Medical Sciences Commons^™

Mail-Back Envelopes For Retrieval Of Opioids After Pediatric Surgery, Adam C Adler, Ammar N Yamani, Caitlin D Sutton, Danielle M Guffey, Arvind Chandrakantan

Faculty, Staff and Students Publications

BACKGROUND: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery.

METHODS: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well …

Age Of Acquisition Impacts The Brain Differently Depending On Neuroanatomical Metric, Hannah Claussenius-Kalman, Kelly A Vaughn, Pilar Archila-Suerte, Arturo E Hernandez

Faculty, Staff and Student Publications

Although researchers generally agree that a certain set of brain areas underlie bilingual language processing, there is discrepancy regarding what effect timing of language acquisition has on these regions. We aimed to investigate the neuroanatomical correlates of age of acquisition (AoA), which has been examined previously, but with inconsistent results, likely influenced by methodological differences across studies. We analyzed gray matter density, volume, and thickness using whole-brain linear models in 334 bilinguals and monolinguals. Neuroanatomical correlates of AoA differed depending on gray matter metric. Relative to early bilinguals, late bilinguals had thicker cortex in language processing and cognitive control regions, …

Rationale And Design Of The Steroids To Reduce Systemic Inflammation After Infant Heart Surgery (Stress) Trial, Kevin D Hill, H Scott Baldwin, David P Bichel, Ryan J Butts, Reid C Chamberlain, Alicia M Ellis, Eric M Graham, Jesse Hickerson, Christoph P Hornik, Jeffrey P Jacobs, Marshall L Jacobs, Robert Db Jaquiss, Prince J Kannankeril, Sean M O'Brien, Rachel Torok, Joseph W Turek, Jennifer S Li, Stress Network Investigators

Faculty, Staff and Students Publications

For decades, physicians have administered corticosteroids in the perioperative period to infants undergoing heart surgery with cardiopulmonary bypass (CPB) to reduce the postoperative systemic inflammatory response to CPB. Some question this practice because steroid efficacy has not been conclusively demonstrated and because some studies indicate that steroids could have harmful effects. STRESS is a randomized, placebo-controlled, double-blind, multicenter trial designed to evaluate safety and efficacy of perioperative steroids in infants (age < 1 year) undergoing heart surgery with CPB. Participants (planned enrollment = 1,200) are randomized 1:1 to methylprednisolone (30 mg/kg) administered into the CPB pump prime versus placebo. The trial is nested within the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. The primary outcome is a global rank score of mortality, major morbidities, and hospital length of stay with components ranked commensurate with their clinical severity. Secondary outcomes include several measures of major postoperative morbidity, postoperative hospital length of stay, and steroid-related safety outcomes including prevalence of hyperglycemia and postoperative infectious complications. STRESS will be one of the largest trials ever conducted in children with heart disease and will answer a decades-old question related to safety and efficacy of perioperative steroids in infants undergoing heart surgery with CPB. The pragmatic "trial within a registry" design may provide a mechanism for conducting low-cost, high-efficiency trials in a heretofore-understudied patient population.

Burden Of Rare Deleterious Variants In Wnt Signaling Genes Among 511 Myelomeningocele Patients, Luke Hebert, Paul Hillman, Craig Baker, Michael Brown, Allison Ashley-Koch, James E Hixson, Alanna C Morrison, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

Genes in the noncanonical WNT signaling pathway controlling planar cell polarity have been linked to the neural tube defect myelomeningocele. We hypothesized that some genes in the WNT signaling network have a higher mutational burden in myelomeningocele subjects than in reference subjects in gnomAD. Exome sequencing data from 511 myelomeningocele subjects was obtained in-house and data from 29,940 ethnically matched subjects was provided by version 2 of the publicly available Genome Aggregation Database. To compare mutational burden, we collapsed rare deleterious variants across each of 523 human WNT signaling genes in case and reference populations. Ten WNT signaling genes were …

Pediatric Immunization Practices In Nephrotic Syndrome: An Assessment Of Provider And Parental Knowledge, Cheryl L Tran, David T Selewski, Gia J Oh, Jonathan P Troost, Susan F Massengill, Samhar I Al-Akash, Shefali Mahesh, Rasheda Amin, Isa F Ashoor, Rahul Chanchlani, Mahmoud Kallash, Robert P Woroniecki, Debbie S Gipson

Faculty, Staff and Student Publications

Background: Children with nephrotic syndrome (NS) are at high risk for vaccine-preventable infections due to the immunological effects from the disease and concurrent treatment with immunosuppressive medications. Immunizations in these patients may be deferred due to their immunosuppressive treatment which may increase the risk for vaccine-preventable infections. Immunization practices in children with NS continue to vary among pediatric nephrologists. This raises the question of whether children with NS are receiving the recommended vaccinations at appropriate times. Therefore, it is critical to understand the practices and patient education provided by physicians to patients on the topic of vaccinations.

Methods: After informed …

Utilization Of A Continuous Pericapsular Nerve Group (Peng) Block With An Opioid-Sparing Repair Of A Femoral Neck Fracture In A Pediatric Patient, Karla Wyatt, Moustafa Zidane, Chyong-Jy Joyce Liu

Faculty, Staff and Students Publications

In the pediatric population, femoral neck fractures are usually associated with high-impact trauma and often present with pain in the groin area. Regional anesthesia can offer adjunctive therapy for acute pain management. Various techniques have been employed to circumvent pain related to hip fractures and resultant hip surgery. Neuraxial, lumbar plexus, caudal, epidural, fascia iliaca, and femoral continuous nerve block techniques are advantageous in mitigating hip pain. However, these approaches require patient repositioning during placement and carry the potential for motor blockade with resultant weakness. A newly described method, the Pericapsular Nerve Group (PENG) block, allows for analgesia of the …

Brain Development: Why The Young Sleep Longer, Budhaditya Chowdhury, Orie T. Shafer

Advanced Science Research Center

From absorbing new languages to mastering musical instruments, young children are wired to learn in ways that adults are not (Johnson and Newport, 1989). This ability coincides with periods of intense brain plasticity during which neurons can easily remodel their connections (Hubel and Wiesel, 1970). Many children are also scandalously good sleepers, typically getting several more hours of sleep per night than their parents (Jenni and Carskadon, 2007). As sleep deprivation has negative effects on learning and memory, learning like a child likely requires sleeping like one (Diekelmann and Born, 2010). Yet, how the ability to sleep for longer is …

Memantine: Can It Be Used To Treat Children With Autism Spectrum Disorder?, Austin Brown, Katherine Liu, Pul Lee, Rachel Muhlenkamp, Manoranjan D'Souza

Pharmacy and Wellness Review

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social, behavior and communicative skills. The current therapy for ASD only targets the associated symptoms such as aggression, self-harming acts or temper tantrums but not the core symptoms of social dysfunction. The pathology of ASD is not fully understood. Interestingly, imaging studies in ASD patients have reported abnormal high levels of glutamate in certain brain regions that play an important role in social interaction and communication. Thus, it has been hypothesized that medications attenuating glutamate transmission may be used as treatment for some of the core symptoms of …

Results Of A Phase 1 Multicentre Investigation Of Dexmedetomidine Bolus And Infusion In Corrective Infant Cardiac Surgery, Athena F Zuppa, Susan C Nicolson, Nicole S Wilder, Juan C Ibla, Erin A Gottlieb, Kristin M Burns, Mario Stylianou, Felicia Trachtenberg, Hua Ni, Tera H Skeen, Dean B Andropoulos

Faculty, Staff and Students Publications

BACKGROUND: Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing.

METHODS: We included 122 neonates and infants (0-180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200-300 pg ml …

Overview Of Kalydeco® (Ivacaftor) For Treatment Of Cystic Fibrosis, Andrew Skouby, Kayti Kintner, Kimberly Loughlin, Emily Blum, Michael Rush

Pharmacy and Wellness Review

Cystic fibrosis (CF) is a genetic disease associated with specific gene mutations that presents with pulmonary inflammation and frequent lung infections, exocrine pancreatic insufficiency, altered sweat composition and declining lung function. Ivacaftor (Kalydeco®) was approved for treatment of cystic fibrosis in patients 6 years of age and older with a G551D mutation on the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a CFTR potentiator and does not work in patients with a mutation of the F508del. Efficacy has been demonstrated in several trials with a primary outcome of improved FEV1, improvements in pulmonary exacerbations, patient-reported decrease in respiratory …

Bridging The Gap On Schistosomiasis: A Cross-Sectional Study Examining The Knowledge Gap And Common Attitudes And Practices Regarding S. Mansoni Infections Among Varying Education Levels In Luanda K’Otieno, Western Kenya, Kathy Zhang

Independent Study Project (ISP) Collection

Background: Schistosomiasis is considered one of the most prevalent neglected tropical diseases in the world. According to the World Health Organization (WHO), the most effective strategy for schistosomiasis control is through preventive chemotherapy with praziquantel (PZQ). In order to successfully control morbidity rates, the WHO recommends mass treatment targeting high risk groups, such as school-age children and adults considered to be at risk.

Methods: This cross-sectional study examined the effects of the National School-Based Deworming Programme (NSBDP) on knowledge of schistosomiasis and subsequent prevalence rates and intensity. A total of 43 residents in Luanda K’Otieno were interviewed, and 34 of …

Pediatric Poisoning: Overview, Treatment, And Prevention, Margaret Rowland, Taylor Gauthier, Kaitlin Sanders, Caitlin Swann, David Bright

Pharmacy and Wellness Review

Pediatric poisoning remains a common and preventable occurrence in the United States. Every year, prescription and over-the-counter medications account for a significant portion of documented poison exposures. Frequent causes of overdose in children include improper medication storage and caregiver or physician dosing error. As easily accessible medication experts, pharmacists have an opportunity to counsel patients in an effort to decrease these preventable poisoning cases. Because children frequently ingest products prescribed for adult use, pharmacist should relay safety considerations to all patients, regardless of age. This article provides a general review of toxicity concerns, discusses clinical implications of common medications resulting …

A Population Pharmacokinetic Model For Simvastatin And Its Metabolites In Children And Adolescents., Kayode Ogungbenro, Jonathan B. Wagner, Susan M. Abdel-Rahman, J Steven Leeder, Aleksandra Galetin

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Poor adherence to dietary/behaviour modifications as interventions for hypercholesterolemia in paediatric patients often necessitates the initiation of statin therapy. The aim of this study was to develop a joint population pharmacokinetic model for simvastatin and four metabolites in children and adolescents to investigate sources of variability in simvastatin acid exposure in this patient population, in addition to SLCO1B1 genotype status.

METHODS: Plasma concentrations of simvastatin and its four metabolites, demographic and polymorphism data for OATP1B1 and CYP3A5 were analysed utilising a population pharmacokinetic modelling approach from an existing single oral dose (10 mg < 17 years and 20 mg ≥ 18 years) pharmacokinetic dataset of 32 children and adolescents.

RESULTS: The population PK model included …

Development Of Substrate Degradation Enzyme Therapy For Mucopolysaccharidosis Iva Murine Model., Kazuki Sawamoto, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Conventional enzyme replacement therapy (ERT) is approved for MPS IVA. However, the fact that the infused enzyme cannot penetrate avascular lesions in cartilage leads to minimal impact on the bone lesion. Moreover, short half-life, high cost, instability, and narrow optimal pH range remain unmet challenges in ERT. Thermostable keratanase, endo-β-N-acetylglucosaminidase, has a unique character of a wide optimal pH range of pH 5.0-7.0. We hypothesized that this endoglycosidase degrades keratan sulfate (KS) polymer in circulating blood and, therefore, ameliorates the accumulation of KS in …

Whole Genome Metagenomic Analysis Of The Gut Microbiome Of Differently Fed Infants Identifies Differences In Microbial Composition And Functional Genes, Including An Absent Crispr/Cas9 Gene In The Formula-Fed Cohort, Matthew D. Di Guglielmo, Karl Franke, Courtney Cox, Erin L. Crowgey

Department of Pediatrics Faculty Papers

Background: Advancements in sequencing capabilities have enhanced the study of the human microbiome. There are limited studies focused on the gastro-intestinal (gut) microbiome of infants, particularly the impact of diet between breast-fed (BF) versus formula-fed (FF). It is unclear what effect, if any, early feeding has on short- term or long-term composition and function of the gut microbiome.

Results: Using a shotgun metagenomics approach, differences in the gut microbiome between BF (n = 10) and FF (n = 5) infants were detected. A Jaccard distance principle coordinate analysis was able to cluster BF versus FF infants based on the presence …

The Effect Of Antihypertensive Medications Dosing On Blood Pressure Control And Left Ventricular Hypertrophy In Children With Chronic Kidney Disease, Benjamin A. Matta

Research Days

No abstract provided.

Predictive Performance Of Existing Population Pharmacokinetic Models Of Tacrolimus In Pediatric Kidney Transplant Recipients, Alenka Chapron

Research Days

No abstract provided.

Gnrh Agonist Improves Hyperandrogenism In An Adolescent Girl With An Insulin Receptor Gene Mutation., Emily Paprocki, Romina Barral, Heidi Vanden Brink, Marla Lujan, Tania S. Burgert

Manuscripts, Articles, Book Chapters and Other Papers

Type A insulin resistance (IR) is caused by heterozygous mutations in the insulin receptor gene. It presents with mild acanthosis nigricans, severe IR, and hyperandrogenism in the absence of obesity or lipodystrophy. Treatment aims to improve insulin sensitivity and decrease androgens. An adolescent girl was evaluated for secondary amenorrhea and prominent hirsutism. She had a normal body mass index, and laboratory testing revealed an elevated LH to FSH ratio (LH 11.6 mIU/mL, FSH 4.2 mIU/mL), testosterone 96 ng/dL (reference range/dL), free testosterone 2.21 ng/dL (reference rangeA(pGly1032Asp)]. After standard treatment of hirsutism and hyperinsulinism failed, a trial of GnRH agonist therapy …

The Physiology And Hormonal Control Of Calcium, Phosphate And Vitamin D, Uri Alon

Presentations

Describes calcium, phophate, and vitamin D in the context of pediatric rickets.

The Effect Of Antihypertensive Dosing On Hypertension In Children With Chronic Kidney Disease, Benjamin A. Matta, Uri S. Alon, Tarak Srivastava, Bradley A. Warady, Darcy Weidemann

Posters

This study's objective was to determine the effect of antihypertensive dose on hypertension status in children with chronic kidney disease. This was the first quantitative analysis of antihypertensive dose expressed as a newly developed measure, cDDI, and is relationship with hypertension status in children with CKD.

Viral Whole Genome Sequencing For Antiviral Resistance In A Child With Dock8 Deficiency And Recurrent Hsv-1, Sean Stout, A. L. Greninger, Rangaraj Selvarangan, A. F. Freeman, Brandon D. Newell, Erin Stahl, Dwight Yin

Posters

We present the case of a child with dedicator of cytokinesis 8 (DOCK8) deficiency and chronic, resistant HSV-1 mucocutaneous infections to illustrate the clinical utility of viral whole genome sequencing to detect active and latent HSV resistance mutations.

Neuroblastoma In Adolescents And Children Older Than 10 Years: Unusual Clinicopathologic And Biologic Features, Laura Mccarthy, Katherine Chastain, Terrie Flatt, Eugenio Taboada, Robert E. Garola, John Herriges, Linda D. Cooley, Atif Ahmed

Posters

This poster describes four cases of neuroblastoma diagnosed since 2008 in children greater than 10 years and presents their clinical, histologic and biologic features, emphasizing unusual clinicopathologic characteristics and the role of DNA microarray analysis and Next Generation Sequencing in their management.

Predictive Performance Of Existing Population Pharmacokinetic Models Of Tacrolimus In Pediatric Kidney Transplant Recipients, Alenka Chapron, Susan M. Abdel-Rahman

Posters

With the goal of developing a clinician-driven tacrolimus (TAC) pharmacokinetic dosing tool, our initial objectives were 1) to examine whether published TAC population pharmacokinetic (popPK) models could serve as a foundation for the dosing tool, and 2) evaluate their performance predicting TAC concentrations in an independent cohort of Children's Mercy patients.

The Effect Of Antihypertensive Dosing On Hypertension In Children With Chronic Kidney Disease, Benjamin A. Matta, Uri S. Alon, Bradley Warady Md, Tarak Srivastava, Darcy Weidemann

Posters

Background

Hypertension (HTN) is a highly prevalent and major risk factor for poor cardiovascular and renal outcomes in chronic kidney disease (CKD). Previous research suggests that HTN is underdiagnosed and undertreated in children with CKD. To our knowledge no studies have investigated the effect of antihypertensive (antiHTN) dose on blood pressure (BP) control in this population.

Objective

To determine the effect of antiHTN dose on HTN status in children with CKD.

Methods

Study population: 255 participants studied in the Chronic Kidney Disease in Children (CKiD) study at their 3rd visit, taking at least 1 antiHTN drug.

Cumulative Drug Dose Index …

Dual Therapy Treatment Of Pediatric Acute Lymphoblastic Leukemia With Blinotumomab And A Standard Chemotherapy Regimen, Tori I. Scheffler

Selected Honors Theses

Leukemia is the number one cancer affecting children in the nation, with acute lymphoblastic leukemia being the most prevalent classification.1 While new and innovative treatment protocols have greatly increased the success rate of primary cancer patients, those who face relapse receive a much more dismal prognosis. Recent studies have shown that patients who relapse quite frequently have developed drug-resistant clones of the original cancer cells, leading to a need for various secondary treatment options. The drug-resistance is due to clonal mutations that take place within the cancer cell, most often because of an outside pressure or stress within the environment …

Considerations For Implementing Precision Therapeutics For Children., Matthew J. Mclaughlin, Jonathan B. Wagner, Valentina Shakhnovich, Bruce Carleton, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

Improving the utilization of pharmacologic agents in the pediatric population yields significant, perhaps life-long, benefits. Genetic factors related to the disposition of a medication or an alteration at the target receptor site contributes to the observed variability of exposure and response between individuals. An additional source of this variability specific to the pediatric population is ontogeny, where age-specific changes during development may require dose adjustments to obtain the same levels of drug exposure and response. With significant improvements in characterizing both the ontogeny and genetic contributions of drug metabolizing enzymes, the time is right to begin placing more emphasis on …

Early Progression Of Krabbe Disease In Patients With Symptom Onset Between 0 And 5 Months., Maria L. Beltran-Quintero, Nicholas A. Bascou, Michele D. Poe, David A. Wenger, Carlos A. Saavedra-Matiz, Matthew J. Nichols, Maria L. Escolar

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurological disorder caused by a deficiency in the lysosomal enzyme, β-galactocerebrosidase, resulting in demyelination of the central and peripheral nervous systems. If left without treatment, Krabbe disease results in progressive neurodegeneration with reduced quality of life and early death. The purpose of this prospective study was to describe the natural progression of early onset Krabbe disease in a large cohort of patients.

METHODS: Patients with early onset Krabbe disease were prospectively evaluated between 1999 and 2018. Data sources included diagnostic testing, parent questionnaires, standardized multidisciplinary neurodevelopmental assessments, and neuroradiological and neurophysiological tests.

RESULTS: We …

Pharmacological And Non-Pharmacological Treatments For The Neonatal Abstinence Syndrome (Nas)., A. K. Mangat, G. M. Schmölzer, W. K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Neonatal abstinence syndrome is defined by signs and symptoms of withdrawal that infants develop after intrauterine maternal drug exposure. All infants with documented in utero opioid exposure, or a high pre-test probability of exposure should have monitoring with a standard assessment instrument such as a Finnegan Score. A Finnegan score of >8 is suggestive of opioid exposure, even in the absence of declared use during pregnancy. At least half of infants in most locales can be treated without the use of pharmacologic means. For this reason, symptom scores will drive the decision for pharmacologic therapy. Nevertheless, all infants, regardless of …

Clinical Genome Sequencing In An Unbiased Pediatric Cohort., Isabelle Thiffault, Emily G. Farrow, Lee Zellmer, Courtney D. Berrios, Neil Miller, Margaret Gibson, Raymond Caylor, Janda L. Jenkins, Deb Faller, Sarah E. Soden, Carol J. Saunders

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: We report for the first time, the use of clinical genome sequencing (GS) in an unbiased pediatric cohort. We describe the clinical validation, patient metrics, ordering patterns, results, reimbursement, and physician retrieval of results for the first consecutive 80 cases.

METHODS: Clinical GS was performed for both inpatients and outpatients undergoing etiologic evaluations. Results were reported in the electronic medical record. Evidence of report retrieval by clinicians and whether interpretation was concordant with laboratory report was obtained through retrospective chart review.

RESULTS: Twenty definitive diagnoses were made in 19 patients (24%; n = 80). Except for two partial gene …

Kangaroo Mother Care And Traditional Care, Arianna Smola, Kirsten Lawson

Williams Honors College, Honors Research Projects

Prematurity and low birth weight are leading causes of infant death. Throughout recent years care methods for this population have evolved from incubator care to Kangaroo Mother Care (KMC). The purpose of this systematic review was to answer the following PICO question: in the case of preterm and low birth weight (LBW) infants, how does the technique of Kangaroo Mother Care (KMC) compare to traditional incubator use, regarding long and short-term outcomes of preterm and LBW infant recovery. Methods of this study included the selection of twenty peer-reviewed articles that studied the effect of incubators and KMC on premature and …