Medicine and Health Sciences Commons^™

Effect Of Kidney Function On Drug Kinetics And Dosing In Neonates, Infants, And Children., Frederique Rodieux, Melanie Wilbaux, Johannes N. Van Den Anker, Marc Pfister

Pediatrics Faculty Publications

Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood …

The Creation Of A Model Pediatric Ward For African American Children In 1920s Kansas City., Jane F. Knapp, Robert Schremmer

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Safety And Immunogenicity Of Human Serum Albumin-Free Mmr Vaccine In Us Children Aged 12-15 Months., Maurice A. Mufson, Clemente Diaz, Michael Leonardi, Christopher J. Harrison, Stanley Grogg, Antonio Carbayo, Simon Carlo-Torres, Robert Jeanfreau, Ana Quintero-Del-Rio, Gisele Bautista, Michael Povey, Christopher Da Costa, Ouzama Nicholson, Bruce L. Innis

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: M-M-R(TM)II (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (Priorix(TM), GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States.

METHODS: In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12-15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis A vaccine …

Mortality-Related Resource Utilization In The Inpatient Care Of Hypoplastic Left Heart Syndrome., David A. Danford, Quentin Karels, Aparna Kulkarni, Aysha Hussain, Yunbin Xiao, Shelby Kutty

Journal Articles: Pediatrics

BACKGROUND: Quantifying resource utilization in the inpatient care of congenital heart diease is clinically relevant. Our purpose is to measure the investment of inpatient care resources to achieve survival in hypoplastic left heart syndrome (HLHS), and to determine how much of that investment occurs in hospitalizations that have a fatal outcome, the mortality-related resource utilization fraction (MRRUF).

METHODS: A collaborative administrative database, the Pediatric Health Information System (PHIS) containing data for 43 children's hospitals, was queried by primary diagnosis for HLHS admissions of patients ≤21 years old during 2004-2013. Institution, patient age, inpatient deaths, billed charges (BC) and length of …

Prognostic Role Of Bnp In Children Undergoing Surgery For Congenital Heart Disease: Analysis Of Prediction Models Incorporating Standard Risk Factors., Massimiliano Cantinotti, Raffaele Giordano, Marco Scalese, Sabrina Molinaro, Francesca Della Pina, Simona Storti, Luigi Arcieri, Bruno Murzi, Marco Marotta, Vitali Pak, Vincenzo Poli, Giorgio Iervasi, Shelby Kutty, Aldo Clerico

Journal Articles: Pediatrics

BACKGROUND: The routine use of brain natriuretic peptide (BNP) in pediatric cardiac surgery remains controversial. Our aim was to test whether BNP adds information to predict risk in pediatric cardiac surgery.

METHODS: In all, 587 children undergoing cardiac surgery (median age 6.3 months; 1.2-35.9 months) were prospectively enrolled at a single institution. BNP was measured pre-operatively, on every post-operative day in the intensive care unit, and before discharge. The primary outcome was major complications and length ventilator stay >15 days. A first risk prediction model was fitted using Cox proportional hazards model with age, body surface area and Aristotle score …

Speckle-Tracking Echocardiographic Measures Of Right Ventricular Function Correlate With Improvement In Exercise Function After Percutaneous Pulmonary Valve Implantation., Shahryar M. Chowdhury, Ziyad M. Hijazi, John T. Fahey, John F. Rhodes, Saibal Kar, Raj Makkar, Michael Mullen, Qi-Ling Cao, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Speckle-tracking echocardiographic (STE) measures of right ventricular (RV) function appear to improve after transcatheter pulmonary valve implantation (TPVI). Measures of exercise function, such as ventilatory efficiency (the minute ventilation [VE]/carbon dioxide production [VCO2] slope), have been shown to be prognostic of mortality in patients who may require TPVI. The aim of this study was to evaluate the correlation between STE measures of RV function and changes in VE/VCO2 after TPVI.

METHODS: Speckle-tracking echocardiography and cardiopulmonary exercise testing were performed at baseline and 6 months after TPVI in 24 patients from four centers. Conventional echocardiographic measures of RV function were …

The Development And Application Of An Oncology Therapy-Related Symptom Checklist For Adults (Trsc) And Children (Trsc-C) And E-Health Applications., Arthur R. Williams, David D. Williams, Phoebe D. Williams, Farrokh Alemi, Hosai Hesham, Blaine Donley, Raya E. Kheirbek

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Studies found that treatment symptoms of concern to oncology/hematology patients were greatly under-identified in medical records. On average, 11.0 symptoms were reported of concern to patients compared to 1.5 symptoms identified in their medical records. A solution to this problem is use of an electronic symptom checklist that can be easily accessed by patients prior to clinical consultations.

PURPOSE: Describe the oncology Therapy-Related Symptom Checklists for Adults (TRSC) and Children (TRSC-C), which are validated bases for e-Health symptom documentation and management. The TRSC has 25 items/symptoms; the TRSC-C has 30 items/symptoms. These items capture up to 80% of the …

Two Novel Genetic Variants In The Mineralocorticoid Receptor Gene Associated With Spontaneous Preterm Birth, Inge Christiaens, Q. Wei Ang, Lindsay N. Gordon, Xin Fang, Scott Williams

Dartmouth Scholarship

Background: Preterm birth is the leading cause of mortality and morbidity in newborn infants. Its etiology is multifactorial with genes and environmental factors, including chronic maternal stress, contributing to its risk. Our objective was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in the stress response are associated with spontaneous preterm birth using a candidate gene approach.

Methods: A total of 210 cases (singleton spontaneous preterm birth at <37 >weeks) and 412 controls (singleton term birth at 38–42 weeks without a history of preterm birth) were studied. High quality maternal DNA was available from saliva samples of 190 cases …

Task Force 2: Pediatric Cardiology Fellowship Training In Noninvasive Cardiac Imaging. Spctpd/Acc/Aap/Aha., Shubhika Srivastava, Beth F Printz, Tal Geva, Girish S. Shirali, Paul M Weinberg, Pierre C Wong, Peter Lang, Society Of Pediatric Cardiology Training Program Directors, American College Of Cardiology, American Academy Of Pediatrics, American Heart Association

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Task Force 2: Pediatric Cardiology Fellowship Training In Noninvasive Cardiac Imaging., Shubhika Srivastava, Beth F. Printz, Tal Geva, Girish S. Shirali, Paul M. Weinberg, Pierre C. Wong, Peter Lang

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Prevalence Of And Risk Factors For Intracranial Abnormalities In Unprovoked Seizures., Peter S. Dayan, Kathleen Lillis, Jonathan Bennett, Gregory P. Conners, Pam Bailey, James Callahan, Cigdem Akman, Neil Feldstein, Joshua Kriger, W Allen Hauser, Nathan Kuppermann

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Prospective data are lacking to determine which children might benefit from prompt neuroimaging after unprovoked seizures. We aimed to determine the prevalence of, and risk factors for, relevant intracranial abnormalities in children with first, unprovoked seizures.

METHODS: We conducted a 6-center prospective study in children aged >28 days to 18 years with seemingly unprovoked seizures. Emergency department (ED) clinicians documented clinical findings on a standardized form. Our main outcome was the presence of a clinically relevant intracranial abnormality on computed tomography (CT) or MRI, defined as those that might change management, either emergently, urgently, or nonurgently.

RESULTS: …

Scarnas Regulate Splicing And Vertebrate Heart Development., Prakash Patil, Nataliya Kibiryeva, Tamayo Uechi, Jennifer A. Marshall, James E. O'Brien, Michael Artman, Naoya Kenmochi, Douglas C. Bittel

Manuscripts, Articles, Book Chapters and Other Papers

Alternative splicing (AS) plays an important role in regulating mammalian heart development, but a link between misregulated splicing and congenital heart defects (CHDs) has not been shown. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF). Moreover, there was a significant decrease in the level of 12 small cajal body-specific RNAs (scaRNAs) that direct the biochemical modification of specific nucleotides in spliceosomal RNAs. We sought to determine if scaRNA levels influence patterns of AS and heart development. We used primary cells derived …

Efficacy Of Galactose And Adalimumab In Patients With Resistant Focal Segmental Glomerulosclerosis: Report Of The Font Clinical Trial Group., Howard Trachtman, Suzanne Vento, Emily Herreshoff, Milena Radeva, Jennifer Gassman, Daniel T. Stein, Virginia J. Savin, Mukut Sharma, Jochen Reiser, Changli Wei, Michael Somers, Tarak Srivastava, Debbie S. Gipson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with resistant focal segmental glomerulosclerosis (FSGS) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease. In the absence of curative treatment, current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS) Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was designed to assess the efficacy of adalimumab and galactose compared to standard medical therapy which was comprised of lisinopril, losartan, and atorvastatin.

METHODS: Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative …

Improving Early Infant Hiv Diagnosis In Kenya: Study Protocol Of A Cluster-Randomized Efficacy Trial Of The Hitsystem., Sarah Finocchario-Kessler, Kathy Goggin, Samoel Khamadi, Brad Gautney, Jacinda K. Dariotis, Charles Bawcom, An-Lin Cheng, Niaman Nazir, Catherine Martin, Andrea Ruff, Michael Sweat, Vincent Okoth

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Early infant diagnosis among human immunodeficiency virus (HIV)-exposed infants is a critical component of prevention of mother-to-child transmission programs. Barriers to early infant diagnosis include poor uptake, low retention at designated re-testing intervals, delayed test results, passive systems of communication, and poor linkage to treatment. This study will evaluate the HIV Infant Tracking System (HITSystem), an eHealth intervention that streamlines communication and accountability between the key early infant diagnosis stakeholders: HIV+ mothers and their HIV-exposed infants, healthcare providers, and central laboratory personnel. It is hypothesized that the HITSystem will significantly improve early infant diagnosis retention at 9 and 18 …

Hla-Dqa1 And Plcg2 Are Candidate Risk Loci For Childhood-Onset Steroid-Sensitive Nephrotic Syndrome., Rasheed A. Gbadegesin, Adebowale Adeyemo, Nicholas J A Webb, Larry A A. Greenbaum, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arundhati Kale, Debbie Gipson, Tarak Srivastava, Jen-Jar Lin, Deepa Chand, Tracy E. Hunley, Patrick D. Brophy, Arvind Bagga, Aditi Sinha, Michelle N. Rheault, Joanna Ghali, Kathy Nicholls, Elizabeth Abraham, Halima S. Janjua, Abiodun Omoloja, Gina-Marie Barletta, Yi Cai, David D. Milford, Catherine O'Brien, Atif Awan, Vladimir Belostotsky, William E. Smoyer, Alison Homstad, Gentzon Hall, Guanghong Wu, Shashi Nagaraj, Delbert Wigfall, John Foreman, Michelle P. Winn, Mid-West Pediatric Nephrology Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were …

Procollagen C-Endopeptidase Enhancer Protein 2 (Pcpe2) Reduces Atherosclerosis In Mice By Enhancing Scavenger Receptor Class B1 (Sr-Bi)-Mediated High-Density Lipoprotein (Hdl)-Cholesteryl Ester Uptake, Ricquita D. Pollard, Christopher N. Blesso, Manal Zabalawi, Brian Fulp, Mark Gerelus, Xuewei Zhu, Erica W. Lyons, Nebil Nuradin, Omar L. Francone, Xiang-An Li, Daisy Sahoo, Michael J. Thomas, Mary G. Sorci-Thomas

Pediatrics Faculty Publications

Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr^-/-, PCPE2^-/- mice, which had elevated HDL levels compared with LDLr^-/- mice with similar …

Prophylactic Methylprednisolone To Reduce Inflammation And Improve Outcomes From One Lung Ventilation In Children: A Randomized Clinical Trial., Mary C. Theroux, Alicia Olivant Fisher, Maria E. Rodriguez, Robert P. Brislin, Kirk W. Reichard, Suken A. Shah, Matt Mccoy, Melinda Brown, Kirk W. Dabney, William G. Mackenzie, Douglas A. Katz, Thomas H. Shaffer

Department of Anesthesiology Faculty Papers

BACKGROUND: One lung ventilation (OLV) results in inflammatory and mechanical injury, leading to intraoperative and postoperative complications in children. No interventions have been studied in children to minimize such injury.

OBJECTIVE: We hypothesized that a single 2-mg·kg(-1) dose of methylprednisolone given 45-60 min prior to lung collapse would minimize injury from OLV and improve physiological stability.

METHODS: Twenty-eight children scheduled to undergo OLV were randomly assigned to receive 2 mg·kg(-1) methylprednisolone (MP) or normal saline (placebo group) prior to OLV. Anesthetic management was standardized, and data were collected for physiological stability (bronchospasm, respiratory resistance, and compliance). Plasma was assayed for …

Central Line-Associated Blood Stream Infections In Pediatric Intensive Care Units: Longitudinal Trends And Compliance With Bundle Strategies., Jeffrey D. Edwards, Carolyn T. Herzig, Hangsheng Liu, Monika Pogorzelska-Maziarz, Philip Zachariah, Andrew W. Dick, Lisa Saiman, Patricia W. Stone, E. Yoko Furuya

College of Nursing Faculty Papers & Presentations

BACKGROUND: Knowing the temporal trend central line-associated bloodstream infection (CLABSI) rates among U.S. pediatric intensive care units (PICUs), the current extent of central line bundle compliance, and the impact of compliance on rates is necessary to understand what has been accomplished and can be improved in CLABSI prevention.

METHODS: This is a longitudinal study of PICUs in National Healthcare Safety Network hospitals and a cross-sectional survey of directors and managers of infection prevention and control departments regarding PICU CLABSI prevention practices, including self-reported compliance with elements of central line bundles. Associations between 2011-2012 PICU CLABSI rates and infection prevention practices …

The Reproducibility And Absolute Values Of Echocardiographic Measurements Of Left Ventricular Size And Function In Children Are Algorithm Dependent., Renee Margossian, Shan Chen, Lynn A. Sleeper, Lloyd Y. Tani, Girish S. Shirali, Fraser Golding, Elif Seda Selamet Tierney, Karen Altmann, Michael J. Campbell, Anita Szwast, Angela Sharkey, Elizabeth Radojewski, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Several quantification algorithms for measuring left ventricular (LV) size and function are used in clinical and research settings. The aims of this study were to investigate the effects of measurement algorithm and beat averaging on the reproducibility of measurements of the left ventricle and to assess the magnitude of agreement among the algorithms in children with dilated cardiomyopathy.

METHODS: Echocardiograms were obtained in 169 children from eight clinical centers. Inter- and intrareader reproducibility was assessed on measurements of LV volumes using the biplane Simpson, modified Simpson, and 5/6 × area × length (5/6AL) algorithms. Percentage error was calculated as …

Oseltamivir-Warfarin Interaction In Hypoplastic Left Heart Syndrome: Case Report And Review., Jonathan B. Wagner, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

An 8-year-old boy with hypoplastic left heart syndrome with a previous history of thrombosis within the inferior vena cava receiving stable warfarin dosing for anticoagulation was diagnosed with influenza B. He was subsequently placed on oseltamivir therapy according to the Centers for Disease Control and Prevention clinical practice guidelines. During the hospitalization, his international normalized ratio steadily increased to supratherapeutic levels and returned to baseline after discontinuation of oseltamivir therapy. This case represents a drug-drug interaction that has not been previously reported in children or adolescents. An extensive review of the pharmacokinetic and pharmacodynamic literature did not uncover a definitive …

Point-Of-Care Ultrasonography By Pediatric Emergency Medicine Physicians., Jennifer R. Marin, Resa E. Lewiss, American Academy Of Pediatrics, Committee On Pediatric Emergency Medicine, Society For Academic Emergency Medicine, Academy Of Emergency Ultrasound, American College Of Emergency Physicians, Pediatric Emergency Medicine Committee, World Interactive Network Focused On Critical Ultrasound, Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

Emergency physicians have used point-of-care ultrasonography since the 1990 s. Pediatric emergency medicine physicians have more recently adopted this technology. Point-of-care ultrasonography is used for various scenarios, particularly the evaluation of soft tissue infections or blunt abdominal trauma and procedural guidance. To date, there are no published statements from national organizations specifically for pediatric emergency physicians describing the incorporation of point-of-care ultrasonography into their practice. This document outlines how pediatric emergency departments may establish a formal point-of-care ultrasonography program. This task includes appointing leaders with expertise in point-of-care ultrasonography, effectively training and credentialing physicians in the department, and providing ongoing …

Intracellular Cd24 Disrupts The Arf-Npm Interaction And Enables Mutational And Viral Oncogene-Mediated P53 Inactivation., Lizhong Wang, Runhua Liu, Peiying Ye, Chunshu Wong, Guo-Yun Chen, Penghui Zhou, +11 Additional Authors

Pediatrics Faculty Publications

CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the …

Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors

Pediatrics Faculty Publications

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar …

Best Practices For Improving Flow And Care Of Pediatric Patients In The Emergency Department., Isabel Barata, Kathleen M. Brown, Laura Fitzmaurice, Elizabeth Stone Griffin, Sally K. Snow, American College Of Emergency Physicians Pediatric Emergency Medicine Committee, Emergency Nurses Association Pediatric Committee, Gregory P. Conners, American Academy Of Pediatrics Committee On Pediatric Emergency Medicine

Manuscripts, Articles, Book Chapters and Other Papers

This report provides a summary of best practices for improving flow, reducing waiting times, and improving the quality of care of pediatric patients in the emergency department.

Patient- And Family-Centered Care Of Children In The Emergency Department., Nanette Dudley, Alice Ackerman, Kathleen M. Brown, Sally K. Snow, American Academy Of Pediatrics Committee On Pediatric Emergency Medicine, American College Of Emergency Physicians Pediatric Emergency Medicine Committee, Emergency Nurses Association Pediatric Committee., Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

Patient- and family-centered care is an approach to the planning, delivery, and evaluation of health care that is grounded in a mutually beneficial partnership among patients, families, and health care professionals. Providing patient- and family-centered care to children in the emergency department setting presents many opportunities and challenges. This revised technical report draws on previously published policy statements and reports, reviews the current literature, and describes the present state of practice and research regarding patient- and family-centered care for children in the emergency department setting as well as some of the complexities of providing such care.