Mechanisms to expedite pediatric clinical trial site activation: The DOSE trial experience.

BACKGROUND: Timely trial start-up is a key determinant of trial success; however, delays during start-up are common and costly. Moreover, data on start-up metrics in pediatric clinical trials are sparse. To expedite trial start-up, the Trial Innovation Network piloted three novel mechanisms in the trial titled Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE), a multi-site, randomized, double-blind, placebo-controlled trial in the pediatric intensive care setting. METHODS: The three novel start-up mechanisms included: 1) competitive activation; 2) use of trial start-up experts, called site navigators; and 3) supplemental funds earned for achieving pre-determined milestones. After sites were activated, they received a web-based survey to report perceptions of the DOSE start-up process. In addition to perceptions, metrics analyzed included milestones met, time to start-up, and subsequent enrollment of subjects. RESULTS: Twenty sites were selected for participation, with 19 sites being fully activated. Across activated sites, the median (quartile 1, quartile 3) time from receipt of regulatory documents to site activation was 82 days (68, 113). Sites reported that of the three novel mechanisms, the most motivating factor for expeditious activation was additional funding available for achieving start-up milestones, followed by site navigator assistance and then competitive site activation. CONCLUSION: Study start-up is a critical time for the success of clinical trials, and innovative methods to minimize delays during start-up are needed. Milestone-based funds and site navigators were preferred mechanisms by sites participating in the DOSE study and may have contributed to the expeditious start-up timeline achieved. CLINICALTRIALS: gov #: NCT03938857.

Pediatric inpatient hospital care.

Pediatrics is a field of medical specialty that focuses on children and their potential to successfully grow and develop into healthy adults. The articles in this special edition of Hospital Practice span a range of issues that affect children and their health care in the inpatient hospital setting, including equity and bias mitigation in health care, efficiency in patient rounding, using patient and family complaints to drive improvement efforts, the diagnostic process and avoiding fundamental diagnostic errors, pediatric palliative care, rapidly identifying and treating sepsis in children, the care and management of children on home ventilation, instituting a rapid response team in the pediatric environment, and quality rating systems for children's hospitals.

Validation of the "CHIIDA" and application for PICU triage in children with complicated mild traumatic brain injury.

BACKGROUND: The Children's Intracranial Injury Decision Aid (CHIIDA) was developed to predict which patients with complicated mild traumatic brain injury (cmTBI; GCS ≥13 with depressed skull fracture or intracranial injury) would achieve the composite outcome of neurosurgical intervention, intubation >24 h, or death. The study also explored the CHIIDA as a triage tool to determine need for PICU care. The purpose of this study is to externally validate the CHIIDA and assess its effects on PICU triage. METHODS: Retrospective cohort study (January 2016 to December 2017) to validate the CHIIDA to predict the composite outcome and assess its effects as a PICU triage tool at a level 1 pediatric trauma center. RESULTS: Of 345 patients with cmTBI, the composite outcome occurred in 16 patients (4.6%). At a cutoff score of 2, the CHIIDA predicted the composite outcome with a sensitivity of 94% (95% CI 67-99%) and specificity of 69% (95% CI 64-74%), similar to the original study. Using the same cutoff score for PICU triage resulted in 48 (71%) more patients admitted to PICU. CONCLUSIONS: In our cohort, the CHIIDA predicted the composite outcome well. If applied as a triage tool, it would have resulted in increased unnecessary PICU admissions. LEVEL OF EVIDENCE: Level III, prognosis.

Always ready, always prepared-preparing for the next pandemic.

A future global pandemic is likely to occur and planning for the care of critically ill children is less robust than that for adults. This review covers the current state of federal and regional resources for pediatric care in pandemics, a strategy for pandemic preparation in pediatric intensive care units and regions focusing on stuff, space, staff and systems, considerations in developing surge capacity and triage protocols, special circumstances such as highly infectious and highly lethal pandemics, and a discussion of ethics in the setting of pediatric critical care in a pandemic.

Pediatric cardiac arrest due to drowning and other respiratory etiologies: Neurobehavioral outcomes in initially comatose children.

AIM: To describe the 1-year neurobehavioral outcome of survivors of cardiac arrest secondary to drowning, compared with other respiratory etiologies, in children enrolled in the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial. METHODS: Exploratory analysis of survivors (ages 1-18 years) who received chest compressions for ≥2min, were comatose, and required mechanical ventilation after return of circulation (ROC). Participants recruited from 27 pediatric intensive care units in North America received targeted temperature management [therapeutic hypothermia (33°C) or therapeutic normothermia (36.8°C)] within 6h of ROC. Neurobehavioral outcomes included 1-year Vineland Adaptive Behavior Scales, Second Edition (VABS-II) total and domain scores and age-appropriate cognitive performance measures (Mullen Scales of Early Learning or Wechsler Abbreviated Scale of Intelligence). RESULTS: Sixty-six children with a respiratory etiology of cardiac arrest survived for 1-year; 60/66 had broadly normal premorbid functioning (VABS-II≥70). Follow up was obtained on 59/60 (30 with drowning etiology). VABS-II composite and domain scores declined significantly from premorbid scores in drowning and non-drowning groups (p<0.001), although declines were less pronounced for the drowning group. Seventy-two percent of children had well below average cognitive functioning at 1-year. Younger age, fewer doses of epinephrine, and drowning etiology were associated with better VABS-II composite scores. Demographic variables and treatment with hypothermia did not influence neurobehavioral outcomes. CONCLUSIONS: Risks for poor neurobehavioral outcomes were high for children who were comatose after out-of-hospital cardiac arrest due to respiratory etiologies; survivors of drowning had better outcomes than those with other respiratory etiologies.

Pediatric Organ Donation Potential at a Children's Hospital.

OBJECTIVES: To estimate the organ donation potential of patients dying at a children's hospital. DESIGN: Retrospective cohort study. SETTING: A free-standing, 271-bed, tertiary Children's Hospital with a pediatric trauma center. PATIENTS: Patients dying in any ICU during 2011-2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 224 deaths, 23 (10%) met neurologic criteria for death: 18 donated organs (conversion rate 78%), 47 (19%) died without prior limitation of life-sustaining therapies, and the remaining 69% had withdrawal of life-sustaining therapies. Among those dying after withdrawal of life-sustaining therapies (n = 154), the organ procurement organization was not notified prior to death in 24%, and older patients were more likely to be referred compared to those less than 1 year old. Infection, cancer, and organ dysfunction were the most frequent conditions that disqualified dying patients from suitability for donation. Just over half of children more than 1 year old were suitable for donation after withdrawal of life-sustaining therapies compared to a fifth of infants (19%). Of 45 suitable for donation, 37 (82%) died within 1 hour. None of 7 infants younger than 1 month old died within 20 minutes, compared with 46% of infants between 1 month and 1 year (n = 6) and 72% of older children. Thirty-three families (73%) did not permit donation after circulatory criteria for death whereas 12 (27%) gave permission for donation, and all 12 were actual donors (conversion rate 12/37 [32%]). CONCLUSIONS: The number of pediatric potential candidates for donation after circulatory determination of death was significantly larger than potential candidates for donation after neurologic determination of death at our hospital, but the actual donation rate was significantly lower. Increasing acceptance of donation after circulatory determination of death could increase organ donation. Among all children having withdrawal of life-sustaining therapies, donation after circulatory determination of death potential is less for infants.

Disaster preparedness, pediatric considerations in primary blast injury, chemical, and biological terrorism.

Both domestic and foreign terror incidents are an unfortunate outgrowth of our modern times from the Oklahoma City bombings, Sarin gas attacks in Japan, the Madrid train bombing, anthrax spores in the mail, to the World Trade Center on September 11(th), 2001. The modalities used to perpetrate these terrorist acts range from conventional weapons to high explosives, chemical weapons, and biological weapons all of which have been used in the recent past. While these weapons platforms can cause significant injury requiring critical care the mechanism of injury, pathophysiology and treatment of these injuries are unfamiliar to many critical care providers. Additionally the pediatric population is particularly vulnerable to these types of attacks. In the event of a mass casualty incident both adult and pediatric critical care practitioners will likely be called upon to care for children and adults alike. We will review the presentation, pathophysiology, and treatment of victims of blast injury, chemical weapons, and biological weapons. The focus will be on those injuries not commonly encountered in critical care practice, primary blast injuries, category A pathogens likely to be used in terrorist incidents, and chemical weapons including nerve agents, vesicants, pulmonary agents, cyanide, and riot control agents with special attention paid to pediatric specific considerations.

Comparison of severity of illness scores to physician clinical judgment for potential use in pediatric critical care triage.

OBJECTIVE: A pediatric triage tool is needed during times of resource scarcity to optimize critical care utilization. This study compares the modified sequential organ failure assessment score (M-SOFA), the Pediatric Early Warning System (PEWS) score, the Pediatric Risk of Admission Score II (PRISA-II), and physician judgment to predict the need for pediatric intensive care unit (PICU) interventions. METHODS: This retrospective cohort study evaluates three illness severity scores for all non-neonatal pediatric patients transported and admitted to a single center in 2006. The outcome of interest was receipt of a PICU intervention (mechanical ventilation, acute dialysis, depressed consciousness, or persistent hypotension). Predictive ability was assessed using receiver operating curves (ROCs). RESULTS: Of 752 patients admitted to the hospital, 287 received a PICU intervention. Median scores for all tools were significantly higher for children receiving an intervention than for those who did not. ROCs showed PEWS had the least discriminatory ability, followed by PRISA-II and pediatric M-SOFA. No value of the pediatric M-SOFA produced both positive and negative predictive values better than clinician judgment. CONCLUSIONS: No score had a clinically acceptable discriminate ability to predict patients who required a PICU intervention from those who did not. Physician judgment outperformed all three triage scores.

Critical appraisal of: triaging pediatric critical care resources during a pandemic: ethical and medical considerations.

OBJECTIVE: To identify the ethical norms that should govern the allocation of pediatric critical care resources during a pandemic. DESIGN: Narrative review. METHODS: Review the literature on triage and pandemics. FINDINGS: When care that is functionally equivalent to usual patient care practices can no longer be maintained, resources should be allocated primarily on the basis of medical need and/or benefit. Unequal treatment may be justified to increase the supply of available resources and thereby save more lives. When ethically relevant distinctions can no longer be made between patients, resources should be distributed by chance. Allocation on the basis of quality of life, general contributions to society, or age are potentially problematic. Existing triage protocols inconsistently articulate the relationship between these ethical norms and their specific recommendations. In addition, they have limited applicability in pediatrics principally because of the lack of a simple validated global scoring system, which predicts mortality and/or resource utilization. CONCLUSIONS: Although research to develop such scoring systems is ongoing, clinicians will need to rely more heavily on individual diagnoses of acute illnesses with high mortality rates and underlying conditions with short life expectancies and on random allocation methods.