Jul 08 2014

60 Minutes Revisits Cancer Therapy Pioneered at CHOP

curing cancerAustralia’s 60 Minutes recently revisited its story from last year about the revolutionary immune therapy treatment spearheaded by The Children’s Hospital of Philadelphia’s Stephan A. Grupp, MD, PhD. The therapy, in which modified versions of patients’ own immune cells are used to treat acute lymphoblastic leukemia (ALL) has led to dramatic, inspirational results, with several patients achieving complete responses.

“It could be one of the greatest medical breakthroughs of the 21st century: a cure for childhood cancer,” said host Michael Usher.

The most common form of leukemia found in children, ALL has a roughly 85 percent cure rate. However, the remaining 15 percent of ALL cases resist standard therapy. The 60 Minutes piece focused on the researchers’ use of HIV, which the program called “one of the most notorious killers of our time,” to treat ALL. Dr. Grupp and his team have used HIV to deliver engineered T cells — the workhorses of the immune system — to selectively kill another type of immune cell called B cells, which had become cancerous.

HIV “is a terrible virus,” Dr. Grupp said, “but there’s a good property, and the good property of the virus is its ability to put a gene into cells. We isolate just that property and we get rid of all of the bad stuff, so yes, HIV’s been retasked to do good in this kind of treatment.”

The piece is also focused on one of Dr. Grupp’s patients, 5-year-old Austin, whom 60 Minutes profiled in its original piece. Diagnosed with ALL when he was 2, Austin is now in complete remission for the first time. “To see him doing normal things is a relief, and a dream come true, because those were things that were put on hold for awhile,” said Austin’s mother Kim, who called the treatment “a miracle.”

“I think we do have a potential new treatment that didn’t exist before that we hope will be available to other patients and other hospitals soon, and across the world, in the next year or two,” Dr. Grupp said.

To watch the 60 Minutes report, see below!

Permanent link to this article: http://www.research.chop.edu/blog/60-minutes-revisits-cancer-therapy-pioneered-chop/

Jul 07 2014

PolicyLab Reports on Students Involved With Child Welfare

child welfare

“Improving outcomes for these students starts with identifying and deploying the appropriate resources that these schools need to support all students,” Dr. Rubin stated.

Educators and policymakers in Philadelphia knew that meeting the complex needs of the most vulnerable students in struggling public schools was a big challenge, but they did not know exactly how big. So they turned to PolicyLab at The Children’s Hospital of Philadelphia to do the math.

A report released in June by PolicyLab revealed that 17 percent of all Philadelphia public school students have been involved with the child welfare or juvenile justice systems, and it described the educational barriers that these students face.

“This report illustrates the magnitude of youth in our school district who have been involved with the child welfare system — 20 percent by the high school years, and for many schools more than a third of their student body,” stated David Rubin, MD, MSCE, co-director of PolicyLab, in a news release.

The analysis showed that students who had interaction with the Philadelphia Department of Human Services (DHS) had poor academic outcomes, were less likely to be promoted to the next grade on time, earned fewer credits during the year, had lower scores on standardized assessment tests, were more likely to receive special education services, and were absent more days from school.

The report — “Supporting the Needs of Students Involved With the Child Welfare and Juvenile Justice System in the School District of Philadelphia” — was commissioned by the Mayor’s Office of Education, School District of Philadelphia (SDP), Philadelphia School Reform Commission, and DHS to help inform policy decisions to align resources to best meet the needs of the diverse student population across the SDP. PolicyLab collected and analyzed data in a targeted cross-system review of students in the third, seventh, ninth, and twelfth grades from the 2011-2012 academic year across all schools within the SDP.

In addition to determining that a substantial percentage of the school population had involvement with DHS, the report also found that these students tend to cluster in certain school types. Within these struggling schools, the report noted, performance was poor even for those students without DHS involvement, demonstrating the need to transform all students’ educational experience in these difficult environments.

“Improving outcomes for these students starts with identifying and deploying the appropriate resources that these schools need to support all students,” Dr. Rubin stated.

At a press conference announcing the report’s key findings, DHS Commissioner Anne Marie Ambrose announced an action plan that will include stationing 27 social workers as educational liaisons in public schools with high concentrations of DHS-served youth to help support their learning needs in the 2014-2015 school year. But the report’s partners admitted that they alone cannot address all of the challenges that PolicyLab uncovered.

“This can only be one part of the solution,” wrote the project’s director, Sophia Hwang, MSED, in a PolicyLab blog. “In order for our most at-risk students to achieve academically, they also need safe school environments, appropriate behavioral health services, and caring and supportive mentors.”

As a former SDP high school science teacher, Hwang brought a unique perspective to the report. She recalled not knowing to what extent the approximately 160 students who she taught every day were touched by the child welfare or juvenile justice system. Based on the report’s data, she estimates it is likely that one in every three students on her roster was involved with DHS in some way.

“Now, as a researcher, I ask myself, ‘What supports did my children deserve? What resources would have helped me as their teacher?’” Hwang wrote.

With data from this new report in hand, those making educational policy decisions in Philadelphia and in large cities throughout the country can address those questions more strategically.

“I hope that our report will inspire conversations in other urban school districts about the resources and supports needed for students in their communities,” Hwang wrote.

For more information and to view the full report, please visit Sophia Hwang’s blog post on PolicyLab’s website

Permanent link to this article: http://www.research.chop.edu/blog/policylab-reports-students-involved-child-welfare/

Jul 03 2014

Researchers Examine Goal Pursuit in Teens with Cancer

cancerSetting and achieving goals is a significant milestone in adolescent and young adults’ (AYA) development that paves the way for independence in adulthood. Teens with cancer often experience fatigue, pain, and other symptoms that can interfere with these personal goals, which psychologists refer to as health-related hindrance (HRH).

Researchers at the Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia are interested in identifying those most at risk for higher HRH because it is a potential marker of poor psychological adjustment during cancer treatment and into survivorship.  One of their studies that appeared in the March issue of the Journal of Clinical Psychology in Medical Settings focused on the interaction between race, ethnicity, and income in predicting HRH.

“This is one of the first studies to look at the psychosocial components of lower income and ethnic minority status on quality of life outcomes,” said Lauren C. Daniel, PhD, a psychology fellow in the division of oncology at CHOP.

Ninety-four study participants between the ages of 13 and 19 were categorized into four groups: lower income minority status, higher income minority status, lower income white, and higher income white. On average, it was 1.65 years since their initial diagnosis, and the majority had received chemotherapy.

The study participants wrote down up to 10 personally meaningful goals. Some examples included spending more time with friends and getting into a good college. Participants rated the difficulty and importance of the goal as well as the impact of pain, fatigue, and other symptoms on achieving each goal.

The research team examined differences in goal-related variables across the four groups, and their findings were not what they had anticipated. Based on previous research on health care disparities, they had hypothesized that adolescents with cancer of minority status living in lower income families would experience the highest amount of HRH. The results showed the opposite: Lower income minority patients had the least amount of HRH, while high income minority patients had the most.

“It may be that higher income minority families are in schools with higher expectations so patients may be more aware of the impediments that cancer poses,” Dr. Daniel said.

On the flip said, the researchers suggested that those adolescents with cancer in the lower income minority groups may rely on a “shift and persist” adaptive coping style that increases their resilience and persistence toward valued goals.

“This study highlights that goal setting may be different across patient populations,” Dr. Daniel said. “Their goals also might be different than what clinicians are expecting. So it’s important for them to talk with patients about things that they want to achieve, especially understanding how fatigue, pain, and symptoms impact their goals.”

During these conversations, clinicians can work with AYA to set realistic goals in the context of cancer to help motivate them to look toward the future. They also can connect them with organizations that offer information and support or scholarships and financial aid. At CHOP, many unique resources are available for AYA who are on and off treatment.

A larger scale study across multiple centers is needed to fully understand these preliminary findings and further explore the impact of sociodemographic factors on HRH.

“We’re hoping to work toward implementing interventions to improve health-related hindrance as an important part of quality of life of AYA with cancer,” Dr. Daniel said.

This study was part of a larger study on developmental outcomes of AYA with cancer by Lisa A. Schwartz, PhD, assistant professor of clinical psychology in pediatrics at CHOP and the psychologist for the Cancer Survivorship Program. Lamia P. Barakat, PhD, a CHOP psychologist, and Lauren D. Brumley, also contributed to the study.

Permanent link to this article: http://www.research.chop.edu/blog/researchers-examine-goal-pursuit-teens-cancer/

Jul 01 2014

Biomarkers for Mitochondrial Diseases Emerging

mitochondrial diseaseA major limitation in many therapeutic interventions is the inability to follow how they affect the early biochemical steps of chronic disease. In some cases, patients and clinicians spend months tracking symptoms to figure out if a treatment is working.

A new approach being developed at The Children’s Hospital of Philadelphia and the University of Pennsylvania could allow investigators to know within days if a chosen therapy reverses the intracellular mechanisms that go awry in Friedreich’s Ataxia (FA), a genetic mitochondrial disease, and other more common secondary mitochondrial disorders such as Parkinson’s disease and Alzheimer’s.

FA is a rare, progressive neurodegenerative disease that is heavily disabling because it affects a variety of body systems. People diagnosed with FA experience general unsteadiness, motor speech problems, increased heart wall thickness, and a higher tendency to develop diabetes over time. Most people with FA are wheelchair bound within 10 years of their symptoms’ initial presentation and die from heart disease by the age of 35.

CHOP clinicians and researchers have developed remarkable expertise in FA, and they help about 250 patients, which is approximately 5 percent of the population with this disease in the U.S.  Earlier this year, a new Penn Medicine/CHOP Friedreich’s Ataxia Center of Excellence opened to carry on this work under the direction of Robert B. Wilson, MD, PhD, professor of pathology and laboratory medicine at the Perelman School of Medicine, and David Lynch, MD, PhD, FA program director at CHOP.

“We are the center for research on FA for the world,” Dr. Lynch said.

One of the center’s first goals was to establish a biomarker development program with the expertise of Ian Blair, PhD, of the Perelman School of Medicine. This collaboration is the focus of a new National Institute of Neurological Disorders and Stroke grant awarded to Dr. Lynch.

“A unique aspect of this grant is our chance to partner on a technique that not only may be useful for understanding the mitochondrial abnormalities that are proposed in FA, but also for monitoring it and related diseases in clinical trials,” Dr. Lynch said. “So it may be crucial for developing new therapies for individuals, but it also is likely to be a key tool in defining the ability of people with FA to respond to such interventions.”

Dr. Blair has discovered a way using mass spectrometry techniques — a highly accurate, quantitative method for exploring compounds — to follow the metabolic events of live behaving mitochondria isolated from platelets of a person with FA. Mitochondria, traditionally known as the powerhouses of cells, are specialized to perform specific functions within tissues. The investigators suspect that the metabolic functions of mitochondria might be crucially compromised in FA, leading to tissue-selective metabolic dysfunction.

“We know that the disease affects the whole body, so what we see happening in platelets is likely to be a mirror of what’s happening everywhere,” Dr. Lynch said.

One of the places where his study team has seen abnormalities is in the Krebs cycle, also known as the tricarboxylic acid cycle, which produces adenosine triphosphate (ATP) that transports chemical energy within cells for metabolism. ATP feeds electrons on the electron transport chain for cells to make more ATP. The investigators suggest that insufficient bioenergetic capacity may lead to decreased metabolism through fatty acid pathways.

“We find that in FA there are specific blockages in this pathway,” Dr. Lynch explained. “This might suggest therapy because it would allow you to bypass those blockages if you gave people the right nutritional supplementation and ameliorate, if not cure, the features of the disease.”

In principle, this approach could be applicable to any mitochondrial disease, Dr. Lynch said, not only on the therapeutic side to identify which metabolic steps to circumvent, but also on the monitoring and biomarker side to measure response to a therapeutic agent. If an intervention works, scientists would expect the metabolic abnormalities that Dr. Blair identified to reverse.

“It provides a powerful way to follow the disease and an ideal biomarker of therapeutic success,” Dr. Lynch said. “This is potentially a way that we could follow many, many disorders.”

In the near future, Dr. Lynch anticipates his study team’s early successes will spin off into investigations of novel nutritional therapies for FA and also be used as an outcomes measure in ongoing clinical trials of FA.

Permanent link to this article: http://www.research.chop.edu/blog/biomarkers-mitochondrial-diseases-emerging/

Jun 30 2014

CHOP Neuroscientist Receives Prestigious NIH Award

NIHThe Children’s Hospital of Philadelphia’s Akiva S. Cohen, PhD, recently received a prestigious MERIT award from the National Institutes of Health. A concussion and traumatic brain injury (TBI) expert, Dr. Cohen has been investigating using an amino acid-based dietary therapy to mitigate TBIs’ long-term effects.

The NIH’s R37 or Method to Extend Research in Time (MERIT) award is designed “to provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner,” according to the NIH’s site. MERIT awardees are chosen by NIH staff and a review board, who make their recommendations based on researchers’ past successes and productivity.

With this award, Dr. Cohen joins an exclusive group of CHOP investigators who have received MERIT awards (including the National Institute of Neurological Disorders and Stroke’s R37, the Javits Neuroscience Investigator Award). Currently, only two other Children’s Hospital researchers have active MERIT awards — hematologist Gerd A. Blobel, PhD, and hyperinsulinism expert Charles Stanley, MD — while several other investigators, including Tom Curran, PhD, FRS, and Douglas A. Coulter, PhD, have received MERIT/Javits support in the past.

Dr. Cohen’s work is focused on the cellular and molecular mechanisms underlying pathologies caused by head injuries. In particular, Dr. Cohen has been studying using a “cocktail” of cellular nutrients to address brain damage associated with TBIs. According to the CDC, roughly 2 million TBIs occur every year in the U.S, and more than 500,000 TBIs are suffered by children aged 14 years and younger. While many reported TBIs are milder forms such as concussions, even “mild” brain injuries can lead to long-term health challenges, such as cognitive and emotional issues.

Late last year, Dr. Cohen led a study published in Science Translational Medicine that found the dietary therapy improved sleep disturbances caused by brain injuries in mice. “If this type of dietary treatment is proved to help patients recover function after traumatic brain injury, it could become an important public health benefit,” Dr. Cohen said at the time.

In addition to his MERIT award, Dr. Cohen was also recently invited to serve as a standing member of the NIH’s Center for Scientific Review’s Brain Injury and Neurovascular Pathologies (BINP) Study Section. During his two years on the BINP Study Section, alongside a number of other experts Dr. Cohen will review grant applications submitted to the NIH “aimed to understanding mechanisms of neural injury, related vascular abnormalities, and alterations in the blood brain barrier in stroke,” among other topics.

“I am honored and humbled to be nominated and receive a MERIT award,” said Dr. Cohen. “And I am driven even more to determine the alterations in brain function that contribute to cognitive impairment caused by brain injury.”

To read more about Dr. Cohen’s work, see Bench to Bedside and the CHOP Research blog.

Permanent link to this article: http://www.research.chop.edu/blog/chop-neuroscientist-receives-prestigious-nih-award/

Jun 27 2014

CHOP Announces Fetal Neuroprotection Program

Fetal Neuroprotection Program_2The Children’s Hospital of Philadelphia launched the Fetal Neuroprotection and Neuroplasticity Program which builds onto already growing evidence of the interaction of heart disease and brain development in the fetus. This program will systematically investigate innovative therapies to protect brain development and to prevent brain injury as early as possible before birth.

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, it 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.

In the U.S., approximately one in every 120 newborns is diagnosed with CHD, making it the most common birth defect. Many newborns with CHD require either corrective or palliative open-heart surgery. As recently as the 1960s, only 20 percent of newborns with critical CHD survived to adulthood.

“Today, thanks to better diagnostic technologies and methods, including prenatal diagnosis, advances in surgery, and improved postoperative care, early survival is over 90 percent,” said J. William Gaynor, MD, cardiac surgeon and director of the Fetal Neuroprotection and Neuroplasticity Program. “However, with improved early outcomes has come the sobering recognition that there is an ongoing risk of late mortality as well as significant morbidity for these children. 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.”

Convincing evidence suggests that in order to prevent brain injury and improve outcomes, treatment to protect the brain must be initiated before birth. This research, much of it developed at CHOP, shows that in utero brain development is abnormal in fetuses with CHD, leading to delayed maturation, poor growth, and white matter injury.

“The lifetime continuum of care for congenital heart disease starts in utero,” said N. Scott Adzick, MD, surgeon-in-chief at CHOP.  “We now have an opportunity to not only offer the best diagnostic care to the fetus with heart disease, but to also begin to explore ways in which we can optimize long-term outcomes from the neurocognitive perspective.”

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.

The Children’s Hospital of Philadelphia has long been a leader in pediatric cardiac care. More than 30 years ago, CHOP pioneered life-saving early surgeries for children with complex heart defects. Today, most forms of heart disease can be detected prior to birth.

“The Fetal Neuroprotection and Neuroplasticity Program is another innovative initiative in a long series of identifying opportunities to ensure that children with CHD not only survive, but truly thrive, as they grow into adulthood,” Dr. Gaynor said. “This program allows us to enhance our continuum of care from conception through adulthood.”

For more information, please visit The Children’s Hospital of Philadelphia’s Fetal Neuroprotection and Neuroplasticity Program.

Permanent link to this article: http://www.research.chop.edu/blog/chop-announces-fetal-neuroprotection-program/

Jun 25 2014

New Teen Drivers Benefit From Practice Quantity, Variety

Teen_Driving_FullWhen a teen learning to drive sits behind the wheel with sweaty palms, it is often up to the parent to keep their child calm and focused on the road. But how can parents prepare to steer these driving lessons in the right direction?

Research released by the Center for Injury Research and Prevention (CIRP) at The Children’s Hospital of Philadelphia found that TeenDrivingPlan (TDP), a web-based intervention designed to help parents more effectively supervise driving practice, improved the driving performance of pre-licensed teenagers. Inexperience is a contributing factor in car crashes involving novice drivers.

“Supervised practice during the permit phase is a common provision of Graduated Driver Licensing programs in most states, yet there is a lack of evidence-based interventions available to support families,” said Jessica H. Mirman, PhD, lead author of the study and a CIRP developmental psychologist. “Evidence-based interventions like TeenDrivingPlan can address this problem by helping busy parents make the most of supervised practice time.”

The goal of TDP is to increase the quantity and variety of parent-supervised practice to develop teenagers’ driving skills before licensure. It offers three main activities for families:

  1. Learning: 53 brief videos guide parents in creating a positive learning environment in the car and provide structure for practice activities across multiple driving environments — from rainy highways to sunny country roads
  2. Planning: helps families to select concrete goals for each practice session
  3. Logging and rating: tracks practice hours and collects information on goal performance.

The research, published in JAMA Pediatrics, involved five years of formative research followed by a randomized, controlled trial of 151 young drivers and their parent supervisors. Youth with learner’s permits who were assigned to use TDP over a 24-week period were 65 percent less likely to fail a rigorous on-road driving assessment administered prior to licensure compared to those who followed a usual practice “control” condition.

Overall, 6 percent of the pre-licensed teenagers in the TDP group had their on-road driving assessment terminated due to unsafe driving performance as compared to 15 percent of those in the control group. Families who used TDP also reported more driving practice in various environments, at night, and in bad weather.

A corresponding CHOP research article, published this month in the Journal of Adolescent Health, examined how TDP exerted its effect on driver performance and found that both greater quantity and variety of practice were associated with better driving performance, but TDP’s effectiveness was primarily through greater practice diversity. Additionally, families in the TDP group reported more parent engagement and support.

A third CHOP analysis, published in Injury Prevention, used state-of-the-art software to capture TDP use data, and researchers examined its association with practice diversity. The results suggest that initiatives aimed at new drivers should provide important information early in the learner period when engagement is greatest.

Future CHOP studies will further explore ways to enhance TDP’s positive effects on young driver performance and supervised practice to develop teenagers’ driving skills before licensure.

Through its multidisciplinary Teen Driver Safety Research program, the CIRP is working continually to reduce the frequency and severity of motor vehicle crashes, which remain the number one cause of death for teens.

State Farm Mutual Automobile Insurance Company (State Farm®) funded this research.

To learn more about CHOP’s TeenDrivingPlan research, visit teendriversource.org.

Permanent link to this article: http://www.research.chop.edu/blog/new-teen-drivers-benefit-practice-quantity-variety/

Jun 23 2014

Gene Study Points to Novel Pathway for Diabetes Treatment

Diabetes_Treatment_ContentNew research from The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania details how a diabetes-related gene functions on a biological pathway that affects the release of insulin. Finding drugs that act on that pathway may eventually lead to a new treatment for type 1 diabetes.

“In 2007, our genomics team found the first gene in a genome-wide search to play a major role in type 1 diabetes, but we did not know its function,” said co-study leader Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at CHOP. “Now we understand how this gene plays a critical role in regulating insulin metabolism.”

The current finding builds on a 2007 genome-wide association study by Dr. Hakonarson and colleagues at CHOP showing that variations in the KIAA0305 gene, also known as CLEC16A, correlate with higher risk of type 1 diabetes and other autoimmune diseases.

The research team subsequently developed a strain of mice in which the CLEC16A gene was deactivated. They then collaborated with endocrinology expert Doris A. Stoffers, MD, PhD, of the Institute for Diabetes, Obesity and Metabolism at UPenn to breed a subset of the knockout mice in which only the pancreatic cells were affected. Dr. Stoffers was co-senior author with Dr. Hakonarson, and is the corresponding author of the study, which appears online in the journal Cell.

The investigators show that the CLEC16A gene acts upon a pathway crucial to insulin secretion. The gene normally helps protect mitochondria, the tiny energy-producing components of cells, but when the CLEC16A gene is knocked out, damaged mitochondria are then digested — a process called mitophagy — and the resulting loss of energy output disrupts beta cells in the pancreas in their normal job of secreting insulin.

“The ultimate result of the deletion of CLEC16A is an accumulation of unhealthy mitochondria, leading to less insulin being secreted by the beta cells,” said Dr. Stoffers.

In humans, an inability to produce insulin is the hallmark of type 1 diabetes. The study team showed that humans with single-base variants in CLEC16A have reduced beta cell function, although with less extreme effects than in the knockout mice.

The researchers showed that the CLEC16A biological pathway has downstream effects on a protein called Parkin, already known to be a master regulator of mitophagy. The current study is the first to link the CLEC16A pathway with regulation of Parkin-mediated mitophagy and to suggest how this process may affect diabetes by dysregulating insulin secretion.

If drugs can be developed to act on the CLEC16A pathway, they could provide a new, targeted therapy for patients with type 1 diabetes who harbor risk variants in the CLEC16A gene, said Hakonarson.

More information about the study is available here.

Permanent link to this article: http://www.research.chop.edu/blog/gene-study-points-novel-pathway-diabetes-treatment/

Jun 19 2014

Early Childhood Bone Density Reference Data Needed

bone densityIn the past decade, clinicians have made significant advancements in the diagnosis of pediatric bone disorders, particularly because national reference data is now available for bone density in children older than 5; however, clinicians do not have the appropriate tools for bone health assessment and research in early childhood.

A study at The Children’s Hospital of Philadelphia aims to address this gap by establishing reference data for children ages 1 to 5 using dual-energy X-ray absorptiometry (DXA), a test that measures bone density. The investigators also will examine factors that influence bone density and bone mineral accrual in this age group. Identifying children at risk for bone fragility is important because inadequate bone accretion may have lifelong consequences, such as susceptibility to fractures and osteoporosis.

“The first main goal of the study is to develop the equivalent of a growth chart for bone density,” said Babette Zemel, PhD, who is a co-principal investigator of the study. “Clinicians will be able to request a DXA scan, interpret it, and get an idea of where a child is relative to normal children of the same age, sex, and ancestry.”

Many serious clinical conditions in childhood threaten bone health due to inflammation and malabsorption, for example major cardiac disease, liver disease, and pulmonary disease. Or a child may have primary bone disorder that is genetic, such as osteogenesis imperfecta, which is characterized by bones that break easily, often from little or no apparent cause. Also, some young children with neuromuscular conditions have delayed gross motor skills and restricted mobility that may adversely affect bone accrual.

Accurate reference data will allow clinicians to identify bone deficits in these patient groups and to monitor how well treatment is working.

“It’s one thing for a healthy child to be running around, fall down, and break a bone, but there are some children who have pretty serious health problems, and they’re just not gaining bone the way that they should,” said Dr. Zemel, who is part of the division of gastroenterology, hepatology, and nutrition at CHOP and a research professor of pediatrics with the Perelman School of Medicine’s Institute for Translational Medicine and Therapeutics.

To give an idea of the scope of the problem posed by compromised bone strength, the Center for Bone Health team at CHOP looked at how many of the patients that they had treated who had already experienced a fracture, and it was more than 30 percent, Dr. Zemel said.

One of the challenges to conducting the current study is that toddlers cannot stay still long enough to complete a full body DXA scan. Dr. Zemel and her research team will use the latest generation of DXA technology, which provides more enhanced resolution that improves the accuracy for measuring small, less dense bones. They will conduct regional scans of the lumbar spine, forearm, and lateral distal femur that are feasible in young children because the scan time is 30 to 60 seconds, and the child can be held still without interfering with the scan.

Dr. Zemel anticipates that participant enrollment will open in April at two study sites – CHOP and Cincinnati’s Children’s Hospital Medical Center (CCHMC). Half of the study’s sample population will be African-American, and the other half will be non-African American. The study will involve a longitudinal cohort that will consist of 280 children ages 1 to 2 years who will be evaluated every six months for three years, resulting in data spanning ages 1 to 5 years. A cross-sectional cohort will include 240 children ages 1 to 1.5 years and 4.5 to 5 years who will undergo the same measurements at one time point. Data from both cohorts will be combined to create the reference curves.

Early childhood is a period of rapid development, so the researchers also will examine how changes in bone mineral content and density are related to growth, body composition, motor development, and physical activity. While previous research of older children has shown that greater growth status, more lean muscle mass, and more weight-bearing physical activity is related to higher bone density, Dr. Zemel pointed out that clinicians have little evidence that applies to the 1 to 5-year-old age range.

“With early identification of compromised bone health, improved awareness of the condition, and better understanding of the mechanisms involved, there is hope that this may soon translate into new and improved therapy for children at-risk for poor bone mineral accrual,” Dr. Zemel said.

An innovative part of the study is its application of new techniques for estimating body composition — the amount of muscle, fat, and bone in the body. A group of physicists from the University of California, San Francisco (UCSF) who are experts in bone and body composition imaging will use novel analysis to determine body composition from all of the children’s regional DXA scans, separating bone from soft tissue and air, and then calculating lean muscle and fat mass.

Since this technique is not yet validated, Dr. Zemel and her team will conduct anthropometric exams at all visits. Anthropometry is the collection of high quality body measurement data using standardized examination procedures and calibrated equipment. Trained anthropometrists will obtain skinfold thickness measurements that can be used in prediction equations, yielding excellent body composition estimates.

In a subset of 120 participants, the researchers will compare DXA and anthropometric body composition methods to the current gold standard, which uses isotope dilution to measure total body water and calculate fat and fat-free mass.

Heidi Kalkwarf, PhD, RD, a nutritional epidemiologist at CCHMC, is co-principal investigator of the study, which received funding from the National Institutes of Health.

Permanent link to this article: http://www.research.chop.edu/blog/early-childhood-bone-density-reference-data-needed/

Jun 17 2014

Concussion Prevention, Care Are Key Targets for Research


Annually, young people make nearly 250,000 visits to emergency rooms in the U.S. to be treated for brain injuries from sports and recreation, according to the Centers for Disease Control and Prevention.

Few healthcare issues reach the presidential podium and ESPN headlines, but the topic of sports-related concussions in youth scored both, gaining momentum as a national priority.

President Obama hosted the first-ever White House Healthy Kids & Safe Sports Concussion Summit May 29, where key stakeholders gathered to promote new efforts that will increase research to expand knowledge of concussions and create a culture of safety that supports children in disclosing symptoms and optimizing their recovery.

“We want our kids participating in sports,” Obama told the audience. “I’d be much more troubled if young people were shying away from sports. As parents, though, we want to keep them safe, and that means we have to have better information.”

A concussion is a mild traumatic brain injury caused by a blow or jolt to the head or body that causes the brain to shake. Annually, young people make nearly 250,000 visits to emergency rooms in the U.S. to be treated for brain injuries from sports and recreation, according to the Centers for Disease Control and Prevention. Some concussion symptoms may appear immediately after the injury, while others may not show up for several days. They can include headache, nausea, dizziness, sleep problems, difficulty concentrating, and moodiness.

Pediatric sports medicine specialist Christina Master, MD, and President and Chief Operating Officer Madeline Bell of The Children’s Hospital of Philadelphia were in attendance at the summit as it was announced that CHOP will begin development of a comprehensive pediatric and adolescent concussion registry. It will provide a database of information about concussion cases to inform scientific research to improve care.

The registry is a result of a Department of Pediatrics Chair’s Initiative project at CHOP called Minds Matter that involved a multidisciplinary team who set out to create tools to standardize and streamline concussion diagnosis and management across the CHOP Care Network so that primary care providers could handle the majority of concussion cases more efficiently and seamlessly.


CHOP will begin development of a comprehensive registry of concussion cases to inform scientific research to improve care.

“We incorporated a SmartSet feature into CHOP’s electronic medical record that gives providers standardized and evidence-based guidance on how to clinically evaluate and manage concussions,” said Kristy B. Arbogast, PhD, director of engineering for CHOP’s Center for Injury Research and Prevention, who led the Minds Matter team along with Dr. Master. “We coupled that with in-person training, and the response has been great. We believe kids are getting much better care.”

The clinical demand for concussion care throughout the CHOP system remains high, with a total of about 12,800 concussion visits in 2013 alone. Consequently, the need for pediatric research is great. Dr. Arbogast contributed to an Institute of Medicine report in 2013 that revealed many gaps in researchers’ understanding of the causes and consequences of sports-related concussions.

“A lot of what we think we know about concussion and prevention, if you pull the curtain back, the fundamental data supporting those ideas aren’t there,” Dr. Arbogast said.

In his remarks at the summit, Obama announced several public-private partnerships to support new concussion research. For example, the National College Athletics Association (NCAA) and the Department of Defense are jointly launching a $30 million effort to fund a comprehensive clinical study of concussion and head impact exposure. And the National Institutes of Health is using funding from the National Football League to begin a longitudinal research effort to detect, characterize, and measure the chronic effects of repetitive concussions.

With so many entities willing to take the ball and run to improve concussion diagnosis, management and prevention, the fundamental science in changing quickly, Dr. Arbogast said. Finding the best way to translate that research into evidence-based advocacy will be the next challenge that she hopes to tackle in her new role as a member of the National Council on Youth Sports Safety.

David Satcher, MD, former U.S. Surgeon General, and Eliot Sorel, MD, a global health expert from George Washington University School of Public Health and Health Services, convened a multidisciplinary panel of experts to form the national council. They invited Dr. Arbogast, the NCAA’s chief medical officer, Safe Kids Worldwide’s chief executive officer, and two former professional football players, among others.

“Its mission is to raise awareness and apply an integrative approach to create a culture of prevention and reduce the number of injuries that children sustain in sports,” Dr. Arbogast said. “We want to think about youth sports in a way that children can gain the benefits of physical activity, leadership, and character development while ensuring that they are as safe as possible while they play.”

During their inaugural meeting in February, the council identified several sports safety concerns — concussion, overuse injury, heat illness, and sudden cardiac death — and decided that their first goal would be to take aim at changing the culture around concussion. Workgroups hold virtual strategy meetings on a monthly basis, and they anticipate that their efforts will culminate in a best practices tour in 2015.

Council members will visit about 10 localities and host town-hall like events that will feature innovative practices and approaches to concussion prevention, diagnosis, treatment, and management. While the spotlight will be on sharing knowledge, they anticipate some sports players will lend their star power to help change society’s norms. Athletes, parents, coaches, school professionals and healthcare providers must realize that, “shake it off” is not an acceptable response to concussion; it is a brain injury that deserves serious attention.

“I like being part of an entity that is tasked with shaping the national tone on this issue,” Dr. Arbogast said. “And I am excited about the opportunities to possibly highlight some of the phenomenal clinical care CHOP sports medicine, primary care, and trauma doctors are providing for kids with concussions and to show that CHOP is a thought leader on this issue.”

Permanent link to this article: http://www.research.chop.edu/blog/concussion-prevention-care-key-targets-research/

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