Beyond What’s Possible
Exploring the Future of Health
Investments in pediatric research hold the opportunity to impact an entire lifespan making it a critical element of Nemours’ strategic vision to redefine the future of children’s health. Nemours’ investments manifest in multiple ways including developing new treatments, personalizing therapies, mining data to inform clinical decisions, and identifying better ways to deliver care where a child or family is — physically, emotionally and socially. A continuous pipeline of innovation requires infrastructure, funding and mentoring — all elements of Nemours’ growing reputation in pediatric research.
Igniting a Sustainable Impact to Improve Children’s Health
Back in 2003, a group of energetic scientists and clinician-scientists at Nemours networked to develop an NIH Centers for Biomedical Research Excellence (COBRE) grant. By brainstorming and exchanging ideas, they produced a proposal that the NIH ranked as one of the best submissions they had received in that round of COBRE funding. The Center for Pediatric Research (CPR) COBRE grant was unique in several ways:
- it was the first COBRE grant awarded to a pediatric research focus;
- Nemours’ center and hospital are primary providers of pediatric care and support for the entire state of Delaware;
- it addressed common barriers to translational research by integrating researchers from a number of major disciplines, enabling and maintaining a focus on mentored research training; and
- its initial narrowed focus (genetics, cardiology and neuroscience during Phase I) helped establish a critical mass of investigators to attract funding and recruit new researchers, ultimately creating a sustainable research center.
The team approach toward solving clinical research questions, exemplified through the CPR, helped further develop the research and clinical programs across all of Nemours.
Today, under the direction of principal investigator Thomas H. Shaffer, MSE, PhD, Nemours CPR remains one of the few (10%) COBRE programs that focus on pediatric disorders. During the past 16 years, the grant (receiving four phases of extension through 2020) has supported nine Target Investigators, two Transitional Investigators, and 12 Pilot Investigators, as well as numerous clinical fellows and grad students.
Each Nemours CPR COBRE investigator has shown remarkable academic progress — being awarded federal, state, corporate and foundation grants; numerous publications and presentations; mentoring students and post-doctoral fellows; and establishing individual investigator laboratories, and enhancing or establishing new core laboratory services at Nemours Children’s Hospital, Delaware.
Of the $485 million NIH distributed nationally through IDeA, $257 million was provided to Delaware researchers through 992 new grant awards; Nemours’ CPR share is estimated at $45.5 million
Adding to the Body of Knowledge on Type 1 Diabetes
A nearly eight-year, multi-center NIH study led by principal investigator Nelly Mauras, MD, Division Chief, Endocrinology, Diabetes & Metabolism, Nemours Children’s Health, Jacksonville, compared brain scans of 144 young children with type 1 diabetes (T1D) with those of 72 non-diabetic children to assess whether previously observed brain and cognitive differences between children with T1D and control subjects persist, worsen or improve as children grow into puberty and whether differences are associated with hyperglycemia.
Over this long study period, spanning two NIH funding cycles, up to four MRIs were performed measuring white- and gray-matter volumes in various brain regions for all participants at Nemours Jacksonville and four other collaborating institutions at Stanford, Yale, University of Iowa and Washington University in St. Louis. In the T1D group, the research team assessed total cumulative hyperglycemic exposure since diagnosis. They found that total brain volume, gray- and white-matter volumes, overall IQ, and verbal IQ were lower in the diabetes group at age 6, 8, 10 and 12 years, compared to the control group.
These unique longitudinal data support the hypothesis that the brain is a target of diabetes complications in young children, and that the effects are seen early in the disease process. Further studies are important to determine how brain and cognitive issues may affect long-term educational and vocational outcomes for children with T1D and whether those changes in the brain can be halted or reversed with scrupulous diabetes control. These seminal studies by Dr. Mauras and her team continue at Nemours.
For more on this study, view the abstract of the article published in Diabetes Care Journal.
Addressing Disease in Infants to Impact Lifelong Health
Bronchopulmonary Dysplasia (BPD) is a chronic lung disease affecting 50-55% of extremely low-birth-weight preterm infants that is often complicated by pulmonary hypertension and is the most common cause of death, severe neurodevelopmental impairment, and hospital readmissions in preterm infants. For babies who survive, BPD is a lifelong disease, and long-term studies show that premature babies with BPD have a much higher risk of Chronic Obstructive Pulmonary Disease (COPD) — one of the leading causes of death in the U.S.
Deepthi Alapati, MD, MS, attending neonatologist at Nemours Children’s Hospital, Delaware, secured a five-year, NIH Mentored Clinical Research Career Development K08 award (a first for Nemours) to investigate the role of CCN2 (a key lung communication factor) in the etiology of BPD and extend the application of lung gene editing techniques among the multiple pulmonary cell types responsive to infection and oxygen, which she developed, as a possible treatment modality.
For Dr. Alapati, this work is deeply personal. She has seen first-hand the variety of respiratory diseases that complicate quality of life or even prove fatal to infants. This research isn’t just about lung disease, but whole-body health and quality of life. Of further importance is a matter of health equity: it is well known that minority mothers are at a higher risk of pre-term births and infants with low birth weight, both connected to a higher risk of BPD — and ultimately, predicative of a variety of adverse health outcomes.
Seeking a Higher Standard of Care Delivery
Nemours Center for Healthcare Delivery Science (CHDS), led by Anne Kazak, PhD, ABPP, is an enterprise-wide research center that studies the many influences that affect the outcomes, quality, cost, safety and value of pediatric healthcare. CHDS faculty and staff use diverse methodologies drawn from behavioral science, informatics and health policy to build a strong base of scientific evidence about how health care can best be delivered to ensure the next generations of children are the healthiest ever.
Established in 2012, today CHDS supports 20 NIH-funded grants, 22 other externally funded grants, and 12 additional grants funded internally.
Areas of emphasis within CHDS include:
- family adaptation to pediatric medical events
- family psychosocial risk screening
- medical traumatic stress and trauma informed care
- models of care delivery and intervention development and evaluation
- implementation science
- technology-supported intervention delivery
- transition from pediatric to adult healthcare settings
- risk and resilience in child health
Nemours Center for Healthcare Delivery Science supports 20 NIH-funded grants, 22 other externally-funded grants and 12 internally-funded grants
Supporting Families in Managing Disease
Approximately half of the current NIH-funded CHDS research projects focus on various aspects of pediatric diabetes, including behaviors and barriers related to glycemic control. Two of these NIH grants are R01 type, meaning they seek to solve a specific problem and provide actionable outcomes backed by significant data that, when published, can often be considered a best practice or standard of care. Typical pediatric diabetes management includes quarterly in-person visits between physician and patient; that means, physicians are managing the disease less than 1% of the time — the other 99% of disease management falls on families. Nemours treats families, not just kids; as such providing support and resources for the whole family is imperative. These two NIH R01 grants (see below) are intended to identify and connect families with the resources they need using the broader perspective of what influences a child’s health.
Remedy to Diabetes Distress: A scalable screen-to-treat program for school-age families
Diabetes distress can be similar to depression and include feelings of sadness, anger, despair, burnout and fear — all related to managing diabetes in yourself or someone else living with diabetes. In addition to being indicative of quality of life, diabetes-specific distress can be one of the largest contributors to glycemic control and patient engagement. It is becoming increasingly important to identify patients and family members experiencing diabetes distress so they can receive appropriate support to reduce the distress.
The Nemours team will work to develop, implement, and test the feasibility and acceptability of a novel, practical, and scalable screen-to-treat program for diabetes distress in parents and school-aged children with type I diabetes. This project, the Remedy to Diabetes Distress (R2D2), is funded by a five-year, $3.2 million NIH R01 grant secured by Susana Patton, PhD, ABPP, CDCES, Florida Center Director, Nemours CHDS, and entails the use of screening tools that will be developed and tested in Phase 1 of the study to appropriately identify parents and children for recruitment.
Phase 2 includes an mHealth and telehealth treatment program designed to teach parents and children cognitive-behavioral therapy, mindfulness, and behavioral activation strategies to help them manage feelings of distress.
Home-based Video Telemedicine to Reduce Parental Fear of Hypoglycemia in Youngs Kids with T1D
Managing type 1 diabetes (T1D) in young children introduces greater risk for low blood sugar or
a hypoglycemic event. In part, this is due to increased insulin sensitivity in young kids as well as their unpredictable behavior, eating habits and ability to communicate how they’re feeling. Hypoglycemia can lead to dangerous complications and poor health outcomes.
Through a five-year, $2.9 million NIH R01 grant, also secured by Susana R. Patton, Nemours is seeking ways to help families better manage and cope around managing the fear of hypoglycemia through a unique at-home, video-based telehealth intervention. The 10-week sessions, led by PhD-level interventionists, teach families cognitive behavior therapy strategies (e.g., mindfulness, behavioral activation) to reduce fear and promote better coping for fear that’s unavoidable.
Throughout the intervention, families complete online surveys, submit data from pump or continuous glucose monitor devices to the cloud, and complete at-home test kits that measure glycated hemoglobin. In addition, Actiwatches are provided to study participants to measure physical activity and sleep behaviors. Currently, 50 families have participated in the remote study; the total sample size is expected to grow to 180 in coming years.
Elevating Sickle Cell Disease Research
The Delaware Comprehensive Sickle Cell Research Center (DCSCRC) was established in 2014 through a $10.2 million, five-year COBRE grant awarded by the NIH to Nemours Center for Cancer and Blood Disorders (NCCBD), in collaboration with Delaware State University (one of two Historically Black colleges in the state of Delaware). The Center builds upon strengths in biomedical research, clinical care and faculty to create a sustainable infrastructure supportive of target investigators and cutting-edge research in sickle cell disease (SCD).
Through the COBRE grant, the DCSCRC investigators and clinicians work side-by-side studying the genetic mutation that causes SCD and improving care and outcomes for affected children, to:
- prevent SCD symptoms
- offer families strong psychosocial support
- study the quality of SCD care
- identify genetic pharmacologic approaches to treatment and cure
To date, researchers from the DCSCRC created 60 presentations and published 66 chapters, abstracts and peer-reviewed manuscripts related to associated projects and trials. Most recently, researchers from the DCSCRC published a manuscript for JAMIA Open titled, “Implementation of a Learning Health System for Sickle Cell Disease.” The objective of the study was to create a comprehensive learning healthcare system to support disease management and research using SCD as a model. The multidisciplinary DCSCRC team developed an SCD clinical data dictionary to standardize bedside data entry and inform a scalable environment capable of converting complex electronic health records into knowledge accessible in real time. A custom application, the Sickle Cell Knowledgebase, was developed to improve data analysis and visualization. The system can be used to facilitate patient care and guide medical decision-making, in addition to enhancing the ability to access patient data for research purposes. While the focus was on SCD, the strategy for implementing a learning healthcare system can be applied to many other chronic disease models.
Read the abstract, to learn more about the learning health system for sickle cell disease.
Approximately one in 500 African American babies and one in 11,000 Hispanic infants are born with sickle cell, while 2.5 million Americans carry the sickle cell trait.