Factors Affecting Length of Postoperative Hospitalization for Pediatric Cardiac Operations in a Large North American Registry (1982-2007).

Surgical treatment of congenital heart disease represents a major cause of pediatric hospitalization and healthcare resource use. Larger centers may provide more efficient care with resulting shorter length of postoperative hospitalization (LOH). Data from 46 centers over 25 years were used to evaluate whether surgical volume was an important determinant of LOH using a competing risk regression strategy that concurrently accounted for deaths, transfers, and discharges with some time interactions. Earlier discharge was more likely for infants and older children compared to neonates [subhazard ratios at postoperative day 6 of 1.64 (99 % confidence interval (CI) 1.57, 1.72) and 2.67 (99 % CI 2.53, 2.80), respectively], but less likely for patients undergoing operations in Risk Adjustment for Congenital Heart Surgery categories 2, 3, 4, and 5/6 compared to category 1 [subhazard ratios at postoperative day 6 of 0.66 (99 % CI 0.64, 0.68), 0.34 (95 % CI 0.33, 0.35), 0.28 (99 % CI 0.27, 0.30), and 0.10 (99 % CI 0.09, 0.11), respectively]. There was no difference by sex [non-time-dependent subhazard ratio 1.019 (99 % CI 0.995, 1.040)]. For every 100-operation increase in center annual surgical volume, the non-time-dependent subhazard for discharge was 1.035 (99 % CI 1.006, 1.064) times greater, and center-specific exponentiated random effects ranged from 0.70 to 1.42 with a variance of 0.023. The conditional discharge rate increased with increasing age and later era. No sex-specific difference was found. Centers performing more operations discharged patients sooner than lower volume centers, but this difference appears to be too small to be of clinical significance. Interestingly, unmeasured institutional characteristics estimated by the center random effects were variable, suggesting that these played an important role in LOH and merit further investigation.

Association of Sport Helmet Status on Concussion Presentation and Recovery in Male Collegiate Student-Athletes.

Sporting helmets contain force attenuating materials which reduce traumatic head injury risk and may influence sport-related concussion (SRC) sequelae. The purpose of this study was to examine the association of sport helmet status with SRC-clinical presentation and recovery trajectories in men's collegiate athletes. Sport helmet status was based on the nature of sports being either helmeted/non-helmeted. 1070 SRCs in helmeted (HELM) sports (Men's-Football, Ice Hockey, and Lacrosse), and 399 SRCs in non-helmeted (NOHELM) sports (Men's-Basketball, Cheerleading, Cross Country/Track & Field, Diving, Gymnastics, Soccer, Swimming, Tennis, and Volleyball) were analyzed. Multivariable negative binomial regression models analyzed associations between sport helmet status and post-injury cognition, balance, and symptom severity, adjusting for covariate effects (SRC history, loss of consciousness, anterograde/retrograde amnesia, event type). Kaplan-Meier curves evaluated median days to: initiation of return to play (iRTP) protocol, and unrestricted RTP (URTP) by sport helmet status. Log-rank tests were used to evaluate differential iRTP/URTP between groups. Two independent multivariable Weibull accelerated failure time models were used to examine differential iRTP and URTP between groups, after adjusting for aforementioned covariates and symptom severity score. Overall, the median days to iRTP and URTP was 6.3 and 12.0, respectively, and was comparable across NOHELM- and HELM-SRCs. Post-injury symptom severity was lower (Score Ratio 0.90, 95%CI 0.82, 0.98), and cognitive test performance was higher (Score Ratio 1.03, 95%CI 1.02, 1.05) in NOHELM-compared to HELM-SRCs. Estimated time spent recovering to iRTP/URTP was comparable between sport helmet status groups. Findings suggest that the grouping of sports into helmeted and non-helmeted show slight differences in clinical presentation but not recovery.

The role of recurrent trauma on post-traumatic stress disorder symptoms and substance use among trauma exposed youth.

Comorbidity between post-traumatic stress disorder (PTSD) and substance use disorder may be explained by a prospective trauma risk conferred by both conditions. The current study modeled concurrent and prospective associations of trauma, PTSD symptoms, and substance use (SU) behavior among trauma exposed youth (ages 8-20). Clinical interviews assessed trauma exposure, PTSD symptom severity, and SU behavior at baseline and at six- and 12-month follow up study visits (N = 2,069). Structural equation models assessed the associations of trauma, PTSD symptoms, and SU behavior. Lifetime trauma was associated with more severe PTSD symptoms and SU behaviors, whereas trauma exposure during the study was only associated with PTSD symptoms. PTSD symptom severity was prospectively associated with trauma exposure. PTSD symptom severity and SU behavior at follow-up study visits were prospectively associated. These results highlight the dynamic interplay between trauma, PTSD symptoms, and SU behavior during youth, a developmental period during which complex psychiatric presentations can have longstanding consequences for health.

Primary and Secondary Risk Factors Associated With Concussion Symptom Clusters in Collegiate Athletes: Results From the NCAA-DoD Grand Alliance CARE Consortium.

Background: There is a broad and diverse range of symptoms after a concussion, from irritability to nausea. This heterogeneity of symptoms is a challenge for clinicians managing the different presentations among injuries. Prior research has investigated the structure of postconcussive symptoms to determine if they can be grouped into clusters of related symptoms. Purpose/Hypothesis: The purpose of this study was to identify symptom clusters during the acute phase after a sports-related concussion using exploratory factor analysis and to understand the relationship between risk factors for postconcussion symptoms (ie, demographics, injury characteristics, mental health, and sleep qualities) and different symptom clusters. We hypothesized that certain factors would be predictive of specific symptom clusters. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Collegiate athletes (N = 1104) from the Concussion, Assessment, Research, and Education (CARE) Consortium completed the Sport Concussion Assessment Tool-Third Edition symptom assessment tool 24 to 48 hours after concussion. Exploratory factor analysis was conducted on the symptom evaluation to determine symptom clusters 24 to 48 hours after concussion. Regression analysis was used to examine the effects of pre- and postinjury characteristics. Results: Exploratory factor analysis revealed a 4-cluster structure for acute postconcussive symptoms that explained 62% of the variance in symptom reporting: vestibular-cognitive, migrainous, cognitive fatigue, and affective. Delayed reporting, less sleep before assessment, female sex, and being hurt outside of competition (during practice/training) was correlated with increased symptoms for 4 symptom clusters. Depression predicted higher vestibular-cognitive and affective symptoms. Amnesia was correlated with higher vestibular-cognitive and migrainous symptoms, whereas migraine history was associated with more migrainous and affective symptoms. Conclusion: Symptoms can be grouped into 1 of 4 distinct clusters. Certain variables were associated with increased symptoms across multiple clusters and may be indicative of greater injury severity. Other factors (ie, migraine history, depression, amnesia) were associated with a more specific symptom presentation and may be mechanistically related to concussion outcomes and biological markers.

Multiple Adipokines Predict Dementia Severity as Measured by δ: Replication Across Biofluids and Cohorts.

BACKGROUND: We have explored dementia's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. Among them are adipokines, i.e., proteins secreted by adipose tissue some of which have been associated with cognitive impairment. OBJECTIVE: To associate adipokines with dementia severity and replicate their association across cohorts and biofluids (serum /plasma). METHODS: We used eight rationally chosen blood-based protein biomarkers as indicators of a latent variable, i.e., "Adipokines". We then associated that construct with dementia severity as measured by the latent dementia-specific phenotype "δ" in structural equation models (SEM). Significant factor loadings and Adipokines' association with δ were replicated across biofluids in the Alzheimer's Disease Neuroimaging Initiative (ADNI). RESULTS: Eight adipokine proteins loaded significantly on the Adipokines construct. Adipokines measured in plasma (ADNI) or serum (TARCC) explained 24 and 70% of δ's variance, respectively. An Adipokine composite score, derived from the latent variables, rose significantly across clinical diagnoses and achieved high areas under the receiver operating characteristic curve (ROC/AUC) for discrimination of Alzheimer's disease from normal controls (NC) or cases of mild cognitive impairment (MCI) and between NC and MCI. CONCLUSION: These results again suggest that SEM can be used to create latent biomarker classifiers that replicate across samples and biofluids, and that a substantial fraction of dementia's variance is attributable to peripheral blood-based protein levels via the patterns codified in those latent constructs.

Effects of White-Matter Tract Length in Sport-Related Concussion: A Tractography Study from the NCAA-DoD CARE Consortium.

Sport-related concussion (SRC) is an important public health issue. White-matter alterations after SRC are widely studied by neuroimaging approaches, such as diffusion magnetic resonance imaging (MRI). Although the exact anatomical location of the alterations may differ, significant white-matter alterations are commonly observed in long fiber tracts, but are never proven. In the present study, we performed streamline tractography to characterize the association between tract length and white-matter microstructural alterations after SRC. Sixty-eight collegiate athletes diagnosed with acute concussion (24-48 h post-injury) and 64 matched contact-sport controls were included in this study. The athletes underwent diffusion tensor imaging (DTI) in 3.0 T MRI scanners across three study sites. DTI metrics were used for tract-based spatial statistics to map white-matter regions-of-interest (ROIs) with significant group differences. Whole-brain white-mater streamline tractography was performed to extract "affected" white-matter streamlines (i.e., streamlines passing through the identified ROIs). In the concussed athletes, streamline counts and DTI metrics of the affected white-matter fiber tracts were summarized and compared with unaffected white-matter tracts across tract length in the same participant. The affected white-matter tracts had a high streamline count at length of 80-100 mm and high length-adjusted affected ratio for streamline length longer than 80 mm. DTI mean diffusivity was higher in the affected streamlines longer than 100 mm with significant associations with the Brief Symptom Inventory score. Our findings suggest that long fibers in the brains of collegiate athletes are more vulnerable to acute SRC with higher mean diffusivity and a higher affected ratio compared with the whole distribution.

Do Head Injury Biomechanics Predict Concussion Clinical Recovery in College American Football Players?

Identifying the associations between head impact biomechanics and clinical recovery may inform better head impact monitoring procedures and identify athletes who may benefit from early treatments aimed to enhance recovery. The purpose of this study was to test whether head injury biomechanics are associated with clinical recovery of symptom severity, balance, and mental status, as well as symptom resolution time (SRT) and return-to-participation (RTP) time. We studied 45 college American football players (n = 51 concussions) who sustained an incident concussion while participating in a multi-site study. Player race/ethnicity, prior concussion, medical history, position, body mass index, event type, and impact location were covariates in our multivariable analyses. Multivariable negative binomial regression models analyzed associations between our study outcomes and (1) injury-causing linear and rotational head impact severity, (2) season repetitive head impact exposure (RHIE), and (3) injury day RHIE. Median SRT was 6.1 days (IQR 5.8 days, n = 45) and median RTP time was 12.3 days (IQR 7.8 days, n = 36) across our study sample. RTP time was 86% (Ratio 1.86, 95% CI [1.05, 3.28]) longer in athletes with a concussion history. Offensive players had SRTs 49% shorter than defensive players (Ratio 0.51, 95% CI [0.29, 0.92]). Per-unit increases in season RHIE were associated with 22% longer SRT (Ratio 1.22, 95% CI [1.09, 1.36]) but 28% shorter RTP time (Ratio 0.72, 95% CI [0.56, 0.93]). No other head injury biomechanics predicted injury recovery.

Concussion Risk Between Individual Football Players: Survival Analysis of Recurrent Events and Non-events.

Concussion tolerance and head impact exposure are highly variable among football players. Recent findings highlight that head impact data analyses need to be performed at the subject level. In this paper, we describe a method of characterizing concussion risk between individuals using a new survival analysis technique developed with real-world head impact data in mind. Our approach addresses the limitations and challenges seen in previous risk analyses of football head impact data. Specifically, this demonstrative analysis appropriately models risk for a combination of left-censored recurrent events (concussions) and right-censored recurrent non-events (head impacts without concussion). Furthermore, the analysis accounts for uneven impact sampling between players. In brief, we propose using the Consistent Threshold method to develop subject-specific risk curves and then determine average risk point estimates between subjects at injurious magnitude values. We describe an approach for selecting an optimal cumulative distribution function to model risk between subjects by minimizing injury prediction error. We illustrate that small differences in distribution fit can result in large predictive errors. Given the vast amounts of on-field data researchers are collecting across sports, this approach can be applied to develop population-specific risk curves that can ultimately inform interventions that reduce concussion incidence.

Academic aptitude mediates the relationship between socioeconomic status and race in predicting ImPACT scores in college athletes.

Objective: To evaluate the influences of sociodemographic factors, estimated head impact exposure, and academic aptitude on ImPACT scores in college athletes.Methods: Data were reported on 18,886 participants (58% male) from the NCAA/DoD CARE Consortium. Race, SES, concussion history, estimated repetitive head impact exposure (eRHIE), and academic aptitude (SAT or ACT score) were our predictors of interest. Cognition was measured using ImPACT composite scores. We evaluated the mediating effects of academic aptitude on sociodemographic predictors and eRHIE on ImPACT scores. We then evaluated a football-only subsample and added age of first exposure to football (AFE) to the model. Males, females, and football players were analyzed separately using structural equation modeling.Results: Academic aptitude was associated with Black/African American race, SES, and each of the ImPACT composite scores. There were significant indirect effects of Black/African American race and SES on all ImPACT composite scores. Academic aptitude fully mediated SES effects and either fully or partially mediated race effects. Contrary to expectation, greater concussion history and eRHIE predicted better ImPACT scores.Conclusions: Academic aptitude, a stable indicator of premorbid cognitive function, consistently and most strongly predicted baseline ImPACT scores in collegiate student-athletes. Concussion and eRHIE history demonstrated a small positive, but non-significant, relationship with cognitive scores at the time of college athletic participation. This study suggests that attempts to characterize cognitive ability across the lifespan must consider premorbid functioning and sociodemographic variables.

Bifactor Model of the Sport Concussion Assessment Tool Symptom Checklist: Replication and Invariance Across Time in the CARE Consortium Sample.

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 <6 hours and 24 to 48 hours after concussion. Item-level SCAT-3 ratings were analyzed using exploratory and confirmatory factor analyses. Bifactor and higher-order models were compared for their fit and interpretability. Measurement invariance tested the stability of the identified factor structure across time. The association between factors and criterion measures (clinical and blood-based markers of concussion severity, symptom duration) was evaluated. RESULTS: The optimal structure for each time point was a 7-factor bifactor model: a General factor, on which all items loaded, and 6 specific factors-Vestibulo-ocular, Headache, Sensory, Fatigue, Cognitive, and Emotional. The model manifested strict invariance across the 2 postinjury time points but only configural invariance from baseline to postinjury. From <6 to 24-48 hours, some dimensions increased in severity (Sensory, Fatigue, Emotional), while others decreased (General, Headache, Vestibulo-ocular). The factors correlated with differing clinical and biomarker criterion measures and showed differing patterns of association with symptom duration at different time points. CONCLUSION: Bifactor modeling supported the predominant unidimensionality of concussion symptoms while revealing multidimensional properties, including a large dominant General factor and 6 independent factors: Headache, Vestibulo-ocular, Sensory, Cognitive, Fatigue, and Emotional. Unlike the widely used SCAT-3 symptom severity score, which declines gradually after injury, the bifactor model revealed separable symptom dimensions that have distinct trajectories in the acute postinjury period and different patterns of association with other markers of injury severity and outcome. CLINICAL RELEVANCE: The SCAT-3 total score remains a valuable, robust index of overall concussion symptom severity, and the specific factors identified may inform management strategies. Because some symptom dimensions continue to worsen in the first 24 to 48 hours after injury (ie, Sensory, Fatigue, Emotional), routine follow-up in this time frame may be valuable to ensure that symptoms are managed effectively.

Cumulative Effects of Prior Concussion and Primary Sport Participation on Brain Morphometry in Collegiate Athletes: A Study From the NCAA-DoD CARE Consortium.

Prior studies have reported long-term differences in brain structure (brain morphometry) as being associated with cumulative concussion and contact sport participation. There is emerging evidence to suggest that similar effects of prior concussion and contact sport participation on brain morphometry may be present in younger cohorts of active athletes. We investigated the relationship between prior concussion and primary sport participation with subcortical and cortical structures in active collegiate contact sport and non-contact sport athletes. Contact sport athletes (CS; N = 190) and matched non-contact sport athletes (NCS; N = 95) completed baseline clinical testing and participated in up to four serial neuroimaging sessions across a 6-months period. Subcortical and cortical structural metrics were derived using FreeSurfer. Linear mixed-effects (LME) models examined the effects of years of primary sport participation and prior concussion (0, 1+) on brain structure and baseline clinical variables. Athletes with prior concussion across both groups reported significantly more baseline concussion and psychological symptoms (all ps < 0.05). The relationship between years of primary sport participation and thalamic volume differed between CS and NCS (p = 0.015), driven by a significant inverse association between primary years of participation and thalamic volume in CS (p = 0.007). Additional analyses limited to CS alone showed that the relationship between years of primary sport participation and dorsal striatal volume was moderated by concussion history (p = 0.042). Finally, CS with prior concussion had larger hippocampal volumes than CS without prior concussion (p = 0.015). Years of contact sport exposure and prior concussion(s) are associated with differences in subcortical volumes in young-adult, active collegiate athletes, consistent with prior literature in retired, primarily symptomatic contact sport athletes. Longitudinal follow-up studies in these athletes are needed to determine clinical significance of current findings.

Validation of prognostic models in intensive care unit-treated pediatric traumatic brain injury patients.

OBJECTIVE: There are few specific prognostic models specifically developed for the pediatric traumatic brain injury (TBI) population. In the present study, the authors tested the predictive performance of existing prognostic tools, originally developed for the adult TBI population, in pediatric TBI patients requiring stays in the ICU. METHODS: The authors used the Finnish Intensive Care Consortium database to identify pediatric patients (< 18 years of age) treated in 4 academic ICUs in Finland between 2003 and 2013. They tested the predictive performance of 4 classification systems-the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) TBI model, the Helsinki CT score, the Rotterdam CT score, and the Marshall CT classification-by assessing the area under the receiver operating characteristic curve (AUC) and the explanatory variation (pseudo-R2 statistic). The primary outcome was 6-month functional outcome (favorable outcome defined as a Glasgow Outcome Scale score of 4-5). RESULTS: Overall, 341 patients (median age 14 years) were included; of these, 291 patients had primary head CT scans available. The IMPACT core-based model showed an AUC of 0.85 (95% CI 0.78-0.91) and a pseudo-R2 value of 0.40. Of the CT scoring systems, the Helsinki CT score displayed the highest performance (AUC 0.84, 95% CI 0.78-0.90; pseudo-R2 0.39) followed by the Rotterdam CT score (AUC 0.80, 95% CI 0.73-0.86; pseudo-R2 0.34). CONCLUSIONS: Prognostic tools originally developed for the adult TBI population seemed to perform well in pediatric TBI. Of the tested CT scoring systems, the Helsinki CT score yielded the highest predictive value.

Immediate Removal From Activity After Sport-Related Concussion Is Associated With Shorter Clinical Recovery and Less Severe Symptoms in Collegiate Student-Athletes.

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

Ellis van Creveld syndrome in a Tunisian child revealed by an Eisenmenger syndrome.

Ellis-van Creveld syndrome (EvC) is an autosomal recessive inherited disease resulting from mutations in EVC1 or EVC2. Patients with this condition normally have chondrodysplasia, postaxial polydactyly, ectodermal dysplasia and congenital heart defects. We report the case of a 13-year-old Tunisian child who was admitted for cyanosis and acute heart failure. On clinical examination, he presented with typical features of EvC, cyanosis and dyspnea. EvC was confirmed by genetic tests, and echocardiography showed a partial atrioventricular canal defect with supra-systemic pulmonary artery pressure. The patient was treated; however, the evolution was fatal.

A genetic association study of D-dimer levels with 50K SNPs from a candidate gene chip in four ethnic groups.

INTRODUCTION: D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations. MATERIALS AND METHODS: We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis. RESULTS: Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p<2.0×10(-6). The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p=0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p=0.006). No additional SNPs were significantly associated with D-dimer. CONCLUSIONS: Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.