Medicine and Health Sciences Commons^™

Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial., Chris A Rees, David C. Brousseau, Daniel M Cohen, Anthony Villella, Carlton Dampier, Kathleen Brown, Andrew Campbell, Corrie E Chumpitazi, Gladstone Airewele, Todd Chang, Christopher Denton, Angela Ellison, Alexis Thompson, Fahd Ahmad, Nitya Bakshi, Keli D Coleman, Sara Leibovich, Deborah Leake, Dunia Hatabah, Hagar Wilkinson, Michelle Robinson, T Charles Casper, Elliott Vichinsky, Claudia R Morris

Department of Pediatrics Faculty Papers

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 …

Prevalence Of High Blood Pressure Among Youth In India And Association With Future Cardiovascular Disease, Abbas H. Zaidi, Sarah D. De Ferranti

Department of Pediatrics Faculty Papers

No abstract provided.

Genetic Testing To Inform Epilepsy Treatment Management From An International Study Of Clinical Practice, Dianalee Mcknight, Ana Morales, Kathryn E. Hatchell, Sara L. Bristow, Joshua L. Bonkowsky, Michael Scott Perry, Anne T. Berg, Felippe Borlot, Edward D. Esplin, Chad Moretz, Katie Angione, Loreto Ríos-Pohl, Robert L. Nussbaum, Swaroop Aradhya, Chad R. Haldeman-Englert, Rebecca J. Levy, Venu G. Parachuri, Guillermo Lay-Son, David J. Dávila-Ortiz De Montellano, Miguel Angel Ramirez-Garcia, Edmar O. Benítez Alonso, Julie Ziobro, Adela Chirita-Emandi, Temis M. Felix, Dianne Kulasa-Luke, Andre Megarbane, Shefali Karkare, Sarah L. Chagnon, Jennifer B. Humberson, Melissa J. Assaf, Sebastian Silva, Katherine Zarroli, Oksana Boyarchuk, Gary R. Nelson, Rachel Palmquist, Katherine C. Hammond, Sean T. Hwang, Susan B. Boutlier, Melinda Nolan, Kaitlin Y. Batley, Devraj Chavda, Carlos Alberto Reyes-Silva, Oleksandr Miroshnikov, Britton Zuccarelli, Louise Amlie-Wolf, James W. Wheless, Syndi Seinfeld, Manoj Kanhangad, Jeremy L. Freeman, Susana Monroy-Santoyo, Natalia Rodriguez-Vazquez, Monique M. Ryan, Michelle Machie, Patricio Guerra, Muhammad Jawad Hassan, Meghan S. Candee, Caleb P. Bupp, Kristen L. Park, Eric Muller, Pamela Lupo, Robert C. Pedersen, Amir M. Arain, Andrea Murphy, Krista Schatz, Weiyi Mu, Paige M. Kalika, Lautaro Plaza, Marissa A. Kellogg, Evelyn G. Lora, Robert P. Carson, Victoria Svystilnyk, Viviana Venegas, Rebecca R. Luke, Huiyuan Jiang, Tetiana Stetsenko, Milagros M. Dueñas-Roque, Joseph Trasmonte, Rebecca J. Burke, Anna C. E. Hurst, Douglas M. Smith, Lauren J. Massingham, Laura Pisani, Carrie E. Costin, Betsy Ostrander, Francis M. Filloux, Amitha L. Ananth, Ismail S. Mohamed, Alla Nechai, Jasmin M. Dao, Michael C. Fahey, Ermal Aliu, Stephen Falchek, Craig A. Press, Lauren Treat, Krista Eschbach, Angela Starks, Ryan Kammeyer, Joshua J. Bear, Mona Jacobson, Veronika Chernuha, Bailey Meibos, Kristen Wong, Matthew T. Sweney, A. Chris Espinoza, Colin B. Van Orman, Arie Weinstock, Ashutosh Kumar, Claudia Soler-Alfonso, Danielle A. Nolan, Muhammad Raza, Miguel David Rojas Carrion, Geetha Chari, Eric D. Marsh, Yael Shiloh-Malawsky, Sumit Parikh, Ernesto Gonzalez-Giraldo, Stephen Fulton, Yoshimi Sogawa, Kaitlyn Burns, Myroslava Malets, Johnny David Montiel Blanco, Christa W. Habela, Carey A. Wilson, Guillermo G. Guzmán, Mariia Pavliuk

Department of Pediatrics Faculty Papers

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.

OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a …

Fasoracetam In Adolescents With Adhd And Glutamatergic Gene Network Variants Disrupting Mglur Neurotransmitter Signaling., Josephine Elia, Grace Ungal, Charlly Kao, Alexander Ambrosini, Nilsa De Jesus-Rosario, Lene Larsen, Rosetta Chiavacci, Tiancheng Wang, Christine Kurian, Kanani Titchen, Brian Sykes, Sharon Hwang, Bhumi Kumar, Jacqueline Potts, Joshua Davis, Jeffrey Malatack, Emma Slattery, Ganesh Moorthy, Athena Zuppa, Andrew Weller, Enda Byrne, Yun R. Li, Walter K. Kraft, Hakon Hakonarson

Department of Pediatrics Faculty Papers

The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50-800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 …

Characterization Of Pulmonary Metastases In Children With Hepatoblastoma Treated On Children's Oncology Group Protocol Ahep0731 (The Treatment Of Children With All Stages Of Hepatoblastoma): A Report From The Children's Oncology Group., Allison F. O'Neill, Alexander J. Towbin, Mark D. Krailo, Caihong Xia, Yun Gao, M. Beth Mccarville, Rebecka L. Meyers, Eugene D. Mcgahren, Greg M. Tiao, Stephen P. Dunn, Max R. Langham, Christopher B. Weldon, Milton J. Finegold, Sarangarajan Ranganathan, Wayne L. Furman, Marcio Malogolowkin, Carlos Rodriguez-Galindo, Howard M. Katzenstein

Department of Pediatrics Faculty Papers

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children's Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and …

A Double-Blind Randomized Trial Of Fish Oil To Lower Triglycerides And Improve Cardiometabolic Risk In Adolescents., Samuel S. Gidding, Carol Prospero, Jobayer Hossain, Frances Zappalla, Prabhakaran Babu Balagopal, Bonita Falkner, Peter Kwiterovich

Department of Pediatrics Faculty Papers

OBJECTIVES: To determine the efficacy of 4 g/day fish oil to lower triglycerides and impact lipoprotein particles, inflammation, insulin resistance, coagulation, and thrombosis.

STUDY DESIGN: Participants (n = 42, age 14 ± 2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol/dL were enrolled in a randomized, double-blind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, fibrinogen, plasminogen activator inhibitor-1, and thrombin generation were measured.

RESULTS: Baseline lipid profile was total cholesterol 194 (5.4) mg/dL (mean …

The Differential Effects Of Maternal Age, Race/Ethnicity And Insurance On Neonatal Intensive Care Unit Admission Rates., Beatriz E De Jongh, Robert Locke, David A Paul, Matthew Hoffman

Department of Pediatrics Faculty Papers

BACKGROUND: Maternal race/ethnicity, age, and socioeconomic status (SES) are important factors determining birth outcome. Previous studies have demonstrated that, teenagers, and mothers with advanced maternal age (AMA), and Black/Non-Hispanic race/ethnicity can independently increase the risk for a poor pregnancy outcome. Similarly, public insurance has been associated with suboptimal health outcomes. The interaction and impact on the risk of a pregnancy resulting in a NICU admission has not been studied. Our aim was, to analyze the simultaneous interactions of teen/advanced maternal age (AMA), race/ethnicity and socioeconomic status on the odds of NICU admission.

METHODS: The Consortium of Safe Labor Database (subset …

Periodic Fever, Aphthous Stomatitis, Pharyngitis, And Adenitis (Pfapa) Is A Disorder Of Innate Immunity And Th1 Activation Responsive To Il-1 Blockade., Silvia Stojanov, Sivia Lapidus, Puja Chitkara, Henry Feder, Juan C Salazar, Thomas A Fleisher, Margaret R Brown, Kathryn M Edwards, Michael M Ward, Robert A Colbert, Hong-Wei Sun, Geryl M Wood, Beverly K Barham, Anne Jones, Ivona Aksentijevich, Raphaela Goldbach-Mansky, Balu Athreya, Karyl S Barron, Daniel L Kastner

Department of Pediatrics Faculty Papers

The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever disease in children. However, the pathogenesis is unknown. Using a systems biology approach we analyzed blood samples from PFAPA patients whose genetic testing excluded hereditary periodic fevers (HPFs), and from healthy children and pediatric HPF patients. Gene expression profiling could clearly distinguish PFAPA flares from asymptomatic intervals, HPF flares, and healthy controls. During PFAPA attacks, complement (C1QB, C2, SERPING1), IL-1-related (IL-1B, IL-1RN, CASP1, IL18RAP), and IFN-induced (AIM2, IP-10/CXCL10) genes were significantly overexpressed, but T cell-associated transcripts (CD3, CD8B) were down-regulated. On the …

State Infant Mortality: An Ecologic Study To Determine Modifiable Risks And Adjusted Infant Mortality Rates., David A. Paul. Md, Amy Mackley, Rnc, Robert G. Locke, Do, John L. Stefano, Md, Charlan Kroelinger, Phd

Department of Pediatrics Faculty Papers

OBJECTIVE: To determine factors contributing to state infant mortality rates (IMR) and develop an adjusted IMR in the United States for 2001 and 2002. DESIGN/METHODS: Ecologic study of factors contributing to state IMR. State IMR for 2001 and 2002 were obtained from the United States linked death and birth certificate data from the National Center for Health Statistics. Factors investigated using multivariable linear regression included state racial demographics, ethnicity, state population, median income, education, teen birth rate, proportion of obesity, smoking during pregnancy, diabetes, hypertension, cesarean delivery, prenatal care, health insurance, self-report of mental illness, and number of in-vitro fertilization …

Continuous Source Of Care Among Young Underserved Children: Associated Characteristics And Use Of Recommended Parenting Practices., Esther K Chung, Leny Mathew, Kelly F Mccollum, Irma T Elo, Jennifer F Culhane

Department of Pediatrics Faculty Papers

OBJECTIVES: The aim of this study was to 1) assess sociodemographic and health characteristics associated with having a continuous source of care (CSOC) among young children and 2) determine the relationship between having a CSOC and use of parenting practices.

METHODS: We conducted a prospective, community-based survey of women receiving prenatal care at Philadelphia community health centers. We conducted surveys at the first prenatal visit and at a mean age +/- standard deviation of 3 +/-1, 11 +/- 1, and 24 +/- 2 months postpartum, obtaining information on sociodemographic and health characteristics, child's health care provider, and 6 parenting practices. …

A Turner Syndrome Neurocognitive Phenotype Maps To Xp22.3., Andrew R Zinn, David Roeltgen, Gerry Stefanatos, Purita Ramos, Frederick F Elder, Harvey Kushner, Karen Kowal, Judith L Ross

Department of Pediatrics Faculty Papers

BACKGROUND: Turner syndrome (TS) is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47) of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. METHODS: Subjects were recruited from North American genetics and …

A Clustering Of Childhood Meningococcal Disease: A Challenge For Physicians, Press And Community., Michael S. Dreyer, Stephen C. Eppes, Joel D. Klein

Department of Pediatrics Faculty Papers

The Delaware Division of Public Health reported only two cases of documented meningococcal infection in the pediatric population in 1992. As of March 1, 1993, the Morbidity and Mortality Weekly Report indicated only one case of meningococcal disease in the state of Delaware for 1993. However, from the end of February to early April 1993, approximately six weeks, there were seven cases of documented meningococcal infection in the pediatric population that either presented or were transferred to one of the pediatric care facilities in the Wilmington, Delaware area. Notification of these cases to the Delaware Division of Public Health prompted …

Childhood Typhoid Fever Diagnosed In An Urban U.S. Setting., Surinder K. Sodhi, Stephen C. Eppes, Joel D. Klein

Department of Pediatrics Faculty Papers

The majority of cases of childhood typhoid fever diagnosed in the United States occur in persons recently returned from travel abroad. We report two childhood cases of typhoid fever acquired in Mexico and India and diagnosed in an urban United States setting. This report describes these cases and provides insights into the pitfalls in recognizing this condition in a nonendemic setting as well as information concerning differential diagnosis and treatment.

Animal Bite Infections., Joel D. Klein, Md

Department of Pediatrics Faculty Papers

Animal bites have become alarmingly common and may represent a quiet epidemic. It is estimated that between 1 and 3.5 million animal bites occur annually in the United States. The highest incidence has consistently been in 5-to-14-year-old schoolchildren, who have greater contact with animals, especially house pets, on a daily basis. This article discusses the epidemiology, microbiology, clinical findings and management of animal bites infections.