Mentorship

Journal of the Pediatric Infectious Diseases Society December 2023

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Zimmerman KO

A unique feature of the Duke Summer Training in Academic Research (STAR) program is its focus on mentorship. STAR is an opportunity for junior faculty members and fellows to learn how to be mentors, and for undergraduate and high school students to learn how to be mentored. These are important and fundamental points; mentorship, from the perspective of mentor or mentee, should be a deliberate and skilled activity that can result from adequate training.

Duke STAR Program

Journal of the Pediatric Infectious Diseases Society December 2023

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Benjamin DK Jr

The DCRI Pediatrics group designed a summer internship program that had a wide reach and reflects its purpose and mission to conduct research to help children everywhere. This led to the creation of the Duke STAR (Summer Training in Academic Research) Program, a program that provides ~20 high school or college students per summer the opportunity to be exposed to clinical research and to work closely with researchers and practicing clinicians. Recruiting efforts prioritized participants from historically marginalized communities in North Carolina, with a goal to include at least several students each year who were “hidden talent.”

Trends in Pediatric Emergency and Inpatient Healthcare Use for Mental and Behavioral Health Among North Carolinians During the Early COVID-19 Pandemic

Journal of the Pediatric Infectious Diseases Society December 2023

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Sielaty R, Boutzoukas AE, Zimmerman KO, Caison B, Charles CO, CoyneSmith T, Darden T, Overman RA, Benjamin, Jr DK, Brookhart MA

Widespread school closures and health care avoidance during the COVID-19 pandemic led to disruptions in access to pediatric mental health care. This study conducted a retrospective analysis of emergency and inpatient administrative claims from privately insured children aged 6-20 years in North Carolina between January 2019 and December 2020.

Developing lay summaries and thank you notes in paediatric pragmatic clinical trials

Health Expectations June 2022

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Zimmerman KO, Perry B, Nsonwu A, Hanlen-Rosado E, Lane MD, Benjamin DK Jr., Becker M, Corneli A; on behalf of the Best Pharmaceuticals for Children Act — Pediatric Trials Network Steering Committee
This study conducted formative research to assess the acceptability of lay summaries and thank you notes, as well as to refine and expand guidance on participant and family engagement in Pediatric Trials Network’s (PTN) pragmatic paediatric clinical research. Researchers conducted in-depth qualitative interviews with adolescent clinical trial participants and caregivers of paediatric participants in four trials conducted by PTN across eight sites. This is the first study to describe stakeholder preferences for thank you note content and layout. Using these findings, researchers finalized PTN’s trial communication guidance for use in future PTN trials.

External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data

Frontiers in Pharmacology March 2022

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Karatza E, Ganguly S, Hornik CD, Muller MJ, Al-Uzri A, James L, Balevic SJ, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Risperidone is approved to treat schizophrenia in adolescents and autistic disorder and bipolar mania in children and adolescents. It is also used off-label in younger children for various psychiatric disorders. The objectives of this study were to assess whether opportunistically collected pediatric data can be used to evaluate risperidone population pharmacokinetic models externally and to identify a robust model for precision dosing in children. All the models had a modest predictive performance, potentially suggesting that sources of inter-individual variability were not entirely captured and that opportunistic data from a highly heterogeneous population are likely not the most appropriate data to evaluate risperidone models externally.

Racial and Ethnic Diversity in Studies Funded Under the Best Pharmaceuticals for Children Act

Pediatrics May 2021

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Abdel-Rahman SM, Paul IM, Hornik C, Sullivan JE, Wade K, Delmore P, Sharma G, Benjamin DK, Zimmerman KO

The Best Pharmaceuticals for Children Act (BPCA) incentivizes the study of on-patent medicines in children and mandates that the NIH sponsor research on off-patent drugs important to pediatric therapeutics. Failing to enroll cohorts that reflect the pediatric population at large restricts the generalizability of such studies. This investigation evaluates racial and ethnic minority representation among participants enrolled in BPCA-sponsored studies. This study revealed no evidence of racial and ethnic bias in enrollment for pediatric studies conducted with funding from BPCA, fulfilling the legislation’s expectation to ensure adequate representation of all children.

Estimation of Body Fat Percentage for Clinical Pharmacokinetic Studies in Children

Clinical and Translational Science • March 2021

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Green TP, Binns HJ, Wu H, Ariza AJ, Perrin EM, Quadri M, Hornik CP, Cohen-Wolkowiez M

Obesity is a prevalent childhood condition and the degree of adiposity is likely to be an important covariate in the pharmacokinetics (PKs) of many drugs. The goal of these studies was to facilitate the evaluation and, where appropriate, quantification of the covariate effect of body fat percentage (BF%) on PK parameters in children. Researchers examined two large databases to determine the values and variabilities of BF% in children with healthy body weights and in those with obesity, comparing the accuracy and precision of BF% estimation by both clinical methods and demographically derived techniques. They also conducted simulation studies to evaluate the utility of the several methods for application in clinical trials. The estimation of BF% from sex and obesity stage can routinely be applied to PK clinical trials to evaluate the contribution of BF% as a potential covariate.

Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation

The Journal of Clinical Pharmacology • March 2021

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Commander SJ, Wu H, Boakye-Agyeman F, Melloni C, Hornik CD, Zimmerman K, Al-Uzri A, Mendley SR, Harper B, Cohen-Wolkowiez M, Hornik CP
Hydrochlorothiazide (HCTZ) is a thiazide diuretic used in adults and children for the treatment of hypertension and edema. The pharmacokinetic (PK) properties of HCTZ in children are not well characterized, particularly among children with obesity who frequently suffer from hypertension and may, therefore, benefit from HCTZ therapy. Simulated exposure decreased with age and was likely due to older children receiving the maximum absolute doses of HCTZ. Further studies with more patients in each age group are required to confirm these PK findings of HCTZ in the children.

Population Pharmacokinetics of Olanzapine in Children

British Journal of Clinical Pharmacology • February 2021
Maharaj AR, Wu H, Zimmerman KO, Autmizguine J, Kalra R, Al-Uzri A, Sherwin CMT, Goldstein SL, Watt K, Cohen-Wolkowiez M, Hornik CP; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed pediatric dosing scheme. This analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and postmenstrual age (PMA) were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance.

Physiologically-Based Pharmacokinetic Modeling Characterizes the CYP3A-Mediated Drug-Drug Interaction Between Fluconazole and Sildenafil in Infants

Clinical Pharmacology & Therapeutics • January 2021

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Salerno SN, Edginton A, Gerhart JG, Laughon MM, Ambalavanan N, Sokol GM, Hornik CD, Stewart D, Mills M, Martz K, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Infants being treated for pulmonary hypertension and prevention or treatment of invasive candidiasis may be given sildenafil with fluconazole concurrently. Physiologically-based pharmacokinetic (PBPK) modeling can potentially predict pediatric drug-drug interactions (DDIs) when clinical DDI data are limited. This study highlights the feasibility of PBPK modeling to predict DDIs in infants and the need to include CYP3A7 parameters.