Jun 02 2014

Children’s Hospital Launches Violence Prevention Initiative

violence_preventionThe Children’s Hospital of Philadelphia recently unveiled its Violence Prevention Initiative (VPI) in a press conference at the Karabots Pediatric Care Center in West Philadelphia. A set of programs designed to reduce the severity and impact of violence and aggression on children and families not only in Philadelphia communities but also across the country, at the VPI’s launch Philadelphia Mayor Michael Nutter, Councilwoman Jannie L. Blackwell, Department of Human Services Commissioner Anne Marie Ambrose, and the School District of Philadelphia’s Chief of Student Services Karyn Lynch delivered remarks in support of the initiative.

“Every day we see the consequences of violence in our Emergency Department, in our operating rooms and on our patient units,” said Steven M. Altschuler, MD, CEO of The Children’s Hospital of Philadelphia. “Just since May 1st, 38 people — including six children — have been injured by gun violence in the City of Philadelphia. This number does not include non-gun-related violence, or the trauma imposed on witnesses, friends, family, and communities in which the threat of violence is a daily reality.”

“As an institution that exists to promote the health and well-being of children and as the nation’s leading pediatric hospital, it is our responsibility to find ways to prevent this epidemic from spreading,” Dr. Altschuler added.

VPI is led by a multidisciplinary team made up of some of the nation’s foremost experts in hospital-based violence intervention, evidence-based anti-bullying methods, and trauma-informed care. Through the strength of its long-time partnerships with community organizations, CHOP’s VPI builds on years of rigorous public health research to address and prevent ongoing concerns such as bullying in schools, intimate partner violence in the home, and assaults in the community.

“More than 40 percent of young people in the U.S. are exposed to some form of violence,” said Stephen Leff, PhD, a CHOP psychologist and co-director of VPI. “Youth can be exposed to violence in their homes, schools and communities with serious, lifelong consequences, including poor emotional and developmental health; long-term changes within the brain and stress reactions; school failure, drug abuse and delinquency; and the likelihood to perpetuate violence.”

The VPI programs concentrate CHOP’s medical training, mental health programs, provider training, research expertise, and knowledge of public health policies to interrupt violence while ensuring that limited resources are spent efficiently with the greatest chance for impact. Interventions occur at locations that are relevant to CHOP patients: within schools, primary care, and hospital sites.

The majority of children reached by VPI may never be CHOP patients, but witness violence in their schools or communities. VPI works within schools to provide evidence-based, whole-school approaches to bullying prevention for children in third through eighth grade. These programs address the multiple forms that aggression and bullying can take, including physical, social (such as gossiping and threatening to withdraw friendships), and cyber-bullying. This training gives them tools to handle and avoid more dire forms of violence as they grow older.

In addition, intimate partner violence (IPV) counselors support clinical staff in screening for and addressing IPV and teen dating violence in our patient population. This is a partnership with Lutheran Settlement House, with the goal of minimizing the adverse effects of childhood IPV exposure. Healthcare provider training and parenting education is also provided.

And children ages 8 through 18 who arrive in CHOP’s Emergency Department with injuries from an assault receive long-term intensive support from a violence prevention counselor in the hospital and after discharge to reduce re-injury or retaliation and to promote physical and emotional healing.

“VPI programs reach beyond the hospital and doctors office into schools, homes, neighborhoods, and recreation centers by empowering and training kids and adults to interrupt the cycle of violence,” said Joel Fein, MD, MPH, a CHOP Emergency Physician and co-director of VPI, adding that the initiative “aims to become a national model for hospital-led youth violence prevention.”

Further information about the Violence Prevention Initiative and its specific programs can be found at chop.edu/violence.

Permanent link to this article: http://www.research.chop.edu/blog/childrens-hospital-launches-violence-prevention-initiative/

May 29 2014

Severe Retinopathy of Prematurity Associated With Functional Disability

retinopathy of prematurity

ROP is a disorder of the blood vessels of the retina, which are not completely developed until a baby reaches full term.

A study led by a CHOP neonatology expert showed that infants with severe retinopathy of prematurity (ROP) diagnosed and treated under modern protocols remain at risk of nonvisual disabilities, even if blindness can be averted in most children.

ROP is a disorder of the blood vessels of the retina, which are not completely developed until a baby reaches full term. A baby born prematurely may have growth of abnormal blood vessels, or damage and scarring of existing blood vessels in the retina. This can lead to retinal scarring or detachment from the back of the eye, resulting in vision loss.

Severe ROP is not a rare condition, and its incidence has been rising. It occurs in at least 10 percent of unselected and extremely preterm infants — those born at less than 29 out of 40 weeks of gestation. Moreover, it is a serious problem in middle-income countries where even moderately preterm babies are affected.

“It is therefore important to research the association between this neonatal complication and adverse long-term child development,” said Barbara Schmidt, MD, MSc, an attending neonatologist at Children’s Hospital of Philadelphia and also a professor of pediatrics and Kristine Sandberg Knisely Chair in Neonatology, Perelman School of Medicine at the University of Pennsylvania.

This exploratory analysis reported in the Journal of the American Medical Association used data from a cohort of very low-birth-weight infants involved in the Caffeine for Apnea of Prematurity trial. Study participants included 1,582 children born at 31 centers between 1999 and 2004 and followed up at age 5. Of the 95 children who had severe ROP, 12 were bilaterally blind at 5 years. The study found that motor impairment, cognitive impairment, and severe hearing loss were three to four times more common in children with severe ROP than those without severe ROP.

These findings remind clinicians and parents that while blindness often can be prevented by timely retinal therapy in the neonatal intensive care unit, severe ROP remains a predictor of functional disability. It reinforces the need for long-term visual and developmental follow-up for infants who are diagnosed with severe ROP.

Yet, it remains unclear why there is an association between the development of severe ROP and the presence of nonvisual disabilities.

“We can only speculate,” Dr. Schmidt said. “The retina has been called a ‘window to the brain;’ hence, severe damage to the developing retina in a very immature baby may also indicate damage to the developing brain.”

Future studies could examine whether the association that investigators observed between severe ROP and nonvisual disability represents a “cause and effect” relationship. Dr. Schmidt also suggested that more research on effective strategies in the neonatal intensive care unit to prevent severe ROP is needed.

Contributing authors to the JAMA study are from the University of Melbourne, Australia; University of Toronto, Canada; the University of British Columbia, Canada; and McMaster University, Canada.

Permanent link to this article: http://www.research.chop.edu/blog/severe-retinopathy-prematurity-associated-functional-disability/

May 28 2014

CHOP, Drexel Consortium to Boost Pediatric Medical Device Pipeline

mecial deviceFor medical devices, as with many medicines, the market for children is a small fraction of the adult market, and there are far fewer child-sized devices. But the need for pediatric medical devices exists, even if proper devices may not.

“It’s not simply a matter of scaling down adult equipment for pediatric use,” said Children’s Hospital bioengineer Matthew Maltese, PhD. “Pediatricians have long known that children are not just small adults, and adults are not just big children.”

Dr. Maltese is the principal investigator of the Philadelphia Regional Pediatric Medical Device Consortium (PPDC), which brings engineers and biomedical researchers from CHOP, Drexel University, and the University of Pennsylvania to address the shortage of medical devices designed for children. The PPDC recently received a $1.5 million, five-year grant from the U.S. Food and Drug Administration (FDA). One of only seven pediatric device consortia nationwide recently funded by the FDA, the consortium will provide clinical, business, and regulatory expertise, as well as seed funding, to help translate innovative ideas into commercial devices for use in young patients.

“For a variety of reasons, it is difficult to advance pediatric medical devices beyond the idea stage,” said Dr. Maltese. “We provide innovators with the support they need to transform concepts into practical and available medical devices that benefit children.”

Robert Levy, MD, who holds William J. Rashkind Endowed Chair in Pediatric Cardiology at CHOP and is a co-principal investigator of the PPDC, also sees opportunities to help children, saying that the consortium “will help to address unmet needs for pediatric medical devices.” Dr. Levy’s medical device experience is reflected in his 35 issued U.S. patents that have led to extensive licensing activities, both to established medical device companies and to start-ups. One such example is the CHOP spinout firm, Vascular Magnetics, which is developing magnetically guided devices to precisely deliver drugs to injured arteries in children and adults.

As the center of the nation’s largest pediatric care network, CHOP offers a large, diverse pool of pediatric patients, allowing for carefully regulated clinical trials to test potential medical devices.

In addition, the PPDC will benefit from Dr. Maltese’s own experience adapting medical devices for children in his position in Critical Care Medicine at CHOP. The Hospital is currently collaborating with industry partners to develop pediatric versions of existing FDA-approved cardiopulmonary resuscitation (CPR) quality feedback tools developed for adults. These smartphone-sized devices measure motion and force on a patient’s chest during CPR to rapidly produce sound and visual prompts that improve the quality of CPR and save lives.

To read more about the PPDC, see the full press release.

Permanent link to this article: http://www.research.chop.edu/blog/chop-drexel-consortium-boost-pediatric-medical-device-pipeline/

May 27 2014

Hat Trick! Cell Therapy Expert Scores Trio of Honors

cell therapy expertIt has been a busy few weeks for The Children’s Hospital of Philadelphia’s Stephan Grupp, MD, PhD. Dr. Grupp, the director of Translational Research at the Center for Childhood Cancer Research, recently received three awards for his groundbreaking immune therapy work using genetically engineered, cancer-fighting T cells. Dr. Grupp received awards from the Clinical Research Forum, the European Society for Blood and Marrow Transplantation, and was honored alongside the University of Pennsylvania by the bioscience organization Pennsylvania Bio.

Dr. Grupp has received a great deal of attention for his investigation of using cell therapy to treat an aggressive form of childhood leukemia, acute lymphoblastic leukemia (ALL). Last year his work — conducted in partnership with the University of Pennsylvania’s Carl June, MD — led to dramatic, extraordinary results published in The New England Journal of Medicine: two children with untreatable ALL achieved a complete response after being treated with immune therapy. Since receiving the treatment one of those patients remains healthy and cancer-free two years later.

The Clinical Research Forum (CRF) award, the 2014 Herbert Pardes Clinical Research Excellence Award, is one of ten recent awards handed out by the CRF to projects “that benefit the health and wellbeing of the general public.” The 2 Herbert Pardes Award is the CRF’s top prize, and was awarded at an April 10 reception in Washington, DC.

The European Society for Blood and Marrow Transplantation (EBMT), meanwhile, handed a team of researchers led by Dr. Grupp the 2014 van Bekkum Award. The EBMT’s van Bekkum award is given to the best abstract presented at the Society’s annual meeting, held March 30 to April 2 in Milan, Italy.

The data presented at the Clinical Research Forum and EBMT update the data published in the New England Journal of Medicine. “Our group has now treated 25 kids and 5 adults with relapsed/refractory ALL,” said Dr. Grupp. “We have seen unexpectedly high rates of complete remission: 90 percent in this group of patients, many of who had no other treatment options. These results are leading to a phase 2 trial at six pediatric hospitals, with CHOP as the lead site.”

Rounding out the list of plaudits, at the recent 2014 Pennsylvania Bio Annual Dinner & Awards Celebration, CHOP and Penn were jointly honored for their cell therapy work with PA Bio’s Patient Impact Award.

“It’s an honor to have our cell therapy research recognized by such prestigious organizations,” said Dr. Grupp. “This is potentially revolutionary work, but its success to date — and going forward — would not have been possible without multidisciplinary, truly collaborative input from investigators across CHOP and Penn. I cannot thank my colleagues enough.”

To learn more about cancer research at The Children’s Hospital of Philadelphia, see the Center for Childhood Cancer Research website or the Hospital’s Cancer Center.

Permanent link to this article: http://www.research.chop.edu/blog/hat-trick-cell-therapy-expert-scores-trio-honors/

May 22 2014

Distinguished Career Award Goes to CHOP Oncologist

BLBeverly J. Lange, MD, an exemplary physician and researcher at The Children’s Hospital of Philadelphia (CHOP) for over 40 years, received the 2014 Distinguished Career Award from the American Society of Pediatric Hematology/Oncology (ASPHO). Given during ASPHO’s 27th Annual Meeting in Chicago, the award recognizes Dr. Lange’s outstanding lifetime contributions to the care of children with cancer.

The ASPHO Distinguished Career Award honors a professional whose career “has had a major impact on the subspecialty through some combination of research, education, patient care, and advocacy.”

Dr. Lange served as a senior physician and director of clinical affairs in the Division of Oncology at CHOP, where she worked from 1976 until her retirement in 2013. She also held the Yetta Deitch Novotny Chair in Pediatric Oncology at the Hospital, and was a professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania. She continues to volunteer with CHOP’s Division of Oncology.

Although Dr. Lange’s clinical work has explored many types of childhood cancer, she is most associated with groundbreaking investigations of pediatric leukemia. There is no question that Dr. Lange “is synonymous with evidence-based improvements in the treatment of pediatric acute myeloid leukemia (AML),” ASPHO said. Much of her work has focused on conducting landmark clinical trials to discover optimum combination treatments for AML, including reducing and even preventing side effects of cancer treatments.

Since Dr. Lange began working on AML, survival rates have improved to their current level of over 55 percent. Her expertise has also produced advancements in treating high-risk forms of another childhood cancer, pediatric acute lymphoblastic leukemia. In addition, Dr. Lange has published extensively in top-tier scientific journals, has contributed her expertise to professional organizations such as ASPHO and the multicenter Children’s Oncology Group, and has mentored countless young investigators.

With the ASPHO award, Dr. Lange joins the ranks of other CHOP oncologists who have previously received the ASPHO Distinguished Career Award, including Giulio D’Angio, MD, in 1990, Audrey E. Evans, MD, in 1995, and Anna Meadows, MD, in 2004.

For more information about cancer research at The Children’s Hospital of Philadelphia, see the Cancer Center.

Permanent link to this article: http://www.research.chop.edu/blog/distinguished-career-award-goes-chop-oncologist/

May 21 2014

Study Reports Outcomes of Tracheostomy in Preterm Infants

preterm infantsNeonatologists at The Children’s Hospital of Philadelphia frequently face the intricate decision of whether to place a tracheostomy in a preterm infant with severe lung disease and when to do it. A lack of relevant literature about this procedure makes it a challenging consideration.

A recent study in the Journal of Pediatrics led by a CHOP neonatologist gives more guidance on this problem by evaluating the developmental outcomes of infants born before 30 weeks’ gestation who underwent tracheostomy. With these data in hand, clinicians contemplating a tracheostomy for a preterm infant can supplement clinical status and medical history to help parents comprehend potential long-term outcomes.

Premature infants’ lungs, especially the air sacs, are not fully developed. While many premature infants must use a mechanical ventilator and extra oxygen for breathing, a minority ultimately undergo tracheostomy placement. A tracheostomy is the insertion of an artificial airway into the windpipe through a surgical incision to provide a safe, long-term way to ventilate a child.

When Sara B. DeMauro, MD, MSCE, an attending neonatologist and medical director of Neonatal Follow-up Programs at CHOP, and co-investigators looked at a dataset collected at 16 sites from 2001 to 2011 by the NICHD Neonatal Research Network, they identified 304 preterm infants with tracheostomies to include in a retrospective cohort study.

“This is the first time anybody has ever performed a comprehensive evaluation of the developmental outcomes of these children at 18-22 months,” Dr. DeMauro said.

The researchers demonstrated that even when they performed adjusted analyses controlling for many of the factors known to be predictive of poor developmental outcomes in preterm infants, those with tracheostomies still had significantly increased odds of adverse outcomes. These outcomes consisted of neurologic impairment, developmental delay, or visual or hearing impairment.

Dr. DeMauro pointed out that while this study suggests that tracheostomy is a marker for a risk of adverse developmental outcomes in this vulnerable population, it does not indicate that tracheostomy causes these problems.

“Based on their entire medical histories, these children are predisposed to having poor developmental outcomes,” Dr. DeMauro said. “This is almost a way to measure that. If they’re so sick that they need a tracheostomy, then they’re so sick that they’re at very high risk for having an adverse outcome.”

This clinical conundrum has another nuance: If a preterm infant needs a tracheostomy, when should the procedure be performed?

Again, Dr. DeMauro and colleagues found a paucity of literature to guide that decision. So they assessed the impact of timing by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. Their study suggests a possible association between earlier (<120 days) tracheostomy and better neurodevelopmental outcomes.

While more studies must be done to determine if earlier decisions about tracheostomy placement are advantageous, Dr. DeMauro described how it is possible that a “sooner than later” approach could have benefits in the NICU.

“Before their tracheostomy is placed, infants aren’t allowed to move around too much because they could dislodge their tube. Therefore, they can’t engage in developmentally appropriate play and are often heavily sedated,” Dr. DeMauro said. “As soon as they have a tracheostomy that is in place and healed, you get them out of bed, you play with them, and you take them off sedation.”

Further data also is needed on the outcomes of tracheostomy in preterm infants who have lung disease compared to those who also have airway disease. Delving into these complexities will help clinicians have more complete information when they speak with families about pursuing tracheostomy placement, Dr. DeMauro said.

“This study is an important first step in understanding what the range of outcomes for these children tends to be,” she said. “When these data are combined with a child’s individual clinical situation and any additional risk factors for poor outcomes, it allows you to make a much more informed decision about whether a tracheostomy is a good choice.”

Grants from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development for the Neonatal Research Network supported this study.

Permanent link to this article: http://www.research.chop.edu/blog/study-reports-outcomes-tracheostomy-preterm-infants/

May 20 2014

Oncologist Honored for Neuroblastoma Research

neuroblastomaThe Advances in Neuroblastoma Research Association (ANRA) recently presented its highest honor to pediatric oncologist Garrett M. Brodeur, MD, of the Cancer Center at The Children’s Hospital of Philadelphia (CHOP). Dr. Brodeur received the ANRA Lifetime Achievement Award at the association’s international meeting. The award singles out a researcher who has achieved worldwide scientific prominence in investigating neuroblastoma over the course of an exceptional career.

The most common solid tumor of childhood, neuroblastoma attacks the peripheral nervous system, typically appearing as a tumor in a child’s abdomen or chest. Neuroblastoma varies greatly in severity, ranging from forms that spontaneously disappear to high-risk subtypes that are difficult to cure. Because of this variability, researchers have sought ways to predict the course of disease to better select the most appropriate treatment for each patient.

Over his career, Dr. Brodeur has focused on identifying the genes, proteins, and biological pathways that give rise to neuroblastoma and drive its clinical behavior. He has also built on this knowledge to help develop more effective and less toxic treatments for children.

In the 1980s, Dr. Brodeur showed some neuroblastoma cells developed multiple copies of the MYCN gene, which identified a high-risk subtype of neuroblastoma, necessitating more aggressive treatment. This discovery ushered in the current era of genomic analysis of tumors, both in adult and pediatric oncology. Profiling specific molecular alterations in a specific patient’s tumor helps guide oncologists toward the most appropriate treatment.

Dr. Brodeur and his fellow colleagues also discovered important neuroblastoma-related genetic changes. He collaborated with other CHOP researchers who identified the ALK gene as the gene responsible for most cases of hereditary neuroblastoma.

Another major focus of his research regards the role of TRK receptor tyrosine kinases, which control the clinical behavior of neuroblastomas. His work led to a clinical trial with a novel drug that selectively blocks these signals. He is now working on the second generation of such drugs, as well as on nanoparticle delivery systems to treat patients with less abrasive treatments.

Dr. Brodeur has been a member of the CHOP medical staff since 1993 and holds the Audrey E. Evans Endowed Chair in Pediatric Oncology at the Hospital. He is also a professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania, where he is an associate director of the Abramson Cancer Center. Last year, Dr. Brodeur received the prestigious Pediatric Oncology Award from the American Society of Clinical Oncology.

To read more about Dr. Brodeur’s award, see the full press release.

Permanent link to this article: http://www.research.chop.edu/blog/lifetime-achievement-award-honors-chop-expert-garrett-brodeur-career-work-neuroblastoma/

May 19 2014

Study Probes Long-term Seizure Freedom on Ketogenic Diet

seizure freedom

The diet consists of 90 percent fats, 7 percent protein, and 3 percent carbohydrates.

Most children with epilepsy can have active and fulfilling lives, with the help of modern therapies. Yet 20 percent to 30 percent of children with epilepsy do not respond to medications, which physicians call medication-resistant or intractable epilepsy.

Researchers at The Children’s Hospital of Philadelphia continually are looking at ways to lower the frequency of seizures that children with medication-resistant epilepsy experience on a sometimes daily basis. Alternative treatment options may include the ketogenic diet, vagal nerve stimulator, or epilepsy surgery.

The ketogenic diet, which is low in carbohydrates and high in fat, achieves seizure freedom in 15 percent to 20 percent of patients and greater than 90 percent seizure reduction in one-third of children with medication-resistant epilepsy; however, few studies have considered its long-term outcomes. Katherine S. Taub, MD, an epileptologist at CHOP and assistant professor of neurology at the Perelman School of Medicine, published a study in the journal Epilepsia that provides evidence to support the continued use of the ketogenic diet in patients with initial seizure freedom even after breakthrough seizures.

“For children who are seizing daily, it has a big impact on their lives,” Dr. Taub said. “Physicians should encourage patients to continue the diet as treatment even if they have seizure recurrence because they can still have a meaningful reduction in their total number of seizures.”

Epilepsy is a brain disorder that affects 1 percent of children in the U.S.  Many types of epilepsy exist, each with its own seizure types and frequent neurological comorbidity. Children are diagnosed with epilepsy if they have had more than two unprovoked (no precipitating cause) seizures. Seizures occur when clusters of nerve cells, or neurons, in the brain have a burst of abnormal electrical signals that temporarily interrupts normal electrical brain function.

Researchers are unsure of exactly how the ketogenic diet inhibits epileptic seizures. The diet consists of 90 percent fats, 7 percent protein, and 3 percent carbohydrates, and it requires precise measuring and steadfast adherence.

In this retrospective cohort study, participants were patients at CHOP between 1991 and 2009 who had been unsuccessfully treated with four or more antiepileptic drugs prior to ketogenic diet initiation. The majority had daily seizures. Sixty-five participants achieved seizure freedom for a minimum of one month during ketogenic diet treatment. When Dr. Taub examined the probability of their sustained seizure freedom, the average time to seizure recurrence was three months or less, and the likelihood of remaining seizure-free at 18 months was 3 percent.

“A high number of patients on the diet did have breakthrough seizures, but none of our patients returned to their baseline seizure frequency,” Dr. Taub said.

Another significant finding that Dr. Taub discovered while comparing this data to previous studies is that a consistent definition of sustained seizure freedom is lacking in the medical literature. Such a consensus would facilitate future studies, such as a head-to-head study comparing the ketogenic diet versus other antiepileptic medications.

“If we’re going to be sharing comparative data between centers, then we should establish an agreed upon definition for seizure freedom, so we can evaluate institutions’ success of the diet,” Dr. Taub said.

The study’s co-authors included Sudha Kilaru Kessler, MD, an attending physician at CHOP, and Christina Bergqvist, MD, an attending physician and director of CHOP’s Ketogenic Diet Program, which is one of the largest of its kind in the country providing resources and training for families.

Permanent link to this article: http://www.research.chop.edu/blog/study-probes-long-term-seizure-freedom-ketogenic-diet/

May 16 2014

Targeting Youth Violence With Advocacy, Research

youth violence

Firearms remain the second leading cause of trauma death in the pediatric population.

Healthcare practitioners at children’s hospitals have a unique and powerful perspective about firearms violence because they witness the devastation that it causes families on a daily basis.

Michael L. Nance, MD, director of the pediatric trauma program and an investigator for the Center for Injury Research and Prevention at The Children’s Hospital of Philadelphia, recently updated the American Pediatric Surgical Association’s (APSA) position statement on firearms injury and children, in response to the 2012 tragedy at Sandy Hook Elementary School. Dr. Nance is still haunted by pictures of the mass shooting in Newport, Conn., that killed 20 children and six adults.

“I find that I can’t turn away from it because I’m worried that I’ll somehow lose sight of the fact that we still have a huge problem and a lot of work ahead of us,” said Dr. Nance, who has been involved in the care of firearms injuries for more than 25 years. “It’s not just these mass shootings that are causing trouble … it is this daily drip, drip, drip of firearm injuries that is the real problem, and by the end of the year, another 30,000 Americans have died.”

Firearms remain the second leading cause of trauma death in the pediatric population. Since 1999, more than 35,000 children under age 19 have died as a result of a firearms injury. In 2010, 2,711 children died by gunshot, with another 15,576 injured.

The Sandy Hook shooting is especially disturbing to Dr. Nance as a surgeon because not a single child survived long enough to receive medical attention that day. The shooter used an assault-style rifle with a high-capacity magazine, and 18 of the 20 children had multiple gunshot wounds.

“So all the systems that we put in place, all this advanced medical care, couldn’t have helped save one of those kids,” Dr. Nance said. “Something has to change, and I think that what has to change in part is advocacy.”

At the time of Sandy Hook, Dr. Nance was chairman of the trauma committee for the APSA, a professional organization of more than 1,200 surgeons who care for young victims of gun violence. In a perspectives article published in the March issue of Pediatrics, he noted that the APSA membership took an unprecedented step by voting to endorse, as an association, the revised position statement to strengthen its message: Firearms-related injury and death must be addressed as a public health issue.

Among its nine position points, the APSA called on Congress to restore funding for firearms-related research. In 1997, an appropriations bill stated: “None of the funds made available for injury prevention and control at the Centers for Disease Control and Prevention may be used to advocate or promote gun control.”

Congress expanded this language in 2003 and later broadly applied it to the National Institutes of Health, effectively shutting down any federally funded firearms-related research. Research dollars have trickled in from a few nonprofits, but the intellectual pool of investigators willing to pursue careers in gun violence research has dried up.

“The moratorium has effectively killed off generations of researchers,” Dr. Nance said. “We’ve had very little funding to do the research, and so we have very little data to go on except body counts — we know how many children are dead.”

President Obama ended the 17-year ban on gun violence research at the CDC when he signed a series of gun safety executive orders in January 2013. One of those orders issued a Presidential Memorandum directing the CDC to research the causes and prevention of gun violence.

It is too soon to tell if the executive order will make a difference in firearms research funding, Dr. Nance said, but he emphasized that data are crucial in trying to understand a problem as complex as firearms injury and desperately needed to accurately inform policy decisions.

“We don’t even have a simple understanding from a pediatric perspective of where the guns are, how they’re accessed, and how that access impacts injury,” Dr. Nance said.

The Institute of Medicine of the National Academies proposed a public health research agenda to reduce the threat of firearms-related violence. Several priorities focus specifically on children, such as determining the effectiveness of childhood education and prevention programs.

For its part, the Children’s Hospital of Philadelphia launched the Violence Prevention Initiative (VPI) in January, which is taking a hospital-wide, multidisciplinary approach to curb youth violence in all forms and keep children safe. The VPI’s Signature Programs will use research protocols to develop proof-of-concept ways that address different aspects of violence and then incorporate these evidence-based interventions into daily practices that interrupt the cycle of violence.

No other institution is “better prepared to lead this very important work, which has the potential to make a difference for children in communities across the United States,” said Children’s Hospital CEO Steven M. Altschuler, MD.

Permanent link to this article: http://www.research.chop.edu/blog/targeting-youth-violence-advocacy-research/

May 14 2014

Three Peanut Immunotherapy Studies Under Way

peanut immunotherapyStrict avoidance of peanuts and the constant fear of accidental exposure cause tremendous stress for children with peanut allergy and their families. As little as 1/44,000 of a peanut kernel can trigger a reaction for severely allergic individuals.

Three studies under way at The Children’s Hospital of Philadelphia are looking at potential ways to desensitize children so that they can develop a level of tolerance to peanut protein that would provide some clinical protection against accidental exposure.

“Accidental ingestions are unfortunately common, with up to 50 percent of food-allergic patients having at least one allergic reaction over a two-year period,” said Jonathan Spergel, MD, PhD, chief of CHOP’s allergy section and co-director of the Center of Pediatric Eosinophilic Disorders.

About 6 percent to 8 percent of children under the age of 3 years have food allergies. Although most children “outgrow” their sensitivity, allergy to peanuts and tree nuts may be lifelong and carry a risk of fatal food-induced anaphylaxis.

A peanut-free diet is the only treatment for children with peanut allergy, so CHOP researchers have been investigating alternative approaches such as oral immunotherapy (OIT), which is a gradual increase in peanut ingestion.

Various proof-of-concept clinical trials have shown that OIT is a slow and safe way to increase tolerance to peanuts, but OIT has not yet been approved by the U.S. Food and Drug Administration. Dr. Spergel’s research team recently received an award from Allergen Research Corp. to conduct a phase 2 study that will put OIT on the licensure pathway.

If the investigators can demonstrate that peanut OIT is effective and safe in desensitizing peanut allergic study participants, “you’ll have evidence supporting a method that may effectively treat 70 to 80 percent of people with peanut allergies,” Dr. Spergel said. “This will be a major therapy.”

Enrollment for the randomized, double-blinded, placebo-controlled study has begun and will include 55 participants from ages 4 to 26 with a history of allergy to peanuts or peanut-containing foods at eight sites in the United States. They initially will receive extremely low doses of characterized peanut allergen, a pharmaceutical-grade formulated peanut protein, followed by an up-dosing regimen every two weeks for six to nine months. The aim is for study participants to build up their tolerance to at least 250 mg of peanut protein, which would afford protection to one peanut.

Dr. Spergel is also principal investigator for CHOP’s arm of the PRROTECT study, a phase 2, randomized, double-blind, placebo-controlled trial that will determine if pretreatment with anti-IgE mAb (omalizumab/Xolair) will allow for faster and safer OIT desensitization. Anti-IgE mAb is an injectable prescription medicine used for patients with moderate to severe persistent allergic asthma. It works by blocking IgE which binds to allergens causing allergic reactions.

While OIT has been shown to be effective for about 80 percent of children with peanut allergy, most experience some type of reaction, such as itchy mouth or hives, and one in five children will require epinephrine, according to Dr. Spergel.

“Using Xolair as pretreatment with oral immunotherapy, we hope to see very little reaction,” he said.

CHOP and Food Allergy Research Education (FARE) are funding the PRROTECT study, which is a joint project with Boston Children’s Hospital, Stanford University, and Lurie Children’s Hospital.

A third study is taking a different approach to peanut immunotherapy that uses a patch to deliver precise quantities of peanut proteins on the upper layers of skin.

“The method of epicutaneous (EPIT) delivery has some potential advantages including fewer side effects seen in earlier human study and possible increased tolerance, which has been seen in murine models,” Dr. Spergel said. “EPIT also may be more palatable to patients due to the method of delivery.”

The VIPES (Viaskin® Peanut’s Efficacy and Safety) study, funded by DBV Technologies, is a 12-month randomized, double-blind, placebo-controlled study of participants ages 6 to 55 with a history of immediate hypersensitive reaction to peanuts. Initiated in 2012, VIPES is the first and only global trial ever in desensitization of peanut-allergic children and adults, and it is by far the largest involving 22 investigators and 221 participants in Europe and North America. This study is finished recruiting and will have preliminary results in late 2014.

Participants who completed the VIPES study were invited to participate in a follow-up extension study (OLFUS-VIPES) to address the crucial question of tolerance post treatment. Subjects enrolled in this study will receive an additional 24 months of Viaskin® Peanut treatment followed by a two-month period without treatment. Before launching VIPES, a study of 100 children and adults with peanut allergy (including anaphylaxis) showed very good safety.

A true partnership among researchers, physicians, nurses, and families allows CHOP’s study teams to work on these peanut immunotherapy studies simultaneously, according to Dr. Spergel.

“There is no approved treatment of peanut allergy, and by doing these three studies, we are looking at which approach is the safest and most effective,” he said. “We will understand which one will be best.”

Permanent link to this article: http://www.research.chop.edu/blog/three-peanut-immunotherapy-studies-way/

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