Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.

Lessons Learned in Neurodevelopmental Outcomes Research in Children Following Extracorporeal Membrane Oxygenation.

Neurodevelopmental outcomes research in children following extracorporeal membrane oxygenationis a complex and evolving field. From systematic reviews to multi-center prospective cohort studies, a variety of research endeavors in this domain have already been conducted. Recent attention has redirected the focus on biomarkers and imaging studies to help better understand the neurological, developmental, and behavioral effects of extracorporeal membrane oxygenation on surviving children. This review provides an overview of major research in the field, ongoing and future studies, and a summary of lessons learned from these efforts.

Parent Satisfaction With Outpatient Telemedicine Services During the COVID-19 Pandemic: A Repeated Cross-Sectional Study.

Prior to the COVID-19 pandemic, the development of hospital-based telemedicine services had been slow and circumscribed in scope due to insurance and licensure restrictions. As these restrictions were eased during the COVID-19 pandemic to facilitate ongoing patient care, the public health emergency facilitated a rapid expansion and utilization of telemedicine services across the ambulatory service sector. Objectives: The current quality improvement (QI) study utilized this unprecedented opportunity to evaluate the use of telemedicine services across a variety of clinical disciplines and patient groups. Methods: Caregivers of patients (ages 0-21) who received care through an outpatient specialty center provided experience ratings of telemedicine services delivered during the initial pandemic months (March-June 2020; N = 1311) or during the national "winter surge" in late 2020 (November 2020-February 2021; N = 1395). Questionnaires were distributed electronically following the clinical visits, and ANCOVA was employed (with patient age as the covariate) to determine if caregiver responses differed based on patient demographic characteristics. Results: Ratings of patient satisfaction with services were very strong at both time points; greater variability in scores was noted when caregivers were asked if they would use telemedicine services again. At both time points, younger patient age (i.e., age 0-5) was associated with decreased caregiver willingness to use telemedicine services in the future. Smaller effects were seen for certain "hands on" therapies (occupational, physical, and speech) during the initial months of the pandemic and for proximity to the hospital during the "winter surge." Conclusions: These data suggest a very positive overall caregiver response to telemedicine-based services during the COVID-19 pandemic. Several areas of potential improvement/innovation were identified, including the delivery of telemedicine therapies (e.g., occupational, physical, and speech) services to young patients (i.e., aged 0-5).

Description of Bone Health Changes in a Cohort of Children With Acute Flaccid Myelitis (AFM).

OBJECTIVES: To qualitatively describe bone health changes in children with acute flaccid myelitis (AFM) and assess relationships with muscle mass and strength and functional performance. METHODS: Retrospective analysis of a cohort of 79 children with AFM seen consecutively in one specialized academic center between January 1, 2007, and December 31, 2019. RESULTS: Of the 79 participants who were aged 4 months to 21 years old, 41 (52%) had bone density measured by dual energy absorptiometry (DXA) and 32 of them (78%) were diagnosed with low bone mass (LBM). We recorded 25 fractures that occurred after onset of neurologic deficit in 14 of the children in the cohort (18%). Lean muscle mass correlated with bone mass and functional performance as assessed by Physical Abilities and Mobility Scale (PAMS) but not with muscle strength as assessed by manual muscle testing (MMT). Bone density in the lower limbs was associated with ambulatory status. CONCLUSION: Children with AFM have a high likelihood of muscle and bone loss and frequently sustain pathologic fractures. Bone health in children with AFM should be carefully monitored, and efforts should be made to preserve bone mass and maximize muscle mass.

Use of the Physical Abilities and Mobility Scale (PAMS) in Children Receiving Inpatient Rehabilitation for Spinal Cord Related Paralysis.

OBJECTIVES: To investigate the performance of the Physical Abilities and Mobility Scale (PAMS) in children receiving inpatient rehabilitation for paralysis related to spinal cord disease and injury (SCD/SCI). METHODS: Participants were 146 children with paralysis related to SCD/SCI, aged 2-21, admitted between January 2010 and 2017 for inpatient rehabilitation at a single free-standing academically affiliated pediatric rehabilitation hospital. Retrospective chart review was performed to obtain admission and discharge scores on the PAMS and the functional independence measure for children (WeeFIM®), collected as part of clinical care. Internal consistency was evaluated using Cronbach's alpha. Inter-rater reliability was evaluated through overall agreement, Pearson correlations, and intraclass correlations. Construct validity was examined through exploratory factor analysis. Criterion validity was explored through correlations of PAMS overall and item scores with WeeFIM® total and subscale scores. Sensitivity to change was tested using paired t-tests examining differences between admission and discharge scores for each item and for the total score on the PAMS. RESULTS: Internal consistency and inter-rater reliability were high (0.94 at admission and 0.95 at discharge). Total PAMS scores are highly correlated with total WeeFIM®, mobility, self-care, and cognitive subscores at admission and discharge. Correlations with the WeeFIM® ranged from low (cognitive) to strong (mobility). Total PAMS score and all individual items increased significantly between admission and discharge. CONCLUSIONS: The PAMS is a useful measure capturing incremental and granular functional motor skills changes occurring during inpatient rehabilitation for children with spinal cord-related paralysis.

Pediatric ECMO: unfavorable outcomes are associated with inflammation and endothelial activation.

BACKGROUND: Inflammatory and endothelial activation responses during extracorporeal membrane oxygenation (ECMO) support in children are poorly understood. In this study, we aimed to determine if circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and with neurologic outcomes in children on ECMO. METHODS: We conducted a secondary analysis of a two-center prospective observational study of 99 neonatal and pediatric ECMO patients. Inflammatory (interferon gamma [IFNγ], interleukin-6 [IL-6], IL-1ß, tumor necrosis factor alpha [TNFα]), endothelial activation (E-selectin, P-selectin, intercellular adhesion molecule-3 [ICAM-3], thrombomodulin [TM]), and fibrinolytic markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1]) were measured in plasma on days 1, 2, 3, 5, 7, and every third day thereafter during the ECMO course. RESULTS: All ECMO day 1 inflammatory biomarkers were significantly elevated in children with abnormal vs. normal neuroimaging. ECMO day 1 and peak levels of IL-6 and PAI-1 were significantly elevated in children who died compared to those who survived to hospital discharge. Tested biomarkers showed no significant association with long-term neurobehavioral outcomes measured using the Vineland Adaptive Behavioral Scales, Second Edition. CONCLUSIONS: High levels of circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and abnormal neuroimaging in children on ECMO. IMPACT: The inflammatory, endothelial activation, and fibrinolytic profile of children on ECMO differs by primary indication for extracorporeal support. Proinflammatory biomarkers on ECMO day 1 are associated with abnormal neurologic imaging in children on ECMO in univariable but not multivariable models. In multivariable models, a pronounced proinflammatory and prothrombotic biomarker profile on ECMO day 1 and longitudinally was significantly associated with mortality. Further studies are needed to identify inflammatory, endothelial, and fibrinolytic profiles associated with increased risk for neurologic injury and mortality through potential mediation of bleeding and thrombosis.

Equivalency of In-Person Versus Remote Assessment: WISC-V and KTEA-3 Performance in Clinically Referred Children and Adolescents.

OBJECTIVE: Teletesting has the potential to reduce numerous barriers to patient care which have only become exacerbated during the COVID-19 pandemic. Although telehealth is commonly utilized throughout medicine and mental health practices, teletesting has remained limited within cognitive and academic evaluations. This may be largely due to concern for the validity of test administration via remote assessment. This cross-sectional study examined the equivalency of cognitive [Wechsler Intelligence Scales for Children - Fifth Edition (WISC-V)] and academic [Kaufman Test of Educational Achievement - Third Edition (KTEA-3)] subtests administered via either teletesting or traditional in-person testing within clinically referred youth. METHOD: Chart review using a retrospective, cross-sectional design included a total of 893 children and adolescents, ranging from 4 to 17 years (Mean age = 10.2 years, SD = 2.9 years) who were administered at least one subtest from the aforementioned cognitive or academic assessments. Of these, 285 received teletesting, with the remaining (n = 608) receiving in-person assessment. A total of seven subtests (five from the WISC-V and two from the KTEA-3) were examined. A series of inverse probability of exposure weighted (IPEW) linear regression models examined differences between groups for each of the seven subtests after adjustment for numerous demographic, diagnostic, and parent-reported symptom variables. RESULTS: Only two significant differences were found, such that WISC-V Visual Puzzles (p < .01) and KTEA-3 Math Concepts (p = .03) scores were slightly higher in the teletesting versus in-person groups. However, these differences were quite small in magnitude (WISC-V Visual Puzzles, d = .33, KTEA-3 Math Concepts, d = .18). CONCLUSIONS: Findings indicate equivalency across methods of service delivery without clinically meaningful differences in scores among referred pediatric patients.

Cyclohexanone Exposure in Children on Extracorporeal Membrane Oxygenation Support.

The aim of this study was to determine if plasma cyclohexanone and metabolites are associated with clinical outcomes of children on extracorporeal membrane oxygenation (ECMO) support. We performed a secondary analysis of a prospective observational study of children on ECMO support at two academic centers between July 2010 and June 2015. We measured plasma cyclohexanone and metabolites on the first and last days of ECMO support. Unfavorable outcome was defined as in-hospital death or discharge Pediatric Cerebral Performance Category score > 2 or decline ≥ 1 from baseline. Among 90 children included, 49 (54%) had unfavorable outcome at discharge. Cyclohexanediol, a cyclohexanone metabolite, was detected in all samples and at both time points; concentrations on the first ECMO day were significantly higher in those with unfavorable versus favorable outcome at hospital discharge (median, 5.7 ng/µl; interquartile range [IQR], 3.3-10.6 ng/µl vs. median, 4.2 ng/µl; IQR, 1.7-7.3 ng/µl; p = 0.04). Twofold higher cyclohexanediol concentrations on the first ECMO day were associated with increased risk of unfavorable outcome at hospital discharge (multivariable-adjusted hazard ratio [HR], 1.24 [95% CI, 1.05-1.48]). Higher cyclohexanediol concentrations on the first ECMO day were not significantly associated with new abnormal neuroimaging or 1-year Vineland Adaptive Behavior Scales-II score < 85 or death among survivors.

Knowledge gaps for functional outcomes after multilobar resective and disconnective pediatric epilepsy surgery: Conference Proceedings of the Patient-Centered Stakeholder Meeting 2019.

For children with medication-resistant epilepsy who undergo multilobar or hemispheric surgery, the goal of achieving seizure freedom is met with a variety of potential functional consequences, both favorable and unfavorable. However, there is a paucity of literature that comprehensively addresses the cognitive, medical, behavioral, orthopedic, and sensory outcomes across the lifespan following large epilepsy surgeries in childhood, leaving all stakeholders underinformed with regard to counseling and expectations. Through collaboration between clinicians, researchers, and patient/caregiver stakeholders, the "Functional Impacts of Large Resective or Disconnective Pediatric Epilepsy Surgery: Identifying Gaps and Setting PCOR Priorities" meeting was convened on July 18, 2019, to identify gaps in knowledge and inform various patient-centered research initiatives. Clinicians and researchers with content expertise presented the best available data in each functional domain which is summarized here. As a result of the meeting, the top three consensus priorities included research focused on postoperative: (1) hydrocephalus; (2) mental health issues; and (3) literacy and other educational outcomes. The proceedings of this meeting mark the first time research on functional outcomes after resective and disconnective pediatric epilepsy surgery has been codified and shared among multidisciplinary stakeholders. This joint initiative promotes continued collaboration in the field and ensures that advancements align with actual patient and family needs and experiences. Collaboration around common objectives will lead to better informed counseling around postoperative expectations and management for children undergoing epilepsy surgery.

Functional Gains in Children Receiving Inpatient Rehabilitation After Brain Tumor Resection.

OBJECTIVE: To examine whether children with brain tumors treated with resection benefit from inpatient rehabilitation and to explore what factors present at admission may predict better functional outcomes. DESIGN: Retrospective cohort design. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Forty patients (N=40; ages 3-21y; 42.5% female) admitted to the rehabilitation unit between 2003 and 2015 after brain tumor resection. INTERVENTIONS: Patients received multidisciplinary rehabilitation therapies as part of their admission to inpatient rehabilitation, including occupational, physical, and speech-language therapy. MAIN OUTCOME MEASURES: Functional outcomes included the FIM for Children (WeeFIM) at discharge and 3-month follow-up as well as WeeFIM efficiency. RESULTS: A repeated-measures analysis of variance using patient WeeFIM Developmental Functional Quotients (DFQs) at admission, discharge, and 3-month follow-up showed significant gains in total WeeFIM DFQ scores across time. Admission WeeFIM DFQ, time from surgery to admission, and age at admission provided the strongest model for predicting discharge and 3-month follow-up WeeFIM DFQ scores. Admission WeeFIM DFQ and time from surgery to admission provided the strongest model for predicting WeeFIM efficiency. Total Neurological Predictor Scale (NPS) at admission did not add predictive power to any of the 3 models over and above patient characteristics (admission WeeFIM DFQ, age at admission, time from surgery to admission). CONCLUSIONS: Patients admitted to inpatient rehabilitation after brain tumor resection made significant functional gains (as measured by the WeeFIM) during inpatient rehabilitation and continued to make significant gains 3 months after discharge. Age and timing of admission provided the strongest models for predicting patient outcomes. The NPS did not predict functional outcomes after rehabilitation when controlling for other variables known to influence rehabilitation outcomes.

Feasibility and utility of transcutaneous spinal cord stimulation combined with walking-based therapy for people with motor incomplete spinal cord injury.

STUDY DESIGN: Prospective case series. OBJECTIVES: To evaluate the feasibility and preliminary efficacy of combining transcutaneous spinal cord stimulation (TSCS) with walking-based physical therapy. SETTING: Hospital-based outpatient center in Maryland, United States. METHODS: Ten individuals with chronic (>1 year) motor incomplete spinal cord injury (iSCI) completed 23 sessions of 2-h therapy over 8 weeks. TSCS was delivered for the first 30 min of each session using a clinically available device with adjustable current. To assess feasibility of the intervention, we tracked pain, adverse events, and participant retention. Preliminary efficacy was assessed by evaluating changes in walking speed, endurance, and quality following the intervention with select functional outcome measures (10-m walk test (10MWT), 6-min walk test (6MWT), timed up and go, and walking index for spinal cord injury II). RESULTS: We found that the combined intervention was feasible in an outpatient clinical setting. Participants tolerated the TSCS well, with no reports of significant adverse events or other issues (e.g., skin irritation or pain that disrupted training). None of the participants elected to discontinue the study. Participants also showed significant improvements in each measure of walking function following the intervention. Changes in walking speed, as measured by the 10MWT (0.56 ± 0.29 m/s to 0.72 ± 0.36 m/s), exceeded the minimal clinically important difference for individuals with iSCI. Changes in walking quality and endurance, as measured by the 6MWT (149.88 ± 99.87 m to 194.53 ± 106.56 m), exceeded the minimal detectable change for individuals with iSCI. CONCLUSIONS: These results indicate that TSCS is clinically feasible and may be useful as an adjunct to walking-based therapy for adults with iSCI.

Pediatric neuropsychological evaluation via telehealth: Novel models of care.

Objective: As the coronavirus pandemic extends across the globe, the impacts have been felt across domains of industry. Neuropsychology services are no exception. Methods for neuropsychological assessments, which typically require an in-person visit, must be modified in order to adhere to social distancing and isolation standards enacted in an effort to slow the pandemic. How can providers continue to meet the needs of patients referred for neuropsychology evaluations, while respecting federal and state guidelines for safety and ethical mandates? We offer a novel, tiered model of care, successfully implemented in response to mandated social distancing, in a large, pediatric neuropsychology program.Method: We describe the considerations and challenges to be addressed in transitioning a large neuropsychology department to a new model of care, including triaging referrals, developing -or rediscovering - types of services to meet the needs of a virtual patient population, and helping patients, parents, and providers to adjust to these new models.Conclusions: Lessons learned as a function of rapid changes in care models have implications for the field of neuropsychology as a whole as well as for future flexibility in meeting the needs of pediatric patients and their families.

Improvements in Function Following Inpatient Activity-Based Therapy for Children With Acute Flaccid Myelitis.

BACKGROUND: Acute flaccid myelitis (AFM) is an illness defined by rapid onset of flaccid paralysis in one or more limbs or bulbar muscles, with MRI findings of predominantly spinal cord gray matter abnormalities spanning one or more spinal segments following a viral illness. Individuals with AFM may require rehabilitation to promote recovery. Activity-based restorative therapy (ABRT) has previously been shown to result in positive outcomes in children with neurologic deficits related to AFM. OBJECTIVES: This study examined functional changes in a group of children with AFM who participated in ABRT in an inpatient setting. METHODS: Retrospective chart review of children with AFM admitted to a single inpatient rehabilitation unit from 2014 to 2018. Children were assessed using the Functional Independence Measure for Children (WeeFIM), Manual Muscle Testing (MMT), Spinal Cord Independence Measure (SCIM), and the Physical Abilities and Mobility Scale (PAMS) as part of routine clinical care; the Modified Rankin Scale for Neurologic Disability was completed retrospectively. RESULTS: Children showed significant improvements across all outcome measures, with effect sizes ranging from moderate to large. Significant change was also seen across all muscle groups on MMT, with effect sizes ranging from small to large. Consistent with previous reports, children demonstrated better function in distal than proximal muscle groups at both admission and discharge. CONCLUSION: Children with AFM who participated in ABRT increased muscle strength and made functional gains across all outcome measures. These results support the utility of rehabilitation in the long-term care of children with AFM and residual neurologic deficit.

Neurologic Outcomes in a Two-Center Cohort of Neonatal and Pediatric Patients Supported on Extracorporeal Membrane Oxygenation.

Contemporary studies of long-term outcomes in children supported on extracorporeal membrane oxygenation (ECMO) in the United States are limited. We enrolled 99 ECMO patients between July 2010 and June 2015 in a two-center prospective observational study that included neurologic and neuropsychologic evaluation at 6 and 12 months, using standardized outcome measures. Pre-ECMO, 20 (20%) had a pre-existing neurologic diagnosis, 40 (40%) had cardiac arrest, and 10 of 47 (21%) children with neuroimaging had acute abnormal findings. Of 50 children eligible for follow-up at 6 or 12 months, 40 (80%) returned for at least one visit. At the follow-up visit of longest interval from ECMO, the median Vineland Adaptive Behavior Scales-II (VABS-II) score was 91 (interquartile range [IQR], 81-98), the median Pediatric Stroke Outcome Measure (PSOM) score was 1 (IQR, 0-2), and the median Mullen Scales of Early Learning composite score was 85 (IQR, 72-96). Presence of new neuroimaging abnormalities during ECMO or within 6 weeks post-ECMO was associated with VABS-II score <85 or death within 12 months after ECMO. The Pediatric Cerebral Performance Category at hospital discharge showed a strong relationship with unfavorable VABS-II and PSOM scores at 6 or 12 months after ECMO. In this study, we report a higher prevalence of pre-ECMO neurologic conditions than previously described. In survivors to hospital discharge, median scores for adaptive behavior and cognitive, neurologic, and quality of life assessments were all below the general population means, but most deficits would be considered minor within each of the domains tested.

Acute flaccid myelitis: Rehabilitation challenges and outcomes in a pediatric cohort.

PURPOSE: To describe one institution's experience in the rehabilitation of children with acute flaccid myelitis (AFM). This study reviews the medical and rehabilitative course and functional outcomes of a cohort of children who underwent Activity Based Restorative Therapy (ABRT) at a single center. METHODS: Children with AFM presenting for rehabilitation between March 2005 and January 2017 were identified and a retrospective chart review was conducted. Changes in medical and functional status were assessed using multiple standardized instruments, as well as a chart review of medical progress. RESULTS: Thirty-one children with AFM treated at our institution in the study time period were identified. Of these, seventeen received inpatient treatment, and fourteen received solely outpatient interventions. Their medical and functional outcomes are described with use of standardized measures when available. CONCLUSIONS: Children with flaccid paralysis due to AFM undergoing structured, comprehensive rehabilitation interventions, even when these are initiated long after paralysis onset, can make significant neurologic and functional gains. Recovery of function and prevention of comorbidities are the main therapeutic targets for interventions in this population.

SmartTots Outcomes Workshop 2017: Notes From a Round Table Discussion About Outcome Measures.

An important element of designing research studies is the selection of appropriate outcome measures to ensure that the question posed is properly answered given the evidence. The selection of outcome measures is especially important when tackling complex, interdisciplinary problems, where appropriate outcome measures may not be as simple as a blood test or a laboratory value. One such area of study is the research into neurodevelopmental outcomes after early exposure to anesthetic agents. Concern has arisen recently that certain anesthetic agents may be toxic to the developing brain; a public-private partnership, SmartTots, was formed in conjunction with the Food and Drug Administration and various stakeholders to develop safe anesthetic regimens for neonates and infants who require surgery. However, as research has progressed, questions have arisen regarding the best outcome measures to use in order to detect a true effect, as well as the optimal window in which to measure. These issues were discussed in a round table meeting during the SmartTots meeting in September 2017, and a summary of the discussion is presented here.

Anesthesia and the developing brain: A way forward for laboratory and clinical research.

All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

Neurologic Outcomes After Extracorporeal Membrane Oxygenation: A Systematic Review.

OBJECTIVES: The goal of this systematic review of the literature was to summarize neurologic outcomes following neonatal and pediatric extracorporeal membrane oxygenation. DATA SOURCES: We conducted electronic searches of PubMed, Scopus, Web of Science, CINAHL, Cochrane, and EMBASE. STUDY SELECTION: Inclusion criteria included publication dates 2000-2016, patient ages 0-18 years, and use of standardized measures to evaluate outcomes after extracorporeal membrane oxygenation. DATA EXTRACTION: We identified 3,497 unique citations; 60 full-text articles were included in the final review. DATA SYNTHESIS: Studies evaluated patients with congenital diaphragmatic hernia (7), cardiac disease (8), cardiac arrest (13), and mixed populations (32). Follow-up was conducted at hospital discharge in 10 studies (17%) and at a median of 26 months (interquartile range, 8-61 mo) after extracorporeal membrane oxygenation in 50 studies (83%). We found 55 outcome measures that assessed overall health and function (4), global cognitive ability (7), development (4), motor function (5), adaptive function (2), behavior/mood (6), hearing (2), quality of life (2), school achievement (5), speech and language (6), learning and memory (4), and attention and executive function (8). Overall, 10% to as many as 50% of children scored more than 2 SDS below the population mean on cognitive testing. Behavior problems were identified in 16-46% of children tested, and severe motor impairment was reported in 12% of children. Quality of life of former extracorporeal membrane oxygenation patients evaluated at school age or adolescence ranged from similar to healthy peers, to 31-53% having scores more than 1 SD below the population mean. CONCLUSIONS: This systematic review of the literature suggests that children who have undergone extracorporeal membrane oxygenation suffer from a wide range of disabilities. A meta-analysis was not feasible due to heterogeneity in pathologies, outcome measures, and age at follow-up, underscoring the importance of developing and employing a core set of outcomes measures in future extracorporeal membrane oxygenation studies.

Preliminary findings of altered functional connectivity of the default mode network linked to functional outcomes one year after pediatric traumatic brain injury.

PURPOSE AND METHOD: This study examined functional connectivity of the default mode network (DMN) and examined brain-behavior relationships in a pilot cohort of children with chronic mild to moderate traumatic brain injury (TBI). RESULTS: Compared to uninjured peers, children with TBI demonstrated less anti-correlated functional connectivity between DMN and right Brodmann Area 40 (BA 40). In children with TBI, more anomalous less anti-correlated) connectivity between DMN and right BA 40 was linked to poorer performance on response inhibition tasks. CONCLUSION: Collectively, these preliminary findings suggest that functional connectivity between DMN and BA 40 may relate to longterm functional outcomes in chronic pediatric TBI.

The influence of comorbid asthma on the severity of symptoms in children with attention-deficit hyperactivity disorder.

OBJECTIVE: The current study examined the association between asthma and attention-deficit hyperactivity disorder (ADHD) symptoms in a clinical pediatric sample. METHODS: Demographic and neuropsychological data for children with a billing diagnosis of ADHD were extracted from a clinical database. Families completed standard rating scales. Seventy-one patients with a co-morbid asthma diagnosis were identified and matched by age to a group of 71 patients with only ADHD. RESULTS: Children with asthma and ADHD were more likely to display clinically elevated levels of hyperactivity, externalizing behaviors, anxiety, and hyperactive/impulsive behaviors compared to children with ADHD alone. Boys with asthma and ADHD had more symptoms than boys with only ADHD of somatization and emotional internalizing, while girls with asthma and ADHD had more symptoms of hyperactivity/impulsivity, conduct problems, anxiety, and emotional internalizing compared to girls with only ADHD. CONCLUSIONS: Findings suggest that in children with ADHD, co-morbid asthma is associated with increased behavioral and internalizing symptoms, with distinct gender differences present. Increased behavioral and internalizing symptoms seen in children with both asthma and ADHD may be due to the burden of their medical condition. No difference was found on cognitive variables, suggesting chronic hypoxia may be less influential in explaining these differences. Future research should determine the specific mechanisms of these differences.