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Nested Partially-Latent, Class Models For Dependent Binary Data, Estimating Disease Etiology, Zhenke Wu, Maria Deloria-Knoll, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

The Pneumonia Etiology Research for Child Health (PERCH) study seeks to use modern measurement technology to infer the causes of pneumonia for which gold-standard evidence is unavailable. The paper describes a latent variable model designed to infer from case-control data the etiology distribution for the population of cases, and for an individual case given his or her measurements. We assume each observation is drawn from a mixture model for which each component represents one cause or disease class. The model addresses a major limitation of the traditional latent class approach by taking account of residual dependence among multivariate binary outcome …

Use Of Modeling And Simulation In The Design And Conduct Of Pediatric Clinical Trials And The Optimization Of Individualized Dosing Regimens, Chris Stockmann, J. S. Barrett, Jessica K. Roberts, Catherine M.T. Sherwin

Pediatrics Faculty Publications

Mathematical models of drug action and disease progression can inform pediatric pharmacotherapy. In this tutorial, we explore the key issues that differentiate pediatric from adult pharmacokinetic (PK) / pharmacodynamic (PD) studies, describe methods to calculate the number of participants to be enrolled and the optimal times at which blood samples should be collected, and therapeutic drug monitoring methods for individualizing pharmacotherapy. The development of pediatric‐specific drug dosing dashboards is also highlighted, with an emphasis on clinical‐relevance and ease of use.

Investigation Of Potential Early Histologic Markers Of Pediatric Inflammatory Bowel Disease, Julie A. Bass, Craig A. Friesen, Amanda D. Deacy, Nancy Neilan, Julia M. Bracken, Valentina Shakhnovich, Vivekanand Singh

Manuscripts, Articles, Book Chapters and Other Papers

© 2015 Bass et al. Background: Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicators of IBD in children. Methods: A retrospective analysis compared histologic findings from initially inconclusive or negative endoscopic studies in 22 patients who were subsequently diagnosed with IBD (after diagnostic endoscopy) to those of 20 comparison patients with functional abdominal pain matched for age, gender, and study type. A pediatric …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Investigation Of Stilbenoids As Potential Therapeutic Agents For Rotavirus Gastroenteritis, Judith M. Ball, Fabricio Medina-Bolivar, Katelyn D. Defrates, Emily Hambleton, Megan E. Hurlburt, Lingling Fang, Tianhong Yang, Luis Nopo-Olazabal, Richard L. Atwill, Pooj Ghai, Rebecca D. Parr

Faculty Publications

Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced …

Predictive Performance Of A Vancomycin Population Pharmacokinetic Model In Neonates, Chris Stockmann, Adam L. Hersh, Jessica K. Roberts, Jiraganya Bhongsatiern, E. Kent Korgenski, Michael G. Spigarelli, Catherine M.T. Sherwin, Adam Frymoyer

Pediatrics Faculty Publications

Introduction

The pharmacokinetics of vancomycin are highly variable among neonates, which makes dosing challenging in this population. However, adequate drug exposure is critical, especially when treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Utilization of population pharmacokinetic models and Bayesian methods offers the potential for developing individualized therapeutic approaches. To meet this need, a neonatal vancomycin population pharmacokinetic model was recently published. The current study sought to externally evaluate the predictive performance and generalizability of this model.

Methods

A retrospective chart review of neonates who received vancomycin and had ≥1 peak and ≥1 trough concentrations at five Intermountain Healthcare neonatal intensive care …

Emergence Of Multidrug Resistant Influenza A(H1n1)Pdm09 Virus Variants In An Immunocompromised Child Treated With Oseltamivir And Zanamivir., Daisuke Tamura, Roberta L. Debiasi, Margaret Okomo-Adhiambo, Vasiliy P. Mishin, Angela P. Campbell, Brett Loechelt, Bernhard L. Wiedermann, Alicia M. Fry, Larisa V. Gubareva

Pediatrics Faculty Publications

Prolonged treatment of an immunocompromised child with oseltamivir and zanamivir for A(H1N1)pdm09 virus infection led to the emergence of viruses carrying H275Y and/or E119G in the neuraminidase. When phenotypically evaluated by neuraminidase inhibition, the dual H275Y-E119G substitution caused highly reduced inhibition by four neuraminidase inhibitors including oseltamivir, zanamivir, peramivir and laninamivir.

Executive Function And Attention-Deficit/Hyperactivity Disorder In Ugandan Children With Perinatal Hiv Exposure, Matthew Burkey, Robert Opoka

Paediatrics and Child Health, East Africa

Background: Attention-deficit/hyperactivity disorder (ADHD) is among the most commonly diagnosed mental disorders in childhood and is associated with substantial deficits in executive functioning and lost academic and occupational attainment. This study evaluates symptoms of ADHD and their association with neurocognitive deficits in a cohort of rural Ugandan children who were born to HIV-infected mothers.

Methods: We assessed ADHD symptoms and executive function (including memory and attention) in a non-clinical sample of children born to HIV-infected mothers in rural eastern Uganda. Analyses included assessments of the psychometric properties, factor structure, and convergent and discriminant validity of the ADHD measure (ADHD-Rating Scale-IV); …

Pediapp Finder: Creating A Pediatric Application Database, Sara Pro, Adrianne Leblanc, April Wasjutin, Robert Williams

Dissertations, Masters Theses, Capstones, and Culminating Projects

It is estimated that of the 85% of Americans that own cell phones, over half of these cell phone owners use apps on their phone (Fox & Duggan, 2012; Purcell, 2011). According to the U.S. Food and Drug Administration (2013), by 2015, 500 million mobile device users will be using mobile health, or “m-Health” apps. Healthcare professionals are increasingly adopting mobile technology as an innovative, cost-efficient, and timesaving tool that may promote patient wellness and disease prevention (Kumar, 2013; mHealth Bible, 2013). Although mobile technology is a natural fit to the field of occupational therapy, research demonstrates that few resources …

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 …

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 …

Use Of N-Acetylcysteine In Children With Fulminant Hepatic Failure Caused By Acute Viral Hepatitis, Ali Faisal Saleem, Qalab Abbas, Anwarul Haque

Department of Paediatrics and Child Health

Objective: To determine the efficacy of N-acetylcysteine (NAC) in children aged > 1 month to 16 years admitted with Fulminant Hepatic Failure (FHF) secondary to Acute Viral Hepatitis (AVH) in a tertiary care center of a developing country.

Study Design: Analytical study.

Place and Duration of Study: Department of Paediatrics, The Aga Khan University Hospital, Karachi, Pakistan, from January 2007 to December 2011.

Methodology: Medical records of children (> 1 month - 16 years) with FHF admitted with AVH of known etiology who received NAC were reviewed retrospectively. Liver function tests (mean ± SD) at baseline, 24 hours after NAC and …

Babies First: Ensuring Proper Infant Nutrition During Emergencies, Abigail M. Alonso

Independent Study Project (ISP) Collection

Background: Breastfeeding is the best source of nutrition for an infant, living in all regions and cultures. Recommendations apply across the board, from developed nations to refugee camps, from women with HIV to those with time constraints regarding feeding. There also exists a complex relationship between corporations that provide BMS and the NGOs working to promote breastfeeding in emergency situations amongst vulnerable populations.

Objective: The objective of this paper is to expose breastfeeding promotion, using the Dadaab camps in Northeastern Kenya as a case study of IYCF programs and support of breastfeeding among low-literacy populations with an emphasis on women …

Isoniazid Induced Acute Pancreatitis In A Young Girl, Ali Faisal Saleem Dr, Saba Arbab, Farah Qamar Naz

Department of Paediatrics and Child Health

Isoniazid (INH) is the mainstay of management against Mycobacterium tuberculosis. INH-induced acute pancreatitis is an uncommon association and with dearth of literature on it. We are reporting a case of an 11 years old girl who developed acute pancreatitis after 2 weeks of antituberculous therapy. An INH free regimen was started. She was discharged and followed without complications.

Predictors Of Resolution And Persistence Of Renal Laboratory Abnormalities In Pediatric Hiv Infection, C. D. Mitchell, M. C. Chernoff, G. R., 3rd Seage, M. U. Purswani, H. M. Spiegel, G. Zilleruelo, C. Abitbol, B. Heckman, J. M. Oleske, V. Bonagura, Impaact 219/219c Study Team

Journal Articles

BACKGROUND: Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications. METHODS: Data collected from HIV-infected youth followed for >/= 48 months were analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. …

Use Of Serogroup B Meningococcal Vaccines In Persons Aged >= 10 Years At Increased Risk For Serogroup B Meningococcal Disease: Recommendations Of The Advisory Committee On Immunization Practices, 2015, T. Folaranmi, L. Rubin, S. W. Martin, M. Patel, J. R. Macneil

Journal Articles

No abstract provided.

Yellow Fever Vaccine Booster Doses: Recommendations Of The Advisory Committee On Immunization Practices, 2015, J. E. Staples, J. A. Bocchini, L. Rubin, M. Fischer

Journal Articles

No abstract provided.

Improving Newborn Care Practices Through Home Visits: Lessons From Malawi, Nepal, Bangladesh, And Uganda., Deborah Sitrin, Tanya Guenther, Peter Waiswa, Sarah Namutamba, Gertrude Namazzi, Srijana Sharma, K. C. Ashish, Sayed Rubayet, Subrata Bhadra, Reuben Ligowe, Emmanuel Chimbalanga, Elizabeth Sewell, Kate Kerber, Allisyn Moran

Pediatrics Faculty Publications

Background: Nearly all newborn deaths occur in low- or middle-income countries. Many of these deaths could be prevented through promotion and provision of newborn care practices such as thermal care, early and exclusive breastfeeding, and hygienic cord care. Home visit programmes promoting these practices were piloted in Malawi, Nepal, Bangladesh, and Uganda.

Objective: This study assessed changes in selected newborn care practices over time in pilot programme areas in four countries and evaluated whether women who received home visits during pregnancy were more likely to report use of three key practices.

Design: Using data from cross-sectional surveys …

The Oral Bacterial Communities Of Children With Well-Controlled Hiv Infection And Without Hiv Infection., Brittany E. Goldberg, Emmanuel F. Mongodin, Cheron E. Jones, Michelle Chung, Claire M. Fraser, Anupama R. Tate, Steven L. Zeichner

Pediatrics Faculty Publications

The oral microbial community (microbiota) plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi's sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV-positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section …

Use Of Serogroup B Meningococcal Vaccines In Adolescents And Young Adults: Recommendations Of The Advisory Committee On Immunization Practices, 2015, J. R. Macneil, L. Rubin, T. Folaranmi, I. R. Ortega-Sanchez, M. Patel, S. W. Martin

Journal Articles

At its June 2015 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended that adolescents and young adults aged 16-23 years may be vaccinated with a serogroup B meningococcal (MenB) vaccine to provide short-term protection against most strains of serogroup B meningococcal disease. This report summarizes the deliberations of ACIP, the rationale for its decision, and recommendations for use of MenB vaccines in adolescents and young adults. Two MenB vaccines have recently been licensed by the Food and Drug Administration (FDA) for use in the United States and approved for use in persons aged 10-25 years: MenB-FHbp (Trumenba, Wyeth Pharmaceuticals, …

Acid-Suppressing Agents And Risk For Clostridium Difficile Infection In Pediatric Patients, Katelyn E. Brown, Chad A. Knoderer, Kristen R. Nichols, Ashley S. Crumby

Scholarship and Professional Work – COPHS

Background. Acid-suppressing agents have been associated with increased Clostridium difficile infection (CDI) in adults. The objective of this study was to evaluate the association of acid-suppressing therapy with the development of CDI in the pediatric population.

Methods. This was a retrospective case-control study. Children aged 1 through 17 years with a positive C difficile polymerase chain reaction (PCR) result obtained between June 1, 2008, and June 1, 2012, were randomly matched to a control population selected from patients with negative PCR.

Results. A total of 458 children were included. No difference was observed in acid-suppressive therapy prior …

Late-Occurring Vancomycin-Associated Acute Kidney Injury In Children Receiving Prolonged Therapy, Chad A. Knoderer, Allison L. Gritzman, Kristen R. Nichols, Amy C. Wilson

Scholarship and Professional Work – COPHS

Background: Acute kidney injury (AKI) in patients receiving vancomycin has been associated with trough concentrations ≥15 mg/L and longer therapy duration. The objective of this study was to determine the incidence and factors associated with late AKI in children receiving ≥8 days of vancomycin therapy. Methods: Children aged 30 days to 17 years who were admitted to our institution and received intravenous vancomycin for at least 8 days during January to December of 2007 and 2010 and had a suspected or proven gram-positive infection were included. Late AKI was categorized as AKI occurring after the first 7 days of therapy …

Making The Leap From Research Laboratory To Clinic: Challenges And Opportunities For Next-Generation Sequencing In Infectious Disease Diagnostics., Brittany Goldberg, Heike Sichtig, Chelsie Geyer, Nathan Ledeboer, George M Weinstock

Pediatrics Faculty Publications

Next-generation DNA sequencing (NGS) has progressed enormously over the past decade, transforming genomic analysis and opening up many new opportunities for applications in clinical microbiology laboratories. The impact of NGS on microbiology has been revolutionary, with new microbial genomic sequences being generated daily, leading to the development of large databases of genomes and gene sequences. The ability to analyze microbial communities without culturing organisms has created the ever-growing field of metagenomics and microbiome analysis and has generated significant new insights into the relation between host and microbe. The medical literature contains many examples of how this new technology can be …

Graduate Medical Education 2014-2015 Annual Report, Children's Mercy Hospital

GME Annual Reports

Annual report of the Children's Mercy Hospital Graduate Medical Education department, including pediatric residency, internal medicine/pediatrics residency, fellowship programs, medical students, continuing medical education, and library services.

Dual Transcriptomic Profiling Of Host And Microbiota During Health And Disease In Pediatric Asthma., Marcos Pérez-Losada, Eduardo Castro-Nallar, Matthew L. Bendall, Robert J. Freishtat, Keith A. Crandall

Pediatrics Faculty Publications

BACKGROUND: High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for …

World Allergy Organization-Mcmaster University Guidelines For Allergic Disease Prevention (Glad-P): Probiotics, Alessandro Fiocchi, Ruby Pawankar, Carlos Cuello-Garcia, Kangmo Ahn, Suleiman Al-Hammadi, Arnav Agarwal, Kirsten Beyer, Wesley Burks, Giorgio W. Canonica, Motohiro Ebisawa, Shreyas Gandhi, Rose Kamenwa, Bee Wah Lee, Haiqi Li, Susan Prescott, John J. Riva, Lanny Rosenwasser, Hugh Sampson, Michael Spigler, Luigi Terracciano, Andrea Vereda-Ortiz, Susan Waserman, Juan José Yepes-Nuñez, Jan L. Brożek, Holger J. Schünemann

Paediatrics and Child Health, East Africa

Background: Prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20–30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.

Objective: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy.

Methods: We identified the most relevant clinical questions and performed a systematic review …

Growing Up With Chronic Kidney Disease: What Parents And Children Really Want To Know, Uptal D. Patel, Debbie S. Gipson, Abiodun Aderogba Omoloja, Caitlin Wise Carter

Pediatrics Faculty Publications

Adolescents with chronic kidney disease have specific questions about how their disease will affect their quality of life, but they may not always bring this up with their nephrologist. This session is designed to provide pediatricians and pediatric nephrologists with practical information to provide to adolescents with chronic kidney disease and their families. All providers who care for adolescents with renal disease need to be equipped to educate this high risk population and help them navigate through this vulnerable period. This session is designed to explore issues related to athletic participation, academic performance, substance use and abuse and sexual and …

Impact Of Service Provision Platforms On Maternal And Newborn Health In Conflict Areas And Their Acceptability In Pakistan: A Systematic Review, Zohra S. Lassi, Wafa Aftab, Shabina Ariff, Rohail Kumar, Imtiaz Hussain, Nabiha Musavi, Zahid Memon, Sajid B. Soofi, Zulfiqar A. Bhutta

Woman and Child Health

Various models and strategies have been implemented over the years in different parts of the world to improve maternal and newborn health (MNH) in conflict affected areas. These strategies are based on specific needs and acceptability of local communities. This paper has undertaken a systematic review of global and local (Pakistan) information from conflict areas on platforms of health service provision in the last 10 years and information on acceptability from local stakeholders on effective models of service delivery; and drafted key recommendations for improving coverage of health services in conflict affected areas.

The literature search revealed ten studies that …

Pfapa: A Periodic Febrile Syndrome Afflicting Children, Jessica Lahti

Physician Assistant Scholarly Project Posters

• Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA).

• Auto-inflammatory disorder occurring in affected children every 3-8 weeks.

• Onset around age 2; lasting into second decade of life.

• A current pathophysiologic theory is PFAPA is a disorder of the innate immune system involving interleukins, chemoattractants, and cytokines that stimulating the inflammatory response causing symptoms associated with PFAPA.

• Early diagnosis of PFAPA may help prevent the unnecessary use of antibiotics.

• Biomarker CD64, galectin-3 and the MPV may be useful in the diagnosis of PFAPA along with other laboratory values during the febrile attack period …

Frequency And Mortality Associated With Hyperglycemia In Critically Ill Children, Sabeen Abid Khan, Mohsina Noor Ibrahim, Anwarul Haque

Department of Paediatrics and Child Health

Objective: To determine the frequency of hyperglycemia in critically ill children admitted in PICU of a tertiary care hospital of Karachi and to compare the mortality of critically ill children with and without hyperglycemia.

Study Design: Cross-sectional study.

Place and Duration of Study: Paediatrics Intensive Care Unit (PICU) of National Institute of Child Health (NICH), Karachi, from November 2011 to April 2012.

Methodology: One hundred fifty critically ill children admitted to PICU were included. Patients who had fasting blood sugar levels more than 126 mg/dl within 48 hours of admission were included in the hyperglycemic group. The normoglycemic and hyperglycemic …