Bench to Bedside

December 2015 – Year in Review

Research Making Impacts Far Beyond the Lab


Most research progresses through incremental advances, but virtually all pediatric researchers want their work to make a big impact. Many of the research advances celebrated at The Children’s Hospital of Philadelphia in 2015 did just that, influencing multiple fields of practice, policy, or society.

Cancer Survivorship

Focusing on survivorship after cancer care is one area where CHOP researchers are having long-lasting impacts on children’s health beyond the specialists involved in treating and studying the initial disease.

“Cancer survivorship and quality of life is an area of intense research,” said Jill P. Ginsberg, MD, a pediatric oncologist and director of the Cancer Survivorship Program at CHOP. “As pediatric oncologists, we want to improve the cure rate with less future toxicity, and part of our responsibility is to focus on young patients’ quality of life afterward, as they have long and productive lives to live.”

Dr. Ginsberg and colleagues have committed to multidisciplinary research at CHOP focused on many physical and psychological health aspects of cancer survivorship including bone health abnormalities, transitions to adult care, and fertility preservation. In addition, the group participates in large national research collaboratives to improve understanding and response to long-term effects of cancer and its therapies.

Patient-Reported Outcomes

Similarly, research on patient-reported outcomes is impacting many children with different diseases. This research aims to improve how clinicians and researchers use outcomes meaningful to patients when monitoring and improving care. CHOP pediatrician Christopher B. Forrest, MD, PhD, has led development of several survey tools to collect children’s self-reported health outcomes under the NIH-funded Pediatric PROMIS initiative, including measures of sleep health developed this year. This fall, a group at CHOP led by Dr. Forrest and Katherine Bevans, PhD, was selected to lead the national NIH-funded consortium to validate pediatric patient-reported outcomes for children with chronic diseases.

Law and Public Policy

CHOP research continues to make an impact far beyond the realm of healthcare, too. Among the noteworthy achievements of CHOP research in law and public policy this year:

Entrepreneurship and Commercial Impact

One more major way CHOP research is beginning to extend its impact is through commercialization in spinoff companies. This year, Patrick FitzGerald joined CHOP to lead efforts in innovation and entrepreneurship. In October, Diagnostic Driving, a startup company spun out from driving safety research at the Center for Injury Research and Prevention (CIRP) at CHOP, took its pitch on the road to seek venture capital investors for its next phase of growth — which goes beyond the youth market the team originally envisioned.

“For driving assessment software, there just so happened to be a market in corporate fleets,” said company co-founder and CIRP project manager Venk Kandadai, MPH — meaning their work could have an impact on saving lives of drivers of all ages, across the country.

For yet more examples of how CHOP research shaped policy and influenced social welfare this year, see the Bench to Bedside article on social impacts.

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Bold, New Initiatives Set in Motion Research Transformation


The year began at an amazing pace, with the announcement in January of a $50 million gift from Philadelphia philanthropist Raymond G. Perelman that provides direct support for a wide range of pediatric research and establishes The Children’s Hospital of Philadelphia as a global center for innovative pediatric study.

In recognition of this generous gift for research, CHOP also established the Raymond G. Perelman Campus, an eight-acre area just south of the main hospital that serves as a hub of state-of-the-art scientific endeavors that offer life-changing opportunities for families facing the toughest and most challenging pediatric illnesses.

Momentum continued to build throughout the year, as several other major initiatives launched with a mission to advance world-class pediatric research and medicine.

Center for Perinatal and Pediatric Health Disparities Research

The new Center for Perinatal and Pediatric Health Disparities Research will seek to support all pediatric patients by conducting research to better understand the root of disparities that exist in care and health outcomes — be they racial, gender-based, or caused by geography.

Scott Lorch, MD, MSCE, who is leading the Center, hopes these efforts ultimately will inspire the next generation of pediatric medical researchers to conduct health disparities research, and to start a dialogue about pediatric and perinatal health disparities, with the goal of improving outcomes for patients.

Dr. Lorch also is director of the Neonatal-Perinatal Medicine Fellowship Program in the Division of Neonatology and Deputy Director of the Center for Outcomes Research at CHOP, as well as an associate professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania.

Fetal Neuroprotection and Neuroplasticity Program

A joint project of the hospital’s Cardiac Center, the Fetal Heart Program, the Center for Fetal Diagnosis and Treatment, and the Division of Neurology, the Fetal Neuroprotection and Neuroplasticity Program is the first-ever comprehensive program dedicated to prenatal neuroprotection. While this program initially will focus on the fetus with congenital heart disease (CHD), it will expand in the future to include fetuses with other birth defects, such as congenital diaphragmatic hernia and pulmonary hypoplasia.

“Indeed, neurodevelopmental disability is now recognized as the most common complication of critical CHD — those patients requiring cardiac surgery in infancy — and has the most negative impact on quality of life, academic performance, and opportunity for independence as an adult,” said J. William Gaynor, MD, cardiac surgeon and director of the Fetal Neuroprotection and Neuroplasticity Program.

The focus of the new program will be to investigate the factors that cause abnormal brain development in the fetus with a congenital heart defect and to conduct clinical trials of fetal interventions to determine whether novel prenatal treatments can reduce brain injury and improve neurodevelopmental outcomes in newborns with CHD who subsequently undergo cardiac surgery. The first such study will evaluate whether the hormone progesterone, administered prenatally to the mother, has a neuroprotective effect on brain development.

FARE Center of Excellence

Food Allergy Research & Education (FARE), a leading advocacy organization working to benefit 15 million American children and adults with food allergies, launched the FARE Clinical Network in June and named CHOP as one of its 22 centers for excellence.

The FARE Clinical Network aims to accelerate drug development in the field by conducting clinical trials of new treatments, as well as to establish patient registries. FARE will initially fund the centers of excellence with an investment of more than $2 million per year.

“We are proud to be selected as a member of FARE’s Clinical Network, and look forward to collaborating in this effort to improve diagnosis and advance treatment for patients with food allergies,” said pediatric allergist Jonathan M. Spergel, MD, PhD, chief of CHOP’s Section of Allergy.

PEPR Consortium

A new grant from the National Institutes of Health to advance the science of patient-reported outcome measures established CHOP as the administrative leader and one of four centers awarded as part of the Validation of Pediatric Patient-Reported Outcomes in Chronic Diseases (PEPR) Consortium. The PEPR Consortium will work to improve pediatric health and well-being by capturing the voice and experience of children and their families living with a variety of chronic diseases and conditions.

“Our vision is that patient-reported outcomes become like lab tests,” said Christopher Forrest, MD, PhD, a pediatrician and researcher at CHOP and professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, who is leading PEPR along with Katherine Bevans, PhD.

The group will test several tools for collecting children’s self-reported outcomes that were previously developed under the Pediatric PROMIS initiative. They intend to connect children’s scores on PROMIS surveys to clinically meaningful outcomes so that doctors and clinical researchers can get an in-depth view from patients’ perspectives on key areas that can help demonstrate how their condition is improving or worsening.

PennCHOP Microbiome Program

The PennCHOP Microbiome Program is exploring a new dimension of research by conducting investigations using deep DNA sequencing technology to characterize the bacterial, fungal, and viral members of the human microbiome and to determine how these microscopic communities influence our health.

“If we take advantage of what they’re trying to tell us, it’s going to change medicine in the future,” said Microbiome Program Co-director Robert Baldassano, MD, a pediatric gastroenterologist who also directs the Center for Pediatric Inflammatory Bowel Disease at CHOP.

Research teams at CHOP and the Perelman School of Medicine at the University of Pennsylvania share all of the Microbiome Program’s resources. The collaboration allows researchers to study the microbiome from infancy into adulthood.

Another unique aspect of the Microbiome Program is its focus on designing human interventions, said Co-director Frederic Bushman, MD, an adjunct faculty member at CHOP and a professor of microbiology at the Perelman School of Medicine. For instance, as scientists begin to identify microbiome environments associated with wellness, perhaps they then can figure out ways to sway the microbiome in healthy directions.

“We are gathering this kind of data to circle back to patients,” Dr. Bushman said. “We can use this knowledge to try experimental therapies to improve patient welfare.”

Read more about the Microbiome Program in the upcoming Annual Report.

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Science is a Team Sport: CHOP Research Collaborations in 2015


The spirit of collaboration shapes the research enterprise at The Children’s Hospital of Philadelphia, and a look back at stories from 2015 is full of examples.

“NIH is funding a lot of multi-PI grants now, two people working on different aspects of the same thing,” said Judith Grinspan, PhD, research professor of Neurology at CHOP. In November, the first paper was published from one such grant she received with Kelly Jordan-Sciutto, PhD, of the University of Pennsylvania School of Dental Medicine, to study the impact of antiretroviral drugs on the development of oligodendroyctes — a subject neither investigator’s lab could address alone.

Many other cross-disciplinary collaborations are occurring across CHOP:

Larger, institutional-level collaborations also are finding common ground. Rebecca A. Simmons, MD, is excited for the potential of a research collaborative established by the March of Dimes Prematurity Research Center at Penn earlier this year.

“This kind of cooperation and collaboration is on a different scale than has ever been developed for preterm birth,” said Dr. Simmons, the project leader for the network’s bioenergetics and genetics theme. “It’s not only collaborative across our campus and many different departments within the Penn/CHOP system, but we also collaborate between centers, which is a very unique structure.”

Many other large multi-institution networks have arisen to find answers that only large datasets can provide. A “super network” for comparative effectiveness research comprising seven large networks is growing beyond its initial project addressing pediatric medication safety to ask other questions about pediatric hypertension. The PEDSNet clinical data network headquartered at CHOP received $8.6 million in renewed funding to enter its next phase this year. And the eMERGE network launched its third phase to bring genomics data closer to clinical applications.

Sometimes, on the other hand, the value of collaboration occurs on an up-close and personal level. Collaborations among clinical teams, patients, and families emerged as important themes in CHOP research this year. Shared decision-making is a growing area of focus in healthcare and pediatric research, and this year a CHOP study in Pediatrics demonstrated that an online portal for asthma care was effective in supporting care for children and families at home. A similar portal for ADHD is the subject of a new study. Researchers are investigating how care teams collaborate in developing patient care plans in the cardiac intensive care unit, while working to improve their communication skills.

For more examples of the importance of collaboration in CHOP research, look for the forthcoming 2015 Research Institute Annual Report.

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Unraveling Genetic Complexities Helps Separate Out Potential Therapies


Genetic discovery is far from ordinary, yet physician scientists at The Children’s Hospital of Philadelphia have become so adept at using sophisticated genomic sequencing technology that pinpointing new genes with connections to pediatric illnesses may have seemed like an everyday occurrence in 2015. Here are some snapshots of their amazing findings.

CHOPS Syndrome Discovered

Genetic experts identified a new syndrome that illuminates key biological processes during human development. The investigators named the disorder CHOPS syndrome, with the acronym representing a group of symptoms seen in the affected children: cognitive impairment and coarse facies (facial features), heart defects, obesity, pulmonary involvement, short stature and skeletal dysplasia (abnormal bone development).

Medical geneticist Ian D. Krantz, MD, co-director of the Individualized Medical Genetics Center at CHOP and an attending physician in CHOP’s comprehensive human genetics program, is the senior author of the study published in Nature Genetics that reported on mutations in the AFF4 gene, which has a critical role in human development. The research team showed that the mutated AFF4 gene produces mutated proteins, which then accumulate and cause a cascade of abnormalities in other genes controlled by AFF4. The result is damage to the heart, skeleton, and intellectual disability, among other effects.

Like many other rare genetic diseases, CHOPS syndrome does not yet have an effective treatment; physicians like Dr. Krantz can only manage the symptoms. But the research team’s insight into the basic biology of this disorder may lay the groundwork for future treatments of this disease. 

New Genes Associated with Eosinophilic Esophagitis

Researchers added to the evidence that genetic factors play key roles in the severe food allergy eosinophilic esophagitis. The study team — which included researchers from CHOP, the University of Pennsylvania, and Rady Children’s Hospital-San Diego — published the study in Nature Communications.

The study team identified four novel loci significantly associated with EoE. Two of them, STAT6 and c11orf30, previously were found in association with both allergies and autoimmune diseases. Two other gene loci, ANKRD27 and CAPN14, were specific to EoE. CAPN14 may be of particular interest, said co-author Jonathan Spergel, MD, PhD, a pediatric allergist-immunologist at CHOP. The gene appears to be expressed only in the esophagus.

“A recent study in a mouse model for asthma showed that a drug that inhibits a related protein reduces inflammation and improves airway functioning in animals,” Dr. Spergel said.

Gene Linked to Immune Defense

Genomics researchers from the Center for Applied Genomics (CAG) at CHOP suspect that mutations in the genes associated with a rare disease called common variable immunodeficiency (CVID) result in a shortage of antibodies that leaves the body vulnerable to infections from bacteria and viruses. The study team reported their findings in the Journal of Allergy and Clinical Immunology.

The researchers found 11 single nucleotide polymorphisms (SNPs) associated with CVID on the 16p11.2 locus of chromosome 16. SNPs are changes in a single DNA building block (A,T, C, or G), compared to the more typical sequence in a certain stretch of DNA. Variants in the gene ITGAM, which carries codes for an integrin protein that regulates cellular contact and adhesion, especially caught the researchers’ attention. The new findings may promote better understanding of ITGAM’s functional role and eventually lead to therapies for patients with CVID.

“This association is of high biological relevance because ITGAM plays an important role in normal immune responses,” said Hakon Hakonarson, MD, PhD, director of the CAG, who led the study team.

Autoimmune Diseases Share Genetic Predispositions

An international study team led by CAG researchers that encompassed 10 pediatric autoimmune diseases found overlaps along gene networks and pathways that may offer useful targets for therapy.

The investigators found 27 genome-wide loci, including five novel loci, among the diseases examined: type 1 diabetes, celiac disease, juvenile idiopathic arthritis, CVID, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, autoimmune thyroiditis, and ankylosing spondylitis. Of those 27 signals, 22 were shared by at least two of the autoimmune diseases, and 19 of them were shared by at least three of them. The results appeared online in Nature Medicine.

Many of the gene signals the investigators discovered were on biological pathways functionally linked to cell activation, cell proliferation, and signaling systems important in immune processes. Characterizing specific autoimmune diseases’ genetic architecture gives researchers opportunities to identify potential therapies, including the possibility of repurposing existing drugs available for non-autoimmune diseases.

Underlying Genetic Defects in Very Early Onset Inflammatory Bowel Disease

Next generation sequencing technology allowed researchers to detect genetic variants that they believe are enriched in patients with very early onset inflammatory bowel disease (VEO-IBD), IBD that presents before age 5.

In an article published online in the journal Gastroenterology, the study team reported the results from performing exome sequencing analysis of 125 patients ages 3 weeks to 4 years with VEO-IBD. They identified several novel and rare gene defects in genes associated with primary immunodeficiencies. These gene variants appear to influence both arms of the immune system, the innate response — our body’s first line of defense — and adaptive response — a more sophisticated response that is not immediately activated.

Melding together genomics technology, disease patterns, immunology, and microbiology, physician-scientist Judith Kelsen, MD, a pediatric gastroenterologist and researcher in the Center for Pediatric Inflammatory Bowel Disease at CHOP who led the study, and colleagues aim to find new and individualized therapies for patients VEO-IBD.

Genetic Culprit Identified in Aggressive Form of Neuroblastoma

Pediatric oncology researchers found that a change in the LMO1 gene results in a “super-enhancer” that causes tumors to arise and grow out of control in an aggressive subtype of neuroblastoma.

This new discovery increases the researchers’ understanding of how the specific protein that functions abnormally in LMO1-driven neuroblastoma sets in motion the molecular mechanisms fueling this high-risk subtype. Components on this biological pathway may offer attractive treatment targets.

“Drugs that inhibit other parts of the gene transcription machinery may offer potential novel treatments for this aggressive subset of neuroblastoma,” said John M. Maris, MD, a pediatric oncologist at CHOP, who is senior author of the study reported online in Nature.

Some Genes Cause Both Heart Defects and Neurodevelopmental Problems

A team of researchers from the Pediatric Cardiac Genomics Consortium studying the role of genetics in congenital heart disease discovered that some of the same gene defects underlie certain cases of congenital heart malformations and neurodevelopmental disorders.

The team reported in Science that they found excess rates of damaging de novo genetic mutations in children with moderate to severe congenital heart disease and neurodevelopmental delay and/or other non-cardiac birth defects, compared to children with congenital heart disease alone. The mutations disproportionately occurred in genes for developmental processes that are highly expressed in the developing heart and brain. The findings may allow researchers to tailor future treatments to children based on their personal genetic risk.

“Congenital heart disease is the most frequent serious birth defect, so as we discover more of these gene alterations, we will be better able to provide genetic counseling and refine patient care for many families and children,” said Elizabeth Goldmuntz, MD, FAAP, FACC, a cardiologist at CHOP and professor at the Perelman School of Medicine at the University of Pennsylvania, and one of the study’s leaders.

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Precision Medicine Takes Center Stage


When precision medicine took center stage in 2015, research at The Children’s Hospital of Philadelphia had a starring role. The curtain opened in January with President Obama’s launch of the Precision Medicine Initiative (PMI), which seeks to spur advances in targeted treatments for disease by supporting genomic research, developing a network of patient volunteers, and partnering with academia and industry. The resulting treatments will be considered precise or personalized because they are designed to act on the specific molecular pathway or gene found to underlie the patient’s own disease.

CTL019 Precision Immunotherapy: A Headlining Example

A prime example is an investigational precision immune therapy for cancer developed at the University of Pennsylvania and CHOP, known as CTL019. After attending the PMI launch event, the first pediatric patient to receive this form of chimeric antigen receptor therapy (CART), 10-year-old Emily Whitehead, was highlighted in a White House blog post about Americans whose lives have been changed by precision medicine.

In Emily’s case of acute lymphoblastic leukemia (ALL), her body’s cancerous B-cells were found to have the protein CD19 on their surface. In the investigational CTL019 therapy, she received an infusion of her own T-cells that were extracted and bioengineered in a way intended to attack the CD19 protein and destroy the B-cells.

Over the course of 2015, results from ongoing CHOP investigations added to researchers’ understanding of CTL019. Clinical trial leaders, including Stephan A. Grupp, MD, PhD, a pediatric oncologist at CHOP and professor of Pediatrics at the Perelman School of Medicine at Penn, reported long-term remissions and other outcomes in December at the American Society of Hematology meeting. Another CHOP team revealed one of the cellular tricks B-cells may use to evade this immune therapy. And CHOP researchers continue to develop other CART approaches for other forms of leukemia and for other cancers.

Genomic Discoveries and Tracking Disease Evolution to Find Precision Targets

The larger unfolding story of precision medicine involves many more discoveries from bench to bedside. Ongoing genomic discoveries at CHOP this year, detailed in a separate article in this issue, form the basis for many potential future precision therapies aimed at disease-involved gene variants.

In addition, CHOP researchers made several advances this year in understanding molecular and genomic evolution of relapsed cancers. One CHOP-led team found distinct patterns of cancer-driving mutations in ALL that were generally different at diagnosis than at relapse. This study, published in Nature Communications, was just “the tip of the iceberg” of what is to come from the collaborative childhood-cancer Therapeutically Applicable Research to Generate Effective Therapies (TARGET) study, according to study leader and TARGET-ALL principal investigator Stephen Hunger, MD, chief of the Division of Oncology and director of the Center for Childhood Cancer Research.

Another such study of cancer evolution through relapse, published in Nature Genetics, has direct implications for a potential precision treatment. Researchers from the lab of John M. Maris, MD, demonstrated that relapsed neuroblastoma tumors show frequent mutations in the RAS-MAPK pathway, which existing drugs have already shown promise targeting in cell and animal studies.

From Genomics to Precision Drug Discovery

The fortuitous existence of drugs targeting a disease-associated pathway, as in Dr. Maris’ team’s study, is one of the fastest ways precision medicine can move from genomic discovery to successful treatment. This was the case with a drug targeted to a molecular subgroup of medulloblastoma (brain cancer) that showed preliminary success in a report in the Journal of Clinical Oncology this year, co-authored by CHOP’s Tom Curran, PhD, FRS.

Drugs that target newfound disease biomarkers and mutations are rarely already known, though. In order to keep precision medicine moving forward, drug discovery must keep pace with genomic discovery. Dr. Maris and colleagues called for academic, federal, and industry leaders to develop new models of drug development in an editorial published in JAMA this year. They suggested that the need will grow as “rare diseases become even more rare” once genetically defined subsets are revealed.

Already beginning to fill some of that drug-discovery gap, CHOP and four other high-profile oncology research programs plus a coordinating center joined the new Pediatric Preclinical Testing Consortium (PPTC) launched by the National Cancer Institute (NCI) to help researchers identify drug candidates for pediatric clinical trials. As part of the PPTC, Dr. Maris’ lab uses animal models of neuroblastoma that incorporate genetic material from patient tumor cells, allowing scientists to design drug tests highly tailored to specific, well characterized subtypes of human neuroblastoma tumors.

Taking Treatments Into Trials

Representing the next stage of the process, testing promising precision drugs in clinical trials, this year saw the announcement of Project:EveryChild Pediatric MATCH (Molecular Analysis for Therapy Choice), a trial due to launch in early 2016 and include about 300 children each year with advanced cancers.

“Pediatric MATCH will try to match genomic changes in certain children’s cancers with drugs that are either approved for adult cancers or with drugs that are still under investigation and not yet approved,” said Peter Adamson, MD, a pediatric oncologist at CHOP and chair of the Children’s Oncology Group, the collaboration of more than 220 children’s hospitals that oversees Pediatric MATCH with the NCI and a range of pharmaceutical companies. The trial will also focus on determining the genomic basis for treatment failures.

With new funding from Alex’s Lemonade Stand Foundation, Dr. Maris and Yael Mosse, MD, plan to launch another new trial in 2016 for relapsed neuroblastoma, using an innovative dynamic design to quickly incorporate new treatments matched to the evolving genetic changes in an individual patient’s tumor that they will track through ongoing lab studies of each patient’s cells.

To learn more about the future of precision medicine and how the concept works in practice on diseases other than cancer, look for an article about how precision medicine approaches are being developed in epilepsy research in the January issue of Bench to Bedside.

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Research Keeping Children Safe in Hospitals and Communities


Safety is a core value at The Children’s Hospital of Philadelphia, so it should come as no surprise that detecting and addressing safety risks is a major area where CHOP researchers advanced knowledge this year. Their work spans safety in inpatient and outpatient settings and in the community at large.

Addressing a Severe Infection Complication

Early in the year, a CHOP-led international team of researchers established the global prevalence of sepsis and other complications in pediatric intensive care units (PICUs) that can cause organ damage and death following infection. The worldwide scope of severe pediatric sepsis was previously only estimated from analyses of billing codes in administrative databases. With the new estimates from the Sepsis, Prevalence, Outcomes, and Therapies (SPROUT) study published in the American Journal of Respiratory and Critical Care Medicine, researchers now have a better idea of how many centers and patients would be available for future interventional studies of severe pediatric sepsis.

“We found an overall prevalence [of pediatric severe sepsis in PICUs] of 8.2 percent, which means that your average PICU is treating at least one child with severe sepsis at any one time,” said Scott Weiss, MD, MSCE, an attending physician in Pediatric Critical Care at CHOP who led SPROUT along with Julie Fitzgerald, MD, PhD, a CHOP pediatric intensivist. “So it is an incredibly common cause of pediatric critical illness, and it highlights the ongoing problem of severe sepsis.”

Reducing In-Hospital Risks

While sepsis is one of the most severe in-hospital safety risks, fortunately it affects relatively few children. More frequently occurring risks are also in the crosshairs for CHOP researchers whose work targets hospital safety:

Maintaining Patients’ Safety After Leaving the Hospital

Even after they are discharged from the hospital, children continue to benefit from CHOP safety research. Some of that research entails making sure that children’s routine care at home keeps them well enough not to return to the hospital. CHOP researchers reported in The Journal of Pediatrics that patients who filled prescriptions for asthma medication after discharge were less likely to be readmitted, and overall only about half of prescriptions were filled. They recommended that clinicians ensure patients have their medication in hand upon leaving the hospital.

Scott Lorch, MD, MSCE, an attending neonatologist at CHOP, reported in Pediatrics that consistent well visits to the pediatrician are associated with fewer negative health outcomes for preterm infants. This year, Dr. Lorch also began a new study of ways to predict risk and prevent readmission to the hospital for preterm infants and other high-risk children.

Keeping Children Safe in the Community

Even beyond the healthcare system, CHOP research keeps children safe at home, at school, and everywhere in between. Among these efforts, CHOP’s Violence Prevention Initiative aims to save and improve the quality of life for at-risk adolescents. Adolescent medicine specialist Alison Culyba, MD, MPH, reported on her findings that supportive family environments were associated with less involvement in youth violence.

Researchers led by Stephen Leff, PhD, reported lasting success from a school-based program to reduce relational aggression among African-American girls in third through fifth grades. In a randomized controlled trial, the program improved the girls’ social problem solving knowledge and decreased their levels of relational aggression.

Traffic safety and injury prevention research at CHOP reached major milestones in improving community safety this year. In November, the Center for Child Injury Prevention Studies (CChIPS) celebrated its 10th anniversary. The multi-institution, National Science Foundation-funded center has established fundamental data about how children’s bodies respond to crashes and is helping to develop safer restraint products and vehicles.

“The high rates of traffic injury and mortality among children have created a public health crisis that requires immediate research solutions,” said Flaura K. Winston, MD, PhD, founder and director of CChIPS and scientific director of CHOP’s Center for Injury Research and Prevention (CIRP).

Looking to the future, CChIPS is expanding beyond its primary focus on traffic safety to pursue topics including bicycle and pedestrian safety, aviation safety, sports injury prevention, and trauma care and treatment.

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Research Reaches Wide Range of Healthy Policy Issues


A common misconception is that researchers exist in an isolated world of beakers and test tubes, yet scientists’ scope of influence can extend far past their laboratories’ walls — even beyond the bedside — and into social beliefs and actions. In 2015, several researchers from The Children’s Hospital of Philadelphia had the opportunity to share their expertise and knowledge of scientific evidence to provide insights about important health policy topics.

Not one to shy away from controversy, Kristen A. Feemster, MD, MPH, MSHP, an attending physician in the Division of Infectious Diseases, a PolicyLab faculty member, and the Vaccine Education Center’s director of research, contributed an opinion piece to The New York Times arguing for an end to philosophical and religious exemptions to school entry vaccine requirements. She emphasized the need to balance religious freedom and responsibility to one’s community, writing that “society has an obligation to stand up on behalf of children who do not yet have their own informed voice.”

Dr. Feemster also wrote an editorial published in JAMA Pediatrics that asserted, “vaccines remain an important and necessary health tool.” Her commentary followed a measles resurgence, with 169 people across the country reported to have the disease between Jan. 1 and May 1, 2015, according to The Centers for Disease Control and Prevention. Dr. Feemster pointed out that exemption laws and increasing vaccine hesitancy mean “the success of vaccines can be fragile.”

Prioritizing Care for Adolescents With HIV

In another editorial published in JAMA Pediatrics, Sarah M. Wood, MD, a Fellow in the Craig-Dalsimer Division of Adolescent Medicine at CHOP advocated for another vulnerable group of young people. She suggested that adolescents who are living with human immunodeficiency virus (HIV) face an enormous equity gap in treatment, noting that while recent data has shown that AIDS-related mortality declined from 2005 to 2012 for adults and children, adolescent mortality has increased by 50 percent.

Dr. Wood encouraged researchers to begin to prioritize adolescent HIV care and pilot test interventions, ranging from finding youth who are HIV positive, to addressing barriers to prescribing antiretroviral therapy, and then identifying facilitators for adolescents to stay in care and adhere to therapy throughout their life cycle.

“We need to begin to build an adolescent care competent world in HIV,” Dr. Wood said.

Looking Out for Marginalized Youth

Pediatrician and adolescent medicine specialist Nadia Dowshen, MD, founder and co-director of CHOP’s Gender and Sexuality Development Clinic, wants to help alleviate the frustration of marginalized youth by improving their access to health resources and services.

In the first phase of a research project, she is working with the City of Philadelphia Department of Public Health’s Division of Maternal, Child, and Family Health to gain insights from the thoughts and experiences of transgender and gender non-conforming youth and other key stakeholders. The study team also will compile national policies that affect transgender and non-conforming youth and determine how they apply practically in the Philadelphia area.

The second phase will involve surveying providers both throughout the CHOP Care Network and within the city health department clinics about their knowledge, attitudes, and practices with transgender and gender non-conforming youth. Based on the responses, Dr. Dowshen will identify focus areas for a curriculum to train the providers on ways that they can help to better care for this patient population.

“We need to do a better job of identifying who these youth are and offering support,” said Dr. Dowshen, who also is a faculty member at CHOP’s PolicyLab and serves as director of Adolescent HIV Services in the Craig-Dalsimer Division of Adolescent Medicine at CHOP.

CHOP’s PolicyLab issued an Evidence in Action brief in December that provides information and recommendations for practitioners, administrators, and policymakers to ensure comprehensive care and support and improve health and well-being for gender non-conforming children and adolescents. 

PolicyLab Informing Practice and Policy

In fact, this was a busy year for the entire PolicyLab team, who informed program and policy changes through their interdisciplinary research. Here are just a few examples of PolicyLab’s remarkable work in 2015:

See the related Bench to Bedside article in the December issue about how other researchers at CHOP are making a difference.

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Technology Takes Research in New Directions


An exhilarating aspect of being a researcher at The Children’s Hospital of Philadelphia is having the opportunity to take the driver’s seat and propel medical technology forward. In 2015, investigators embarked on fascinating trips of discovery.

Researchers at CHOP Center for Injury Research and Prevention (CIRP) published a validation study in the journal Injury Prevention of their Simulated Driving Assessment (SDA) software, a culmination of more than a decade of foundational research regarding young driver crashes. The software runs on commercially available driving simulators and is a safe way to assess drivers’ skills in high-risk driving scenarios.

“We’re providing the science behind the answer to why teens — and some adults — don’t drive well,” said Flaura K. Winston, MD, PhD, scientific director of the CIRP and principal investigator for the SDA line of research. “Some haven’t developed the skills they need to navigate complex driving situations and are crashing due to error.”

Contemplating how to get the most mileage from the newly validated tool to improve driver safety, Dr. Winston proposed the idea for a company called Diagnostic Driving along with co-founder Venk Kandadai, MPH, a project manager and statistician at CIRP, to the DreamIt Health startup business accelerator program this spring. During a four-month incubation period, they mapped out the business venture’s course and began to market the driving assessment software to corporate fleets.

Several other technological innovations fueled noteworthy research efforts in 2015:

Staying in Touch With Families After Discharge

Indeed, technology offers myriad ways to facilitate reliable and effective patient care, and it also provides new avenues for clinicians to personally engage patients and parents in a meaningful and timely way. A pilot quality improvement project at CHOP is looking at how conducting virtual visits via video chat on mobile devices could potentially reduce the emotional and operational stress on families who are discharged home with sophisticated medical equipment.

Lead investigator John Chuo, MD, who is an attending neonatologist and medical director of telemedicine at CHOP, hopes that the study will help to define how telemedicine could be of value to augment the standard of care during the transition to home care and perhaps avoid emergency room visits and readmissions.

The clinicians will use a hosted service to connect with the families by video call and interview the parents based on a checklist of questions that are pertinent to their child’s care. For example, the clinician will ask, “Are you having any problems administering the medication?” and then follow up with, “Please show me how to draw up one of your medications.” Having parents demonstrate their technique using the syringe could help to avoid medication errors.

Afterward, the clinician will document the virtual patient encounter in a database and communicate information to other providers, as they normally would do. The researchers will track call rates, home visit rate, emergency room referrals, readmission rates, patient and provider satisfaction, and the number of equipment and patient issues that were identified and resolved.

Game Targets Children’s Coping Skills

Unfortunately, millions of children will likely experience some kind of unexpected traumatic event, from an emergency room visit to a home disaster to school violence. Researchers at CHOP have developed a web-based intervention called Coping Coach that aims to prevent post-traumatic stress in school-aged children by using game-like activities.

“It’s a different way of engaging kids,” said Nancy Kassam-Adams, PhD, a CHOP psychologist and associate director of Behavioral Research at CIRP. “We’ve worked hard to build in items that are useful and therapeutic while keeping it fun.”

The study team tested the online tool’s feasibility in a randomized controlled trial of 72 children ages 8 to 12 who had been admitted to the hospital for an acute medical event, and the investigators reported positive results in the Journal of Pediatric Psychology. The next step is to test Coping Coach in a bigger trial, Dr. Kassam-Adams said. Once the researchers have enough data to validate Coping Coach’s effectiveness, it could be publicly available within the next five years.

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