Recommendations for the design of therapeutic trials for neonatal seizures.

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures.

Development of a Retinopathy of Prematurity Activity Scale and Clinical Outcome Measures for Use in Clinical Trials.

Importance: To facilitate drug and device development for neonates, the International Neonatal Consortium brings together key stakeholders, including pharmaceutical companies, practitioners, regulators, funding agencies, scientists, and families, to address the need for objective, standardized clinical trial outcome measurements to fulfill regulatory requirements. Retinopathy of prematurity (ROP) is a disease that affects preterm neonates. The current International Classification of Retinopathy of Prematurity does not take into account all of the characteristics of ROP and does not adequately discriminate small changes in disease after treatment.

Identifying clinical practice guidelines for the supportive care of children with cancer: A report from the Children's Oncology Group.

Providing evidence-based supportive care for children with cancer has the potential to optimize treatment outcomes and improve quality of life. The Children's Oncology Group (COG) Supportive Care Guidelines Subcommittee conducted a systematic review to identify current supportive care clinical practice guidelines (CPGs) relevant to childhood cancer or pediatric hematopoietic stem cell transplant. Only 22 papers met the 2011 Institute of Medicine criteria to be considered a CPG.

Barriers to Medication Access in Pediatric Oncology in the United States.

Timely medication access in pediatric oncology is important; yet barriers are poorly described. We surveyed pediatric oncology health care providers at National Cancer Institute Community Oncology Research Program sites on their experience with the impact of drug acquisition difficulties, prior authorization (PA) requests, insurance denials, and patient copays leading to deviations or delays from prescribed treatment for their pediatric/adolescent/young adult patients in calendar year 2016. PA requests, the most frequently cited issue, created a deviation or delay from planned chemotherapy and supportive care treatment in at least 61% of respondents.

Changes in Urinary Tract Infection Hospitalizations Post 2011 Revised American Academy Pediatrics Guidelines.

Background: Multiple randomized trials over the past 2 decades have supported oral antimicrobial treatment for urinary tract infection (UTI), and the 2011 revised American Academy Pediatrics guidelines on the management of UTI provide further support for outpatient management. It is unknown whether practice patterns have changed as a result of these developments.

Objective: To examine temporal trends in UTI hospitalizations between 1997 and 2012 as measured by the Kids' Inpatient Database.

Comparison of Safety and Efficacy of Methadone vs Morphine for Treatment of Neonatal Abstinence Syndrome: A Randomized Clinical Trial.

Importance: Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established.

Objective: To compare the safety and efficacy of methadone and morphine in NAS.

Design, Setting, And Participants: In this randomized, double-blind, intention-to-treat trial, term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy were eligible.

Early-stage Hodgkin lymphoma in the modern era: simulation modelling to delineate long-term patient outcomes.

We developed a novel simulation model integrating multiple data sets to project long-term outcomes with contemporary therapy for early-stage Hodgkin lymphoma (ESHL), namely combined modality therapy (CMT) versus chemotherapy alone (CA) via F-fluorodeoxyglucose positron emission tomography response-adaption. The model incorporated 3-year progression-free survival (PFS), probability of cure with/without relapse, frequency of severe late effects (LEs), and 35-year probability of LEs. Furthermore, we generated estimates for quality-adjusted life years (QALYs) and unadjusted survival (life years, LY) and used model projections to compare outcomes for CMTversusCA for two index patients.

Concern for mortality in the neonatal intensive care unit (NICU): parent and physician perspectives.

Objective: The objectives of this study are as follows: (1) to determine the incidence of parental concern for mortality (PCM) and any potential predictors for it among parents of infants admitted to the Neonatal Intensive Care Unit (NICU), and (2) to explore physicians' perspectives with respect to PCM in the NICU and to examine current practices of addressing it.

Study Design: Separate questionnaires were distributed to members of the AAP Section on Perinatal-Neonatal Medicine District I and to NICU parents post discharge, to gather perspectives from each group. A χ-analysis and linear regression were performed.

Targeted Increase in Pulmonary Blood Flow in a Bidirectional Glenn Circulation.

In patients with a Glenn shunt and unilateral pulmonary vascular abnormalities, supplemental pulmonary blood flow may improve antegrade flow in the target lung and may permit eventual Fontan completion, while mitigating the risks of uncontrolled additional flow to the contralateral lung. We attempted this by inserting a small aortopulmonary shunt into the affected pulmonary artery and banding the central pulmonary artery. We performed a retrospective review of all patients who underwent this procedure from 2000 to 2015.

Efficacy of a Web-Based Oral Case Presentation Instruction Module: Multicenter Randomized Controlled Trial.

Objective: Effective self-directed educational tools are invaluable. Our objective was to determine whether a self-directed, web-based oral case presentation module would improve medical students' oral case presentations compared to usual curriculum, and with similar efficacy as structured oral presentation faculty feedback sessions.

Methods: We conducted a pragmatic multicenter cluster randomized controlled trial among medical students rotating in pediatric clerkships at 7 US medical schools.

Screening for fetal chromosomal and subchromosomal disorders.

Screening for fetal chromosomal disorders has evolved greatly over the last four decades. Initially, only maternal age-related risks of aneuploidy were provided to patients. This was followed by screening with maternal serum analytes and ultrasound markers, followed by the introduction and rapid uptake of maternal plasma cell-free DNA-based screening.

A Practical Approach to Neonatal Opiate Withdrawal Syndrome.

Perinatal opioid misuse and neonatal opioid withdrawal syndrome (NOWS) are a significant public health problem that has grown exponentially over the past decade. In the United States, a woman seeks emergency room care for prescription opioid misuse every 3 minutes and approximately every 25 minutes, a child is born with signs of drug withdrawal. The economic impact of perinatal opioid misuse is significant with annual hospital charges for NOWS in 2012 as $1.

The Genomics of Neonatal Abstinence Syndrome.

Significant variability has been observed in the development and severity of neonatal abstinence syndrome (NAS) among neonates exposed to prenatal opioids. Since maternal opioid dose does not appear to correlate directly with neonatal outcome, maternal, placental, and fetal genomic variants may play important roles in NAS. Previous studies in small cohorts have demonstrated associations of variants in maternal and infant genes that encode the μ-opioid receptor (), catechol--methyltransferase (), and prepronociceptin () with a shorter length of hospital stay and less need for treatment in neonates exposed to opioids .

Intravenous Iron Sucrose for Children With Iron Deficiency Anemia.

Iron deficiency anemia (IDA) is the most common nutritional deficiency in children. Most children with IDA are treated with oral iron preparations. However, intravenous (IV) iron is an alternative for children with severe IDA who have difficulty in adhering to or absorbing oral iron.

Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia.

Background: Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness.

Methods: A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model.

Early Nutrition and Physical Activity Interventions in Childhood Cancer Survivors.

Purpose Of Review: Childhood cancer survivors experience excessive weight gain early in treatment. Lifestyle interventions need to be initiated early in cancer care to prevent the early onset of obesity and cardiovascular disease (CVD). We reviewed the existing literature on early lifestyle interventions in childhood cancer survivors and consider implications for clinical care.

Parent and Health Care Provider Perceptions for Development of a Web-Based Weight Management Program for Survivors of Pediatric Acute Lymphoblastic Leukemia: A Mixed Methods Study.

Background: Survivors of pediatric acute lymphoblastic leukemia (ALL) may experience unhealthy weight gain during treatment, which has been associated with higher risk for chronic health issues.

Objective: The purpose of this study was to obtain feedback on weight management in pediatric ALL survivors and on the content and implementation of a Web-based weight management program.

Methods: Study participants included 54 parent survey respondents and 19 pediatric oncology professionals in 4 focus groups.

"When the Prescription Pad Is Not Enough": Attention-Deficit Hyperactivity Disorder Management 2.0.

Jose is a 13-year-old boy who presents to his primary care provider after struggling in school for many years. When he was in the first grade, he was diagnosed at a tertiary center with attention-deficit hyperactivity disorder. Multiple medication trials have produced few benefits and many side effects including poor sleep, morbid thoughts, lack of motivation, and, according to his parents, "he seemed like a robot.

Challenges and opportunities to enhance global drug development in neonates.

Purpose Of Review: This study reviews the history of neonatal drug development, recent legislative efforts designed to facilitate the study of therapeutic agents in neonates, and future steps necessary to advance drug development.

Recent Findings: Although many federal regulations have been introduced over the past 15 years to encourage pediatric and neonatal drug development, the majority of medications that are used in the Neonatal Intensive Care Unit are not approved by the Food and Drug Administration (FDA) for use in neonates. There are many challenges that investigators encounter in conducting neonatal clinical trials.

Development of a Pediatric Adverse Events Terminology.

In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute's Enterprise Vocabulary Services participated.

Evaluation of Club Cell 10-kDa Protein (CC10) Levels in Full-Term Infants.

Background: The club cell 10-kDa protein (CC10) is a homeostatic protein that is produced in the lung, diffuses into the blood, and is then excreted into the urine and stool. CC10 is known to have anti-inflammatory properties and to have lower endogenous production in preterm infants.

Objectives: As recombinant human CC10 (rhCC10) is being studied in preterm infants to reduce lung injury, understanding CC10 levels in term infants with normal lungs is needed to establish appropriate target dosing ranges.

A core outcome set for neonatal abstinence syndrome: study protocol for a systematic review, parent interviews and a Delphi survey.

Background: The prevalence of neonatal abstinence syndrome (NAS) is increasing globally resulting in an increased incidence of adverse neonatal outcomes and health system costs. Evidence regarding the effectiveness of NAS prevention and management strategies is very weak and further research initiatives are critically needed to support meta-analysis and clinical practice guidelines. In NAS research, the choice of outcomes and the use of valid, responsive and feasible measurement instruments are crucial.