Since the CCTR Pediatric Pilot Fund program began in 2008, these funds have been used to support a wide variety of research. Below are descriptions of the personnel and goals of each Pilot Fund project as stated at the time of the award.

2015 Pediatric Pilot Award Recipients

Doug Opel, MD, MPH

Provider-Parent Communication About Influenza Vaccine

Influenza causes significant pediatric morbidity and mortality in the United States annually. Despite the availability of a vaccine for influenza and recommendations that children 6 months and younger be vaccinated annually, influenza vaccination among children remains poor. A factor known to increase parental acceptance of the influenza vaccine is a clear vaccine recommendation from a pediatric provider. Little is known, however, about how providers communicate with parents about the influenza vaccine. The primary goal of this study is to characterize provider communication with parents about the influenza vaccine in the primary care setting. The study aims to identify communication behaviors that may be effective at improving parental acceptance of influenza vaccine for their child. To do so, Dr. Doug Opel and his team will conduct a secondary analysis of 50 previously videotaped provider-parent vaccine discussions during health supervision visits at primary care pediatric practices. This project is an extension of Opel’s overall research program that is focused on increasing childhood vaccine rates by improving provider-parent communication about vaccines.

Francisco Perez, MD, PhD, and Gretchen Gudmundsen, PhD

Anhedonia and Reward Responsivity in Adolescent Depression

Adolescent depression is a common illness that can result in significant disability and morbidity. Among depressed adolescents, those with greater symptoms of anhedonia (inability to experience pleasure from activities usually found enjoyable) are more likely to have poor outcomes. Clinical measurement of anhedonia has been limited to self- and parent-report. Developing treatments specifically targeted to improving anhedonia is critical for improving care of depressed adolescents. This pilot study will evaluate functional magnetic resonance imaging (fMRI) and behavioral measures in depressed adolescents with and without elevated anhedonia compared to non-depressed adolescents. This information will help develop techniques to improve how anhedonia is measured, and ultimately, improve care and treatment for depressed adolescents.

Danielle Zerr, MD, MPH, and Arianna Miles-Jay, MPH

Genomic Epidemiology of Escherichia coli ST 131-H30 in a Pediatric Setting

Extraintestinal pathogenic Escherichia coli (E. coli) are the most common cause of urinary tract and bloodstream infections across all ages. Over the last 15 years E. coli has displayed increasing rates of multidrug resistance. E. coli sequence type 131 subclone H30 (ST131-H30) is a recently emerged pathogen that appears to be driving this increase. The purpose of this study is to investigate ST131-H30 in the pediatric population so that it can be ultimately be controlled and treated more efficiently and effectively. The information generated from this project will provide valuable insights into the patterns of E. coli ST131-H30, laying a foundation for the development of future studies, interventions, and diagnostic tools that will target these problematic pathogens in pediatric populations.

2014 Pediatric Pilot Award Recipients

Janet Englund, MD

A prospective study on transplacental transfer of maternal antibodies in mother-infant pairs

Respiratory syncytial virus (RSV) is the most common cause of viral pneumonia worldwide. Maternal vaccination is being considered as a potential strategy to protect young infants through the transfer of antibody across the placenta in the third trimester. Little data exist to characterize the effects of RSV-specific antibody during pregnancy. Dr. Janet Englund’s study will evaluate the transmission of maternally derived RSV antibody to the infant and describe the factors that affect antibody transfer. Study results will provide pilot data to guide maternal RSV vaccine strategies.

Katherine Gentry, MD

Understanding parent-provider communication in pediatric anesthesiology

This study aims to characterize the conversations that occur between parents and providers in the pre-operative setting and examine how this communication affects parental satisfaction and understanding. Dr. Katherine Gentry will audio record pre-anesthesia conversations and analyze the transcripts to identify communication techniques and elements of informed consent. Parents will complete a post-consent questionnaire to assess their recall and understanding of the interaction, as well as their satisfaction. Data from this pilot project will be used to design a multicenter study in which the research team will enroll a broader sample of providers and parents to characterize the practice of preoperative assessment and informed consent in pediatric anesthesia. This, in turn, will inform the development of educational tools and interventions to improve communication in the pre-operative period.

Holly Tabor, PhD

Innovative approaches to communication and dissemination of genetic testing results: Characterizing parent perspectives on patient-centered outcomes research

Rare genetic diseases and conditions in children have a substantial impact on the health and well-being of patients and their families. Many children undergo clinical genetic testing in an effort to correctly identify and, if possible, treat the condition. There is little information about the perspective of the parent of a child with a genetic condition regarding their experience of genetic testing. Dr. Holly Tabor’s study will characterize the perspective of parents to find what tools and approaches can be used to improve the genetic testing experience. Information from this study will be used to conduct usability pilot testing of My46 (, an innovative Web-based tool that enables individuals to manage their own genetic testing results. This study will provide the foundation for a PCORI application in 2015.

Raymond Tse, MD

Computer-based objective assessment of cleft lip nasal severity and treatment success using 3D stereophotogrammetry

Although treatment of cleft lip can produce dramatic changes in appearance, understanding the relative effect of individual treatments, techniques or protocols relies upon provider experience and expertise. The lack of objective measures limits advances in care due to the inability to correlate treatments with outcomes. Dr. Raymond Tse and team have combined 3D stereophotogrammetry and computer vision techniques to develop novel methods of analyzing facial features. The automated, computer-based nature of these measurements makes analysis rapid and convenient. This study will further develop and validate these tools for cleft lip severity and treatment success.

2013 Pediatric Pilot Award Recipients

Claudia Crowell, MD

A pilot study of the effect of the Mediational Intervention of Sensitizing Caregivers (MISC) on neurodevelopment in HIV-infected children in Kenya

Pediatric HIV infection is associated with an increased risk of neurocognitive deficits. The Mediational Intervention for Sensitizing Caregivers (MISC) seeks to facilitate caregiver-directed mediated learning. The MISC has been studied extensively in resource-limited settings and has been shown to be an effective early childhood intervention for improving neurocognition and child behavior. In her project, Dr. Claudia Crowell will measure the effectiveness of the MISC on neurocognitive outcomes and the behavior of HIV-infected children. She and her research team will perform neurocognitive and behavior testing with patients at the time of enrollment and again 6 months after enrollment and compare the changes in test scores over time. They will also measure the effect of the MISC on caregivers’ mental health and attitudes as well as their acceptance of the tool. Results of this study will be used to design a larger clinical trial.

Evelyn Hsu, MD

A pilot study of frailty in children with end-stage liver disease: Moving beyond PELD

In the United States, the allocation of organs to children with end-stage lived disease (ESLD) is based on the Pediatric End-Stage Liver Disease (PELD) scoring system. The PELD system, however, does not accurately capture the extent of illness; as a result, more than 50% of children in the U.S. are allocated livers by an exception system, bypassing the PELD score. PELD has not been shown to predict post-transplant outcomes and does not identify children at risk from significant morbidities following transplantation. In adults, frailty has been found to be a more powerful predictor of functional status than age or comorbidity. Measures of frailty might assist in the identification of the sickest children awaiting liver transplantation in order to properly prioritize them for transplant and improve post-transplant outcomes. Dr. Evelyn Hsu’s pilot project will measure frailty in a multicenter cohort of children with end-stage liver disease awaiting transplantation and explore the association of the frailty score with the PELD score.

Thomas Jinguji, MD

Use of diffusion tension imaging in the evaluation of pediatric concussions

Standard MRIs on concussed brains do not typically show abnormality. New imaging techniques such as diffusion tensor imaging (DTI) might be able to detect regional water-mobility changes. In his pilot project, Dr. Thomas Jinguji and team will determine the differences in DTI results between children with persistent symptoms lasting for more than 6 weeks after a concussion and those who do not show persistent symptoms. They will also determine normal values of DTI results in children with no history of a concussion and compare them with the DTI results from concussed children. Understanding the changes in the brain that are cause by a concussion will allow improvements with clinical practice guidelines for this condition. The result of this study will serve as preliminary data for a larger study.

Margaret Rosenfeld, MD, MPH

Development of an observer-reported outcome of respiratory signs for young children with cystic fibrosis

Patient-reported outcomes measures (PROs) directly evaluate how a patient feels or functions. As infants and children under the age of 12 may not reliably report their own symptoms, the U.S. Food and Drug Administration (FDA) and the outcomes field in general recommend that parent reports be used in this age range, particularly for birth to age 6. In cystic fibrosis (CF), PROs have been validated for patients 12 years and older, but no widely used observer-reported measure exists for children under 12. Such measures might serve as important clinical trial endpoints in young children with CF. In her previous work, Dr. Margaret Rosenfeld and her team have developed two age-specific instruments to assist parents with reporting their child’s symptoms. In her pilot project, Rosenfeld will evaluate these instruments. Based on the results of this pilot study, Rosenfeld will revise and simplify the instrument, and continue to further testing.

David Suskind, MD

Fecal microbiota transplantation in pediatric Crohn's disease: A double-blinded, placebo-controlled pilot study

Fecal microbiota transplantation (FMT) is a standard therapy for Clostridium difficile infections (C. difficile) – a dangerous intestinal bacterium. Dr. David Suskind’s pilot project is a single center randomized, double-blinded, placebo-controlled pilot study to gather data on the efficacy of FMT in patients with Crohn’s. If the results show it is effective, this would shift the treatment paradigm for this disease. Seattle Children’s was the first research center in the nation to receive federal approval to test the effectiveness of fecal transplants in pediatric patients with inflammatory bowel disease and it is the only center studying the treatment in children with Crohn’s disease.

Joyce Yi-Frazier, PhD, and Abby Rosenberg, MD, MS

Development of the Promoting Resilience in Stress Management in Parents/caregivers (PRISM-P) intervention: Building resilience in caregivers of youth with chronic/serious illness

Serious illness such as cancer and diabetes greatly impacts the well-being of patients, their parents and other children in the home. Individual differences in stress management and coping skills contribute to patient and family outcomes, including emotional distress and quality of life. In their previous work, Drs. Joyce Yi-Frazier and Abby Rosenberg developed Promoting Resilience in Stress Management (PRISM), a patient-focused resilience intervention that they are currently piloting among adolescents and young adults with cancer or type 1 diabetes. In their pilot project, Yi-Frazier and Rosenberg will create and test a parent-centered version of the PRISM intervention for parents of patients. Findings from the study will inform the development of larger investigations designed to test the efficacy of the intervention, with the goal of improving outcomes for patients and families alike.

2012 Pediatric Pilot Fund Recipients

Grace John-Stewart, MD, MPH, PhD, and Lisa Cranmer, MD, MPH

The effect of maternal immunity on infant vaccine response to BCG

Mycobacterial infection is a significant world-wide public health problem, with one third of the world's population infected with tuberculosis (TB). BCG is the most widely used vaccine, but it has variable efficacy. In their pilot project, Drs. Grace John-Stewart and Lisa Cranmer will investigate whether maternal mycobacterial immunity diminishes infants' vaccine response to BCG. Using a longitudinal cohort of mother-infant pairs in Kenya, the investigators will measure anti-mycobacterial cellular and humoral immunity prior to BCG at the birth and evaluate BCG immunogenicity among infants at 10 weeks. John-Stewart and Cranmer suggest that these results could better define the effect of maternal immunity on infant BCG response and could lead to an improved vaccine or an improved vaccine schedule.

Joseph Flynn, MD

Intravenous hydralazine for management of acute hypertension in children and adolescents

Acute severe hypertension in children typically requires treatment with an intravenous antihypertensive medication. One of the most commonly used is hydralazine. However, despite recommendations in the literature for use of IV hydralazine for such patients, there are no published clinicals trails or case series of IV hydralazine in children with acute severe hypertension, and therefore no evidence-based or FDA-endorsed pediatric doses available. Dr. Joseph Flynn and his research team will conduct a retrospective review of blood pressure response to individual does of IV hydralazine in hospitalized children with hypertension. The data generated from this study will help to develop improved dosing recommendations for IV hydralazine and inform the design of prospective, multi-center clinical trials to generate better-quality evidence. Thus, the results have the potential to improve the quality and safety of care of children with acute severe hypertension.

Ryan McAdams, MD

Is prolonged exposure to dexmedetomidine safe for neonates?

Dexmedetomidine (DEX) is a sedative medication that has reported to produce sedative effects without inducing significant respiratory depression. However, minimal data exists describing the pharmacokinetics, efficacy, safety or neuropathologic effects of prolonged exposure to DEX in infants. Dr. Ryan McAdams' pilot project proposes to establish the pharmacokinetics of the DEX in neonates and to evaluate neuronal density, reactive astrogliosis and cell proliferation in specific regions of the brain after neonatal DEX treatment. The goal of this research is to provide evidence-based information that can improve the long-term intensive care of preterm infants and optimize their neurodevelopmental outcome.

Margaret Rosenfeld, MD, MPH

Novel home cough monitor in young children with cystic fibrosis: a pilot and feasibility study

Recent studies have demonstrated that cystic fibrosis (CF) begins in the first years of life. Therefore, there is a high level of interest in conducting clinical trials of early interventions to delay or present irreversible lung damage. Dr. Shwetak Patel and his research team at the University of Washington have recently developed a novel, fully automated cough sensor that has demonstrated feasibility and accuracy in ambulatory adults. In her pilot study, Dr. Margaret Rosenfeld will collaborate with Patel to assess the accuracy and feasibility of cough monitoring in CF patients from birth to 6 years of age and obtain longitudinal data in this age range necessary for the planning of future studies. This device could potentially serve as an important resource for clinical trials of disease-modifying therapies in children with CF.

Cate Pihoker, MD

Examining the role of vitamin D deficiency in diabetic kidney disease in children

Nearly a third of children with diabetes will develop diabetic kidney disease (DKD) as adults, the earliest sign of which is albuminuria (increased excretion of protein in urine). Several lines of evidence connect low vitamin D levels with albuminuria and DKD, including a recent clinical trial that demonstrated that supplementation with activated vitamin D reduces albuminuria in adults with DRD. This has not been studied in children. In her pilot project, Dr. Cate Pihoker and her research team will evaluate this association in two nationally representative cohorts for children. If the findings for adults hold true for children, vitamin D may be a cost-effective, low-side-effect tool for early intervention in the course of DKD in children.

Jerry Zimmerman, MD, PhD

Catabolism and morbidity after pediatric sepsis

Pediatric sepsis is a leading cause of childhood mortality worldwide. Sepsis is also likely an important cause of long term morbidity. However, the causes of long-term sepsis morbidity have been inadequately investigated. In his pilot project, Dr. Jerry Zimmerman and his research team will characterize the role of muscle catabolism on multi-dimensional fatigue and functional impairment among children hospitalized with severe sepsis. This knowledge of the role of muscle catabolism on long term physical outcomes following pediatric sepsis will facilitate the design of targeted intervention to help maximize functional outcomes among children surviving sepsis. It will also identify children who might benefit from early rehabilitation interventions following sepsis.

2011 Pediatric Pilot Fund Recipients

Scott Baker, MD, MS, and Abby Rosenberg, MD

Understanding resilience in parents of children with cancer

In their pilot project, Drs. Scott Baker and Abby Rosenberg will implement a cross-sectional study using both quantitative and qualitative instruments to assess overall resilience and psychological functioning among bereaved and non-bereaved parents of children with cancer. The research team will evaluate medical and psychosocial factors of resilience in both sets of parents. Results from this study will inform providers of the prevalence of various psychosocial outcomes among parents of children with cancer and will relate those findings to the medical experience. Ultimately, this research will direct future studies aimed at fostering resilient outcomes not only among parents, but also whole families facing pediatric cancer.

Janet Englund, MD, and Helen Chu, MD

Respiratory syncytial viral disease in Nepalese children: the effect of clean cook stove installation

Acute lower respiratory tract infection (ALRI) is the leading cause of childhood mortality globally, and respiratory syncytial virus (RSV) is an important viral pathogen in ALRI. There is recent evidence that household air pollution caused by indoor cook stoves using vegetable matter, cow dung and wood matter increases the risk of ALRI in children. In Drs. Janet Englund and Helen Chu's pilot project, study personnel will observe children with ALRI living in Nepal in families with and without clean cook stoves. The study team will perform weekly surveillance during the respiratory viral season for ALRI signs and symptoms in children ages 1 month to 36 months. They will collect nasopharyngeal swab specimens from the children during illness episodes both before and after a clean cook stove has been installed. This study will establish the baseline incidence, severity and duration of RSV illness in children in Nepalese households with traditional cook stoves and determine the impact of clean cook stoves in reduction of RSV illness.

Kelly Evans, MD

Sleep outcomes and airflow in Robin sequence (RS)

Craniofacial anomalies, such as Robin sequence (RS), are the leading cause of obstructive sleep apnea (OSA) in infants. In her pilot project, Dr. Kelly Evans will conduct overnight studies to measure sleep disturbance and sleep-impacted outcomes in five infants from birth to 6 months old with RS and five healthy infants. In addition to collecting standard phenotypic information, the study team will capture a three dimensional shape of the infants' faces, allowing for more accurate assessment of craniofacial shape and systematic evaluation of relationships between facial structures. This collective data will provide Evans with information to characterize the nature and severity of OSA in infants with RS that can be used for further research.

Sangeeta Hingorani, MD, MPH

Assessment of endothelial function and hypertension in patients after hematopoietic cell transplant

Hematopoietic cell transplant (HCT) is an increasingly common treatment for many malignancies and some genetic disorders. Dr. Sangeeta Hingorani's recent work has identified that at day 100 after this type of transplant, albuminuria and proteinuria are associated with an increased risk of chronic kidney disease (CKD), non-relapse and overall mortality. In the U.S., approximately 1,500 patients per year will develop proteinuria at day 100 and will die within the first year after transplant. The cause of this increase in mortality is unknown. In her pilot project, Hingorani and her team will evaluate whether endothelial dysfunction, a condition in which the endothelium (inner lining) of blood vessels do not function normally, predicts albuminuria and proteinuria at day 100. The information generated from this study will be used as preliminary data for further research in this patient population and to support the necessity for a targeted intervention trial.

Sarah Ringold, MD, and Anne Stevens, MD, PhD

Is there a link between prophyromonas gingivalis infection and juvenile idiopathic arthritis?

In their pilot project, Drs. Sarah Ringold and Anne Stevens will test the hypothesis that exposure to Porphyromonas gingivalis, a bacteria associated with periodontitis/gingivitis, is a trigger for polyarticular juvenile idiopathic arthritis (JIA). Evidence suggests that P. gingivalis may trigger rheumatoid arthritis (RA) via mimicry, a process where antibodies to this bacteria cross-react with certain proteins found in joint tissue. Although polyarticular JIA is believed to share a cause with adult RA, it is not yet clear whether P. gingivalis plays a similar role in the JIA pathogenesis. In this study, investigators will measure the levels of cross-reactive antibodies of children with JIA and the association between the levels of these antibodies and clinically assessed JIA disease activity. These data will pave the way for additional research on the relationship between periodontal disease and JIA, hopefully leading to a better understanding of the etiology of JIA and novel treatment strategies. Peggy Lee, BDS, MSD, PhD, in the Division of Dentistry at the University of Washington School of Medicine, is also a co-investigator on the project.

Klane White, MD

Identifying access barriers in children with developmental dysplasia of the hip

Developmental dysplasia of the hip (DDH) is a fairly common pediatric orthopedic disorder. While early detection and treatment of DDH is critical for the best chances of obtaining a well-functioning, pain-free hip joint into adulthood, there continue to be ongoing cases of delayed presentation of DDH patients at Seattle Children's Orthopedic Clinic. In his pilot project, Dr. Klane White and his research team will conduct a study to identify different factors that may be contributing to the delayed patient visits to a pediatric orthopedic specialist. White will use the results to do educational outreach to address healthcare providers for children who are "at risk" of missed DDH diagnoses. Co-investigators on the project include Vivian Bompadre, PhD, and Antoinette Lindberg, MD, both in the Division of Orthopedics at Seattle Children's.