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Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era, such that adult CHD (ACHD) patients now outnumber their pediatric counterparts. ACHD patients demonstrate domain-specific neurocognitive deficits associated with reduced quality of life that include deficits in educational attainment and social interaction. Our hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits modified by behavioral and environmental enrichment proxies of cognitive reserve (e.g., level of education and lifestyle/social habits). This technical note describes an ancillary study to the National Heart, Lung, and Blood Institute (NHLBI)-funded Pediatric Heart Network (PHN) “Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD)”. Leveraging clinical, neuropsychological, and biospecimen data from the parent study, our study will provide structural–physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging initiative to be performed in ACHD patients. Limitations of the study include recruitment challenges inherent to an ancillary study, implantable cardiac devices, and harmonization of neuroimaging biomarkers. Results from this research will help shape the care of ACHD patients and further our understanding of the interplay between brain injury and cognitive reserve.

The incidence of Neonatal Abstinence Syndrome (NAS) continues to rise and there remains a critical need to develop non-pharmacological interventions for managing opioid withdrawal in newborns. Objective physiologic markers of opioid withdrawal in the newborn remain elusive. Optimal treatment strategies for improving short-term clinical outcomes and promoting healthy neurobehavioral development have yet to be defined. This dual-site randomized controlled trial (NCT02801331) is designed to evaluate the therapeutic efficacy of stochastic vibrotactile stimulation (SVS) for reducing withdrawal symptoms, pharmacological treatment, and length of hospitalization, and for improving developmental outcomes in opioid-exposed neonates. Hospitalized newborns (n = 230) receiving standard clinical care for prenatal opioid exposure will be randomly assigned within 48-hours of birth to a crib with either: 1) Intervention (SVS) mattress: specially-constructed SVS crib mattress that delivers gentle vibrations (30–60 Hz, ~12 μm RMS surface displacement) at 3-hr intervals; or 2) Control mattress (treatment as usual; TAU): non-oscillating hospital-crib mattress. Infants will be studied throughout their hospitalization and post discharge to 14-months of age. The study will compare clinical measures (i.e., withdrawal scores, cumulative dose and duration of medications, velocity of weight gain) and characteristic progression of physiologic activity (i.e., limb movement, cardio-respiratory, temperature, blood-oxygenation) throughout hospitalization between opioid-exposed infants who receive SVS and those who receive TAU. Developmental outcomes (i.e., physical, social, emotional and cognitive) within the first year of life will be evaluated between the two study groups. Findings from this randomized controlled trial will determine whether SVS reduces in-hospital severity of NAS, improves physiologic function, and promotes healthy development.

Introduction Blood and imaging biomarkers show promise in prognosticating outcomes after paediatric cardiac arrest in pilot studies. We describe the methods and early recruitment challenges and solutions for an ongoing multicentre (n=14) observational trial, Personalising Outcomes following Child Cardiac Arrest to validate clinical, blood and imaging biomarkers individually and together in a clinically relevant panel.Methods and analysis Children (n=164) between 48 hours and 17 years of age who receive chest compressions irrespective of provider, duration, or event location and are admitted to an intensive care unit are eligible. Blood samples will be taken on days 1–3 for the measurement of brain-focused biomarkers analysed to predict the outcome. Clinically indicated and timed brain MRI and spectroscopy biomarkers will be analysed to predict the outcome. The primary outcome for the trial is survival with favourable (Vineland Adaptive Behavioural Scale score >70) outcome at 1 year. Secondary outcomes include mortality and pre-event and postdischarge measures of emotional, cognitive, physical and family functioning and health-related quality of life. Early enrollment targets were not met due to prolonged regulatory and subcontract processes. Multiple, simultaneous interventions including modification to inclusion criteria, additional sites and site visits were implemented with successful improvement in recruitment. Study procedures including outcomes and biomarker analysis are ongoing.Ethics and dissemination Twelve of 14 sites will use the centralised Institutional Review Board (IRB) at the University of Pittsburgh (PRO14030712). Two sites will use individual IRBs: Children’s Healthcare of Atlanta Institutional Review Board and Children’s Hospital of Wisconsin IRB. Parents and/or guardians are consented and children assented (when possible) by the site Primary investigator (PI) or research coordinator for enrollment. Study findings will be disseminated through scientific conferences, peer-reviewed journal publications, public study website materials and invited lectures.Trial registration number NCT02769026.

Neuroelectric measures derived from human magnetoencephalographic (MEG) recordings hold promise as aides to diagnosis and treatment monitoring and targeting for chronic sequelae of traumatic brain injury (TBI). This study tests novel MEG-derived regional brain measures of tonic neuroelectric activation for long-term test-retest reliability and sensitivity to symptoms. Resting state MEG recordings were obtained from a normative cohort (CamCAN, baseline: n = 613; mean 16-month follow-up: n = 245) and a chronic symptomatic TBI cohort (TEAM-TBI, baseline: n = 62; mean 6-month follow-up: n = 40). The MEG-derived neuroelectric measures were corrected for the empty-room contribution using a random forest classifier. The mean 16-month correlation between baseline and 16-month follow-up CamCAN measures was 0.67; test-retest reliability was markedly improved in this study compared with previous work. The TEAM-TBI cohort was screened for depression, somatization, and anxiety with the Brief Symptom Inventory and for insomnia with the Insomnia Severity Index and was assessed via adjudication for six clinical syndromes: chronic pain, psychological health, and oculomotor, vestibular, cognitive, and sleep dysfunction. Linear classifiers constructed from the 136 regional measures from each TEAM-TBI cohort member distinguished those with and without each symptom, p < 0.0003 for each, i.e., the tonic regional neuroelectric measures of activation are sensitive to the presence/absence of these symptoms and clinical syndromes. The novel regional MEG-derived neuroelectric measures obtained and tested in this study demonstrate the necessary and sufficient properties to be clinically useful, i.e., good test-retest reliability, sensitivity to symptoms in each individual, and obtainable using automatic processing without human judgement or intervention.

Neuroelectric measures derived from human magnetoencephalographic (MEG) recordings hold promise as aides to diagnosis and treatment monitoring and targeting for chronic sequelae of traumatic brain injury (TBI). This study tests novel MEG-derived regional brain measures of tonic neuroelectric activation for long-term test-retest reliability and sensitivity to symptoms. Resting state MEG recordings were obtained from a normative cohort, Cambridge Centre for Ageing and Neuroscience (CamCAN), baseline: n = 619; mean 16-month follow-up: n = 253) and a chronic symptomatic TBI cohort, Targeted Evaluation, Action and Monitoring of Traumatic Brain Injury (TEAM-TBI), baseline: n = 64; mean 6-month follow-up: n = 39). For the CamCAN cohort, MEG-derived neuroelectric measures showed good long-term test-retest reliability for most of the 103 automatically identified stereotypic regions. The TEAM-TBI cohort was screened for depression, somatization, and anxiety with the Brief Symptom Inventory and for insomnia with the Insomnia Severity Index. Linear classifiers constructed from the 103 regional measures from each TEAM-TBI cohort member distinguished those with and without each symptom, with p < 0.01 for each—i.e., the tonic regional neuroelectric measures of activation are sensitive to the presence/absence of these symptoms. The novel regional MEG-derived neuroelectric measures obtained and tested in this study demonstrate the necessary and sufficient properties to be clinically useful—i.e., good test-retest reliability, sensitivity to symptoms in each individual, and obtainable using automatic processing without human judgement or intervention.