Pediatrics Commons^™

Using Multiple Imputation Of Real-World Data To Estimate Clinical Remission In Pediatric Inflammatory Bowel Disease, Nanhua Zhang, Chunyan Liu, Steven J. Steiner, Richard B. Colletti, Robert Baldassano, Shiran Chen, Stanley Cohen, Michael D. Kappelman, Shehzad Saeed, Laurie S. Conklin, Richard Strauss, Sheri Volger, Eileen King, Kim Hung Lo

Pediatrics Faculty Publications

Aim: To evaluate the performance of the multiple imputation (MI) method for estimating clinical effectiveness in pediatric Crohn's disease in the ImproveCareNow registry; to address the analytical challenge of missing data. Materials & methods: Simulation studies were performed by creating missing datasets based on fully observed data from patients with moderate-to-severe Crohn's disease treated with non-ustekinumab biologics. MI was used to impute sPCDAI remission statuses in each simulated dataset. Results: The true remission rate (75.1% [95% CI: 72.6%, 77.5%]) was underestimated without imputation (72.6% [71.8%, 73.3%]). With MI, the estimate was 74.8% (74.4%, 75.2%). Conclusion: MI reduced nonresponse bias and …

A Mini Review Of What Matters In The Management Of Nas, Is Esc The Best Care?, Enrique Gomez Pomar

Pediatrics Faculty Publications

As the use of opioids and polysubstance by pregnant women has increased over the years, there has also been a sharp increase in cases of neonatal abstinence syndrome (NAS). Classically, infants affected by NAS have been cared for in neonatal intensive care units resulting in an increase of healthcare expenditure and resource utilization as well as separation from the families. Consequently, the Eat, Sleep, and Console (ESC) tool was developed and promoted as a novel method that focuses on maternal/infant dyad during hospital stay while decreasing the use of pharmacological interventions and therefore decreasing the length of stay and healthcare …

Optimal Dosing Of Enoxaparin In Overweight And Obese Children, Abdallah Derbalah, Stephen Duffull, Catherine M. Sherwin, Kathleen Job, Hesham Al‐Sallami

Pediatrics Faculty Publications

Aim:Current enoxaparin dosing guidelines in children are based on total bodyweight. This is potentially inappropriate in obese children as it may overestimate thedrug clearance. Current evidence suggests that obese children may require lower ini-tial doses of enoxaparin, therefore the aim of this work was to characterise the phar-macokinetics of enoxaparin in obese children and to propose a more appropriatedosing regimen.Methods:Data from 196 unique encounters of 160 children who received enoxa-parin treatment doses were analysed. Enoxaparin concentration was quantified usingthe chromogenic anti factor Xa (anti-Xa) assay. Patients provided a total of 552 anti-Xa samples. Existing published pharmacokinetic (PK) models were fitted …

Hypothesis: Hypermobile Ehlers Danlos Syndrome Is A Determinant Of Fetal And Young Infant Bone Strength, Marvin E. Miller

Pediatrics Faculty Publications

Several studies have demonstrated that young infants who present with unexplained fractures have a higher frequency of joint hypermobility, either in themselves or their parents, compared to the general population. The joint hypermobility is often associated with the autosomal dominant hypermobile form of Ehlers Danlos Syndrome (h-EDS) in which the mother is far more likely the affected parent. Most of these infants have metabolic bone disease as their radiographs often show poor bone mineralization. Some have alleged these infants were abused, while others have stated infants who have h-EDS or a parent with h-EDS are at increased risk to fracture …

Use Of Physiologically-Based Pharmacokinetic Modeling To Inform Dosing Of The Opioid Analgesics Fentanyl And Methadone In Children With Obesity, Jacqueline G. Gerhart, Fernando O. Carreño, Jennifer L. Ford, Andrea N. Edginton, Eliana M. Perrin, Kevin M. Watt, William J. Muller, Andrew M. Atz, Amira Al-Uzri, Paula Delmore, Daniel Gonzalez, Catherine Sherwin

Pediatrics Faculty Publications

Obesity is an increasingly alarming public health threat, with nearly 20% of children classified as obese in the United States today. 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, pharmacokinetic studies in children with obesity are challenging to conduct, so there is limited information to guide fentanyl and methadone dosing in these children. To address this clinical knowledge gap, physiologically-based pharmacokinetic models of fentanyl and methadone were developed in adults and scaled to children with and without obesity to explore …

Oral Drug Dosing Following Bariatric Surgery: General Concepts And Specific Dosing Advice, Jurjen S. Kingma, Desirée M. T. Burgers, Valerie M. Monpellier, Marinus J. Wiezer, Heleen J. Blussé Van Oud‐Alblas, Janelle D. Vaughns, Catherine M. T. Sherwin, Catherijne A. J. Knibbe

Pediatrics Faculty Publications

Bariatric or weight-loss surgery is a popular option for weight reduction. Depending on the surgical procedure, gastric changes like decreased transit time and volume and increased pH, decreased absorption surface in the small intestine, decreased exposure to bile acids and enterohepatic circulation, and decreased gastrointestinal transit time may be expected. In the years after bariatric surgery, patients will also substantially lose weight. As a result of these changes, the absorption, distribution, metabolism and/or elimination of drugs may be altered. The purpose of this article is to report the general influence of bariatric surgery on oral drug absorption, and to provide …

Metabolic Bone Disease Of Infancy In The Offspring Of Mothers With Bariatric Surgery: A Series Of 5 Infants In Contested Cases Of Child Abuse, Marvin E. Miller, David Ayoub

Pediatrics Faculty Publications

Background and aims: Metabolic Bone Disease of Infancy is a multifactorial disorder of bone fragility in infants who typically present under 6 months of age with multiple unexplained fractures. Major risk factors for this disorder relate to the fetal time period and include decreased provision of the essential nutrients for bone formation during pregnancy (calcium, phosphate, vitamin D, and protein), prema- turity, and decreased fetal bone loading. Methods: This study presents 5 infants with multiple unexplained fractures born to women who had prior bariatric surgery in which child abuse was alleged, and the alleged perpetrator denied wrong doing. Results: The …

Toward An Ontology Of Collaborative Learning Healthcaresystems, Alexandra H. Vinson, Michael Seid, Breck Gamel, Shehzad Ahmed Saeed, Brandy Fureman, Susan C. Cronin, Katherine Bates, David Hartley

Pediatrics Faculty Publications

Objective:To establish a basis for a domain ontology - a formal, explicit specificationof a shared conceptualization - of collaborative learning healthcare systems (CLHSs)in order to facilitate measurement, explanation, and improvement.Methods:We adapted the“Methontology”approach to begin building an ontologyof CLHSs. We specified the purpose of an ontology, acquired domain knowledge vialiterature review, conceptualized a common framework of CLHSs using a groundedapproach, refined these concepts based on expert panel input, and illustrated con-cept application via four cases.Results:The set of concepts identified as important to include in an ontologyincludes goals, values, structure, actors, environment, and products. To establish thisset of concepts, we gathered input …

Clinical Utility Of Anti-Mullerian Hormone In Pediatrics, Roopa Kanakatti Shankar, Tazim Dowlut-Mcelroy, Andrew Dauber, Veronica Gomez-Lobo

Pediatrics Faculty Publications

CONTEXT: Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females. In this mini-review, we offer an updated synopsis on AMH and its clinical utility in pediatric patients.

DESIGN AND RESULTS: A systematic search was undertaken for studies related to the physiology of AMH, normative data, and clinical role in pediatrics. In males, AMH, secreted by Sertoli cells, is found at high levels prenatally and throughout childhood and declines with progression through puberty to overlap with levels in females. …

Stop The Beat To See The Rhythm: Excitation-Contraction Uncoupling In Cardiac Research., Luther M Swift, Matthew W. Kay, Crystal M Ripplinger, Nikki Gillum Posnack

Pediatrics Faculty Publications

No abstract provided.

Sports Bra Preferences By Age And Impact Of Breast Size On Physical Activity Among American Females, Katherine H. Rizzone, Bianca Edison, Nailah Coleman, Cordelia Carter, Ingrid Ichesco, Paige Cassidy, Jane Chung, Courtney Marie Cora Jones

Pediatrics Faculty Publications

No abstract provided.

Using Nature To Nurture: Breast Milk Analysis And Fortification To Improve Growth And Neurodevelopmental Outcomes In Preterm Infants, Katherine Marie Ottolini, Elizabeth V. Schulz, Catherine Limperopoulos, Nickie Andescavage

Pediatrics Faculty Publications

No abstract provided.

Technology-Enabled Health Care Collaboration In Pediatric Chronic Illness: Pre-Post Interventional Study For Feasibility, Acceptability, And Clinical Impact Of An Electronic Health Record–Linked Platform For Patient-Clinician Partnership, Shehzad Ahmed Saeed, Lisa Opipari-Arrigan, Dana M. H. Dykes, Sunny Thakkar, Lisa Burns, Barbara A. Chini, Gary L. Mcphail, Ian Eslick, Peter A. Margolis, Heather C. Kaplan

Pediatrics Faculty Publications

Background: Mobile health (mHealth) technology has the potential to support the Chronic Care Model's vision of closed feedback loops and patient-clinician partnerships. Objective: This study aims to evaluate the feasibility, acceptability, and short-term impact of an electronic health record-linked mHealth platform (Orchestra) supporting patient and clinician collaboration through real-time, bidirectional data sharing. Methods: We conducted a 6-month prospective, pre-post, proof-of-concept study of Orchestra among patients and parents in the Cincinnati Children's Hospital inflammatory bowel disease (IBD) and cystic fibrosis (CF) clinics. Participants and clinicians used Orchestra during and between visits to complete and view patient-reported outcome (PRO) measures …

Randomized And Non-Randomized Designs For Causal Inference With Longitudinal Data In Rare Disorders., Rima Izem, Robert Mccarter

Pediatrics Faculty Publications

In the United States, approximately 7000 rare diseases affect 30 million patients, and only 10% of these diseases have existing therapies. Sound study design and causal inference methods are essential to demonstrate the therapeutic efficacy, safety, and effectiveness of new therapies. In the rare diseases setting, several factors challenge the use of typical parallel control designs: the small patient population size, genotypic and phenotypic diversity, and the complexity and incomplete understanding of the disorder's progression. Repeated measures, when spaced appropriately relative to disease progression and exploited in design and analysis, can increase study power and reduce variability in treatment effect …

Muc1 Ectodomain Is A Flagellin-Targeting Decoy Receptor And Biomarker Operative During Pseudomonas Aeruginosa Lung Infection., Avelino C Verceles, Pavan Bhat, Zain Nagaria, Destiny Martin, Harsh Patel, Afua Ntem-Mensah, Sang W Hyun, Andrea Hahn, Jean Jeudy, Alan S Cross, Erik P Lillehoj, Simeon E Goldblum

Pediatrics Faculty Publications

No abstract provided.

All In The Family: Child And Adolescent Weight Loss Surgery In The Context Of Parental Weight Loss Surgery., Eleanor R. Mackey, Megan M York, Evan P. Nadler

Pediatrics Faculty Publications

No abstract provided.

2021 Paces Expert Consensus Statement On The Indications And Management Of Cardiovascular Implantable Electronic Devices In Pediatric Patients: Executive Summary., Michael J Silka, Maully J Shah, Jennifer N Avari Silva, Seshadri Balaji, Cheyenne M Beach, Monica N Benjamin, Charles I. Berul, Bryan Cannon, Frank Cecchin, Mitchell I Cohen, Aarti S Dalal, Brynn E Dechert, Anne Foster, Roman Gebauer, M Cecilia Gonzalez Corcia, Prince J Kannankeril, Peter P Karpawich, Jeffery J Kim, Mani Ram Krishna, Peter Kubuš, Martin J Lapage, Douglas Y Mah, Lindsey Malloy-Walton, Aya Miyazaki, Kara S Motonaga, Mary C Niu, Melissa Olen, Thomas Paul, Eric Rosenthal, Elizabeth V Saarel, Massimo Stefano Silvetti, Elizabeth A Stephenson, Reina B Tan, John Triedman, Nicholas H Von Bergen, Philip L Wackel

Pediatrics Faculty Publications

No abstract provided.

A Prospective Observational Study Of Antihemophilic Factor (Recombinant) Prophylaxis Related To Physical Activity Levels In Patients With Hemophilia A In The United States (Space), Barbara A. Konkle, Doris V. Quon, Leslie Raffini, Michael Recht, Vlad C. Radulescu, Shannon L. Carpenter, Amy L. Dunn, Mei Lu, Maureen Watt

Pediatrics Faculty Publications

Introduction: High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding.

Aim: To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE^®; Baxalta US Inc., a Takeda company, Lexington, MA, USA).

Methods: SPACE was a 6-month, prospective, multicenter, observational outcomes study (NCT02190149). Enrolled patients received an eDiary application and …

Heterogeneity Of Magnitude, Allergen Immunodominance, And Cytokine Polarization Of Cockroach Allergen-Specific T Cell Responses In Allergic Sensitized Children., Ricardo Da Silva Antunes, Aaron Sutherland, April Frazier, Veronique Schulten, Anna Pomés, Jill Glesner, Agustin Calatroni, Matthew C Altman, Robert A Wood, George T O'Connor, Jacqueline A Pongracic, Gurjit K Khurana Hershey, Carolyn M Kercsmar, Rebecca S Gruchalla, Michelle Gill, Andrew H Liu, Edward Zoratti, Meyer Kattan, Paula J Busse, Leonard B Bacharier, Stephen J. Teach, Lisa M Wheatley, Alkis Togias, William W Busse, Daniel J Jackson, Alessandro Sette

Pediatrics Faculty Publications

Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma.

Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. …

Kawasaki Disease Shock Syndrome Vs Classical Kawasaki Disease: A Meta-Analysis And Comparison With Sars-Cov-2 Multisystem Inflammatory Syndrome., Loubna Lamrani, Cedric Manlhiot, Matthew D Elias, Nadine F Choueiter, Audrey Dionne, Ashraf S. Harahsheh, Michael A Portman, Brian W Mccrindle, Nagib Dahdah

Pediatrics Faculty Publications

No abstract provided.

Triglyceride-Glucose Index: A Potential New Biomarker For Lung Disease Associated With Metabolic Dysregulation., Xilei Xu Chen, Deepa Rastogi

Pediatrics Faculty Publications

No abstract provided.

Moving Beyond Size: Vorticity And Energy Loss Are Correlated With Right Ventricular Dysfunction And Exercise Intolerance In Repaired Tetralogy Of Fallot., Yue-Hin Loke, Francesco Capuano, Vincent Cleveland, Jason G. Mandell, Elias Balaras, Laura J. Olivieri

Pediatrics Faculty Publications

BACKGROUND: The global effect of chronic pulmonary regurgitation (PR) on right ventricular (RV) dilation and dysfunction in repaired Tetralogy of Fallot (rTOF) patients is well studied by cardiovascular magnetic resonance (CMR). However, the links between PR in the RV outflow tract (RVOT), RV dysfunction and exercise intolerance are not clarified by conventional measurements. Not all patients with RV dilation share the same intracardiac flow characteristics, now measurable by time resolved three-dimensional phase contrast imaging (4D flow). In our study, we quantified regional vorticity and energy loss in rTOF patients and correlated these parameters with RV dysfunction and exercise capacity.

METHODS: …

Trauma-Informed Care, Heather Forkey, Moira Szilagyi, Erin T. Kelly, James Duffee, Sarah H. Springer, Moira Szilagyi, Heather Forkey, Kristine Fortin, Mary Booth Vaden Greiner, Todd J. Ochs, Anu N. Partap, Linda Davidson Sagor, Deborah L. Shropshire, Jonathan D. Thackeray, Douglas Waite, Lisa Weber Zetley

Pediatrics Faculty Publications

No abstract provided.

The Value Of Cognitive Pretesting: Improving Validity And Revealing Blind Spots Through The Development Of A Newborn Screening Parent Experiences Survey., Norma-Jean Simon, Anne Atkins, Brianne Miller, Natasha Bonhomme, Beth Tarini

Pediatrics Faculty Publications

Surveys are used to gather a range of data on newborn screening (NBS) processes. We describe the development of a survey about parents' NBS experiences, in the United States, informed by cognitive pretest interviews among parents with varying NBS test results (true-positive, false-positive, normal). Cognitive pretest interviews were conducted following a semi-structured script and notes were taken to identify problematic survey items. The study team met weekly to discuss pretest feedback, draft changes, and generate revised items. Pretests indicated that parent experiences with NBS are varied and NBS screening procedures are not well understood. Substantial modifications were made to survey …

Integrated Omics Endotyping Of Infants With Respiratory Syncytial Virus Bronchiolitis And Risk Of Childhood Asthma., Yoshihiko Raita, Marcos Pérez-Losada, Robert J. Freishtat, Brennan Harmon, Jonathan M Mansbach, Pedro A Piedra, Zhaozhong Zhu, Carlos A Camargo, Kohei Hasegawa

Pediatrics Faculty Publications

Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinical

Aerosolized Surfactant For Preterm Infants With Respiratory Distress Syndrome, Mandy Brasher, Thomas M. Raffay, M. Douglas Cunningham, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

Currently, the administration of surfactant to preterm infants with respiratory distress syndrome (RDS) mainly relies on intratracheal instillation; however, there is increasing evidence of aerosolized surfactant being an effective non-invasive strategy. We present a historical narrative spanning sixty years of development of aerosolization systems. We also offer an overview of the pertinent mechanisms needed to create and manage the ideal aerosolization system, with a focus on delivery, distribution, deposition, and dispersion in the context of the human lung. More studies are needed to optimize treatment with aerosolized surfactants, including determination of ideal dosages, nebulizer types, non-invasive interfaces, and breath synchronization. …

Gaba And Glutamate In The Preterm Neonatal Brain: In-Vivo Measurement By Magnetic Resonance Spectroscopy., Sudeepta K. Basu, Subechhya Pradhan, Adre J. Du Plessis, Yehezkel Ben-Ari, Catherine Limperopoulos

Pediatrics Faculty Publications

Cognitive and behavioral disabilities in preterm infants, even without obvious brain injury on conventional neuroimaging, underscores a critical need to identify the subtle underlying microstructural and biochemical derangements. The gamma-aminobutyric acid (GABA) and glutamatergic neurotransmitter systems undergo rapid maturation during the crucial late gestation and early postnatal life, and are at-risk of disruption after preterm birth. Animal and human autopsy studies provide the bulk of current understanding since non-invasive specialized proton magnetic resonance spectroscopy (

Dosing Recommendations For Vancomycin In Children And Adolescents With Varying Levels Of Obesity And Renal Dysfunction: A Population Pharmacokinetic Study In 1892 Children Aged 1–18 Years, Cornelis Smit, Sebastiaan C. Goulooze, Roger J. M. Brüggemann, Catherine M. Sherwin, Catherijne A. J. Knibbe

Pediatrics Faculty Publications

Vancomycin is an effective but potentially nephrotoxic antibiotic commonly used for severe infections. Dosing guidelines for vancomycin in obese children and adolescents with or without renal impairment are currently lacking. This study describes the pharmacokinetics of vancomycin in a large pediatric cohort with varying degrees of obesity and renal function to design practical dosing guidelines for this population. A multi-center retrospective population pharmacokinetic study was conducted using data from patients aged 1−18 years who received >1 dose of vancomycin and had ≥1 vancomycin concentration measured between January 2006 and December 2012. Besides pharmacokinetic data, age, gender, body weight, creatinine clearance …

Observing Pediatric Residents' Communication Skills During Sick Visits: Do They Determine Concern And Their Reasons For Concern And Are Caregivers Satisfied?, Carter Guice, Kristine Schmitz, Annette Aldous, Larrie Greenberg

Pediatrics Faculty Publications

Fifty years ago, Dr. Barbara Korsch published her seminal work on pediatric resident communication skills, demonstrating that residents did not always ascertain the caregivers’ main concern for the visit was and specifically, why those caregivers were concerned.

Repeating her study using a direct observation methodology, the authors evaluated 103 pediatric sick visits at a large children’s hospital primary care clinic to determine 1) if residents elicited the caregiver’s main concern about their child’s acute illness, 2) why they were concerned, and 3) whether asking these questions was statistically associated with caregiver satisfaction, which was determined by an exit survey.

Results …

Effects Of Neonatal Nutrition Interventions On Neonatal Mortality And Child Health And Development Outcomes: A Systematic Review, Aamer Imdad, Faseeha Rehman, Evans Davis, Deepika Ranjit, Gamael S. S. Surin, Suzanna L. Attia, Sarah Lawler, Abigail A. Smith, Zulfiqar A. Bhutta

Pediatrics Faculty Publications

Background
The last two decades have seen a significant decrease in mortality for children < 5 years of age in low and middle‐income countries (LMICs); however, neonatal (age, 0–28 days) mortality has not decreased at the same rate. We assessed three neonatal nutritional interventions that have the potential of reducing morbidity and mortality during infancy in LMICs.

Objectives
To determine the efficacy and effectiveness of synthetic vitamin A, dextrose oral gel, and probiotic supplementation during the neonatal period.

Search Methods
We conducted electronic searches for relevant studies on the following databases: PubMed, CINAHL, LILACS, SCOPUS, and CENTRAL, Cochrane Central Register for Controlled Trials, up to November 27, 2019.

Selection Criteria
We aimed to include randomized and quasi‐experimental studies. The target population was neonates in LMICs. The interventions included synthetic vitamin A supplementation, oral dextrose gel supplementation, and probiotic supplementation during the neonatal period. …