Publications

Ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship

Posted on by Kayla Korzekwinski

Journal of Perinatology • July 2022

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Le J, Greenberg RG, Yoo Y, Clark RH, Benjamin DK Jr., Zimmerman KO, Cohen-Wolkowiez M, Wade K
This study simulated ampicillin concentrations in newborns to define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. For EOS in preterm infants, two ampicillin doses (50 mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.

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

Posted on by Kayla Korzekwinski

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.

Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity

Posted on by Kayla Korzekwinski

CPT: Pharmacometrics & Systems Pharmacology • June 2022

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Gerhart JG, Carreno FO, Ford JL, Edginton AN, Perrin EM, Watt KM, Muller WJ, Atz AM, Al-Uzri A, Delmore P, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reducing the risk of serious adverse events associated with overexposure. However, there is limited information to guide fentanyl and methadone dosing in these children. This study addresses the clinical knowledge gap using physiologically-based pharmacokinetic models of fentanyl and methadone developed in adults and scaled to children with and without obesity to explore the interplay of obesity, age, and pharmacogenomics.

External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data

Posted on by Kayla Korzekwinski

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.

Development and Evaluation of a Virtual Population of Children with Obesity for Physiologically Based Pharmacokinetic Modeling

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • February 2022

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Gerhart JG, Carreno FO, Edginton AN, Sinha J, Perrin E, Kumar KR, Rikhi A, Hornik CP, Harris V, Ganguly S, Cohen-Wolkowiez M, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act — Pediatric Trials Network Steering Committee
A virtual population of children with obesity was developed using national survey, electronic health record, and clinical trial data, as well as data extracted from the literature. The objective of this study was to develop a virtual population of children with obesity to enable physiologically based pharmacokinetic modeling, then use the novel virtual population in conjunction with previously developed models of clindamycin and trimethoprim/sulfamethoxazole to better understand dosing of these drugs in children with obesity. Model simulations supported current recommended weight-based dosing in children with obesity for clindamycin and trimethoprim/sulfamethoxazole, as they met target exposure despite these changes in clearance and volume of distribution.

Impact of Personal Protective Equipment on the Performance of Emergency Pediatric Tasks

Posted on by Kayla Korzekwinski

Pediatric Emergency Care • December 2021

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Adler MD, Krug S, Eiger C, Good GL, Kou M, Nash M, Henretig FM, Hornik CP, Gosnell L, Chen JY, Debski J, Sharma G, Siegel D, Donoghue A
This study evaluated the impacts of personal protective equipment (PPE) on timeliness or success of emergency procedures performed by pediatric health care providers (HCPs). For session 1, HCPs wore normal attire; for session 2, they wore full-shroud PPE garb with 2 glove types: Ebola level or chemical. During each session, they performed clinical tasks on a patient simulator: intubation, bag-valve mask ventilation, venous catheter (IV) placement, push-pull fluid bolus, and defibrillation. Personal protective equipment did not affect procedure timeliness or success on a simulated child, with the exception of IV placement. Further study is needed to investigate PPE’s impact on procedures performed in a clinical care context.

Capacity Building in a New Clinical Trials Network through Inter-Network Collaboration

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • January 2022

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Knight L, Pahud BA, Scheffler M, Euteneuer JC, Allen C, Ross J, Ali W, Meyer M, Purohit PJ, Zimmerman KO, Sullivan JE; on behalf of the ECHO IDeA States Pediatric Clinical Trials Network
The Institutional Development Award (IDeA) is a congressionally mandated program helping to build research capacity by supporting research, faculty development, and infrastructure improvements in states with low National Institutes of Health (NIH) funding levels. Children, racial, and ethnic minorities, rural populations, and patients of low socioeconomic status are underrepresented in clinical research, which limits the generalizability of results. To address this gap, 17 institutions were awarded funding in 2016 to establish the IDeA States Pediatric Clinical Trials Network (ISPCTN) by the NIH’s Environmental Influences on Child Health Outcomes Program.

Safety of sildenafil in extremely premature infants: a phase I trial

Posted on by Kayla Korzekwinski

Journal of Perinatology • January 2022

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Jackson W, Gonzalez D, Smith PB, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Ahlfeld SK, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP, Laughon MM; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
This study sought to characterize the safety of sildenafil in premature infants. Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. There was one serious AE related to the study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.

External Evaluation of Two Pediatric Population Pharmacokinetics Models of Oral Trimethoprim and Sulfamethoxazole

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • June 2021

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Wu YSS, Cohen-Wolkowiez M, Hornik CP, Gerhart JG, Autmizguine J, Cobbaert M, Gonzalez D
This study tested the pediatric pharmacokinetics (PK) of the antibiotic combination trimethoprim (TMP)-sulfamethoxazole (SMX) that is used to treat a variety of infections. Both models used supported TMP-SMX dose increases in infants and young children for resistant pathogens with a MIC of 1 mg/liter, although the required dose increase based on the external model was lower.

Pediatric Trials Network: Stakeholder views on thanking families and providing study findings on pragmatic pediatric clinical research

Posted on by Kayla Korzekwinski

Contemporary Clinical Trials Communications • May 2021

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Corneli A, Perry B, Benjamin DK Jr, Zimmerman KO
This study conducted formative research using in-depth interviews to identify preferences for and anticipated responses to receiving thank you notes and lay summaries of aggregate results among caregivers and adolescent participants of pragmatic pediatric studies conducted by the National Institute of Health-sponsored Pediatric Trials Network. Nearly all participants said receiving a thank you note would make them feel valued, appreciated, and proud because they contributed to science. Similarly, nearly all participants said that receiving a summary of research results would make them aware of their role in improving the lives of children, feel like they are an active partner in research, and believe that researchers want to keep them informed.