HDX-MS performed on BtuB in E. coli outer membranes delineates the luminal domain's allostery and unfolding upon B12 and TonB binding.

To import large metabolites across the outer membrane of gram-negative bacteria, TonB-dependent transporters (TBDTs) undergo significant conformational change. After substrate binding in BtuB, the Escherichia coli vitamin B12 TBDT, TonB binds and couples BtuB to the inner-membrane proton motive force that powers transport [N. Noinaj, M. Guillier, T. J. Barnard, S. K. Buchanan, Annu. Rev. Microbiol. 64, 43­60 (2010)]. However, the role of TonB in rearranging the plug domain of BtuB to form a putative pore remains enigmatic. Some studies focus on force-mediated unfolding [S. J. Hickman, R. E. M. Cooper, L. Bellucci, E. Paci, D. J. Brockwell, Nat. Commun. 8, 14804 (2017)], while others propose force-independent pore formation by TonB binding [T. D. Nilaweera, D. A. Nyenhuis, D. S. Cafiso, eLife 10, e68548 (2021)], leading to breakage of a salt bridge termed the "Ionic Lock." Our hydrogen­deuterium exchange/mass spectrometry (HDX-MS) measurements in E. coli outer membranes find that the region surrounding the Ionic Lock, far from the B12 site, is fully destabilized upon substrate binding. A comparison of the exchange between the B12-bound and the B12+TonB­bound complexes indicates that B12 binding is sufficient to unfold the Ionic Lock region, with the subsequent binding of a TonB fragment having much weaker effects. TonB binding accelerates exchange in the third substrate-binding loop, but pore formation does not obviously occur in this or any region. This study provides a detailed structural and energetic description of the early stages of B12 passage that provides support both for and against current models of the transport process.

Clinical Practice Guideline Recommendations in Pediatric Mild Traumatic Brain Injury: A Systematic Review.

STUDY OBJECTIVE: Our primary objectives were to identify clinical practice guideline recommendations for children with acute mild traumatic brain injury (mTBI) presenting to an emergency department (ED), appraise their overall quality, and synthesize the quality of evidence and the strength of included recommendations. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and medical association websites from January 2012 to May 2023 for clinical practice guidelines with at least 1 recommendation targeting pediatric mTBI populations presenting to the ED within 48 hours of injury for any diagnostic or therapeutic intervention in the acute phase of care (ED and inhospital). Pairs of reviewers independently assessed overall clinical practice guideline quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The quality of evidence on recommendations was synthesized using a matrix based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework. RESULTS: We included 11 clinical practice guidelines, of which 6 (55%) were rated high quality. These included 101 recommendations, of which 34 (34%) were based on moderate- to high-quality evidence, covering initial assessment, initial diagnostic imaging, monitoring/observation, therapeutic interventions, discharge advice, follow-up, and patient and family support. We did not identify any evidence-based recommendations in high-quality clinical practice guidelines for repeat imaging, neurosurgical consultation, or hospital admission. Lack of strategies and tools to aid implementation and editorial independence were the most common methodological weaknesses. CONCLUSIONS: We identified 34 recommendations based on moderate- to high-quality evidence that may be considered for implementation in clinical settings. Our review highlights important areas for future research. This review also underlines the importance of providing strategies to facilitate the implementation of clinical practice guideline recommendations for pediatric mTBI.

Folding and misfolding of potassium channel monomers during assembly and tetramerization.

The dynamics and folding of potassium channel pore domain monomers are connected to the kinetics of tetramer assembly. In all-atom molecular dynamics simulations of Kv1.2 and KcsA channels, monomers adopt multiple nonnative conformations while the three helices remain folded. Consistent with this picture, NMR studies also find the monomers to be dynamic and structurally heterogeneous. However, a KcsA construct with a disulfide bridge engineered between the two transmembrane helices has an NMR spectrum with well-dispersed peaks, suggesting that the monomer can be locked into a native-like conformation that is similar to that observed in the folded tetramer. During tetramerization, fluoresence resonance energy transfer (FRET) data indicate that monomers rapidly oligomerize upon insertion into liposomes, likely forming a protein-dense region. Folding within this region occurs along separate fast and slow routes, with τfold ∼40 and 1,500 s, respectively. In contrast, constructs bearing the disulfide bond mainly fold via the faster pathway, suggesting that maintaining the transmembrane helices in their native orientation reduces misfolding. Interestingly, folding is concentration independent despite the tetrameric nature of the channel, indicating that the rate-limiting step is unimolecular and occurs after monomer association in the protein-dense region. We propose that the rapid formation of protein-dense regions may help with the assembly of multimeric membrane proteins by bringing together the nascent components prior to assembly. Finally, despite its name, the addition of KcsA's C-terminal "tetramerization" domain does not hasten the kinetics of tetramerization.

Exploring the challenges of avoiding collisions with virtual pedestrians using a dual-task paradigm in individuals with chronic moderate to severe traumatic brain injury.

BACKGROUND: Individuals with a moderate-to-severe traumatic brain injury (m/sTBI), despite experiencing good locomotor recovery six months post-injury, face challenges in adapting their locomotion to the environment. They also present with altered cognitive functions, which may impact dual-task walking abilities. Whether they present collision avoidance strategies with moving pedestrians that are altered under dual-task conditions, however, remains unclear. This study aimed to compare between individuals with m/sTBI and age-matched control individuals: (1), the locomotor and cognitive costs associated with the concurrent performance of circumventing approaching virtual pedestrians (VRPs) while attending to an auditory-based cognitive task and; (2) gaze behaviour associated with the VRP circumvention task in single and dual-task conditions. METHODOLOGY: Twelve individuals with m/sTBI (age = 43.3 ± 9.5 yrs; >6 mo. post injury) and 12 healthy controls (CTLs) (age = 41.8 ± 8.3 yrs) were assessed while walking in a virtual subway station viewed in a head-mounted display. They performed a collision avoidance task with VRPs, as well as auditory-based cognitive tasks (pitch discrimination and auditory Stroop), both under single and dual-task conditions. Dual-task cost (DTC) for onset distance of trajectory deviation, minimum distance from the VRP, maximum lateral deviation, walking speed, gaze fixations and cognitive task accuracy were contrasted between groups using generalized estimating equations. RESULTS: In contrast to CTLs who showed locomotor DTCs only, individuals with m/sTBI displayed both locomotor and cognitive DTCs. While both groups walked slower under dual-task conditions, only individuals with m/sTBI failed to modify their onset distance of trajectory deviation and maintained smaller minimum distances and smaller maximum lateral deviation compared to single-task walking. Both groups showed shorter gaze fixations on the approaching VRP under dual-task conditions, but this reduction was less pronounced in the individuals with m/sTBI. A reduction in cognitive task accuracy under dual-task conditions was found in the m/sTBI group only. CONCLUSION: Individuals with m/sTBI present altered locomotor and gaze behaviours, as well as altered cognitive performances, when executing a collision avoidance task involving moving pedestrians in dual-task conditions. Potential mechanisms explaining those alterations are discussed. Present findings highlight the compromised complex walking abilities in individuals with m/sTBI who otherwise present a good locomotor recovery.

Navigating the healthcare system with my child with CHD: parental perspectives on developmental follow-up practices.

BACKGROUND: Parents of children with CHD face several barriers when trying to access the services needed to support their child's development. In fact, current developmental follow-up practices may not identify developmental challenges in a timely manner and important opportunities for interventions may be lost. This study aimed to explore the perspectives of parents of children and adolescents with CHD with respect to developmental follow-up in Canada. METHODS: Interpretive description was used as a methodological approach for this qualitative study. Parents of children aged 5-15 years with complex CHD were eligible. Semi-structured interviews that aimed to explore their perspectives regarding their child's developmental follow-up were conducted. RESULTS: Fifteen parents of children with CHD were recruited for this study. They expressed that the lack of systematic and responsive developmental follow-up services and limited access to resources to support their child's development placed an undue burden on their families, and as a result, they needed to assume new roles as case managers or advocates to address these limitations. This additional burden resulted in a high level of parental stress, which, in turn, affected the parent-child relationship and siblings. CONCLUSIONS: The limitations of the current Canadian developmental follow-up practices put undue pressure on the parents of children with complex CHD. The parents stressed the importance of implementing a universal and systematic approach to developmental follow-up to allow for the timely identification of challenges, enabling the initiation of interventions and supports and promoting more positive parent-child relationships.

Clinical Practice Guideline Recommendations For Pediatric Multisystem Trauma Care: A Systematic Review.

OBJECTIVE: To systematically review clinical practice guidelines (CPGs) for pediatric multisystem trauma, appraise their quality, synthesize the strength of recommendations and quality of evidence, and identify knowledge gaps. BACKGROUND: Traumatic injuries are the leading cause of death and disability in children, who require a specific approach to injury care. Difficulties integrating CPG recommendations may cause observed practice and outcome variation in pediatric trauma care. METHODS: We conducted a systematic review using Medline, Embase, Cochrane Library, Web of Science, ClinicalTrials, and grey literature, from January 2007 to November 2022. We included CPGs targeting pediatric multisystem trauma with recommendations on any acute care diagnostic or therapeutic interventions. Pairs of reviewers independently screened articles, extracted data, and evaluated the quality of CPGs using "Appraisal of Guidelines, Research, and Evaluation II." RESULTS: We reviewed 19 CPGs, and 11 were considered high quality. Lack of stakeholder engagement and implementation strategies were weaknesses in guideline development. We extracted 64 recommendations: 6 (9%) on trauma readiness and patient transfer, 24 (38%) on resuscitation, 22 (34%) on diagnostic imaging, 3 (5%) on pain management, 6 (9%) on ongoing inpatient care, and 3 (5%) on patient and family support. Forty-two (66%) recommendations were strong or moderate, but only 5 (8%) were based on high-quality evidence. We did not identify recommendations on trauma survey assessment, spinal motion restriction, inpatient rehabilitation, mental health management, or discharge planning. CONCLUSIONS: We identified 5 recommendations for pediatric multisystem trauma with high-quality evidence. Organizations could improve CPGs by engaging all relevant stakeholders and considering barriers to implementation. There is a need for robust pediatric trauma research, to support recommendations.

"What If?": Caregivers' Experiences Following Early Childhood Concussion.

OBJECTIVE: Little is known about the symptoms, signs, and management guidelines for children under the age of 6 years after they sustain a concussion. Caregivers of such young children may have unique concerns and encounter different challenges from those of school-age children given the distinctive developmental characteristics of the early childhood period. This study aimed to explore the experience of caregivers through semistructured interviews to inform clinical practice. METHODS: Fifty caregivers of children aged 6 months to 5.99 years were interviewed 3 months postinjury for this qualitative study to document their experience in relation to their child's accident, recovery, and healthcare provisions. RESULTS: Four main themes were identified: (1) visible changes associated with caregiver concerns, (2) a roller-coaster of emotions after the injury, (3) healthcare providers' role in addressing the need for reassurance, and (4) the need for better information after the injury. CONCLUSION: The findings provide critical insight into the unique experiences and information needs of caregivers of young children who sustain concussion. The challenges identified can inform healthcare professionals regarding the needs of caregivers after early concussion and contribute to building a knowledge base for the development of age-appropriate anticipatory guidance for caregiver mental health and child recovery.

Altered Oculomotor and Vestibulo-ocular Function in Children and Adolescents Postconcussion.

OBJECTIVE: To document (1) oculomotor (OM) and vestibulo-ocular (VO) function in children with concussion who were symptomatic at the time of assessment and to compare it with that in children with concussion who were clinically recovered (asymptomatic) and in children with no concussive injury, and (2) the extent to which OM and VO function relates to postconcussion symptom severity in injured children. SETTING: Participants were recruited from a concussion clinic or the community. PARTICIPANTS: A total of 108 youth with concussion (72 symptomatic; 36 recovered) and 79 healthy youth (aged 9-18 years). Youth with concussion were included if aged 9 to 18 years, had no previous concussion within the last 12 months, less than 90 days since injury, and no known existing visual disorders or learning disabilities. STUDY DESIGN: A prospective cross-sectional study. MAIN MEASURES: All participants were tested for OM and VO function with a commercial virtual reality (VR) eye-tracking system (Neuroflex®, Montreal,Québec, Canada). Participants in the concussion group who completed the postconcussion symptoms were scored with the Post-Concussion Symptom Inventory. RESULTS: There was a significant group effect for vergence during smooth pursuit (F2,176 = 10.90; P < .05), mean latency during saccades (F2,171 = 5.99; P = .003), and mean response delay during antisaccades (F2,177 = 9.07; P < .05), where children with symptomatic concussion showed poorer performance than clinically recovered and healthy children. Similar results were found in VO for average vestibular ocular reflex gain in the horizontal leftward (F2,168 = 7; P = .001) and rightward directions (F2,163 = 13.08; P < .05) and vertical upward (F2,147 = 7.60; P = .001) and downward directions (F2,144 = 13.70; P < .05). Mean saccade error was positively correlated to total Post-Concussion Symptom Inventory scores in younger clinically recovered children. CONCLUSION: VR eye tracking may be an effective tool for identifying OM and VO deficits in the subacute phase (<90 days) postconcussion.

Behavioral-play familiarization for non-sedated magnetic resonance imaging in young children with mild traumatic brain injury.

BACKGROUND: Mild traumatic brain injury (mTBI) sustained in early childhood affects the brain at a peak developmental period and may disrupt sensitive stages of skill acquisition, thereby compromising child functioning. However, due to the challenges of collecting non-sedated neuroimaging data in young children, the consequences of mTBI on young children's brains have not been systematically studied. In typically developing preschool children (of age 3-5years), a brief behavioral-play familiarization provides an effective alternative to sedation for acquiring awake magnetic resonance imaging (MRI) in a time- and resource-efficient manner. To date, no study has applied such an approach for acquiring non-sedated MRI in preschool children with mTBI who may present with additional MRI acquisition challenges such as agitation or anxiety. OBJECTIVE: The present study aimed to compare the effectiveness of a brief behavioral-play familiarization for acquiring non-sedated MRI for research purposes between young children with and without mTBI, and to identify factors associated with successful MRI acquisition. MATERIALS AND METHODS: Preschool children with mTBI (n=13) and typically developing children (n=24) underwent a 15-minutes behavioral-play MRI familiarization followed by a 35-minutes non-sedated MRI protocol. Success rate was compared between groups, MRI quality was assessed quantitatively, and factors predicting success were documented. RESULTS: Among the 37 participants, 15 typically developing children (63%) and 10 mTBI (77%) reached the MRI acquisition success criteria (i.e., completing the two first sequences). The success rate was not significantly different between groups (p=.48; 95% CI [-0.36 14.08]; Cramer's V=.15). The images acquired were of high-quality in 100% (for both groups) of the structural images, and 60% (for both groups) of the diffusion images. Factors associated with success included older child age (Β=0.73, p=.007, exp(B)=3.11, 95% CI [1.36 7.08]) and fewer parental concerns (Β=-1.56, p=.02, exp(Β)=0.21, 95% CI [0.05 0.82]) about the MRI procedure. CONCLUSION: Using brief behavioral-play familiarization allows acquisition of high-quality non-sedated MRI in young children with mTBI with success rates comparable to those of non-injured peers.

Rest and exercise early after sport-related concussion: a systematic review and meta-analysis.

OBJECTIVE: To synthesise the evidence regarding the risks and benefits of physical activity (PA), prescribed aerobic exercise treatment, rest, cognitive activity and sleep during the first 14 days after sport-related concussion (SRC). DESIGN: Meta-analysis was performed for PA/prescribed exercise interventions and a narrative synthesis for rest, cognitive activity and sleep. Risk of bias (ROB) was determined using the Scottish Intercollegiate Guidelines Network and quality assessed using Grading of Recommendations, Assessment, Development and Evaluations. DATA SOURCES: MEDLINE, Embase, APA PsycInfo, Cochrane Central Register of Controlled Trials, CINAHL Plus and SPORTDiscus. Searches were conducted in October 2019 and updated in March 2022. ELIGIBILITY CRITERIA: Original research articles with sport-related mechanism of injury in >50% of study sample and that evaluated how PA, prescribed exercise, rest, cognitive activity and/or sleep impact recovery following SRC. Reviews, conference proceedings, commentaries, editorials, case series, animal studies and articles published before 1 January 2001 were excluded. RESULTS: 46 studies were included and 34 had acceptable/low ROB. Prescribed exercise was assessed in 21 studies, PA in 15 studies (6 PA/exercise studies also assessed cognitive activity), 2 assessed cognitive activity only and 9 assessed sleep. In a meta-analysis of seven studies, PA and prescribed exercise improved recovery by a mean of -4.64 days (95% CI -6.69, -2.59). After SRC, early return to light PA (initial 2 days), prescribed aerobic exercise treatment (days 2-14) and reduced screen use (initial 2 days) safely facilitate recovery. Early prescribed aerobic exercise also reduces delayed recovery, and sleep disturbance is associated with slower recovery. CONCLUSION: Early PA, prescribed aerobic exercise and reduced screen time are beneficial following SRC. Strict physical rest until symptom resolution is not effective, and sleep disturbance impairs recovery after SRC. PROSPERO REGISTRATION NUMBER: CRD42020158928.

What tests and measures accurately diagnose persisting post-concussive symptoms in children, adolescents and adults following sport-related concussion? A systematic review.

OBJECTIVE: To determine what tests and measures accurately diagnose persisting post-concussive symptoms (PPCS) in children, adolescents and adults following sport-related concussion (SRC). DESIGN: A systematic literature review. DATA SOURCES: MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL and SPORTDiscus through March 2022. ELIGIBILITY CRITERIA: Original, empirical, peer-reviewed findings (cohort studies, case-control studies, cross-sectional studies and case series) published in English and focused on SRC. Studies needed to compare individuals with PPCS to a comparison group or their own baseline prior to concussion, on tests or measures potentially affected by concussion or associated with PPCS. RESULTS: Of 3298 records screened, 26 articles were included in the qualitative synthesis, including 1016 participants with concussion and 531 in comparison groups; 7 studies involved adults, 8 involved children and adolescents and 11 spanned both age groups. No studies focused on diagnostic accuracy. Studies were heterogeneous in participant characteristics, definitions of concussion and PPCS, timing of assessment and the tests and measures examined. Some studies found differences between individuals with PPCS and comparison groups or their own pre-injury assessments, but definitive conclusions were not possible because most studies had small convenience samples, cross-sectional designs and were rated high risk of bias. CONCLUSION: The diagnosis of PPCS continues to rely on symptom report, preferably using standardised symptom rating scales. The existing research does not indicate that any other specific tool or measure has satisfactory accuracy for clinical diagnosis. Future research drawing on prospective, longitudinal cohort studies could help inform clinical practice.

Targeted interventions and their effect on recovery in children, adolescents and adults who have sustained a sport-related concussion: a systematic review.

OBJECTIVES: We evaluated interventions to facilitate recovery in children, adolescents and adults with a sport-related concussion (SRC). DESIGN: Systematic review including risk of bias (modified Scottish Intercollegiate Guidelines Network tool). DATA SOURCES: MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, APA PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL Plus with Full Text, SPORTDiscus and Scopus searched until March 2022. STUDY ELIGIBILITY CRITERIA: (1) Original research including randomised controlled trials (RCTs), quasi-experimental designs, cohort, comparative effectiveness studies; (2) focus on SRC; (3) English; (4) peer-reviewed and (5) evaluated treatment. RESULTS: 6533 studies were screened, 154 full texts reviewed and 13 met inclusion (10 RCTs, 1 quasi-experimental and 2 cohort studies; 1 high-quality study, 7 acceptable and 5 at high risk of bias). Interventions, comparisons, timing and outcomes varied, precluding meta-analysis. For adolescents and adults with dizziness, neck pain and/or headaches >10 days following concussion, individualised cervicovestibular rehabilitation may decrease time to return to sport compared with rest followed by gradual exertion (HR 3.91 (95% CI 1.34 to 11.34)) and when compared with a subtherapeutic intervention (HR 2.91 (95% CI 1.01 to 8.43)). For adolescents with vestibular symptoms/impairments, vestibular rehabilitation may decrease time to medical clearance (vestibular rehab group 50.2 days (95% CI 39.9 to 60.4) compared with control 58.4 (95% CI 41.7 to 75.3) days). For adolescents with persisting symptoms >30 days, active rehabilitation and collaborative care may decrease symptoms. CONCLUSIONS: Cervicovestibular rehabilitation is recommended for adolescents and adults with dizziness, neck pain and/or headaches for >10 days. Vestibular rehabilitation (for adolescents with dizziness/vestibular impairments >5 days) and active rehabilitation and/or collaborative care (for adolescents with persisting symptoms >30 days) may be of benefit.

Identifying developmental challenges of youth with congenital heart defects: A patient-oriented perspective.

BACKGROUND: Youth with congenital heart disease (CHD) are at high risk for a range of developmental impairments that become evident at different times across childhood and adolescence. This study aimed to explore perspectives of youth with CHD with respect to their developmental follow-up across childhood. METHODS: Interpretive description was used as a methodological approach for this qualitative study. Youth aged 12-22 years with CHD requiring open-heart surgery before 2 years of age and who had received health services in Canada since birth were enrolled. RESULTS: Ten youth with CHD, two males and eight females, aged 13-22 years (mean 19.8) participated in this study. With higher social and academic demands as well as increased level of autonomy associated with older age, some youth faced new challenges that they had not encountered as children. Youth with CHD identified four aspects of the continuum of care as needing to be changed to better respond to their needs. First, the format of developmental follow-up needs to be adapted to their unique challenges. Second, resources must be more easily accessible throughout childhood and adolescence. Third, planning for transition to adult care is essential to ensure continuity of services. Finally, they identified that the school system is an essential component of the continuum of care. CONCLUSIONS: Adolescents and young adults with CHD are at high risk of developing physical, academic and psychosocial challenges; however, timely identification of challenges does not appear to be optimal across domains and transition points, from the perspective of the youth themselves. Youth with CHD reported not having the resources and supports they required to optimize their functioning. Our findings suggest that several approaches could be adopted to enhance identification and outcomes to address the limitations of current Canadian practices.

Clinical Practice Guideline Recommendations in Pediatric Orthopaedic Injury: A Systematic Review.

BACKGROUND: Lack of adherence to recommendations on pediatric orthopaedic injury care may be driven by lack of knowledge of clinical practice guidelines (CPGs), heterogeneity in recommendations or concerns about their quality. We aimed to identify CPGs for pediatric orthopaedic injury care, appraise their quality, and synthesize the quality of evidence and the strength of associated recommendations. METHODS: We searched Medline, Embase, Cochrane CENTRAL, Web of Science and websites of clinical organizations. CPGs including at least one recommendation targeting pediatric orthopaedic injury populations on any diagnostic or therapeutic intervention developed in the last 15 years were eligible. Pairs of reviewers independently extracted data and evaluated CPG quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. We synthesized recommendations from high-quality CPGs using a recommendations matrix based on the GRADE Evidence-to-Decision framework. RESULTS: We included 13 eligible CPGs, of which 7 were rated high quality. Lack of stakeholder involvement and applicability (i.e., implementation strategies) were identified as weaknesses. We extracted 53 recommendations of which 19 were based on moderate or high-quality evidence. CONCLUSIONS: We provide a synthesis of recommendations from high-quality CPGs that can be used by clinicians to guide treatment decisions. Future CPGs should aim to use a partnership approach with all key stakeholders and provide strategies to facilitate implementation. This study also highlights the need for more rigorous research on pediatric orthopaedic trauma. LEVEL OF EVIDENCE: Level II-therapeutic study.

Report of Early Childhood Traumatic Injury Observations & Symptoms: Preliminary Validation of an Observational Measure of Postconcussive Symptoms.

OBJECTIVE: To report preliminary empirical data on a novel, developmentally appropriate, observational postconcussive symptoms inventory for infants, toddlers, and preschoolers. SETTING: Emergency departments of 2 tertiary, urban pediatric hospitals. PARTICIPANTS: Ninety-eight children (0-8 years of age; mean age at injury = 33.00, SD = 24.7 months) with mild traumatic brain injury (concussion) divided into younger (0-2 years) and older (3-8 years) age groups. DESIGN: Observational study. MAIN MEASURE: The Report of Early Childhood Traumatic Injury Observations & Symptoms (REACTIONS) documents 17 postconcussive symptoms representing observable manifestations thereof and was completed by parents in the acute (24-48 hours; n = 65), subacute (7-14 days; n = 78), and/or persistent phase (25-35 days; n = 72) post-mild traumatic brain injury. RESULTS: Different patterns of postconcussive symptoms were reported by age group, with behavioral manifestations particularly salient in younger children. More children younger than 2 years had sleep and comfort-seeking symptoms at each of the 3 postinjury time points. CONCLUSION: Postconcussive symptoms may manifest differently after mild traumatic brain injury sustained during early childhood. To fully understand and address their presence and evolution, developmentally sound measures such as the REACTIONS inventory are required.

Association Between Preinjury Symptoms and Postconcussion Symptoms at 4 Weeks in Youth.

OBJECTIVE: To investigate whether preinjury physical, emotional, cognitive, and sleep symptoms on the Post-Concussion Symptoms Inventory (PCSI) are associated with persistent postconcussion symptoms (PPCS) at 4 weeks and whether any associations are moderated by sex or age. STUDY SETTING AND PARTICIPANTS: A total of 3063 participants with acute concussion, presenting to 9 Canadian pediatric emergency departments, were enrolled from August 2013 to June 2015. DESIGN: A planned secondary analysis of a prospective, multicenter cohort study (Predicting Persistent Post-concussive Problems in Pediatrics or 5P). Primary outcome was PPCS at 4 weeks, defined as 3 or more new or worsening individual symptoms compared with the preinjury score at 28 days on the PCSI. The association between preinjury scores and PPCS was analyzed with a multivariable logistic regression analysis that included preinjury, sex, age, sex × preinjury, and age × preinjury interactions as predictors. Missing baseline covariates were imputed. RESULTS: A total of 2123 (n = 844 [39.8%] girls; median [IQR] age = 12.9 [10.7, 15.0] participants were included in the analysis. Preinjury physical symptom score was associated with PPCS at 4 weeks (χ2 = 13.87, df = 6, P = .031). The preinjury emotional score also contributed to the variability in PPCS (χ2 = 11.79, df = 6, P = .067). While girls reported higher preinjury physical, emotional, and cognitive scores than boys, neither sex nor age interacted with preinjury to predict PPCS at 4 weeks. Independent of age and sex, preinjury physical symptoms were associated with PPCS at 4 weeks (OR = 1.40; 95% CI, 1.15-1.70). CONCLUSION: Preinjury physical symptoms are associated with the probability of having PPCS at 4 weeks postconcussion independent of age and sex. Providers should consider preinjury symptoms to inform prognosis and recovery management.

The magnitude of parental stress is highly variable following pediatric concussion: using the transactional model of stress to understand parent experiences.

OBJECTIVES: To use the Transactional Model of Stress to understand variations in parental stress following pediatric concussion. METHODS: Mixed-methods design. 49 children with concussion (13.8 ± 2.3 years, nfemales = 27) and their parent (nfemales = 40) were recruited from a specialty clinic. Quantitative data were collected via surveys at the child's initial clinic visit. Qualitative data were collected through an eleven-question, semi-structured interview with 12 parents. Interview questions focused on post-concussion stressors and data were analyzed using thematic analysis. Multivariable linear regression analyzed predictors of parental stress . RESULTS: Ten of the parents interviewed (83%) described the concussion as having a negative overall effect on their stress, while two parents described the overall experience as positive. Coping abilities and other life stressors were described as reasons for varying stress levels. Neurotic and conscientious personality factors and the child's quality of life total score accounted for 45% of the variance in parental stress (R2 = 0.451, F(3,33) = 9.03, p < 0.001). CONCLUSIONS: Parental stress following pediatric concussion is highly variable. The Transactional Model of Stress appears useful to understand this phenomenon. Future studies should investigate interventions to reduce stress for parents experiencing high levels following their child's concussion.

Developing a conceptual framework to identify and classify sources of parental stress following pediatric concussion.

OBJECTIVES: To create a conceptual framework that classifies the various stresses parents experience following their child's concussion. METHODS: Twelve parents of children with concussion completed a semi-structured interview with the lead author. Questions broadly focused on post-concussion stress, with specific probes for caregiving responsibilities, concussion knowledge, and athletic participation. Data were analyzed using thematic analysis. RESULTS: Ten mothers and 2 fathers participated. Five themes stemmed from our analysis: 1) Concussion Knowledge (central theme): stressors related to sources of concussion information; 2) Child Health Factors: stressors related to injury and illness, including concussion; 3) Activity Factors: stressors related to academic and athletic performance; 4) Parent-Injured Child Relationship Factors: stressors related to providing care to the child; and 5) Personal Factors: stressors unrelated to the concussion (e.g. family, social, career, etc.). Child Health Factors was most frequently identified as the primary stressor (n = 9). CONCLUSIONS: Sources of parental stress were varied following pediatric concussion. Issues relating to the child's post-injury dysfunction and the uncertain recovery from concussion were key stressors identified by parents. Moving forward, this framework can be used to ground the development of specific parental stress screening tools and interventions, which may benefit the parent's mental health and the child's clinical recovery.

The Cardiac Autonomic Response Recovery to the Modified Tilt Test in Children Post Moderate-Severe Traumatic Brain Injury.

OBJECTIVE: To assess the recovery of the cardiac autonomic control system (CACS) response to the modified tilt-test during rehabilitation, in children post moderate-severe TBI at the subacute phase post-injury. METHOD: Thirty-seven children aged 6-18 years, 14-162 days post moderate-severe TBI, participated in the study. The assessment included CACS values evaluation (heart rate (HR), heart rate variability (HRV) and blood pressure) during the modified tilt-test: five minutes lying supine and five minutes passive standing. Re-assessment was performed after eight weeks of rehabilitation. RESULTS: In both assessments, only four children reported symptoms associated with orthostatic intolerance during the modified tilt-test. No change was found over time in the HR and HRV values at rest. In response to the modified tilt-test, the systolic blood pressure showed change over time, with a significant interaction effect (p=0.04); while in the first assessment the SBP values showed a hypertension trend in the second assessment the SBP values showed a hypotension trend. CONCLUSIONS: Children post moderate-severe TBI at the sub-acute phase post-injury, have a better systolic blood pressure response during the modified tilt-test after eight weeks of individually tailored rehabilitation program, despite no change in the CACS values at rest. CLINICAL TRIAL GOV. NUMBER: NCT03215082.

Paediatric post-concussive symptoms: symptom clusters and clinical phenotypes.

OBJECTIVE: To assess the co-occurrence and clustering of post-concussive symptoms in children, and to identify distinct patient phenotypes based on symptom type and severity. METHODS: We performed a secondary analysis of the prospective, multicentre Predicting and Preventing Post-concussive Problems in Pediatrics (5P) cohort study, evaluating children 5-17 years of age presenting within 48 hours of an acute concussion. Our primary outcome was the simultaneous occurrence of two or more persistent post-concussive symptoms on the Post-Concussion Symptom Inventory at 28 days post-injury. Analyses of symptom and patient clusters were performed using hierarchical cluster analyses of symptom severity ratings. RESULTS: 3063 patients from the parent 5P study were included. Median age was 12.1 years (IQR: 9.2-14.6 years), and 1857 (60.6%) were male. Fatigue was the most common persistent symptom (21.7%), with headache the most commonly reported co-occurring symptom among patients with fatigue (55%; 363/662). Headache was common in children reporting any of the 12 other symptoms (range: 54%-72%). Physical symptoms occurred in two distinct clusters: vestibular-ocular and headache. Emotional and cognitive symptoms occurred together more frequently and with higher severity than physical symptoms. Fatigue was more strongly associated with cognitive and emotional symptoms than physical symptoms. We identified five patient groups (resolved/minimal, mild, moderate, severe and profound) based on symptom type and severity. CONCLUSION: Post-concussive symptoms in children occur in distinct clusters, facilitating the identification of distinct patient phenotypes based on symptom type and severity. Care of children post-concussion must be comprehensive, with systems designed to identify and treat distinct post-concussion phenotypes.