Trauma-Informed Care as a Universal Precaution: A Brief, Case-Based, Educational Primer Featuring Role-Playing and Individual Self-Reflection Exercises.

ABSTRACT: Despite its growing popularity, the implementation of Trauma-Informed Care (TIC) in standard medical practices remains insufficient. A workshop, featuring role-playing scenarios and individual self-reflection exercises, was developed to enhance compassion among health care providers. The workshop was created by a multidisciplinary team of community pediatricians, pediatric intensivists, psychologists, and palliative care physicians, was structured around key elements and principles of TIC, and was based on actual patient encounters. The 90-minute session included didactics, role-playing, writing and self-reflection exercises, and large-group debriefings, and it was presented at two academic meetings. It is currently available as an open-sourced, freely accessible website. The workshop was attended by individuals with varying levels of training and experience. Of approximated 80 participants, 39 responded to surveys about baseline knowledge and workshop satisfaction, and 24 completed self-perceived pre- and postknowledge surveys. Nearly 90% had limited prior exposure to TIC. All rated the workshop highly, with no significant differences based on workshop facilitation. Nearly 95% felt that they learned something that would impact their day-to-day practices. Self-perceived pre-post knowledge showed statistically significant improvements. This workshop is feasible and can potentially increase health care professionals' capacity to care, decrease moral injury, and alleviate burnout from difficult cases.

Post-discharge outcomes of hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C.

Introduction: Hospitalized children diagnosed with SARS-CoV-2-related conditions are at risk for new or persistent symptoms and functional impairments. Our objective was to analyze post-hospital symptoms, healthcare utilization, and outcomes of children previously hospitalized and diagnosed with acute SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C). Methods: Prospective, multicenter electronic survey of parents of children <18 years of age surviving hospitalization from 12 U.S. centers between January 2020 and July 2021. The primary outcome was a parent report of child recovery status at the time of the survey (recovered vs. not recovered). Secondary outcomes included new or persistent symptoms, readmissions, and health-related quality of life. Multivariable backward stepwise logistic regression was performed for the association of patient, disease, laboratory, and treatment variables with recovered status. Results: The children [n = 79; 30 (38.0%) female] with acute SARS-CoV-2 (75.7%) or MIS-C (24.3%) had a median age of 6.5 years (interquartile range 2.0-13.0) and 51 (64.6%) had a preexisting condition. Fifty children (63.3%) required critical care. One-third [23/79 (29.1%)] were not recovered at follow-up [43 (31, 54) months post-discharge]. Admission C-reactive protein levels were higher in children not recovered vs. recovered [5.7 (1.3, 25.1) vs. 1.3 (0.4, 6.3) mg/dl, p = 0.02]. At follow-up, 67% overall had new or persistent symptoms. The most common symptoms were fatigue (37%), weakness (25%), and headache (24%), all with frequencies higher in children not recovered. Forty percent had at least one return emergency visit and 24% had a hospital readmission. Recovered status was associated with better total HRQOL [87 (77, 95) vs. 77 (51, 83), p = 0.01]. In multivariable analysis, lower admission C-reactive protein [odds ratio 0.90 (95% confidence interval 0.82, 0.99)] and higher admission lymphocyte count [1.001 (1.0002, 1.002)] were associated with recovered status. Conclusions: Children considered recovered by their parents following hospitalization with SARS-CoV-2-related conditions had less symptom frequency and better HRQOL than those reported as not recovered. Increased inflammation and lower lymphocyte count on hospital admission may help to identify children needing longitudinal, multidisciplinary care. Clinical Trial Registration: ClinicalTrials.gov (NCT04379089).

Long-Term Neurobehavioral and Functional Outcomes of Pediatric Extracorporeal Membrane Oxygenation Survivors.

There are limited reports of neurobehavioral outcomes of children supported on extracorporeal membrane oxygenation (ECMO). This observational study aims to characterize the long-term (≥1 year) neurobehavioral outcomes, identify risk factors associated with neurobehavioral impairment, and evaluate the trajectory of functional status in pediatric ECMO survivors. Pediatric ECMO survivors ≥1-year postdecannulation and ≥3 years of age at follow-up were prospectively enrolled and completed assessments of adaptive behavior (Vineland Adaptive Behavior Scales, Third Edition [Vineland-3]) and functional status (Functional Status Scale [FSS]). Patient characteristics were retrospectively collected. Forty-one ECMO survivors cannulated at 0.0-19.8 years (median: 2.4 [IQR: 0.0, 13.1]) were enrolled at 1.3-12.8 years (median: 5.5 [IQR: 3.3, 6.5]) postdecannulation. ECMO survivors scored significantly lower than the normative population in the Vineland-3 Adaptive Behavior Composite (85 [IQR: 70, 99], P < 0.001) and all domains (Communication, Daily Living, Socialization, Motor). Independent risk factors for lower Vineland-3 composite scores included extracorporeal cardiopulmonary resuscitation, electrographic seizures during ECMO, congenital heart disease, and premorbid developmental delay. Of the 21 patients with impaired function at discharge (FSS ≥8), 86% reported an improved FSS at follow-up. Pediatric ECMO survivors have, on average, mild neurobehavioral impairment related to adaptive functioning years after decannulation. Continued functional recovery after hospital discharge is likely.

Post-PICU sleep efficiency and quality of life in infants and toddlers with acquired brain injury.

STUDY OBJECTIVES: We aimed to investigate the use of sleep efficiency (SE) as a measure of sleep disturbance in infants and toddlers with acquired brain injury (ABI) and evaluate associations between SE and child health-related quality of life and family outcomes. METHODS: Retrospective cohort study of 101 children ages 3-36 months who survived critical care for ABI. SE was quantified from the Brief Infant Sleep Questionnaire as a ratio of nighttime sleep to total time in bed; poor SE was defined as < 80%. Outcome measures included the Pediatric Quality of Life Inventory Core Total Score (health-related quality of life) and Family Impact Module Total Score. Spearman's correlation quantified associations between SE and outcomes. Multivariable linear regression tested association between poor SE and health-related quality of life controlling for significant covariates (age, diagnosis, comorbidities, worsening Functional Status Scale). RESULTS: Following ABI, median SE was 91.7 (interquartile range = 83.3, 95.5). Nineteen (19%) children had poor SE (< 80%). SE correlated significantly with quality of life (Spearman's correlation = .307) and Family Impact Module (Spearman's correlation = .309; both P < .01). When controlling for covariates, poor SE significantly increased risk for lower health-related quality of life (ß-coefficient = -7.0; 95% confidence interval= -13.4, -0.6). CONCLUSIONS: One in five infants and young children with ABI have poor SE that is associated with poorer child and family health outcomes. Our study underscores the potential importance of sleep following ABI to optimize recovery and the need for additional investigation of SE in infants and young children. CITATION: Klapp JM, Hall TA, Riley AR, Janzen D, Williams CN. Post-PICU sleep efficiency and quality of life in infants and toddlers with acquired brain injury. J Clin Sleep Med. 2024;20(1):75-83.

Exposure to Sedation and Analgesia Medications: Short-term Cognitive Outcomes in Pediatric Critical Care Survivors With Acquired Brain Injury.

Background/Objective: Pediatric intensive care unit (PICU) survivors risk significant cognitive morbidity, particularly those with acquired brain injury (ABI) diagnoses. Studies show sedative and analgesic medication may potentiate neurologic injury, but few studies evaluate impact on survivor outcomes. This study aimed to evaluate whether exposures to analgesic and sedative medications are associated with worse neurocognitive outcome. Methods: A retrospective cohort study was conducted of 91 patients aged 8 to 18 years, undergoing clinical neurocognitive evaluation approximately 1 to 3 months after PICU discharge. Electronic health data was queried for sedative and analgesic medication exposures, including opioids, benzodiazepines, propofol, ketamine, and dexmedetomidine. Doses were converted to class equivalents, evaluated by any exposure and cumulative dose exposure per patient weight. Cognitive outcome was derived from 8 objective cognitive assessments with an emphasis on executive function skills using Principal Components Analysis. Then, linear regression was used to control for baseline cognitive function estimates to calculate a standardized residualized neurocognitive index (rNCI) z-score. Multivariable linear regression evaluated the association between rNCI and medication exposure controlling for covariates. Significance was defined as P < .05. Results: Most (n = 80; 88%) patients received 1 or more study medications. Any exposure and higher cumulative doses of benzodiazepine and ketamine were significantly associated with worse rNCI in bivariate analyses. When controlling for Medicaid, preadmission comorbid conditions, length of stay, delirium, and receipt of other medication classes, receipt of benzodiazepine was associated with significantly worse rNCI (ß-coefficient = -0.48, 95% confidence interval = -0.88, -0.08). Conclusions: Exposure to benzodiazepines was independently associated with worse acute phase cognitive outcome using objective assessments focused on executive function skills when controlling for demographic and illness characteristics. Clinician decisions regarding medication regimens in the PICU may serve as a modifiable factor to improve outcomes. Additional inquiry into associations with long-term cognitive outcome and optimal medication regimens is needed.

Follow-up after PICU discharge for patients with acquired brain injury: the role of an abbreviated neuropsychological evaluation and a return-to-school program.

Objective: To present the results of an abbreviated testing protocol used to screen for neurocognitive and psychological sequelae of critical illness among pediatric intensive care unit (PICU) survivors with acquired brain injury in our post-discharge follow-up programs, and describe our process for facilitating this population's return to academic life. Design: Retrospective cohort study. Setting: Neurocritical care follow-up programs at two U.S. academic, tertiary medical/surgical PICUs. Patients: Children age > 4 years enrolled in the neurocritical care follow-up programs (n=289) at these institutions who underwent neurocognitive and psychological testing between 2017-2021. Interventions: None. Measurements and Main Results: One month after discharge from the hospital, nearly half of the children and/or their parents (48%) in our neurocritical care follow-up programs identified some type of emotional or behavioral concern compared to their premorbid state, and 15% reported some type of cognitive concern. On evaluation, 35% of the children were given a new neurocognitive diagnosis. Neurocognitive domains regulated by the executive functioning system were the most commonly affected, including attention (54%), memory (31%) and processing speed (27%). One-quarter of the children were given a new psychological diagnosis, most commonly post-traumatic stress disorder (PTSD) or stress-related symptoms (12%). Over 80% of patients in the programs were given new recommendations for school, for both new academic services and new classroom accommodations. Over half of children (57%) were referred for comprehensive follow-up neuropsychological evaluation. Conclusions: Abbreviated neurocognitive and psychological evaluation successfully identifies the same deficits commonly found among PICU survivors who undergo longer, more complete testing protocols. When combined with services aimed at successfully re-integrating PICU survivors back to school, this focused evaluation can provide an effective and efficient means of screening for cognitive and emotional deficits among PICU survivors, and establish a rationale for early academic support upon the child's return to school.

Bilingual randomized controlled trial design, of a telephone-based intervention to promote rehabilitation adherence; A study focus on recruitment of Hispanic children with traumatic brain injury.

BACKGROUND: While Hispanic children experience large long-term disparities in disability after traumatic Brain Injury (TBI), there is a gap in evidenced-based interventions to improve outcomes among this rapidly growing and at high-risk population. We developed and pilot tested a bilingual/bicultural intervention informed by Hispanic families consisting of Brain Injury Education and outpatient Navigation (1st BIEN). It integrates bilingual in-person education enriched by video content delivered through mobile phone devices, with outpatient navigation by bilingual and bicultural navigators during transitions of care and school return. METHODS: Randomized controlled trial to test the efficacy of 1st BIEN to maintain long-term adherence to rehabilitation and determine its effect on children's functional outcomes. The primary outcome is treatment adherence at 6 months post-discharge at centralized acute facilities and community providers. Secondary outcomes are functional status of the child using PROMIS parental report measures and parental health literacy, self-efficacy, and mental health; measured at baseline (pre-injury and discharge) 3-,6- and 12- months post discharge. Children's academic performance is assessed using school records the year before and the year after injury. DISCUSSION: Our study evaluates a novel, flexible and scalable approach using mobile phone devices to aid transitions of care, increase treatment adherence and improve TBI outcomes. It addresses the needs of an understudied population and builds upon their strengths. It is implemented by a bilingual and bicultural team with a deep understanding of the study population. It can serve as a model for TBI family centered interventions for at risk groups. TRIAL REGISTRATION: ClinicalTrials.govNCT05261477. Registered on March 2, 2022.

Long-term Pain Symptomatology in PICU Survivors Aged 8-18 Years.

BACKGROUND AND OBJECTIVES: Children discharged from the PICU often experience long-term physical, psychological, social and cognitive challenges, described as postintensive care syndrome. This study fills a critical gap by describing the long-term pain symptoms many children experience using child self-report. METHODS: Participants in this cross-sectional study were children aged 8 to 18 years (and 1 parent, n = 64 dyads) who were 8 to 24 months post-PICU discharge. Participants completed measures assessing pain, psychosocial function, and treatment utilization. Health information relevant to the PICU admission was obtained from the electronic medical record. RESULTS: Children were an average age of 14.3 years and 50% female. Average pain intensity in the past month was 3.65 (0-10 numeric rating scale), with 36% of children reporting pain ≥2 to 3 days a week. Youth with higher intensity (≥4) and more frequent pain (≥2-3 days a week) had greater pain catastrophizing, pain-related fear, anxiety, and sleep disturbance than those with less frequent and intense pain. Higher pain frequency was also associated with greater pain-related disability and depressive symptoms. Pain was not associated with any PICU-related variables abstracted from the electronic medical record. Parents reported children frequently accessed pain treatment services postdischarge; however, 37.5% reported the coronavirus disease 2019 pandemic impacted access to recommended services. CONCLUSIONS: A significant portion of children experience pain post-PICU discharge. For many of these children, pain is frequent and is associated with impairments in psychosocial function. Future prospective research studies can be used to identify risk factors of poor pain outcomes so children can receive targeted interventions.

Variability Across Caregiver and Performance-Based Measures of Executive Functioning in an Acute Pediatric Neurocritical Care Population.

Youth admitted to the pediatric intensive care unit (PICU) for traumatic brain injury (TBI) commonly struggle with long-term residual effects in the domains of physical, cognitive, emotional, and psychosocial/family functioning. In the cognitive domain, executive functioning (EF) deficits are often observed. The Behavior Rating Inventory of Executive Functioning, Second Edition (BRIEF-2) is a parent/caregiver-completed measure that is regularly utilized to assess caregivers' perspectives of daily EF abilities. Using parent/caregiver-completed measures like the BRIEF-2 in isolation as outcome measures for capturing symptom presence and severity might be problematic given that caregiver ratings are vulnerable to influence from external factors. As such, this study aimed to investigate the association between the BRIEF-2 and performance-based measures of EF in youth during the acute recovery period post-PICU admission for TBI. A secondary aim was to explore associations among potential confounding factors, including family-level distress, injury severity, and the impact of pre-existing neurodevelopmental conditions. Participants included 65 youths, 8-19 years of age, admitted to the PICU for TBI, who survived hospital discharge and were referred for follow-up care. Non-significant correlations were found between BRIEF-2 outcomes and performance-based measures of EF. Measures of injury severity were strongly correlated with scores from performance-based EF measures, but not BRIEF-2. Parent/caregiver-reported measures of their own health-related quality of life were related to caregiver responses on the BRIEF-2. Results demonstrate the differences captured by performance-based versus caregiver-report measures of EF, and also highlight the importance of considering other morbidities related to PICU admission.

The Impact of Sleep Disturbances on Health-Related Quality of Life in Children With Acquired Brain Injury After Critical Care.

BACKGROUND: Over 60,000 children with acquired brain injury (ABI) in the United States require admission to pediatric intensive care units annually. Over 50% suffer sleep-wake disturbances (SWDs) months after discharge. Given the importance of sleep to brain repair, we hypothesized that SWD would be associated with poorer health-related quality of life (HRQOL). METHODS: Cross-sectional analysis of prospectively collected data in children with ABI aged 3 to 18 years evaluated 1 to 3 months after critical care hospitalization (N = 151). SWD measured by Sleep Disturbances Scale for Children and defined as T-score ≥60 signifying moderate-severe risk of sleep disorders. HRQOL measured by Pediatric Quality of Life Inventory, which defines minimal clinically important difference as 4.5 points in total score. Secondary outcomes included scores for Physical, Emotional, Social, and School Function domains. SWD groups were compared with Mann-Whitney tests. Multiple linear regression evaluated association between SWD and HRQOL controlling for patient and ABI characteristics. Significance was defined as P < 0.05. RESULTS: SWDs were present in 66% (n = 100). HRQOL total score was significantly lower in children with SWD (median = 70; interquartile range [IQR] = 54, 80) versus without (median = 85; IQR = 67, 94; P < 0.001). Median scores in emotional, social, and school domains were significantly lower in SWD group (all P < 0.01). When controlling for age, sex, critical care interventions, preadmission comorbidities, and decline from preadmission Functional Status Scale, presence of SWD significantly reduced HRQOL total score nearly three times minimal clinically important difference (ß-coefficient = -12.1; 95% confidence Interval = -17.9, -6.2). CONCLUSIONS: SWD following ABI significantly decreased HRQOL overall and across multiple health domains. Sleep is potentially modifiable. Our data support future studies targeting sleep to improve outcomes after ABI.

Clinical and Demographic Factors Associated with Receiving an Opioid Prescription following Admission to the Pediatric Intensive Care Unit.

Opioids are commonly used to treat pain in the pediatric intensive care unit (PICU), and many children receive opioid prescription(s) at discharge. The frequency of opioid prescriptions at discharge and associations with individual characteristics and clinical factors are unknown. This study aimed to identify (1) the number of children who receive an opioid prescription at PICU discharge and (2) the demographic and clinical factors associated with receiving an opioid prescription. Data were collected via the electronic medical record. The sample was 3345 children (birth to 18 years) admitted to the PICU and discharged to home or an inpatient rehabilitation setting. In total, 23.7% of children were prescribed an opioid at discharge. There were group differences in who received opioid prescriptions (yes/no) related to PICU diagnosis, length of hospital stay, number of days on mechanical ventilation, number of previous hospitalizations, organ dysfunction score, and admission type (surgical versus non-surgical). Binary logistic regression models examined predictors of opioid prescription at discharge for the total sample and diagnostic subgroups. Older age and surgical admission type were the most consistent predictors of receiving an opioid prescription. Future research should examine prescription usage patterns and how use of opioids is associated with pain and functional outcomes over time.

Social Functioning and Autistic Behaviors in Youth Following Acquired Brain Injury.

Children and adolescents who survive the pediatric intensive care unit (PICU) with an acquired brain injury (ABI) often demonstrate a variety of physical, cognitive, emotional/behavioral, and social sequelae termed post-intensive care syndrome (PICS). Social communication and interaction challenges have also been observed clinically, and there is growing literature documenting these occurrences in youth following ABI. The extent of these social changes varies among patients, and a subset of patients go on to exhibit social and behavioral profiles closely resembling those of autistic youth. We reviewed empirical research regarding social functioning in youth following ABI, as well as the overlap between individuals with ABI and autistic youth, published from January 2009 to August 2022 on PubMed and Scopus databases. Clinical case examples from a well-established post-PICU follow-up program are also provided to exemplify the complexity of this phenomenon.

Is Pediatric Intensive Care Trauma-Informed? A Review of Principles and Evidence.

Pediatric critical illness and injury, along with the experience of recovering from critical illness are among the most potentially traumatic experiences for children and their families. Additionally, children often come to the Pediatric Intensive Care Unit (PICU) with pre-existing trauma that may sensitize them to PICU-related distress. Trauma-informed care (TIC) in the PICU, while under-examined, has the potential to enhance quality of care, mitigate trauma-related symptoms, encourage positive coping, and provide anticipatory guidance for the recovery process. This narrative review paper first describes the need for TIC in the PICU and then introduces the principles of TIC as outlined by the American Academy of Pediatrics: awareness, readiness, detection and assessment, management, and integration. Current clinical practices within PICU settings are reviewed according to each TIC principle. Discussion about opportunities for further development of TIC programs to improve patient care and advance knowledge is also included.

Sleep disturbances in infants and young children following an acquired brain injury.

STUDY OBJECTIVES: Sleep disturbances impact over half of older children and teens with acquired brain injury (ABI) following critical care hospitalization but are underevaluated in infants and young children. Given the importance of sleep in brain development and healing after injury, we hypothesized sleep disturbances would be associated with worse neurodevelopmental outcomes in infants with ABI. METHODS: We performed a retrospective cohort study of 68 children aged 2-32 months following critical care hospitalization for ABI. The Brief Infant Sleep Questionnaire assessed sleep disturbances. Bayley Scales of Infant and Toddler Development, third edition and Adaptive Behavior Assessment System, third edition assessed developmental and adaptive functioning outcomes, respectively. t tests compared sleep characteristics in infants with ABI to historical healthy controls. Spearman's correlation evaluated relationships among sleep and outcomes. Multiple linear regression investigated relationships controlling for demographic and ABI characteristics. RESULTS: Compared to healthy controls, children with ABI had shorter nighttime sleep duration (P = .01), longer daytime sleep duration (P < .001), and longer duration of nighttime awakenings (P < .001). Duration of night awakenings negatively correlated with Bayley Cognitive scores (Spearman's correlation = -.40). Night awakenings negatively correlated with worse Adaptive Behavior Assessment System, third edition General Adaptive Composite scores (Spearman's correlation = -.42). When controlling for demographic and ABI characteristics, ≥ 3 awakenings was significantly associated with worse Adaptive Behavior Assessment System, third edition General Adaptive Composite (ß = -11.3; 95% confidence interval = -19.2, -3.5). CONCLUSIONS: Sleep disturbances are associated with poorer outcomes in infants and toddlers after ABI. Sleep is vital to recovery and a potentially modifiable target to improve outcomes. CITATION: Klapp JM, Hall TA, Riley AR, Williams CN. Sleep disturbances in infants and young children following an acquired brain injury. J Clin Sleep Med. 2022;18(10):2387-2395.

Sleep and Executive Functioning in Pediatric Traumatic Brain Injury Survivors after Critical Care.

Over 50,000 children are hospitalized annually for traumatic brain injury (TBI) and face long-term cognitive morbidity. Over 50% develop sleep/wake disturbances (SWDs) that can affect brain development and healing. We hypothesized SWDs would portend worse executive function outcomes in children aged 3−18 years with TBI 1−3 months after hospital discharge. SWDs were defined using the Sleep Disturbances Scale for Children (t-scores ≥ 60). Outcomes included the Global Executive Composite (GEC, t-score) from the Behavior Rating Inventory of Executive Function, Second and Preschool Editions, and multiple objective executive function assessments combined through Principal Components Analysis into a Neurocognitive Index (NCI, z-score). Multiple linear regression evaluated associations between SWDs and executive function outcomes, controlling for covariates. Among 131 children, 68% had clinically significant SWDs, which were associated with significantly worse median scores on the GEC (56 vs. 45) and NCI (−0.02 vs. 0.42; both p < 0.05). When controlling for baseline characteristics and injury severity in multivariable analyses, SWDs were associated with worse GEC (ß-coefficient = 7.8; 95% Confidence Interval = 2.5, 13.1), and worse NCI (ß-coefficient = −0.4; 95% Confidence Interval = −0.8, −0.04). SWDs in children with TBI are associated with worse executive function outcomes after hospital discharge, and may serve as modifiable targets to improve outcomes.

Continuing Care For Critically Ill Children Beyond Hospital Discharge: Current State of Follow-up.

OBJECTIVES: Survivors of the PICU face long-term morbidities across health domains. In this study, we detail active PICU follow-up programs (PFUPs) and identify perceptions and barriers about development and maintenance of PFUPs. METHODS: A web link to an adaptive survey was distributed through organizational listservs. Descriptive statistics characterized the sample and details of existing PFUPs. Likert responses regarding benefits and barriers were summarized. RESULTS: One hundred eleven respondents represented 60 institutions located in the United States (n = 55), Canada (n = 3), Australia (n = 1), and the United Kingdom (n = 1). Details for 17 active programs were provided. Five programs included broad PICU populations, while the majority were neurocritical care (53%) focused. Despite strong agreement on the need to assess and treat morbidity across multiple health domains, 29% were physician only programs, and considerable variation existed in services provided by programs across settings. More than 80% of all respondents agreed PFUPs provide direct benefits and are essential to advancing knowledge on long-term PICU outcomes. Respondents identified "lack of support" as the most important barrier, particularly funding for providers and staff, and lack of clinical space, though successful programs overcome this challenge using a variety of funding resources. CONCLUSIONS: Few systematic multidisciplinary PFUPs exist despite strong agreement about importance of this care and direct benefit to patients and families. We recommend stakeholders use our description of successful programs as a framework to develop multidisciplinary models to elevate continuity across inpatient and outpatient settings, improve patient care, and foster collaboration to advance knowledge.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

Post-intensive care syndrome in a cohort of infants & young children receiving integrated care via a pediatric critical care & neurotrauma recovery program: A pilot investigation.

OBJECTIVE: Children treated in the pediatric intensive care unit (PICU) often face difficulties with long-term morbidities associated with neurologic injuries and lifesaving PICU interventions termed Post-Intensive Care Syndrome (PICS). In an effort to identify and address critical issues related to PICS, we developed an integrated model of care whereby children and families participate in follow-up clinics with a neuropsychologist and a critical care physician. To demonstrate preliminary impact, we present pilot findings on the early identification and treatment of PICS in a cohort of infants and young children in our program through a combination of multi-professional direct assessment and parent proxy questionnaires. METHOD: Thirty-three infants and children, ages 3-72 months, participated in our initial follow-up clinic where issues related to physical health/recovery, development/cognition, mood/behavior, and quality of life were screened 1-3 months after discharge from the PICU. RESULTS: In comparison to pre-hospitalization functioning, direct assessment revealed new neurological concerns identified by the critical care physician in 33.3% of participants and new neurocognitive concerns identified by the neuropsychologist in 36.4% of participants. Caregiver reported measures showed significant issues with patient cognitive functioning, emotional functioning, sleep, and impact on the family. Participants and families experienced significant difficulties related to changes in functioning and disability. Parents/caregivers and clinicians demonstrated agreement on functioning across a variety of indicators; however, important divergence in assessments were also found highlighting the importance of multiple assessments and perspectives. CONCLUSIONS: New PICS morbidities are common in the early phase of recovery after discharge in infants, young children and their families. Results demonstrate the benefits and need for timely PICU follow-up care that involves collaboration/integration of physicians, neuropsychologists, and families to identify and treat PICS issues.

Extracellular Vesicle Levels of Nervous System Injury Biomarkers in Critically Ill Trauma Patients with and without Traumatic Brain Injury.

Moderate/severe traumatic brain injury (TBI) causes injury patterns with heterogeneous pathology producing varying outcomes for recovery. Extracellular vesicles (EVs) are particles containing a myriad of molecules involved in cell signaling. EVs may hold promise as biomarkers in TBI because of their encapsulation, including improved stability/decreased degradation. A subset of subjects with and without TBI from a prospective, observational trial of critically ill trauma patients were analyzed. Total EV levels of glial (glial fibrillary acidic protein; GFAP) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], neurofilament light chain [NfL], and total-tau) proteins were measured using single-molecule array technology. Protein levels were winsorized to address outliers and log transformed for analysis. Patients with multiple injuries (n = 41) and isolated body injury (n = 73) were of similar age and sex. Patients with multiple injuries were, as expected, more severely injured with higher Injury Severity Scores (29 [26-41] vs. 21 [14-26], p < 0.001) and lower Glasgow Coma Scale scores (12 [4-13] vs. 13 [13-13], p < 0.001). Total body EVs of GFAP, UCH-L1, and NfL were higher in those with multiple injuries (1768 [932-4780] vs. 239 [63-589], p < 0.001; 75.4 [47.8-158.3] vs. 41.5 [21.5-67.1], p = 0.03; 7.5 [3.3-12.3] vs. 2.9 [2.1-4.8], p < 0.001, respectively). There was a moderate correlation between the Head Abbreviated Injury Score and GFAP (free circulating rho = 0.62, EV rho = 0.64; both p < 0.001). Brain-derived proteins contained in EV holds promise as an informative approach to biomarker measurement after TBI in hospitalized patients. Future evaluation and longitudinal studies are necessary to draw conclusions regarding the clinical utility of these biomarkers.