Medicine and Health Sciences Commons^™

A Novel Way To Describe Variation In Antibiotic Use, Adrienne G. Deporre, Troy Richardson, Jason Newland, Mark Neuman

Posters

Background: A broader understanding of antibiotic variation can inform stewardship efforts. Diversity indices are frequently calculated in ecologic studies to measure the variety of species in a given habitat, however they have not yet been used to study variation in antibiotic use in the healthcare setting.


Objective: To develop a novel assessment of antibiotic variation, based on the breadth of an antibiotic’s associated conditions as well as its use, measured by days of therapy (DOT).


Design/Methods: We assessed antibiotic use in children aged 60 days-18 years hospitalized at a US Children’s hospital included in the Pediatric Health Information System (PHIS) …

Parental Health Literacy And Acute Care Utilization In Children With Medical Complexity, Emily J. Goodwin, Joy L. Solano, Jessica L. Bettenhausen, Ryan Coller, Adrienne G. Deporre, Rupal Gupta, Kayla R. Heller, Lauren Jones, Leah Jones, Kathyrn Kyler, Ingrid Larson, Laura Plencner, Margaret Queen, Timothy Ryan Smith, Tyler Smith, Jacqueline M. Walker, Margaret Wright, Isabella Zaniletti, Jeffrey D. Colvin

Posters

Background: Inadequate health literacy, defined as inadequate ability to find, understand and use health information is associated with poor health outcomes and high health care costs. Children with medical complexity (CMC) have high rates of acute care utilization. Understanding parental health literacy in CMC and its relationship to acute care utilization may inform interventions designed to lower utilization.


Objective: To examine parental health literacy for CMC and determine its association with acute care utilization.


Design/Methods: In this single-site cross-sectional study, 250 parents of CMC completed a self-administered survey (response rate of 66.1%). CMC were included if they had a complex …

Medical Neglect: Trends In Reporting Practices And Patient Characteristics, Danielle Horton, Emily Killough, Mary Moffatt

Posters

Background: Medical neglect has significant consequences on child health and well-being. Improved processes for defining, recognizing, and reporting medical neglect are needed, however there is limited published data on the subject. Insight into patient characteristics and current reporting practices will help identify areas for intervention to improve outcomes for children at risk for medical neglect.


Objective: To describe characteristics of children identified for concern of medical neglect and trends in reporting of cases to child protective services (CPS).


Design/Methods: We performed a 1-year retrospective descriptive study of subjects < 18 years of age at a single, tertiary-care, academic pediatric institution for whom a Patient at Risk (PAR) assessment was completed exclusively for the concern of medical neglect. The PAR is a unique institutional process by which health professionals and social workers document concerns for child maltreatment. Medical records were reviewed for data regarding demographics, medical history, health care utilization and psychosocial risk factors. The role of the initiating provider and healthcare setting in which the PAR was recorded were also obtained.


Results: Of 270 children with a PAR completed for medical neglect concerns, …

Educating Providers: Timely Post-Operative Pain Management In A Level Iv Neonatal Intensive Care Unit (Nicu), Jamesia Donato, Darian Younger, Rebecca Palmer, Denise Smith, Alexandra Oschman, Meredith Kopp, Daphne Reavey, Eugenia K. Pallotto

Posters

Background: NICU patients often encounter painful procedures and can have significant short and long-term consequences from inadequately treated pain. Ensuring adequate pharmacological and non-pharmacological pain management while minimizing associated risks is paramount. Our NICU is part of the Children’s Hospitals Neonatal Consortium “Erase Pain” collaborative to improve management of postop pain in neonates.


Objective: SMART

Aim: Increase the percentage of patients receiving acetaminophen within one hour after surgery to greater than 70% by July 2020.


Design/Methods: A multidisciplinary team developed pain treatment algorithms and postop order plans to standardize the approach to postop pain management. Providers were educated about their …

Outpatient Antimicrobial Stewardship Programs In Children’S Hospitals: Status, Needs, Barriers, Rana El Feghaly, Elizabeth Monsees, Alaina N. Burns, Brian Lee, Ann L. Wirtz, Adam L. Hersh, Jason Newland

Posters

Background: Antimicrobial stewardship programs (ASPs) are an essential tool to combat the increasing threat of antibiotic resistance. ASPs traditionally reside in acute care settings with a focus on inpatient prescribing. However, in 2016, the Centers for Disease Control and Prevention affirmed the importance of outpatient ASP through its 4 core elements. Incorporation of these elements requires time, personnel, and funding, which may not be available in many institutions.


Objective: This study aimed to evaluate the current state of outpatient ASP in a large network of children’s hospitals and inform a programming agenda.


Design/Methods: This cross-sectional study used an investigator-developed survey …

Peripartum Antibiotics Induce Dysbiosis And Predispose The Neonatal Gut Towards Inflammation, Alain Cuna, Marianne N. Nsumu, Venkatesh Sampath

Posters

Background: Broad-spectrum antibiotics in preterm infants have been associated with necrotizing enterocolitis (NEC), but the exact mechanisms that explain this association remain poorly defined.


Objective: To examine the impact of peripartum antibiotics on gut microbiota and intestinal inflammation in the developing gut.


Design/Methods: C57BL6 dams were administered broad spectrum antibiotics mixed with sterile drinking water from E15 to postnatal day (P)14 (Fig 1). Gut microbiota were analyzed by targeted 16S PCR for total bacterial density and relative abundance of major bacterial phyla. Effects of antibiotics on inflammatory TLR-signaling and injury in the neonatal gut were evaluated with PCR and histology. …

Response To Dexamethasone Predicts Diagnosis Of Severe (Type 2) Bronchopulmonary Dysplasia Or Death, Christopher R. Nitkin, Keith Feldman, Alain Cuna, Alexandra Oschman, William E. Truog, Michael Norberg, Jane Taylor, Tamorah Lewis

Posters

Background: Bronchopulmonary dysplasia (BPD) is the most common respiratory morbidity after preterm birth but requires diagnosis at 36 weeks postmenstrual age (PMA). Dexamethasone is often used to treat infants at high-risk of BPD. The ability for earlier prediction of BPD, based on steroid response, could be useful as a surrogate marker for new therapies.


Objective: To construct a model that predicts severe BPD or death at 36 weeks PMA based on clinical response to dexamethasone.


Design/Methods: Retrospective chart review of preterm infants treated with dexamethasone between 2010-2020 at a Level IV NICU with data collected on demographics, age of steroid …

Characterization Of Comorbidities In Patients With A Dual Diagnosis Of Down Syndrome And Autism Spectrum Disorder Using Cerner Health Facts, Michael Slogic, Earl F. Glynn, Cy Nadler, Meredith Dreyer, Sarah T. Edwards

Presentations

Background: Up to 19% of patients with Down syndrome (DS) meet diagnostic criteria for autism spectrum disorder (ASD) (Channell, et al, 2019). While the medical and psychological comorbidities for patients with DS or ASD are well characterized, outcomes for patients with a dual diagnosis (DS-ASD) are poorly understood. Large DS-ASD cohorts and comparison samples are needed to fill this gap, as well as methods for grouping and analyzing complex diagnostic phenotypes. Objective: Our objective is to utilize Cerner Health Facts, a multi-institutional healthcare database, to identify large populations with DS, ASD, and DS-ASD, allowing for characterization and comparison of their …

Direct Hyperbilirubinemia In Infants With Trisomy 13 And 18, Jeffrey Kepple, Eric Peeples

Child Health Research Institute Pediatric Research Forum

Background: Survival in trisomy 13 (T13) and 18 (T18) has increased in recent years, but little is known about the prevalence and management of the non-lethal complications in these populations.

Significance of Problem: A subjectively high rate of direct hyperbilirubinemia (DH) was noted at Children’s Hospital & Medical Center compared to the general population. Defining the prevalence, timing, and risk factors for DH will allow for the development of screening and management guidelines.

Hypothesis, Problem or Question: We hypothesized that infants with T13 and T18 would have high rates of DH, with no significant difference in prevalence between …

Profound Neonatal Anemia Due To A Fetal To Maternal Hemorrhage: A Case Study, Margaret Hogan Smoot, Terrance Zach

Child Health Research Institute Pediatric Research Forum

A female infant was born by cesarean section at 36 weeks of gestation after the mother presented with perceived decreased fetal movement, blood-tinged mucous vaginal discharge, and a non-reactive non-stress test. Upon delivery, the infant appeared extremely pale and in mild respiratory distress. A complete blood count upon admission showed profound neonatal anemia, and a Kleihaur-Betke test confirmed fetomaternal hemorrhage as the cause. Transfusions corrected the infant’s hematocrit levels, and she was discharged on day 8 following a normal brain MRI. Fetal to maternal hemorrhage is a known cause of neonatal anemia, however the presentation is nonspecific leading to underdiagnosis …

Mir-1253 Potentiates Cisplatin Response In Pediatric Medulloblastoma By Regulating Ferroptosis, Ranjana K. Kanchan, Naveenkumar Perumal, Pranita Atri, Ramakanth C. Venkata, Ishwor Thapa, Mohd W. Nasser, Surinder K. Batra, Sidharth Mahapatra

Child Health Research Institute Pediatric Research Forum

Introduction Among CNS tumors, medulloblastoma (MB) is the most common malignant pediatric brain tumor. Of the four subgroups, group 3 (G3MB) tumors fare the worst. Haploinsufficiency of 17p13.3 is a hallmark of these high-risk tumors; included within this locus is miR-1253, which has tumor suppressive properties in medulloblastoma. Therapeutic strategies capitalizing on the anti-neoplastic properties of miRNAs can provide promising adjuncts that can improve efficacy while mitigating toxicity of current chemotherapeutic drugs.

Objective In this study, we explored the potentiation of miR-1253 on cisplatin cytotoxicity in group 3 MB.

Methods We used RNA Sequencing to isolate a putative target for …

Fit For Life: Educating About A Healthy Lifestyle In Omaha Elementary Schools, Emilee Greager, Mary Conklin, Jordan Nustad, Tyler Bendrick, Haley Bremer, Tavishi Chopra, Jane Driano, Connor Eggleston, Lily Foley, Jeffrey Kepple, Ryan Leuty, Taylor Mattice, Alison Mause, Elizabeth Mause, Molly Olsen, Breanne Parets, Heerali Patel, Thomas Pennington, Miranda Prints, Eva Schaible, Christopher Toivonen, Grace Vitek, Claire Willman, Allen Zheng, Kody Moffatt

Child Health Research Institute Pediatric Research Forum

Background: The prevalence of childhood obesity is increasing across the country. Health education at a young age is critical for children to establish healthy habits. The Fit for Life program is put together by Creighton medical students to inspire elementary students to lead a healthy lifestyle. The curriculum integrates physical exercise, real organ demonstrations, emotional wellness exercises, and nutritious meal building to model and encourage healthy habits.

Methods: Over four weeks, medical students taught the 4^th and 5^th graders of two Omaha schools over live video while they followed along with hands-on activities. Before and after the program, …

Klinefelter’S Syndrome: A Fortuitously Diagnosed By Non-Invasive Prenatal Testing, Steven V. Yackley, Terence L. Zach

Child Health Research Institute Pediatric Research Forum

Case Report: A male infant born at 37 weeks gestation. His mother was a 29-year-old, gravida 4 para 3 woman. During her pregnancy she was curious as to the gender of the fetus and requested a non-invasive prenatal test (NIPT) rather than fetal ultrasound. The NIPT returned with a karyotype of XXY. The male infant was born vaginally with a birth weight of 2670 grams. Apgar scores were 8 and 9 at one and five minutes respectively. He was admitted to the newborn intensive care unit secondary to respiratory distress. He had no obvious dysmorphic features. He had normal appearing …

Severe Colitis And Malnutrition In Association With Neonatal Hemophagocytic Lymphohistiocytosis, Laura Tarantino

Child Health Research Institute Pediatric Research Forum

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of overwhelming immune activation causing multiorgan dysfunction that may be genetic and/or acquired. Patients with familial HLH often present by one year of age, though most are asymptomatic in the first month of life. We present the case of a neonate with diarrhea and malnutrition who developed signs and symptoms consistent with a clinical diagnosis of HLH.

Case: A neonate born at 35 5/7 weeks was transferred to a Level IV neonatal intensive care unit at 39 4/7 weeks for failure to thrive. Though feeding adequately and non-dysmorphic, he had …

Expanding The Phenotype Of Hnrnpu-Related Disorders To Include Brief, Resolved, Unexplained Events (Brue), Jonah Scheffler, Kristen P. Fishler, Lois J. Starr

Child Health Research Institute Pediatric Research Forum

hnRNP-U deficiency is caused by pathogenic variants in HNRNPU, which encodes the heterogeneous nuclear ribonucleoprotein U (HNRNPU), a highly conserved protein responsible for assisting spliceosomes in mediating transcription and alternative splicing activity. HnRNPs are responsible for the regulation of translation at the presynaptic sites as well as the transportation of stabilized mRNAs along the axonal cytoskeleton. Here, we report a 2-year-old-male with a HNRNPU variant with a new presentation of apparent recurrent apneic spells with an underlying epileptic origin. These were described as apnea followed by desaturation and tachycardia in the 180's-200 range prior to resolution of symptoms. He also …

Relationship Between Mir-335 And Sterol Levels After In Vitro Hypoxia-Ischemia Of Primary Brain Cells, Namood-E Sahar, Zeljka Korade, Eric Peeples

Child Health Research Institute Pediatric Research Forum

Background/Purpose: Cholesterol homeostasis is vital for synaptogenesis and myelination during fetal and neonatal brain development. Both brain and plasma sterol levels have been shown to be associated with outcomes in adult stroke, and animal studies have suggested brain and plasma sterol changes in neonatal hypoxic-ischemic brain injury. MicroRNA-335 (miR-335) has been associated with brain sterol metabolism and our preliminary data showed that sterol metabolism is dysregulated in the brain after hypoxic-ischemic injury in a mouse model. This study sought to describe the effect of oxygen-glucose deprivation in vitro on individual brain cell populations and to validate the associations between sterol …

Postnatal Diagnosis Of Dandy Walker Malformation With Encephalocele, Heerali Patel

Child Health Research Institute Pediatric Research Forum

Encephalocele is a defect of the neural tube. Dandy Walker malformation (DWM) is a defect involving agenesis or hypoplasia of the cerebellar vermis, cystic dilation of the fourth ventricle, and enlargement of the posterior fossa. This is a case of a female preterm infant born at 36 weeks’ gestation who presented with DWM and an encapsulated occipital encephalocele at birth. The pregnancy was complicated by poorly controlled maternal diabetes. Prenatal ultrasound indicated a central nervous system anomaly. Amniocentesis did not show chromosomal abnormality. The infant also presented with polydactyly of the right thumb. MRI showed evidence of soft tissue within …

3d Printed Adjustable Glasses: A New Model Of Corrective Lens Delivery For Pediatric Refractive Error In Underserved Communities, Nathan Ostlie, Mari Ogino, Donny Suh, Gabe Linke, James Hermsen

Child Health Research Institute Pediatric Research Forum

Purpose:

Uncorrected refractive error (URE) remains a major cause of preventable vision impairment in the pediatric population with large inequities in disease burden. The present study aims to elucidate the global burden of pediatric URE and explore the current lens delivery systems which address this problem. Within this framework, we introduce a new model of corrective lens delivery that may improve upon existing models.

Methods:

The present study involved an extensive literature review of epidemiological data to determine the global prevalence of URE. Prevalence data was then compared against WHO data on refractionist coverage gaps divided by region. …

Perceptions Of Pediatricians On The Sars-Cov2 Vaccine, Karl Khandalavala, Kari Simonsen, Jeffrey A. Robinson

Child Health Research Institute Pediatric Research Forum

Introduction: The novel SARs-CoV2 coronavirus has infected approximately 30,000,000 people in the USA. To date, approximately 146 million doses of SARs-CoV2 vaccines have been administered. Perceptions of rapid vaccine development have resulted in reported vaccine hesitancy and refusal. Though not currently FDA approved for use in pediatric populations, but pediatric vaccination may contribute to herd immunity. Previous study demonstrates that physician recommendations significantly impact perceptions of routine pediatric immunizations among parents. Given this historical data, this study aimed to describe the strength of recommendation by pediatricians for the SARs-CoV2 vaccine for pediatric patients and their parents.

Methods: A …

The Role And Challenges Of Cluster Randomised Trials For Global Health, Louis Dron, Monica Taljaard, Yin Bun Cheung, Rebecca Grais, Nathan Ford, Kristian Thorlund, Fyezah Jehan, Etheldreda Nakimuli-Mpungu, Denis Xavier, Zulfiqar Ahmed Bhutta, Jay J H. Park, Edward J. Mills

Department of Paediatrics and Child Health

Evaluating whether an intervention works when trialled in groups of individuals can pose complex challenges for clinical research. Cluster randomised controlled trials involve the random allocation of groups or clusters of individuals to receive an intervention, and they are commonly used in global health research. In this paper, we describe the potential reasons for the increasing popularity of cluster trials in low-income and middle-income countries. We also draw on key areas of global health research for an assessment of common trial planning practices, and we address their methodological shortcomings and pitfalls. Lastly, we discuss alternative approaches for population-level intervention trials …

Recalibration Of The Renal Angina Index For Pediatric Septic Shock., Natalja L. Stanski, Hector R. Wong, Rajit K. Basu, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Scott L. Weiss, Michael T. Bigham, Parag N. Jain, Adam Schwarz, Riad Lutfi, Jeffrey Nowak, Geoffrey L. Allen, Neal J. Thomas, Jocelyn R. Grunwell, Michael Quasney, Bereketeab Haileselassie, Lakhmir S. Chawla, Stuart L. Goldstein

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Sepsis-associated acute kidney injury (AKI) is a common diagnosis in children that is associated with poor outcomes. The lack of therapeutic options once present makes early identification of at-risk patients essential. The renal angina index (RAI) has been previously validated to predict severe AKI in heterogeneous populations of critically ill children. The performance of this score specifically in children with septic shock is unknown.

Methods: A secondary analysis of a multicenter, prospective, observational study of 379 children with septic shock to determine the ability of the RAI to predict severe AKI at day 3, and to assess for the …

Sex As A Moderator In The Relationship Between Post-Operative Pain And Analgesics Administered In Children Undergoing Elective Surgery, Amber M. Osorno, Michelle A. Fortier, Zeev N. Kain, Brooke N. Jenkins

Student Scholar Symposium Abstracts and Posters

About 85% of children who undergo elective surgery experience pain post-operatively and many do not receive proper pain management care after discharge. Most parents lack an understanding of proper pain care management using analgesics upon discharge. Research reveals that adults rate girls as more sensitive to pain and that they display a greater amount of pain in a pediatric post-operative environment. In adulthood, women report more sensations of pain and have a higher pain tolerance, which can be attributed to physiological characteristics. Nonetheless, the social differences by which boys and girls experience pain and express their pain cannot be denied. …

Do I Add Value? A Mixed Methods Study Comparing Medical Students’ Experiences With Patient Documentation, Shannon Haines, Kari Nelson, Kaeli Samson, Nathan Gollehon

Child Health Research Institute Pediatric Research Forum

Background

Clinical documentation is an essential skill for practicing physicians, yet many medical students are not prepared for the documentation demands required during residency.^1,2 Recent CMS rule changes now allow medical students’ notes to be used for billing.³ Previous studies have shown positive perceptions of medical students whose notes were used in an outpatient setting.⁴ We utilized Constructivist Learning Theory to frame our work, where students construct their knowledge as faculty and residents facilitate the process.⁵

Objectives

To explore if using student documentation for billing impacts student perceptions and experiences during the pediatric clerkship.

Methods

Pediatric …

Food Protein Induced Enterocolitis Syndrome Triggers At Children’S Hospital, Rachel Nelson, Russell Hopp

Child Health Research Institute Pediatric Research Forum

Background

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food disease characterized by delayed vomiting and diarrhea, often at the first ingestion of the food. The clinical phenotype of FPIES, including trigger food and disease course, varies by region. A literature review of the most common FPIES foods in children in the United States and worldwide includes cow’s milk, soy, oats, rice, and egg.

Objective:

We sought to survey the most common FPIES foods seen at Children’s hospital in the past five years.

Methods:

A data search of the EPIC electronic medical record using FPIES codes ICD-10 (K52.21) and ICD-9 …

Urgently Seeking Efficiency And Sustainability Of Clinical Trials In Global Health, Jay J H. Park, Rebecca F. Grais, Monica Taljaard, Etheldreda Nakimuli-Mpungu, Fyezah Jehan, Jean B. Nachega, Nathan Ford, Denis Xavier, Andre P. Kengne, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

This paper shows the scale of global health research and the context in which we frame the subsequent papers in the Series. In this Series paper, we provide a historical perspective on clinical trial research by revisiting the 1948 streptomycin trial for pulmonary tuberculosis, which was the first documented randomised clinical trial in the English language, and we discuss its close connection with global health. We describe the current state of clinical trial research globally by providing an overview of clinical trials that have been registered in the WHO International Clinical Trial Registry since 2010. We discuss challenges with current …

Prospective Patient-Reported Symptom Profiles Associated With Pediatric Acute Lymphoblastic Leukemia Relapse, Austin L Brown, Kimberly P Raghubar, Olga A Taylor, Melanie Brooke Bernhardt, Lisa S Kahalley, Wei Pan, Philip J Lupo, Marilyn J Hockenberry, Michael E Scheurer

Faculty, Staff and Students Publications

PURPOSE: Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention.

METHODS: Pediatric patients with ALL (age 2-18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2). Symptom clusters for co-occurring fatigue, pain, sleep disruptions, and nausea were defined using latent profile analysis. Hazard ratios (HR) and 95% …

Global Trends In Norovirus Genotype Distribution Among Children With Acute Gastroenteritis., Jennifer L. Cannon, Joseph Bonifacio, Filemon Bucardo, Javier Buesa, Leesa Bruggink, Martin Chi-Wai Chan, Tulio M. Fumian, Sidhartha Giri, Mark D. Gonzalez, Joanne Hewitt, Jih-Hui Lin, Janet Mans, Christian Muñoz, Chao-Yang Pan, Xiao-Li Pang, Corinna Pietsch, Mustafiz Rahman, Naomi Sakon, Rangaraj Selvarangan, Hannah Browne, Leslie Barclay, Jan Vinjé

Manuscripts, Articles, Book Chapters and Other Papers

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children(genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains …

Critical Need For Pharmacologic Treatment Options In Nafld: A Pediatric Perspective., Chance S. Friesen, Sherwin S. Chan, Jonathan B. Wagner, Chelsea Hosey-Cojocari, Iván L Csanaky, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

Nonalcoholic fatty liver disease (NAFLD) affects up to 70% of children with obesity and has become the number one etiology for liver transplant in the United States. Early, effective intervention is critical to prevent disease progression into adulthood. Yet, it is seldom achieved through lifestyle modification alone. Thus, children must be included in NAFLD pharmacology trials, which, to date, continue to focus primarily on adult populations. This commentary serves as a call to action.

Factors Associated With Reduced Infliximab Exposure In The Treatment Of Pediatric Autoimmune Disorders: A Cross-Sectional Prospective Convenience Sampling Study., Ryan S. Funk, Valentina Shakhnovich, Yu Kyoung Cho, Kishore Polireddy, Taina Hudson, Kyle Gress, Mara L. Becker

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Inadequate systemic exposure to infliximab (IFX) is associated with treatment failure. This work evaluated factors associated with reduced IFX exposure in children with autoimmune disorders requiring IFX therapy.

METHODS: In this single-center cross-sectional prospective study IFX trough concentrations and anti-drug antibodies (ADAs) were measured in serum from children diagnosed with inflammatory bowel disease (IBD) (n = 73), juvenile idiopathic arthritis (JIA) (n = 16), or uveitis (n = 8) receiving maintenance IFX infusions at an outpatient infusion clinic in a tertiary academic pediatric hospital. IFX concentrations in combination with population pharmacokinetic modeling were used to estimate IFX clearance. Patient …

Investigation Of Alpl Variant States And Clinical Outcomes: An Analysis Of Adults And Adolescents With Hypophosphatasia Treated With Asfotase Alfa., Priya S. Kishnani, Guillermo Del Angel, Shanggen Zhou, Eric T. Rush

Manuscripts, Articles, Book Chapters and Other Papers

Background: Hypophosphatasia (HPP), a rare metabolic disease, can be inherited in an autosomal recessive (biallelic) or an autosomal dominant (monoallelic) manner. Most of the severe, early-onset, frequently lethal HPP in infants is acquired through recessive inheritance; less severe, later-onset, typically nonlethal HPP phenotypes are acquired through either dominant or recessive inheritance. HPP's variable clinical presentation arises from >400 identified ALPL pathogenic variants with likely variable penetrance, especially with autosomal dominant inheritance. This post hoc analysis investigated the relationship between ALPL variant state (biallelic and monoallelic) and clinical outcomes with asfotase alfa in HPP.

Methods: Data were pooled from two phase …