Utility of the 13 C-pantoprazole breath test as a CYP2C19 phenotyping probe for children.

The 13 C-pantoprazole breath test (PAN-BT) is a safe, noninvasive, in vivo CYP2C19 phenotyping probe for adults. Our objective was to evaluate PAN-BT performance in children, with a focus on discriminating individuals who, according to guidelines from the Clinical Pharmacology Implementation Consortium (CPIC), would benefit from starting dose escalation versus reduction for proton pump inhibitors (PPIs). Children (n = 65, 6-17 years) genotyped for CYP2C19 variants *2, *3, *4, and *17 received a single oral dose of 13 C-pantoprazole. Plasma concentrations of pantoprazole and its metabolites, and changes in exhaled 13 CO2 (termed delta-over-baseline or DOB), were measured 10 times over 8 h using high performance liquid chromatography with ultraviolet detection and spectrophotometry, respectively. Pharmacokinetic parameters of interest were generated and DOB features derived using feature engineering for the first 180 min postadministration. DOB features, age, sex, and obesity status were used to run bootstrap analysis at each timepoint (Ti ) independently. For each iteration, stratified samples were drawn based on genotype prevalence in the original cohort. A random forest was trained, and predictive performance of PAN-BT was evaluated. Strong discriminating ability for CYP2C19 intermediate versus normal/rapid metabolizer phenotype was noted at DOBT30 min (mean sensitivity: 0.522, specificity: 0.784), with consistent model outperformance over a random or a stratified classifier approach at each timepoint (p < 0.001). With additional refinement and investigation, the test could become a useful and convenient dosing tool in clinic to help identify children who would benefit most from PPI dose escalation versus dose reduction, in accordance with CPIC guidelines.

How to Conduct Clinical Trials in Children: A Tutorial.

Despite a growing interest in, and commitment to, implementing pediatric clinical trials, approximately one in every five trials in children fails because of inappropriate study design, suboptimal experiment planning, or inadequate participant enrollment. This tutorial, presented from the perspectives of seasoned pediatric investigators, an experienced research coordinator, and an established pediatric clinical trials network, is designed to provide practical guidance for successfully implementing pediatric clinical trials at an academic center or another comparable institution.

Validation of an improved pediatric weight estimation strategy.

OBJECTIVES: To validate the recently described Mercy method for weight estimation in an independent cohort of children living in the United States. METHODS: Anthropometric data including weight, height, humeral length, and mid upper arm circumference were collected from 976 otherwise healthy children (2 months to 14 years old). The data were used to examine the predictive performances of the Mercy method and four other weight estimation strategies (the Advanced Pediatric Life Support [APLS] method, the Broselow tape, and the Luscombe and Owens and the Nelson methods). RESULTS: THE MERCY METHOD DEMONSTRATED ACCURACY COMPARABLE TO THAT OBSERVED IN THE ORIGINAL STUDY (MEAN ERROR: -0.3 kg; mean percentage error: -0.3%; root mean square error: 2.62 kg; 95% limits of agreement: 0.83-1.19). This method estimated weight within 20% of actual for 95% of children compared with 58.7% for APLS, 78% for Broselow, 54.4% for Luscombe and Owens, and 70.4% for Nelson. Furthermore, the Mercy method was the only weight estimation strategy which enabled prediction of weight in all of the children enrolled. CONCLUSIONS: The Mercy method proved to be highly accurate and more robust than existing weight estimation strategies across a wider range of age and body mass index values, thereby making it superior to other existing approaches.