Scoping Review on the Diagnosis, Prognosis, and Treatment of Pediatric Disorders of Consciousness.

peer reviewed[en] BACKGROUND AND OBJECTIVES: Comprehensive guidelines for diagnosis, prognosis, and treatments of disorders of consciousness (DoCs) in pediatric patients have not yet been released. We aim to summarize available evidence for DoCs with >14 days duration, to support the future development of guidelines for children aged 6 months to 18 years. METHODS: This scoping review was reported based on PRISMA-ScR guidelines. A systematic search identified records from 4 databases: PubMed, Embase, Cochrane Library, and Web of Science. Abstracts received 3-blind reviews. Corresponding full-text articles rated as "in-scope" and reporting data not published in any other retained article (i.e., no double reporting) were identified and assigned to 5 thematic evaluating teams. Full-text articles were reviewed using a double-blind standardized form. Level of evidence was graded, and summative statements were generated. RESULTS: On November 9, 2022, 2167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the last 5 years. Overall, 2161 individuals met the inclusion criteria; female patients were 527 of 1554 (33.9%) cases included, whose sex was identifiable. Of 132 articles, 57 (43.2%) were single case reports, and only 5 (3.8%) clinical trials; the level of evidence was prevalently low (80/132; 60.6%). Most studies included neurobehavioral measures (84/127; 66.1%), and neuroimaging (81/127; 63.8%); 59 (46.5%) were mainly related to diagnosis, 56 (44.1%) to prognosis, and 44 (34.6%) to treatment. Most frequently used neurobehavioral tools included the Coma Recovery Scale-Revised, Coma/Near Coma Scale, Level of Cognitive Functioning Assessment Scale and Post-Acute Level of Consciousness scale. Electroencephalography, event related potentials, structural computerized tomography and Magnetic Resonance Imaging were the most frequently used instrumental techniques. In 29/53 (54.7%) cases DoC improvement was observed, which was associated to treatment with amantadine. DISCUSSION: The literature on pediatric DoCs is mainly observational, and clinical details are either inconsistently presented or absent. Conclusions drawn from many studies convey insubstantial evidence, and have limited validity, and low potential for translation in clinical practice. Despite these limitations, our work summarizes the extant literature and constitutes a base for future guidelines related to diagnosis, prognosis and treatment of pediatric DoCs

A Core Outcome Set for Pediatric Critical Care

Objectives: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs.Design: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% “critical” and less than 15% “not important” advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components.Setting: Multinational survey.Patients: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates.Measurements and Main Results: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% “critical” and less than 15% “not important” and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set—extended.Conclusions: The PICU core outcome set and PICU core outcome set—extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families

Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials

OBJECTIVES: The THAPCA trials will determine if therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition (VABS-II), in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during THAPCA protocol development. DESIGN: Consensus assessment of potential outcomes and evaluation timepoints. METHODS: We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. RESULTS: Twelve months post-arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in VABS-II from pre-arrest level, measured as quasi-continuous with death and vegetative status being worst possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes due to easier interpretability, and favored outcomes based solely on post-arrest status, due to concerns about accurate parental assessment of pre-arrest status and differing clinical impact of a given VABS-II change depending on pre-arrest status. Simulations found only modest power loss from categorizing or dichotomizing quasi-continuous outcomes, due to high expected mortality. The primary outcome selected was survival with 12-month VABS-II no less than two standard deviations below a reference population mean (70 points), necessarily evaluated only among children with pre-arrest VABS-II ≥ 70. Two secondary efficacy outcomes, twelve-month survival and quasi-continuous VABS-II change from pre-arrest level, will be evaluated among all randomized children including those with compromised function pre-arrest. CONCLUSIONS: Extensive discussion of optimal efficacy assessment timing, and of the advantages versus drawbacks of incorporating pre-arrest status and using quasi-continuous versus simpler outcomes, was highly beneficial to the final THAPCA design. A relatively simple, binary primary outcome evaluated at 12 months was selected, with two secondary outcomes that address the primary outcome’s potential disadvantages