Built to Discover
Pediatric research holds the key to unlocking mysteries that could prevent or reverse the course of disease across an entire lifespan.
Throughout Nemours, mission-driven physician and research scientists are engaged in nearly 200 externally funded grants and 216 clinical trials. This work is focused on improving the lives of today’s children — and contributing to a body of knowledge that will guide the future of health. These efforts are buoyed by cross-institutional cooperation and the most extensive network of longitudinal pediatric patient data.
Shifting Clinical Research Studies from Investigator-Driven to Patient-Centered
Through PEDSnet, eight contributing institutions including Nemours convert EHR data from more than 6.2 million de-identified pediatric medical records to a common data model and make it available in an analysis-ready database. This collaborative infrastructure affords researchers from all institutions access to uniform data to conduct research. To date, PEDSnet has been the source for 37 studies. Active PEDSnet institutions also leverage the network data for internal studies.
We’re gaining the ability to extract important information about patients in a defined cohort with a particular disease. We can drill down into factors that distinguish them from the average Nemours patient — and that can tell us what we need to watch out for.
— Tim Bunnell, PhD, PEDSnet Site PI and Site Informatics Lead
The Nemours Bioinformatics team is using advanced machine learning methods within PEDSnet datasets to develop the analytic infrastructure necessary to map out a predictive course for certain pediatric disorders. The results will establish dashboards that direct clinicians in what to look for in defined populations as well as potentially generate new research questions related to conditions such as epilepsy, obesity, cerebral palsy and asthma.
With this information, Nemours clinicians can be proactive in delivering health interventions to children — helping them avoid unnecessary emergency department visits, hospital stays and even common colds.
Nemours Precision Medicine Launches Clinical Pharmacogenetics Service
By understanding how a patient’s genetic make-up may affect drug response, providers can choose safer, more effective medications.
The Nemours pharmacogenomics team developed an in-house panel that encompasses 10 genes associated with response to more than 50 medications commonly prescribed to Nemours patients. These include certain antidepressants, opioids, NSAIDs, thiopurines, and many others.
When a physician prescribes the medication, we want them to have this pharmacogenomic information right away, so they can either choose a different drug or a different dose if need be, for that particular patient.
— Kathryn Blake, PharmD, Director, Nemours Center for Pharmacogenomics & Translational Research
The clinical service includes:
- pharmacogenomic testing on an in-house multigene panel orderable within the EHR
- clinical consult service orderable within the EHR to determine:
- appropriateness of testing and test selection
- pharmacogenomic-based drug and dosing recommendations
- assistance with insurance authorization for test coverage
- active clinical decision support in the form of Best Practice Alerts
- pharmacogenomics profile within the EHR with links for more information
- education for providers, nurses, researchers and clinical staff
The service launched at Nemours in the Delaware Valley in February 2020 and will expand to Nemours’ Florida locations by late 2020.
Making Practice More Precise
At age 18 months, Piper Lee was diagnosed with Denys-Drash syndrome characterized by kidney disease that leads to kidney failure. Children with this condition also face a 90 percent chance of developing Wilms tumor, a rare kidney cancer.
Genetic testing plays a critical role in treating certain kidney diseases categorized as steroid resistant nephrotic syndromes (SRNS), as a variety of mutations complicate the efficacy of treatment. At the time of Piper’s diagnosis, there were no labs in the U.S. that could quickly offer the genetic tests that Piper required. Special genetic testing done in England, arranged by her Nemours doctors, proved essential in guiding Piper’s treatment. Determined to make testing accessible to other families at Nemours and throughout the country, Piper’s parents, Chris and Erin Lee, formed Piper’s Kidney Beans Foundation (PKBF). They raised money to develop reliable genetic testing for nephrotic disorders, as well as cover the cost of testing for families with limited means.
With funding from PKBF, Nemours developed a 46-gene SRNS panel that is certified by Clinical Laboratory Improvement Amendments, affordable and provides reliable results quickly. By understanding the genomic variants present for each child, Nemours can determine the best course of treatment and ultimately save lives.
The genetic testing program went live in March 2019. During the next nine months, 12 patients were tested for SRNS, providing physicians with personalized genetic information to guide clinical care.
Using AI and Machine Learning to Help Triage Radiology Reads
Nemours employs one of the largest groups of pediatric radiologists in the nation. Reading for the Nemours health system providers and many of its collaborating hospitals and other institutions, Nemours experts read more than 320,000 images in 2019 with a median turnaround time on stat exams of approximately 14 minutes.
With its investment in Fuji’s new leading-edge Picture Archiving and Communications System (PACS) and Vendor Neutral Archive (VNA), Nemours is positioned to potentially further reduce turnaround time. Clear imaging can now even be visualized securely on mobile devices. Nemours is working on industry partnerships that will enable the system to aggregate imaging data using machine learning to increase efficiency in triaging, screening and prioritizing scans.
Where we’re hoping artificial intelligence will be most beneficial to us is triaging, screening and prioritizing which study comes to the top of our list to be read next.
— Dan Podberesky, MD, Nemours Radiologist-in-Chief
Active research studies are already being conducted to teach the computer to quickly and accurately flag congenital dysplasia of the hips from ultrasound screening exams. Nemours is also exploring other projects to look at AI for identifying brain bleeds on CT scans and picking up pneumonias or pneumothoraces on chest X-rays. In these scenarios, critical scans could automatically be prioritized to ensure children with the most urgent care needs are attended to most quickly.
Giving Kids a Unique Voice
With the support of a National Science Foundation grant, Nemours is working to provide an authentic voice to children through advancements in speech synthesis. Current systems do not convey inflection or the subtlety of meaning that is a product of natural speech. By leveraging a lesser-used technology called Corban synthesis, Nemours is exploring new algorithms to learn the patterns associated with different types of expressiveness, to control a speech synthesizer that is more expressive, conveys more accurate meaning, and is just as good at capturing the voice of an individual user.
The goal is personalized speech synthesis where the synthetic voice sounds like the child — or as they would sound if they were able to speak for themselves. Even for nonverbal children, researchers can extract some characteristics of the child’s voice quality and impose that on the speech synthesizer so that every child can have a unique voice.
Some of this research is funded by a fee-for-service program that allows adults with neurodegenerative disease to submit their speech to the Nemours Center for Pediatric Auditory and Speech Sciences lab to have a synthetic voice created for them to use when they are unable to speak.
Shannon’s was one of the first voices we developed using technology that allows us to blend characteristics of her own vocalizations with the speech of a voice donor to create a voice that is uniquely Shannon’s. Our technology is maturing along with Shannon, and we look forward to providing voice updates consistent with her growth as her story continues.
— H. Timothy Bunnell, PhD, Director, Nemours Center for Pediatric Auditory and Speech Sciences
Fighting Fire With Fire
Researchers are one step closer to determining if Zika virus may hold potential as a cancer treatment for neuroblastoma, a rare but deadly childhood cancer.
A basic research study, published in 2018 by a group of researchers from Nemours Children’s Hospital and Burnett School of Biomedical Sciences at the University of Central Florida College of Medicine, showed Zika virus successfully destroying most neuroblastoma cells that had been cultured in the lab.
We have begun initial discussions with the FDA to start laying out the roadmap to a phase one clinical trial.
— Tamarah Westmoreland, MD, PhD, Nemours Children’s Hospital
This collaborative research was an early, but important first step in the potential use of Zika virus as a cancer therapy. During 2019, the same research collaborative was able to move the study to an animal model, opening the door to a possible clinical trial in the near future. The one-time dose of Zika virus was shown to decrease the size of the neuroblastoma tumors grown in mice by more than 50 percent.
The team has also expanded the cell culture research to include hepatoblastoma (liver tumor) and Wilms tumor (kidney tumor) as well as cervical cancer, sarcoma and Diffuse Intrinsic Pontine Glioma — a deadly pediatric cancer that has a zero percent survival rate. All have shown sensitivity to the Zika virus and will likely move into the animal model phase.