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Introduction: There is significant unexplained variability in behavioral and executive functioning after pediatric traumatic brain injury (TBI). Prior research indicates that there are likely genetic contributions; however, current research is limited. The purpose of this study is to use a systems biology informed approach to characterize the genomic signature related to behavioral and executive functioning ~12 months after moderate through severe TBI in children. Methods: Participants were from two prospective cohorts of children with severe TBI (Cohort #1) and moderate-severe TBI and an orthopedic injury (OI) group (Cohort #2). Participants included 196 children (n = 72 and n = 124 total from each respective cohort), ranging in age between 0--17 years at the time of injury. In total, 86 children had severe TBI, 49 had moderate TBI, and 61 had an OI. Global behavioral functioning assessed via the Child Behavior Checklist and executive function assessed via the Behavioral Rating Inventory of Executive Function at ~ 12 months post injury served as outcomes. To test for a genomic signature, we compared the number of nominally significant (p < 0.05) polymorphisms associated with the outcomes in our systems biology identified genes to a set 10,000 permutations using control genes (e.g., not implicated by systems biology). We used the ToppFun application from Toppgene Suite to identify enriched biologic processes likely to be associated with behavioral and executive function outcomes. Results: At 12 months post injury, injury type (TBI vs OI) by polymorphism interaction was significantly enriched in systems biology selected genes for behavioral and executive function outcomes, suggesting these genes form a genomic signature. Effect sizes of the associations from our genes of interest ranged from .2--.5 for the top 5% of variants. Systems biology analysis of the variants associated with the top 5% effect sizes indicated enrichment in several specific biologic processes and systems. Discussion: Findings indicate that a genomic signature may explain heterogeneity of behavioral and executive outcomes after moderate and severe TBI. This work provides the foundation for constructing genomic signatures and integrating systems biology and genetic information into future recovery, prognostic, and treatment algorithms. [ABSTRACT FROM AUTHOR]

Objective: To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation. Setting: Inpatient pediatric rehabilitation. Participants: In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission. Design: Multicenter, retrospective medical record review. Main Measure(s): Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day). Results: Patients who received MPH were older (P =.011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P =.001) and at discharge (P =.030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported. Conclusion: This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored. [ABSTRACT FROM AUTHOR]

Through automated electronic health record (EHR) data extraction and analysis, this project systematically quantified actual care delivery for children with cerebral palsy (CP) and evaluated alignment with current evidence-based recommendations. Utilizing EHR data for over 8000 children with CP, we developed an approach to define and quantify receipt of optimal care, and pursued proof-of-concept with two children with unilateral CP, Gross Motor Function Classification System (GMFCS) Level II. Optimal care was codified as a cluster of four components including physical medicine and rehabilitation (PMR) care, spasticity management, physical therapy (PT), and occupational therapy (OT). A Receipt of Care Score (ROCS) quantified the degree of adherence to recommendations and was compared with the Pediatric Outcomes Data Collection Instrument (PODCI) and Pediatric Quality of Life Inventory (PEDS QL). The two children (12 year old female, 13 year old male) had nearly identical PMR and spasticity component scores while PT and OT scores were more divergent. Functional outcomes were higher for the child who had higher adjusted ROCS. ROCSs demonstrate variation in real-world care delivered over time and differentiate between components of care. ROCSs reflect overall function and quality of life. The ROCS methods developed are novel, robust, and scalable and will be tested in a larger sample. Optimal practice, with an emphasis on integrated multidisciplinary care, can be defined and quantified utilizing evidence-based recommendations. Receipt of optimal care for childhood cerebral palsy can be scored using existing electronic health record data. Big Data approaches can contribute to the understanding of current care and inform approaches for improved care. [ABSTRACT FROM AUTHOR]

Objective: The present study examined the differential effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on neuropsychological functioning in children with traumatic brain injury (TBI) relative to orthopedic injury (OI). Methods: Participants were drawn from a prospective, longitudinal study of children who sustained a TBI (n = 69) or OI (n = 72) between 3 and 7 years of age. Children completed a battery of neuropsychological measures targeting attention, memory, and executive functions at four timepoints spanning the immediate post-acute period to 18 months post-injury. Children also completed a comparable age-appropriate battery of measures approximately 7 years post-injury. Parents rated children's dysexecutive behaviors at all timepoints. Results: Longitudinal mixed models revealed a significant allele status × injury group interaction with a medium effect size for verbal fluency. Cross-sectional models at 7 years post-injury revealed non-significant but medium effect sizes for the allele status x injury group interaction for fluid reasoning and immediate and delayed verbal memory. Post hoc stratified analyses revealed a consistent pattern of poorer neuropsychological functioning in Met carriers relative to Val/Val homozygotes in the TBI group, with small effect sizes; the opposite trend or no appreciable effect was observed in the OI group. Conclusions: The results suggest a differential effect of the BDNF Val66Met polymorphism on verbal fluency, and possibly fluid reasoning and immediate and delayed verbal memory, in children with early TBI relative to OI. The Met allele—associated with reduced activity-dependent secretion of BDNF—may confer risk for poorer neuropsychological functioning in children with TBI. [ABSTRACT FROM AUTHOR]

Aim: To predict ambulatory status and Gross Motor Function Classification System (GMFCS) levels in patients with cerebral palsy (CP) by applying natural language processing (NLP) to electronic health record (EHR) clinical notes. Method: Individuals aged 8 to 26 years with a diagnosis of CP in the EHR between January 2009 and November 2020 (~12 years of data) were included in a cross‐sectional retrospective cohort of 2483 patients. The cohort was divided into train‐test and validation groups. Positive predictive value, sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated for prediction of ambulatory status and GMFCS levels. Results: The median age was 15 years (interquartile range 10–20 years) for the total cohort, with 56% being male and 75% White. The validation group resulted in 70% sensitivity, 88% specificity, 81% positive predictive value, and 0.89 AUC for predicting ambulatory status. NLP applied to the EHR differentiated between GMFCS levels I–II and III (15% sensitivity, 96% specificity, 46% positive predictive value, and 0.71 AUC); and IV and V (81% sensitivity, 51% specificity, 70% positive predictive value, and 0.75 AUC). Interpretation: NLP applied to the EHR demonstrated excellent differentiation between ambulatory and non‐ambulatory status, and good differentiation between GMFCS levels I–II and III, and IV and V. Clinical use of NLP may help to individualize functional characterization and management. What this paper adds: Natural language processing (NLP) applied to the electronic health record (EHR) can predict ambulatory status in children with cerebral palsy (CP).NLP provides good prediction of Gross Motor Function Classification System level in children with CP using the EHR.NLP methods described could be integrated in an EHR system to provide real‐time information. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Congress on the Management of Traumatic Brain Injury (TBI) showing the management of TBI in children as an important public health issue. Topics include TBI during childhood, changes in health, cognition, family environment, and behavior affecting learning, self-regulation, and social participation; and effects of TBI evolve beyond the initial injury period, requiring ongoing screening, prevention.