, and neuropsychological impairment. CONCLUSIONS:Sub-groups of patients with mTBI can be identified according to clinical variables that are relatively easy to obtain at the time of initial patient evaluation. A patient's sub-group assignment is associated with multidimensional patient outcomes at 90 and 180 days. These findings support the notion that there are clinically meaningful subgroups of patients amongst those currently classified as having mTBI.

Intervertebral disk (IVD) degeneration is a common, chronic, and complex degeneration process that frequently leads to back pain and disability, resulting in a major public health issue. In this review we describe biological therapies under preclinical or clinical development with an emphasis on stem cell-based multimodal approaches that target prevention and treatment of IVD degeneration. Systematical review of the basic science and clinical literature was performed to summarize the current status of devising biological approaches to treating IVD degeneration. Since the exact mechanisms underlying IVD degeneration have not yet been fully elucidated and conservative managements appear to be mostly ineffective, current surgical treatment focuses on removal of the pathological disk tissues combined with spinal fusion. The treatment options, however, often produce insufficient efficacy and even serious complications. Therefore, there have been growing demands and endeavors for developing novel regenerative biology-guided strategies for repairing the IVD via delivery of exogenous growth factors, introduction of therapeutic genes, and transplantation of stem cells, or combinatorial therapies. Overall, the data suggest that when applied under a recovery neurobiology principle, multimodal regimens comprising ex vivo engineered stem cell-based disks hold a high potential promise for efficacious clinical translations.

ObjectiveAcute care readmission risk is an increasingly recognized problem that has garnered significant attention, yet the reasons for acute care readmission in the inpatient rehabilitation population are complex and likely multifactorial. Information on both medical comorbidities and functional status is routinely collected for stroke patients participating in inpatient rehabilitation. We sought to determine whether functional status is a more robust predictor of acute care readmissions in the inpatient rehabilitation stroke population compared with medical comorbidities using a large, administrative data set.MethodsA retrospective analysis of data from the Uniform Data System for Medical Rehabilitation from the years 2002 to 2011 was performed examining stroke patients admitted to inpatient rehabilitation facilities. A Basic Model for predicting acute care readmission risk based on age and functional status was compared with models incorporating functional status and medical comorbidities (Basic-Plus) or models including age and medical comorbidities alone (Age-Comorbidity). C-statistics were compared to evaluate model performance.FindingsThere were a total of 803,124 patients: 88,187 (11%) patients were transferred back to an acute hospital: 22,247 (2.8%) within 3 days, 43,481 (5.4%) within 7 days, and 85,431 (10.6%) within 30 days. The C-statistics for the Basic Model were 0.701, 0.672, and 0.682 at days 3, 7, and 30 respectively. As compared to the Basic Model, the best-performing Basic-Plus model was the Basic+Elixhauser model with C-statistics differences of +0.011, +0.011, and + 0.012, and the best-performing Age-Comorbidity model was the Age+Elixhauser model with C-statistic differences of -0.124, -0.098, and -0.098 at days 3, 7, and 30 respectively.ConclusionsReadmission models for the inpatient rehabilitation stroke population based on functional status and age showed better predictive ability than models based on medical comorbidities.

A significant percentage of individuals diagnosed with mild traumatic brain injury (mTBI) experience persistent post-concussive symptoms (PPCS). Little is known about the pathology of these symptoms and there is often no radiological evidence based on conventional clinical imaging. We aimed to utilize methods to evaluate microstructural tissue changes and to determine whether or not a link with PPCS was present. A novel analysis method was developed to identify abnormalities in high-resolution diffusion tensor imaging (DTI) when the location of brain injury is heterogeneous across subjects. A normative atlas with 145 brain regions of interest (ROI) was built from 47 normal controls. Comparing each subject's diffusion measures to the atlas generated subject-specific profiles of injury. Abnormal ROIs were defined by absolute z-score values above a given threshold. The method was applied to 11 PPCS patients following mTBI and 11 matched controls. Z-score information for each individual was summarized with two location-independent measures: "load" (number of abnormal regions) and "severity" (largest absolute z-score). Group differences were then computed using Wilcoxon rank sum tests. Results showed statistically significantly higher load (p = 0.018) and severity (p = 0.006) for fractional anisotropy (FA) in patients compared with controls. Subject-specific profiles of injury evinced abnormally high FA regions in gray matter (30 occurrences over 11 patients), and abnormally low FA in white matter (3 occurrences over 11 subjects). Subject-specific profiles provide important information regarding the pathology associated with PPCS. Increased gray matter (GM) anisotropy is a novel in-vivo finding, which is consistent with an animal model of brain trauma that associates increased FA in GM with pathologies such as gliosis. In addition, the individualized analysis shows promise for enhancing the clinical care of PPCS patients as it could play a role in the diagnosis of brain injury not revealed using conventional imaging.