Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons^™

Risk Stratification Of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture., Paul L. Aronson, Marie E. Wang, Eugene D. Shapiro, Samir S. Shah, Adrienne G. Deporre, Russell J Mcculloh, Christopher M. Pruitt, Sanyukta Desai, Lise E. Nigrovic, Richard D. Marble, Rianna C. Leazer, Sahar N. Rooholamini, Laura F. Sartori, Fran Balamuth, Christopher Woll, Mark I. Neuman, Febrile Young Infant Research Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

Video Abstract: media-1vid110.1542/5840460609001PEDS-VA_2018-1879

OBJECTIVES: To evaluate the Rochester and modified Philadelphia criteria for the risk stratification of febrile infants with invasive bacterial infection (IBI) who do not appear ill without routine cerebrospinal fluid (CSF) testing.

METHODS: We performed a case-control study of febrile infants ≤60 days old presenting to 1 of 9 emergency departments from 2011 to 2016. For each infant with IBI (defined as a blood [bacteremia] and/or CSF [bacterial meningitis] culture with growth of a pathogen), controls without IBI were matched by site and date of visit. Infants were excluded if they appeared ill or had a …

The Impact Of Pulmonary Hypertension In Preterm Infants With Severe Bronchopulmonary Dysplasia Through 1 Year., Joanne M. Lagatta, Erik B. Hysinger, Isabella Zaniletti, Erica M. Wymore, Shilpa Vyas-Read, Sushmita Yallapragada, Leif D. Nelin, William E. Truog, Michael A. Padula, Nicolas F M Porta, Rashmin C. Savani, Karin P. Potoka, Steven M. Kawut, Robert Digeronimo, Girija Natarajan, Huayan Zhang, Theresa R. Grover, William A. Engle, Karna Murthy, Children's Hospital Neonatal Consortium Severe Bpd Focus Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess the effect of pulmonary hypertension on neonatal intensive care unit mortality and hospital readmission through 1 year of corrected age in a large multicenter cohort of infants with severe bronchopulmonary dysplasia.

STUDY DESIGN: This was a multicenter, retrospective cohort study of 1677 infants bornChildren's Hospital Neonatal Consortium with records linked to the Pediatric Health Information System.

RESULTS: Pulmonary hypertension occurred in 370 out of 1677 (22%) infants. During the neonatal admission, pulmonary hypertension was associated with mortality (OR 3.15, 95% CI 2.10-4.73, P < .001), ventilator support at 36 weeks of postmenstrual age (60% vs 40%, P < .001), duration of ventilation (72 IQR 30-124 vs 41 IQR 17-74 days, P < .001), and higher respiratory severity score (3.6 IQR 0.4-7.0 vs 0.8 IQR 0.3-3.3, P < .001). At discharge, pulmonary hypertension was associated with tracheostomy (27% vs 9%, P < .001), supplemental oxygen use (84% vs 61%, P < .001), and tube feeds (80% vs 46%, P < .001). Through 1 year of corrected age, pulmonary hypertension was associated with increased frequency of readmission (incidence rate ratio [IRR] = 1.38, 95% CI 1.18-1.63, P < .001).

CONCLUSIONS: Infants with severe bronchopulmonary dysplasia-associated pulmonary hypertension have increased morbidity and mortality through …

A Multicenter Study To Evaluate Pulmonary Function In Osteogenesis Imperfecta., Allison Tam, Shan Chen, Evan Schauer, Ingo Grafe, Venkata Bandi, Jay R. Shapiro, Robert D. Steiner, Peter A. Smith, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeffrey Krischer, Mary Mullins, Peter H. Byers, Robert A. Sandhaus, Michaela Durigova, Francis H. Glorieux, Frank Rauch, Vernon Reid Sutton, Brendan Lee, Members Of The Brittle Bone Disorders Consortium, Eric T. Rush, Sandesh C S Nagamani

Manuscripts, Articles, Book Chapters and Other Papers

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁ ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV₁ which do not follow the expected trends of the …

Genetic Predisposition To Necrotizing Enterocolitis In Premature Infants: Current Knowledge, Challenges, And Future Directions., Alain Cuna, Lovya George, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

The role of genetics in the pathogenesis of necrotizing enterocolitis (NEC) was initially informed by epidemiological data indicating differences in prevalence among different ethnic groups as well as concordance in twins. These early observations, together with major advances in genomic research, paved the way for studies that begin to reveal the contribution of genetics to NEC. Using the candidate gene or pathway approach, several potential pathogenic variants for NEC in premature infants have already been identified. More recently, genome-wide association studies and exome-sequencing based studies for NEC have been reported. These advances, however, are tempered by the lack of adequately …

Azithromycin For Early Pseudomonas Infection In Cystic Fibrosis. The Optimize Randomized Trial., Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, Annemarie Cairns, Stephanie D. Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey, Optimize Study Group

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.

OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence.

METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial …

An Eqtl Landscape Of Kidney Tissue In Human Nephrotic Syndrome., Christopher E. Gillies, Rosemary Putler, Rajasree Menon, Edgar Otto, Kalyn Yasutake, Viji Nair, Paul Hoover, David Lieb, Shuqiang Li, Sean Eddy, Damian Fermin, Michelle T. Mcnulty, Nephrotic Syndrome Study Network (Neptune), Nir Hacohen, Krzysztof Kiryluk, Matthias Kretzler, Xiaoquan Wen, Matthew G. Sampson, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian "Deterministic Approximation of Posteriors" (DAP) to fine-map …

Ursodeoxycholic Acid Versus Phenobarbital For Cholestasis In The Neonatal Intensive Care Unit., Tamorah Lewis, Simisola Kuye, Ashley Sherman

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Although neonates and young infants with cholestasis are commonly treated with either phenobarbital or ursodeoxycholic acid (ursodiol), there is no evidence that phenobarbital is effective for this indication. Our objective was to compare the effectiveness of ursodiol and phenobarbital for the treatment of cholestasis in a diverse NICU population.

METHODS: This is a retrospective cohort study including infants with cholestasis who were admitted to a Level IV NICU between January 2010 and December 2015. Drug courses of phenobarbital and ursodiol were identified within the medical record, and medical, demographic, and drug information were extracted. The primary outcome was reduction …

Agreement Between Clinician-Rated Versus Patient-Reported Outcomes In Huntington Disease, Noelle E Carlozzi, Nicholas R Boileau, Joel S Perlmutter, Kelvin L Chou, Julie C Stout, Jane S Paulsen, Michael K Mccormack, David Cella, Martha A Nance, Jin-Shei Lai, Praveen Dayalu

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Clinician-rated measures of functioning are often used as primary endpoints in clinical trials and other behavioral research in Huntington disease. As study costs for clinician-rated assessments are not always feasible, there is a question of whether patient self-report of commonly used clinician-rated measures may serve as acceptable alternatives in low risk behavioral trials.

AIM: The purpose of this paper was to determine the level of agreement between self-report and clinician-ratings of commonly used functional assessment measures in Huntington disease.

DESIGN: 486 participants with premanifest or manifest Huntington disease were examined. Total Functional Capacity, Functional Assessment, and Independence Scale assessments …

Factors Associated With End-Of-Life Planning In Huntington Disease., Nancy R Downing, Siera Goodnight, Sena Chae, Joel S Perlmutter, Michael Mccormack, Elizabeth Hahn, Stacey K Barton, Noelle Carlozzi

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

OBJECTIVE: Knowledge of one's gene status for adult onset conditions provides opportunity to make advance end-of-life (EOL) plans. The purposes of these analyses were to (1) determine the prevalence of EOL plans, including advance directives (ADs) among persons across 3 stages of Huntington disease (HD) and (2) examine factors associated with having ADs in this sample.

METHODS: Data are from 503 participants in the HD Quality of Life study. Participants completed an online health-related quality-of-life survey that included questions regarding EOL planning and self-reported HD symptoms. Frequencies were calculated for EOL planning by the HD stage. Bivariate analysis and logistic …

Evaluating Cognition In Individuals With Huntington Disease: Neuroqol Cognitive Functioning Measures, Jin-Shei Lai, Siera Goodnight, Nancy R Downing, Rebecca E Ready, Jane S Paulsen, Anna L Kratz, Julie C Stout, Michael K Mccormack, David Cella, Christopher Ross, Jenna Russell, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

PURPOSE: Cognitive functioning impacts health-related quality of life (HRQOL) for individuals with Huntington disease (HD). The Neuro-QoL includes two patient-reported outcome (PRO) measures of cognition-Executive Function (EF) and General Concerns (GC). These measures have not previously been validated for use in HD. The purpose of this analysis is to evaluate the reliability and validity of the Neuro-QoL Cognitive Function measures for use in HD.

METHODS: Five hundred ten individuals with prodromal or manifest HD completed the Neuro-QoL Cognition measures, two other PRO measures of HRQOL (WHODAS 2.0 and EQ5D), and a depression measure (PROMIS Depression). Measures of functioning The Total …

Relationships Among Apathy, Health-Related Quality Of Life, And Function In Huntington's Disease., Nora E Fritz, Nicholas R Boileau, Julie C Stout, Rebecca Ready, Joel S Perlmutter, Jane S Paulsen, Kimberly Quaid, Stacey Barton, Michael K Mccormack, Susan L Perlman, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Up to 90% of individuals with Huntington's disease (HD)-a progressive, inherited neurodegenerative disorder-experience apathy. Apathy is particularly debilitating because it is marked by a reduction in goal-directed behaviors, including self-care, social interactions, and mobility. The objective of this study was to examine relationships between variables of apathy, functional status, physical function, cognitive function, behavioral status/emotional function, and health-related quality of life. Clinician-rated measures of physical, cognitive, and behavioral function, including one clinician-rated item on apathy, and self-reported measures of physical function, health-related quality of life, and emotional, cognitive, and social function were collected in a single session from 487 persons …

Suicidal Ideation Assessment In Individuals With Premanifest And Manifest Huntington Disease., Melissa Wesson, Nicholas R Boileau, Joel S Perlmutter, Jane S Paulsen, Stacey K Barton, Michael K Mccormack, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Huntington disease (HD) is associated with increased risk of suicide.

OBJECTIVE: This study compares suicide ideation in HD to the general population, assesses factors associated with increased prevalence of suicidal thoughts, and compares clinician-rated to self-reported assessments of suicidal ideation.

METHODS: We examined 496 participants with premanifest or manifest HD. Clinician-rated suicidal ideation was measured using the Problem Behaviors Assessment - short form. Self-reported ideation was measured using two items from the HDQLIFE Concern with Death and Dying item bank. Independent sample t-tests were conducted to compare the prevalence of suicidal thoughts between our HD sample and the U.S. …

A New Measure For End Of Life Planning, Preparation, And Preferences In Huntington Disease: Hdqlife End Of Life Planning, Noelle E Carlozzi, E A Hahn, S A Frank, J S Perlmutter, N D Downing, M K Mccormack, S Barton, M A Nance, S G Schilling, Hdqlife Site Investigators And Coordinators

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Huntington disease is a fatal inherited neurodegenerative disease. Because the end result of Huntington disease is death due to Huntington disease-related causes, there is a need for better understanding and caring for individuals at their end of life.

AIM: The purpose of this study was to develop a new measure to evaluate end of life planning.

DESIGN: We conducted qualitative focus groups, solicited expert input, and completed a literature review to develop a 16-item measure to evaluate important aspects of end of life planning for Huntington disease. Item response theory and differential item functioning analyses were utilized to examine …