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Intravenous Versus Oral Antibiotics For Postdischarge Treatment Of Complicated Pneumonia., Samir S. Shah, Rajendu Srivastava, Susan Wu, Jeffrey D. Colvin, Derek J. Williams, Shawn J. Rangel, Waheeda Samady, Suchitra Rao, Christopher Miller, Cynthia Cross, Caitlin Clohessy, Matthew Hall, Russell Localio, Matthew Bryan, Gong Wu, Ron Keren, Pediatric Research In Inpatient Settings Network Dec 2016

Intravenous Versus Oral Antibiotics For Postdischarge Treatment Of Complicated Pneumonia., Samir S. Shah, Rajendu Srivastava, Susan Wu, Jeffrey D. Colvin, Derek J. Williams, Shawn J. Rangel, Waheeda Samady, Suchitra Rao, Christopher Miller, Cynthia Cross, Caitlin Clohessy, Matthew Hall, Russell Localio, Matthew Bryan, Gong Wu, Ron Keren, Pediatric Research In Inpatient Settings Network

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Postdischarge treatment of complicated pneumonia includes antibiotics administered intravenously via a peripherally inserted central venous catheter (PICC) or orally. Antibiotics administered via PICC, although effective, may result in serious complications. We compared the effectiveness and treatment-related complications of postdischarge antibiotics delivered by these 2 routes.

METHODS: This multicenter retrospective cohort study included children ≥2 months andadministration, classified as PICC or oral. The primary outcome was treatment failure. Secondary outcomes included PICC complications, adverse drug reactions, other related revisits, and a composite of all 4 outcomes, termed "all related revisits."

RESULTS: Among 2123 children, 281 (13.2%) received antibiotics …


Infant Sleep Problems And Childhood Overweight: Effects Of Three Definitions Of Sleep Problems, Arsham Alamian, Liang Wang, Amber M. Hall, Melanie Pitts, Joseph Ikekwere Dec 2016

Infant Sleep Problems And Childhood Overweight: Effects Of Three Definitions Of Sleep Problems, Arsham Alamian, Liang Wang, Amber M. Hall, Melanie Pitts, Joseph Ikekwere

ETSU Faculty Works

Sleep problems have been defined using a variety of definitions. No study has assessed the longitudinal association between infant sleep problems and childhood overweight or obesity using existing definitions of sleep problems. This study used longitudinal data (n=895) from the multi-site Study of Early Child Care and Youth Development (SECCYD) to investigate the effects of infant sleep problems on childhood weight status in Grade 6. Infants with sleep problems in Phase I (1991) and with complete data through Phase III (2004) of SECCYD were included. Sleep problems were assessed using maternal reports of night wakings and duration of a waking …


Indoor Tobacco Legislation Is Associated With Fewer Emergency Department Visits For Asthma Exacerbation In Children., Christina E. Ciaccio, Tami Gurley-Calvez, Theresa I. Shireman Dec 2016

Indoor Tobacco Legislation Is Associated With Fewer Emergency Department Visits For Asthma Exacerbation In Children., Christina E. Ciaccio, Tami Gurley-Calvez, Theresa I. Shireman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: During the past 3 decades, numerous cities and states have adopted laws that ban smoking in public indoor spaces. The rationale for these policies has been to protect nonsmokers from the adverse health effects of secondhand smoke.

OBJECTIVE: To determine whether the implementation of indoor smoking legislation is associated with a decrease in emergency department visits for asthma in children.

METHODS: This retrospective analysis used a natural experiment to estimate the impact of clean indoor air legislation on the rate of emergency department admissions for asthma exacerbation in children. Data were obtained from the Pediatric Health Information System. A …


Mir-155 Expression And Correlation With Clinical Outcome In Pediatric Aml: A Report From Children's Oncology Group., Ranjani Ramamurthy, Maya Hughes, Valerie Morris, Hamid Bolouri, Robert B. Gerbing, Yi-Cheng Wang, Michael R. Loken, Susana C. Raimondi, Betsy A. Hirsch, A S. Gamis, Vivian G. Oehler, Todd A. Alonzo, Soheil Meshinchi Dec 2016

Mir-155 Expression And Correlation With Clinical Outcome In Pediatric Aml: A Report From Children's Oncology Group., Ranjani Ramamurthy, Maya Hughes, Valerie Morris, Hamid Bolouri, Robert B. Gerbing, Yi-Cheng Wang, Michael R. Loken, Susana C. Raimondi, Betsy A. Hirsch, A S. Gamis, Vivian G. Oehler, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Aberrant expression of microRNA-155 (miR-155) has been implicated in acute myeloid leukemia (AML) and associated with clinical outcome.

PROCEDURE: We evaluated miR-155 expression in 198 children with normal karyotype AML (NK-AML) enrolled in Children's Oncology Group (COG) AML trial AAML0531 and correlated miR-155 expression levels with disease characteristics and clinical outcome. Patients were divided into quartiles (Q1-Q4) based on miR-155 expression level, and disease characteristics were then evaluated and correlated with miR-155 expression.

RESULTS: MiR-155 expression varied over 4-log10-fold range relative to its expression in normal marrow with a median expression level of 0.825 (range 0.043-25.630) for the entire …


Cataract Surgery In Children From Birth To Less Than 13 Years Of Age: Baseline Characteristics Of The Cohort., Michael X. Repka, Trevano W. Dean, Elizabeth L. Lazar, Kimberly G. Yen, Phoebe D. Lenhart, Sharon F. Freedman, Denise Hug, Bahram Rahmani, Serena X. Wang, Raymond T. Kraker, David K. Wallace, Pediatric Eye Disease Investigator Group Dec 2016

Cataract Surgery In Children From Birth To Less Than 13 Years Of Age: Baseline Characteristics Of The Cohort., Michael X. Repka, Trevano W. Dean, Elizabeth L. Lazar, Kimberly G. Yen, Phoebe D. Lenhart, Sharon F. Freedman, Denise Hug, Bahram Rahmani, Serena X. Wang, Raymond T. Kraker, David K. Wallace, Pediatric Eye Disease Investigator Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe baseline characteristics, initial postoperative refractive errors, operative complications, and magnitude of the intraocular lens (IOL) prediction error for refractive outcome in children undergoing lensectomy largely in North America.

DESIGN: Prospective registry study of children from birth to enrollment.

PARTICIPANTS: Total of 1266 eyes of 994 children; 49% female and 59% white.

METHODS: Measurement of refractive error, axial length, and complete ophthalmic examination.

MAIN OUTCOME MEASURES: Eye and systemic associated conditions, IOL style, refractive error, pseudophakic refraction prediction error, operative and perioperative complications.

RESULTS: Mean age at first eligible lens surgery was 4.2 years; 337 (34%) were(59%). Additional …


A 9-Year-Old Boy With A Chest Mass And Eosinophilia., Laura E. Norton, Sean N. Curtis, Jennifer L. Goldman Dec 2016

A 9-Year-Old Boy With A Chest Mass And Eosinophilia., Laura E. Norton, Sean N. Curtis, Jennifer L. Goldman

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


A Trial Of Unrelated Donor Marrow Transplantation For Children With Severe Sickle Cell Disease., Shalini Shenoy, Mary Eapen, Julie A. Panepinto, Brent R. Logan, Juan Wu, Allistair Abraham, Joel Brochstein, Sonali Chaudhury, Kamar Godder, Ann E. Haight, Kimberly A. Kasow, Kathryn Leung, Martin Andreansky, Monica Bhatia, Jignesh Dalal, Hilary Haines, Jennifer Jaroscak, Hillard M. Lazarus, John E. Levine, Lakshmanan Krishnamurti, David Margolis, Gail C. Megason, Lolie C. Yu, Michael A. Pulsipher, Iris Gersten, Nancy Difronzo, Mary M. Horowitz, Mark C. Walters, Naynesh Kamani Nov 2016

A Trial Of Unrelated Donor Marrow Transplantation For Children With Severe Sickle Cell Disease., Shalini Shenoy, Mary Eapen, Julie A. Panepinto, Brent R. Logan, Juan Wu, Allistair Abraham, Joel Brochstein, Sonali Chaudhury, Kamar Godder, Ann E. Haight, Kimberly A. Kasow, Kathryn Leung, Martin Andreansky, Monica Bhatia, Jignesh Dalal, Hilary Haines, Jennifer Jaroscak, Hillard M. Lazarus, John E. Levine, Lakshmanan Krishnamurti, David Margolis, Gail C. Megason, Lolie C. Yu, Michael A. Pulsipher, Iris Gersten, Nancy Difronzo, Mary M. Horowitz, Mark C. Walters, Naynesh Kamani

Manuscripts, Articles, Book Chapters and Other Papers

Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, …


Cardiovascular Disease Risk Factors And Left Ventricular Hypertrophy In Girls And Boys With Ckd., Rebecca L. Ruebner, Derek Ng, Mark Mitsnefes, Bethany J. Foster, Kevin Meyers, Bradley A. Warady, Susan L. Furth Nov 2016

Cardiovascular Disease Risk Factors And Left Ventricular Hypertrophy In Girls And Boys With Ckd., Rebecca L. Ruebner, Derek Ng, Mark Mitsnefes, Bethany J. Foster, Kevin Meyers, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

Background and objectives: Prior studies suggested that women with CKD have higher risk for cardiovascular disease (CVD) and mortality than men, although putative mechanisms for this higher risk have not been identified. We assessed sex differences in (1) CVD risk factors and left ventricular hypertrophy (LVH), and (2) the relationship of left ventricular mass (LVM) with different measures of body size in children with CKD.

Design, setting, participants, and measurements: The study population comprised 681 children with CKD from the Chronic Kidney Disease in Children cohort, contributing 1330 visits. CVD risk factors were compared cross-sectionally by sex. LVH was defined …


Processing Information After A Child's Cancer Diagnosis-How Parents Learn., Cheryl C. Rodgers, Kristin Stegenga, Janice S. Withycombe, Karen Sachse, Katherine Patterson Kelly Nov 2016

Processing Information After A Child's Cancer Diagnosis-How Parents Learn., Cheryl C. Rodgers, Kristin Stegenga, Janice S. Withycombe, Karen Sachse, Katherine Patterson Kelly

Manuscripts, Articles, Book Chapters and Other Papers

Parents of a child newly diagnosed with cancer must receive an extensive amount of information before their child's initial hospital discharge; however, little is known about best practices for providing this education. An interpretive descriptive study design was used to describe actual and preferred educational content, timing, and methods among parents of children newly diagnosed with cancer prior to their child's first hospital discharge. Twenty parents of children diagnosed with various malignancies participated in individual interviews 2 to 12 months after their child's diagnosis. Data were analyzed using constant comparative analysis. Education delivery occurred in a telling manner at diagnosis …


Association Between Prolonged Neutropenia And Reduced Relapse Risk In Pediatric Aml: A Report From The Children's Oncology Group., Lillian Sung, Richard Aplenc, Todd A. Alonzo, Robert B. Gerbing, Yi-Cheng Wang, Soheil Meshinchi, A S. Gamis Nov 2016

Association Between Prolonged Neutropenia And Reduced Relapse Risk In Pediatric Aml: A Report From The Children's Oncology Group., Lillian Sung, Richard Aplenc, Todd A. Alonzo, Robert B. Gerbing, Yi-Cheng Wang, Soheil Meshinchi, A S. Gamis

Manuscripts, Articles, Book Chapters and Other Papers

Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five …


Assessment Of Diastolic Function In Single-Ventricle Patients After The Fontan Procedure., Renee Margossian, Lynn A. Sleeper, Gail D. Pearson, Piers C. Barker, Luc Mertens, Michael D. Quartermain, Jason T. Su, Girish S. Shirali, Shan Chen, Steven D. Colan, Pediatric Heart Network Investigators Nov 2016

Assessment Of Diastolic Function In Single-Ventricle Patients After The Fontan Procedure., Renee Margossian, Lynn A. Sleeper, Gail D. Pearson, Piers C. Barker, Luc Mertens, Michael D. Quartermain, Jason T. Su, Girish S. Shirali, Shan Chen, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics. The aims of this study were to determine factors that influence diastolic function and to describe associations of diastolic function with current clinical status.

METHODS: Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonymization (grade 2), or restrictive (grade 3). Studies were also classified dichotomously (restrictive pattern present or absent). Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery) and …


Progress Toward Eliminating Mother To Child Transmission Of Hiv In Kenya: Review Of Treatment Guideline Uptake And Pediatric Transmission At Four Government Hospitals Between 2010 And 2012., Sarah Finocchario-Kessler, Kristine F. Clark, Samoel Khamadi, Brad J. Gautney, Vincent Okoth, Kathy Goggin, Hitsystem Study Team Nov 2016

Progress Toward Eliminating Mother To Child Transmission Of Hiv In Kenya: Review Of Treatment Guideline Uptake And Pediatric Transmission At Four Government Hospitals Between 2010 And 2012., Sarah Finocchario-Kessler, Kristine F. Clark, Samoel Khamadi, Brad J. Gautney, Vincent Okoth, Kathy Goggin, Hitsystem Study Team

Manuscripts, Articles, Book Chapters and Other Papers

We analyzed prevention of mother-to-child transmission (PMTCT) data from a retrospective cohort of n = 1365 HIV+ mothers who enrolled their HIV-exposed infants in early infant diagnosis services in four Kenyan government hospitals from 2010 to 2012. Less than 15 and 20 % of mother-infant pairs were provided with regimens that met WHO Option A and B/B+ guidelines, respectively. Annually, the gestational age at treatment initiation decreased, while uptake of Option B/B+ increased (all p's < 0.001). Pediatric HIV infection was halved (8.6-4.3 %), yet varied significantly by hospital. In multivariable analyses, HIV-exposed infants who received no PMTCT (AOR 4.6 [2.49, 8.62], p < 0.001), mixed foods (AOR 5.0 [2.77, 9.02], p < 0.001), and care at one of the four hospitals (AOR 3.0 [1.51, 5.92], p = 0.002) were more likely to be HIV-infected. While the administration and uptake of WHO PMTCT guidelines is improving, an expanded focus on retention and medication adherence will further reduce pediatric HIV transmission.


Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From The Children's Oncology Group., Robert B. Gerbing, Todd A. Alonzo, Lillian Sung, Alan S. Gamis, Soheil Meshinchi, Sharon E. Plon, Alison A. Bertuch, Maria M. Gramatges Nov 2016

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From The Children's Oncology Group., Robert B. Gerbing, Todd A. Alonzo, Lillian Sung, Alan S. Gamis, Soheil Meshinchi, Sharon E. Plon, Alison A. Bertuch, Maria M. Gramatges

Manuscripts, Articles, Book Chapters and Other Papers

Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment-related mortality. Telomeres, the repetitive DNA-protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children's Oncology Group study AAML0531, and included those with (n = 53) and without (n …


New Findings, Classification And Long-Term Follow-Up Study Based On Mri Characterization Of Brainstem Encephalitis Induced By Enterovirus 71, Hongwu Zeng, Feiqiu Wen, Wenxian Huang, Yungen Gan, Weibin Zeng, Ranran Chen, Yanxia He, Yonker Wang, Zaiyi Liu, Changhong Liang, Kelvin K. L. Wong Oct 2016

New Findings, Classification And Long-Term Follow-Up Study Based On Mri Characterization Of Brainstem Encephalitis Induced By Enterovirus 71, Hongwu Zeng, Feiqiu Wen, Wenxian Huang, Yungen Gan, Weibin Zeng, Ranran Chen, Yanxia He, Yonker Wang, Zaiyi Liu, Changhong Liang, Kelvin K. L. Wong

Radiology Faculty Publications

Background To report the diversity of MRI features of brainstem encephalitis (BE) induced by Enterovirus 71. This is supported by implementation and testing of our new classification scheme in order to improve the diagnostic level on this specific disease.

Methods Neuroimaging of 91 pediatric patients who got EV71 related BE were hospitalized between March, 2010 to October, 2012, were analyzed retrospectively. All patients underwent pre- and post-contrast MRI scan. Thereafter, 31 patients were randomly called back for follow-up MRI study during December 2013 to August 2014. The MRI signal patterns of BE primary lesion were analyzed and classified according to …


Validation Of Noninvasive Measures Of Left Ventricular Mechanics In Children: A Simultaneous Echocardiographic And Conductance Catheterization Study., Shahryar M. Chowdhury, Ryan J. Butts, Carolyn L. Taylor, Varsha M. Bandisode, Karen S. Chessa, Anthony M. Hlavacek, Girish S. Shirali, G Hamilton Baker Jul 2016

Validation Of Noninvasive Measures Of Left Ventricular Mechanics In Children: A Simultaneous Echocardiographic And Conductance Catheterization Study., Shahryar M. Chowdhury, Ryan J. Butts, Carolyn L. Taylor, Varsha M. Bandisode, Karen S. Chessa, Anthony M. Hlavacek, Girish S. Shirali, G Hamilton Baker

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The accuracy of echocardiography in evaluating left ventricular contractility has not been validated in children. The objective of this study was to compare echocardiographic measures of contractility with those derived from pressure-volume loop (PVL) analysis in children.

METHODS: Patients with relatively normal loading conditions undergoing routine left heart catheterization were prospectively enrolled. PVLs were obtained via conductance catheters. The gold-standard measure of contractility, end-systolic elastance (Ees), was obtained via balloon occlusion of one or both vena cavae. Echocardiograms were performed immediately after PVL analysis under the same anesthetic conditions. Single-beat estimations of echocardiographic Ees were calculated using four different …


Asymptomatic Left Ventricular Myxoma In A 12-Year-Old Male., Meghan Chlebowski, James O'Brien, Casey Hertzenberg, Jonathan B. Wagner Jun 2016

Asymptomatic Left Ventricular Myxoma In A 12-Year-Old Male., Meghan Chlebowski, James O'Brien, Casey Hertzenberg, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Cardiac myxoma is the most common cardiac tumor in patients of all ages; the majority are encountered as single left atrial tumors. Left ventricular myxomas are exceedingly rare, having been recorded in a small number of case reports involving children worldwide. We report a case of a left ventricular myxoma with left ventricular outflow tract obstruction in a previously healthy, asymptomatic adolescent black male. Transthoracic echocardiograms revealed a single, large (2.5 × 5-cm), lobulated, mobile mass within the left ventricular cavity that oscillated into the outflow tract, thereby causing moderate obstruction during systole. Advanced images delineated the location and tissue …


Kidney Disease Progression In Autosomal Recessive Polycystic Kidney Disease., Katherine M. Dell, Matthew Matheson, Erum A. Hartung, Bradley A. Warady, Susan L. Furth Apr 2016

Kidney Disease Progression In Autosomal Recessive Polycystic Kidney Disease., Katherine M. Dell, Matthew Matheson, Erum A. Hartung, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.

STUDY DESIGN: GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.

RESULTS: Annualized GFR change in subjects …


Pharmacokinetics And Bioequivalence Of A Liquid Formulation Of Hydroxyurea In Children With Sickle Cell Anemia., Jeremie H. Estepp, Chiara Melloni, Courtney D. Thornburg, Paweł Wiczling, Zora Rogers, Jennifer A. Rothman, Nancy S. Green, Robert Liem, Amanda M. Brandow, Shelley E. Crary, Thomas H. Howard, Maurine H. Morris, Andrew Lewandowski, Uttam Garg, William J. Jusko, Kathleen A. Neville, Best Pharmaceuticals For Children Act-Pediatric Trials Network Administrative Core Committee Mar 2016

Pharmacokinetics And Bioequivalence Of A Liquid Formulation Of Hydroxyurea In Children With Sickle Cell Anemia., Jeremie H. Estepp, Chiara Melloni, Courtney D. Thornburg, Paweł Wiczling, Zora Rogers, Jennifer A. Rothman, Nancy S. Green, Robert Liem, Amanda M. Brandow, Shelley E. Crary, Thomas H. Howard, Maurine H. Morris, Andrew Lewandowski, Uttam Garg, William J. Jusko, Kathleen A. Neville, Best Pharmaceuticals For Children Act-Pediatric Trials Network Administrative Core Committee

Manuscripts, Articles, Book Chapters and Other Papers

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability …


Techniques And Approaches To Genetic Analyses In Nephrological Disorders., Laurel K. Willig Mar 2016

Techniques And Approaches To Genetic Analyses In Nephrological Disorders., Laurel K. Willig

Manuscripts, Articles, Book Chapters and Other Papers

Inherited renal disease is a leading cause of morbidity and mortality in pediatric nephrology. High throughput advancements in genomics have led to greater understanding of the biologic underpinnings of these diseases. However, the underlying genetic changes explain only part of the molecular biology that contributes to disease manifestation and progression. Other omics technologies will provide a more complete picture of these cellular processes. This review discusses these omics technologies in the context of pediatric renal disease.


Molecular Evolution And Intraclade Recombination Of Enterovirus D68 During The 2014 Outbreak In The United States., Yi Tan, Ferdaus Hassan, Jennifer E. Schuster, Ari Simenauer, Rangaraj Selvarangan, Rebecca A. Halpin, Xudong Lin, Nadia Fedorova, Timothy B. Stockwell, Tommy Tsan-Yuk Lam, James D. Chappell, Tina V. Hartert, Edward C. Holmes, Suman R. Das Feb 2016

Molecular Evolution And Intraclade Recombination Of Enterovirus D68 During The 2014 Outbreak In The United States., Yi Tan, Ferdaus Hassan, Jennifer E. Schuster, Ari Simenauer, Rangaraj Selvarangan, Rebecca A. Halpin, Xudong Lin, Nadia Fedorova, Timothy B. Stockwell, Tommy Tsan-Yuk Lam, James D. Chappell, Tina V. Hartert, Edward C. Holmes, Suman R. Das

Manuscripts, Articles, Book Chapters and Other Papers

In August 2014, an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data, there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipeline for EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, MO, collected during the 2014 …


Hydroxycarbamide Versus Chronic Transfusion For Maintenance Of Transcranial Doppler Flow Velocities In Children With Sickle Cell Anaemia-Tcd With Transfusions Changing To Hydroxyurea (Twitch): A Multicentre, Open-Label, Phase 3, Non-Inferiority Trial., Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Lori Luchtman-Jones, +Several Additional Authors Feb 2016

Hydroxycarbamide Versus Chronic Transfusion For Maintenance Of Transcranial Doppler Flow Velocities In Children With Sickle Cell Anaemia-Tcd With Transfusions Changing To Hydroxyurea (Twitch): A Multicentre, Open-Label, Phase 3, Non-Inferiority Trial., Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Lori Luchtman-Jones, +Several Additional Authors

Pediatrics Faculty Publications

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.

METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible …


Therapeutic Effect Of Melatonin On Pediatric Functional Dyspepsia: A Pilot Study., Katherine Zybach, Craig A. Friesen, Jennifer V. Schurman Feb 2016

Therapeutic Effect Of Melatonin On Pediatric Functional Dyspepsia: A Pilot Study., Katherine Zybach, Craig A. Friesen, Jennifer V. Schurman

Manuscripts, Articles, Book Chapters and Other Papers

AIM: To study the effectiveness of melatonin vs placebo in children with functional dyspepsia (FD).

METHODS: The study was conducted as a double blind, randomized, placebo controlled crossover trial. Subjects were aged 8-17 years and diagnosed with FD based on Rome III criteria. All subjects had failed to respond to 4 wk of acid suppression. Subjects receive a continuous two weeks of placebo and a continuous two weeks of melatonin in an order blinded to the participant and the study team. A Global Clinical Score was obtained to assess changes in abdominal pain. Pain was self-reported to be worse (grade …


Long-Term Velaglucerase Alfa Treatment In Children With Gaucher Disease Type 1 Naïve To Enzyme Replacement Therapy Or Previously Treated With Imiglucerase., Laurie Smith, William Rhead, Joel Charrow, Suma P. Shankar, Ashish Bavdekar, Nicola Longo, Rebecca Mardach, Paul Harmatz, Thomas Hangartner, Hak-Myung Lee, Eric Crombez, Gregory M. Pastores Feb 2016

Long-Term Velaglucerase Alfa Treatment In Children With Gaucher Disease Type 1 Naïve To Enzyme Replacement Therapy Or Previously Treated With Imiglucerase., Laurie Smith, William Rhead, Joel Charrow, Suma P. Shankar, Ashish Bavdekar, Nicola Longo, Rebecca Mardach, Paul Harmatz, Thomas Hangartner, Hak-Myung Lee, Eric Crombez, Gregory M. Pastores

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427).

METHODS: Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30-60U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty.

RESULTS: The study included 24 pediatric patients. …


Typical Hus: Evidence Of Acute Phase Complement Activation From A Daycare Outbreak, T M. Brady, C Pruette, L F. Loeffler, Darcy Weidemann, J J. Strouse, E Gavriilaki, R A. Brodsky Jan 2016

Typical Hus: Evidence Of Acute Phase Complement Activation From A Daycare Outbreak, T M. Brady, C Pruette, L F. Loeffler, Darcy Weidemann, J J. Strouse, E Gavriilaki, R A. Brodsky

Manuscripts, Articles, Book Chapters and Other Papers

The clinical manifestations of typical hemolytic uremic syndrome (HUS) encompass a wide spectrum. Despite the potentially severe sequelae from this syndrome, treatment approaches remain supportive. We present the clinical course of a child who contracted Shiga toxin-positive E. coli (STEC) from a daycare center during an outbreak. Utilizing the modified Ham test which is a rapid, serum-based functional assay used to detect activation of the alternative pathway of complement as observed in atypical HUS, patient sera revealed evidence of increased complement activation in the acute phase of the syndrome but not after resolution. Further, this complement activation was attenuated by …


Hematologic Outcomes After Total Splenectomy And Partial Splenectomy For Congenital Hemolytic Anemia., Brian R Englum, Jennifer Rothman, Sarah Leonard, Audra Reiter, Courtney Thornburg, Mary Brindle, Nicola Wright, Matthew M Heeney, C Jason Smithers, Rebeccah L Brown, Theodosia Kalfa, Jacob C Langer, Michaela Cada, Keith T Oldham, J Paul Scott, Mukta Sharma, Andrew M Davidoff, Kerri Nottage, Kathryn Bernabe, David B Wilson, Sanjeev Dutta, Bertil Glader, Shelley E Crary, Melvin S Dassinger, Levette Dunbar, Saleem Islam, Manjusha Kumar, Fred Rescorla, Steve Bruch, Andrew Campbell, Mary Austin, Robert Sidonio, Martin L Blakely, Henry E Rice, Splenectomy In Congenital Hemolytic Anemia Consortium, Shawn D. St Peter Jan 2016

Hematologic Outcomes After Total Splenectomy And Partial Splenectomy For Congenital Hemolytic Anemia., Brian R Englum, Jennifer Rothman, Sarah Leonard, Audra Reiter, Courtney Thornburg, Mary Brindle, Nicola Wright, Matthew M Heeney, C Jason Smithers, Rebeccah L Brown, Theodosia Kalfa, Jacob C Langer, Michaela Cada, Keith T Oldham, J Paul Scott, Mukta Sharma, Andrew M Davidoff, Kerri Nottage, Kathryn Bernabe, David B Wilson, Sanjeev Dutta, Bertil Glader, Shelley E Crary, Melvin S Dassinger, Levette Dunbar, Saleem Islam, Manjusha Kumar, Fred Rescorla, Steve Bruch, Andrew Campbell, Mary Austin, Robert Sidonio, Martin L Blakely, Henry E Rice, Splenectomy In Congenital Hemolytic Anemia Consortium, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: The purpose of this study was to define the hematologic response to total splenectomy (TS) or partial splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD).

Methods: The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling, we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin. We also compared laparoscopic to open splenectomy.

Results: The analysis included 130 children, with 62.3% (n=81) undergoing TS. For children with HS, all …


Genetic Variation In The Histamine Production, Response, And Degradation Pathway Is Associated With Histamine Pharmacodynamic Response In Children With Asthma., Bridgette Jones, Catherine M T Sherwin, Xiaoxi Liu, Hongying Dai, Carrie A. Vyhlidal Jan 2016

Genetic Variation In The Histamine Production, Response, And Degradation Pathway Is Associated With Histamine Pharmacodynamic Response In Children With Asthma., Bridgette Jones, Catherine M T Sherwin, Xiaoxi Liu, Hongying Dai, Carrie A. Vyhlidal

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma. Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD …


Renal And Cardiovascular Morbidities Associated With Apol1 Status Among African-American And Non-African-American Children With Focal Segmental Glomerulosclerosis., Robert P. Woroniecki, Derek K. Ng, Sophie Limou, Cheryl A. Winkler, Kimberly J. Reidy, Mark Mitsnefes, Matthew G. Sampson, Craig S. Wong, Bradley A. Warady, Susan L. Furth, Jeffrey B. Kopp, Frederick J. Kaskel Jan 2016

Renal And Cardiovascular Morbidities Associated With Apol1 Status Among African-American And Non-African-American Children With Focal Segmental Glomerulosclerosis., Robert P. Woroniecki, Derek K. Ng, Sophie Limou, Cheryl A. Winkler, Kimberly J. Reidy, Mark Mitsnefes, Matthew G. Sampson, Craig S. Wong, Bradley A. Warady, Susan L. Furth, Jeffrey B. Kopp, Frederick J. Kaskel

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children.

DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.

RESULTS: A total of 140 AA children in the CKiD study were genotyped. High …


Allergic Diseases And Internalizing Behaviors In Early Childhood., Maya K. Nanda, Grace K. Lemasters, Linda Levin, Marc E. Rothenberg, Amal H. Assa'ad, Nicholas Newman, David Bernstein, Gurjit Khurana-Hershey, James E. Lockey, Patrick H. Ryan Jan 2016

Allergic Diseases And Internalizing Behaviors In Early Childhood., Maya K. Nanda, Grace K. Lemasters, Linda Levin, Marc E. Rothenberg, Amal H. Assa'ad, Nicholas Newman, David Bernstein, Gurjit Khurana-Hershey, James E. Lockey, Patrick H. Ryan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years.

METHODS: Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. …


The Challenge Of Analyzing The Results Of Next-Generation Sequencing In Children., Isabelle Thiffault, John Lantos Jan 2016

The Challenge Of Analyzing The Results Of Next-Generation Sequencing In Children., Isabelle Thiffault, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

In recent years, next-generation sequencing technologies have revolutionized approaches to genetic studies. Whole-exome or whole-genome sequencing allows diagnoses in many patients who have complex phenotypes and unusual clinical presentations. As genomic and exomic testing expands in both the research and clinical settings, pediatricians will need to understand the technology of next-generation sequencing and the complexity of interpreting genomic variants relevant to patient phenotypic features. This article briefly explains the technology by which genomes are sequenced and discusses some of the complexity related to interpreting genomic variants. We conclude with some thoughts on the clinical applications of such testing.