Feb 23 2015

CPCE Supports New Pilot Projects on Clinical Decision-Making

CPCEThe Center for Pediatric Clinical Effectiveness (CPCE) at The Children’s Hospital of Philadelphia supports outstanding pilot research studies designed to produce evidence for what works best for treating, diagnosing, and preventing disease. Winners chosen for the fall round of the CPCE’s Pilot Grant Program will focus on two projects that aim to have an impact on clinical decision-making.

Maya Dewan, MD, MPH, a fellow in CHOP’s Department of Anesthesiology and Critical Care Medicine, will evaluate a low-cost intervention with the goal of reducing the rates of unnecessary alarm signals. It has been well-established that alarm fatigue is a growing threat to patient safety, but little research has been done that focuses on approaches to solve the problem of excessive alarms in the pediatric setting.

“Often when you’re in the pediatric intensive care unit (PICU), you’re overwhelmed by the amount of noise,” Dr. Dewan said. “You’ll go into a sick patient’s room, and sometimes it’s even hard for you to communicate or hear someone speaking because everything is beeping in the room.”

The barrage of alarms also can be stressful for families, Dr. Dewan added. She recalled sitting at 2 a.m. beside a concerned mother who was fixated on her child’s monitors and would jump at every blip.

Physiologic alarms display heart rate, respiratory rate, blood pressure, and oxygen saturation and are important tools to alert clinicians to signs of instability and prevent cardiac and respiratory arrest. In CHOP’s PICU, patients average 100 to 110 crisis and warning alarms per day, yet the majority are false, which can interrupt patient care and reduce nurses’ trust in the alarms.

“We decided to devise an intervention that could safely decrease alarms that are unnecessary,” Dr. Dewan said. “But our goal isn’t just to get rid of the false alarms. We want to ensure that the alarms you hear are true and people respond to them faster. If you filter out the false alarms, maybe we’ll pay more attention and identify kids who are getter sicker sooner.”

Preliminary data show that 25 percent to 30 percent of the crisis and warning alarms in CHOP’s PICU are caused by just 4 percent to 8 percent of patients who are mainly low acuity and require less complicated care. On a daily basis, Dr. Dewan and her study team will identify one or two low-acuity patients in the PICU who have high physiologic monitor alarm rates. During safety huddles — brief, structured conversations with physicians, nurses, and other staff to mitigate safety risks — they will review the alarm data and determine if the patients could benefit from adjustment of the alarm parameters. Patients recognized during the safety huddles as eligible for intervention will be discussed further during rounds, when their physicians will decide if safe tailoring of alarm limits is warranted.

“We wanted to individualize the approach for every patient,” Dr. Dewan said. “And we didn’t want to take away any of the autonomy of the providers at the bedside who know the patient best.”

Dr. Dewan was excited to receive funding from the CPCE, which will pay for research assistance to help launch the project by early spring. She expects the pilot study to include about 200 intervention patients over a six-month period and anticipates that their alarm rates will decrease by at least 10 percent when compared to control patients.

If the huddle intervention is shown to be safe and effective in the PICU, the next step would be to integrate the data-driven approach into the workflow throughout the hospital. The data they collect eventually could be used to support application for funding from the National Institutes of Health to evaluate the intervention’s effectiveness in a multicenter study of PICUs across the U.S.

Nephrology fellow Aadil Kakajiwala, MBBS, is equally as thrilled to have been chosen by the CPCE to conduct a research project that will focus on the variability in measures of mineral metabolism in pediatric end-stage kidney disease. Chronic kidney disease (CKD) is associated with nearly universal disturbances in metabolism of calcium, phosphate, parathyroid hormone, and vitamin D that present multiple obstacles to children’s bone and cardiovascular health, nutrition, and growth.

As part of his training at CHOP, Dr. Kakajiwala spent six months getting to know the young patients who visited the pediatric hemodialysis center, usually three times a week. As part of the standard of care, the patients were monitored monthly for calcium, phosphate, parathyroid hormone. These measurements aided clinicians in making adjustments to the patients’ medications and growth hormone therapy.  Dr. Kakajiwala and his mentors, including Michelle Denburg, MD, MSCE, an attending physician in the Division of Nephrology, suspect that flux in these parameters may occur often in children on dialysis, so they planned a pilot study to investigate if more frequent assessment of mineral homeostasis could help clinicians to assess bone health more closely.

“Our concern is that patients on dialysis have vitamin D and parathyroid hormone levels that are variable, and they need a lot of fine-tuning and management,” Dr. Kakajiwala said. “What we want to show from this study is whether we need to check these levels more than just every month, with the intention that we can intervene quicker and not lead to any bone or cardiovascular issues.”

As a major goal of the study is to see how decision-making would differ based on serial measures, the study will not alter usual care in any way except that an extra 3 mL of blood will be drawn pre-dialysis twice weekly from about 10 study participants over a 12-week period during the winter season. The study team will collect, store, and then analyze the blood samples, also taking note of any medication changes that were made based on the usual monthly laboratory results.

The investigators will determine how many times an intervention would have been made based on the weekly results. Dr. Kakajiwala noted that a similar study of adults showed that almost 25 percent to 40 percent of the time, the physician would have made changes to the patient’s care plan.

Dr. Kakajiwala is especially thankful for the guidance from Dr. Denburg, an assistant professor of pediatrics for the Perelman School of Medicine at the University of Pennsylvania, during his application for the CPCE grant.

“With Dr. Denburg’s expertise in chronic kidney disease and metabolic bone health, and my passion for the dialysis patients, I think this is going to be a fantastic study,” Dr. Kakajiwala said.

The CPCE accepts proposals for its pilot grant program twice a year, and promising projects undergo at least two rounds of reviews to determine that they fully meet the selection criteria. Read more about the program’s winners chosen in spring 2014: http://www.research.chop.edu/blog/investigators-excited-receive-cpce-pilot-grant-awards/

Permanent link to this article: http://www.research.chop.edu/blog/cpce-supports-new-pilot-projects-clinical-decision-making/

Feb 20 2015

Pediatric Medical Device Innovators Receive PPDC Seed Grants

medical device

The Bili-Hut is a portable phototherapy device for treating newborns with neonatal jaundice.

The Philadelphia Pediatric Medical Device Consortium (PPDC) announced that it will provide seed grants of $25,000 each to three companies to transform their innovative ideas into commercial devices that benefit young patients.

The PPDC brings together engineers and biomedical researchers from The Children’s Hospital of Philadelphia, Drexel University, and the University of Pennsylvania to address the shortage of medical devices designed for children. In addition to financial support, they provide clinical, business, and regulatory expertise to help overcome common hurdles of commercialization. Nineteen organizations responded to the PPDC’s first request for proposals in June 2014.

“Our request for proposals sought projects from academia and industry from around the globe,” said bioengineer Matthew R. Maltese, PhD, the PPDC’s executive director and principal investigator. Dr. Maltese also is director of Biomechanics Research in the Department of Anesthesiology and Critical Care Medicine at The Children’s Hospital of Philadelphia, as well as an adjunct assistant professor in the University of Pennsylvania’s Perelman School of Medicine. “All projects were rigorously reviewed by our clinical and industry experts, and we are excited to fund these innovators of promising medical devices for children.”

The three PPDC awards will help to advance the development of medical devices that aim to improve pediatric care for jaundice, ear infections, and prosthetic limbs:

  • The Bili-Hut, proposed by Little Sparrows Technologies, is a portable, high-intensity phototherapy device designed for use in medically underserved areas to treat newborns with neonatal jaundice. The condition responds to phototherapy, typically provided by fluorescent lights. The Bili-Hut offers a three-pound, collapsible enclosure that uses low-energy-requiring LED lights, enabling use with either line power or alternative sources such as a 12-volt battery.
  • OtoNexus Medical Technologies designed a handheld ultrasound tool to detect and identify the type of fluid behind a child’s eardrum, which is crucial to correctly diagnosing middle ear infections, called otitis media. Obtaining more accurate diagnoses for otitis media — currently half of diagnoses are in error — could lower unnecessary antibiotic usage and reduce medical costs.
  • RasLabs is using a polymer-based material to line the socket of a pediatric-sized artificial leg or other limb in order to provide a more snug fit during normal daily use. The material contracts or expands like muscle, in response to low-voltage electricity.

The PPDC is one of seven regional pediatric device consortia that received funding from the U.S. Food and Drug Administration to address the unmet need for child-specific medical devices. Pediatric medical device innovators’ next opportunity to apply for a PPDC grant will be in March.

Read the full press release.

Permanent link to this article: http://www.research.chop.edu/blog/pediatric-medical-device-innovators-receive-ppdc-seed-grants/

Feb 18 2015

Transparent Microelectrodes Allow for Dynamic Imaging to Study Epilepsy

epilepsyThe brain is the body’s control center, and it relies on an intricate circuitry of thousands of neurons that communicate with each other through electrical and chemical signals. An electroencephalogram (EEG), which is a recording of brain activity using small button electrodes, helps neuroscience researchers to better understand the cellular mechanisms involved with brain disorders, such as how epileptic seizures occur.

One of the most common disorders of the nervous system, epilepsy affects 2.7 million Americans of all ages, races, and ethnic background. A seizure takes place when spontaneous high-frequency bursting of neural networks appears that temporarily interrupts normal electrical brain function.

Neuroscience researcher Hajime Takano, PhD, who works in Douglas Coulter, PhD’s, epilepsy research laboratory at The Children’s Hospital of Philadelphia, is especially interested in which specific neurons could be inciting the neural network. But pinpointing those neurons’ locations and plotting the intensity of their activity in real time has been problematic because traditional metal electrodes cause interference when used in conjunction with sophisticated, multicellular calcium imaging techniques that investigators couple with high-speed microscopes to see and record when neurons are firing.

Dr. Takano, who is also a research assistant professor in the Neurology Department in the Perelman School of Medicine at the University of Pennsylvania, collaborated with other Penn researchers from the School of Engineering to test a new type of transparent, flexible microelectrode they developed that could solve this problem. It is made of the strongest material known to man: graphene, a two-dimensional form of carbon only one atom thick. Because it is see-through, the graphene microelectrode allows for simultaneous optical imaging and electrophysiological recordings of neural circuits.

“The idea of applying this technology to basic neuroscience for brain recording is something new and very exciting,” said Dr. Takano, who also has an engineering background.

In a study published in Nature Communications, Dr. Takano; senior author Brian Litt, PhD; Penn Engineering Postdoc Duygu Kuzum; and colleagues described how they were able to use the graphene microelectrode technology in combination with calcium imaging involving confocal and two-photon microscopy to observe seizure-like activity that they induced in neural tissue from rats. The investigators were able to obtain both high spatial and temporal resolution, which is the ability to discriminate between two points in space and time.

Neurons and their processes are small, with a spatial extent measured in micrometers. In contrast, the circuits within which neurons function may extend millimeters to a centimeter or more. The new microelectrode allows for dynamic imaging that can provide valuable information on individual cells, while at the same time probing the regions that they may span.

“By monitoring a seizure with the transparent electrodes and imaging individual neurons at the same time, we can try to pinpoint where a seizure started,” Dr. Takano said. “If there are repeated seizures, we can see if the seizure-initiating cell is always the same or not. And if there is an initiating cell, what is different about it?”

At the Society for Neuroscience’s Annual Meeting held Nov. 15-19 in Washington, D.C., Dr. Takano presented a poster describing how the study team used the graphene electrodes to record high-frequency bursting activity. The response from attendees was overwhelmingly positive, Dr. Takano said.

In the future, Dr. Takano plans to use the graphene electrodes in conjunction with other advanced imaging approaches to provide new insights into the functions of neural circuits during seizures. For example, they will allow him to use chloride imaging to explore factors that control the level of electrical activation in cellular regions.

Development of the transparent microelectrode technology involved a multidisciplinary effort from Penn’s new Center for NeuroEngineering and Therapeutics, Penn’s departments of Neuroscience, Pediatrics, and Materials Science, and the Division of Neurology at CHOP.

Permanent link to this article: http://www.research.chop.edu/blog/transparent-microelectrodes-allow-dynamic-imaging-study-epilepsy/

Feb 16 2015

New Gene Test to Improve Transplantation, Research

geneThe Children’s Hospital of Philadelphia has long been a leader in the world of genomic medicine. CHOP Research investigators regularly publish groundbreaking studies that span the gamut of childhood disease, from those focused on autism to studies of the childhood cancer neuroblastoma, to investigations of common conditions like obesity and more rare diseases.

During fiscal 2013, Children’s Hospital immunogenetics experts developed a unique laboratory test to characterize the genes that encode human leukocyte antigen (HLA) molecules, which are complex proteins on cell surfaces that are essential to immune function. By using faster, more comprehensive gene sequencing technology to type HLAs, the new test may improve transplantation outcomes through a more refined assessment of donor compatibility.

“This faster, more thorough technology allows us to better account for subtle genetic differences between individuals,” said Dimitri Monos, PhD, director of the Immunogenetics Laboratory in the Division of Genomic Diagnostics, and professor of Pathology and Laboratory medicine at the Perelman School of Medicine at the University of Pennsylvania.

“We expect this knowledge to yield clinical benefits, by facilitating more precise matches between transplant donors and recipients, and assessing the significance of mismatches in genomic regions of the HLAs that were previously uncharacterized,” Dr. Monos added.

For more information about this groundbreaking program, see the Research Annual Report.

Permanent link to this article: http://www.research.chop.edu/blog/new-gene-test-improve-transplantation-research/

Feb 13 2015

Young Girls Help Inform Breast Cancer Prevention

breast cancerWith a megawatt smile and adventurous spirit, Marlena Penn, 16, is a high school junior, master scuba diver, and talented underwater photographer. She has been eye-to-eye with an octopus and captured its spectacular changes in color. Evidently, her bravery and glossy, auburn curls come from her mother, Norma Roth, who is a writer, speaker, volunteer extraordinaire, and breast cancer survivor.

Put them together in an interview room, and you can feel the girl power about to burst through the door.

Even though they have a packed schedule, twice a year the pair travels from Cherry Hill, N.J., to visit The Children’s Hospital of Philadelphia as participants in the “Lessons in Epidemiology and Genetics of Adult Cancer from Youth” (LEGACY Girls Study).

Funded by the National Cancer Institute, the LEGACY study is unique in its focus on healthy, young girls and how their habits and development are related to breast health. LEGACY researchers hope to identify risk factors and lifestyle modifications that could potentially be addressed early enough to prevent or diminish the effects of cancer.

“We’ve seen a lot of death on both sides of my mother’s family from breast cancer, but as detection and treatment has advanced, we’ve seen better outcomes,” Norma said. “I always thought there also was some kind of environmental link. So it was interesting to me to see that the LEGACY study was tracking the health and diet of young girls to see what effects it might have on breast cancer development in the future.”

To learn more about this exciting program, see the 2014 Research Annual Report!

Permanent link to this article: http://www.research.chop.edu/blog/young-girls-help-inform-breast-cancer-prevention/

Feb 11 2015

Genetic Clues Found in Food Allergy Eosinophilic Esophagitis

Eosinophilic EsophagitisScientists have identified four new genes associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the findings may point toward potential new treatments for EoE.

“This research adds to the evidence that genetic factors play key roles in EoE, and broadens our knowledge of biological networks that may offer attractive targets for therapy,” said study leader Hakon Hakonarson, MD, PhD, director of The Children’s Hospital of Philadelphia’s Center for Applied Genomics.

The study team — which included researchers from CHOP, the University of Pennsylvania, and Rady Children’s Hospital-San Diego — published the study recently in Nature Communications. The research builds on a 2010 study by Dr. Hakonarson and colleagues that identified TSLP as the first major gene associated with EoE. Children’s Hospital’s Patrick M.A. Sleiman, PhD, also of the Center for Applied Genomics, was the first author of the study, and performed the data analysis.

Only recently recognized as a distinct condition, eosinophilic esophagitis has been rapidly increasing in prevalence over the past 20 years. Its hallmark is inflammation and painful swelling in the esophagus, along with high levels of immune cells called eosinophils. It can affect people of any age, but is more common among young men who have a history of other allergic diseases such as asthma and eczema.

EoE is often first discovered in children with feeding difficulties and failure to thrive. Because children with EoE are often allergic to many foods, they may be placed on a highly restricted diet containing no large food proteins, to allow time for their symptoms to resolve. Physicians then perform tests to determine which foods a child can or cannot eat.

In the current research, the investigators performed a genome-wide association study (GWAS), first in a discovery cohort of 603 EoE patients compared to 3,637 control subjects, then in a replication cohort of 333 patients versus 675 controls. All the subjects were of European ancestry. 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,” he said.

While a similar drug might relieve esophageal inflammation in children with EoE, he added, “However, the finding of four genes indicates that a single drug might not work for all patients with EoE, and we may need a tailored approach to treatment, based on patients’ genetic profiles.”

Dr. Spergel was a co-author with Dr. Hakonarson on the 2010 study that identified the first EoE-associated gene. He directs CHOP’s Center for Pediatric Eosinophilic Disorders, one of the nation’s premier programs for such diseases. The CHOP center recently joined a new NIH-funded network, the Consortium of Eosinophilic Gastrointestinal Disease Researchers, which brings together leading centers in the field.

To learn more about eosinophilic esophagitis, see Children’s Hospital’s website.

Permanent link to this article: http://www.research.chop.edu/blog/genetic-clues-found-food-allergy-eosinophilic-esophagitis/

Feb 09 2015

Researchers Developing Reliable Measures of Children’s Sleep Health

sleep healthHealthy sleep is essential for children’s happiness, attentiveness, and energy, yet estimates suggest that up to 30 percent of children are affected by sleep problems. While parents usually have no difficulty describing their poor sleepers’ crankiness and fussiness, physicians have not had a standard, reliable way to measure these patient reports of children’s sleep.

Patient reported outcome measures are ways of obtaining information about your health or your well-being from your own perspective, without any translation from a clinician or an interviewer. The National Institutes of Health offers assessment tools called the Patient Reported Outcomes Measurement Information System (PROMIS) to help physicians precisely measure what patients are able to do and how they feel by asking a set of questions that have undergone rigorous scientific testing.

The PROMIS Pediatric Profile has core measures covering domains such as anxiety, depression, fatigue, pain, physical function, and social participation, but the big missing piece of the portfolio is sleep health. Christopher B. Forrest, MD, PhD, a CHOP pediatrician and professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, recently received a two-year grant from the Patient-Centered Outcomes Research Institute (PCORI) to develop PROMIS pediatric sleep health measures that will fill this gap and enable patients and their families to express exactly how health conditions and treatments affect their sleep.

“These questions address the dimensions of life that I like to call feelings, doings, and beings,” said Dr. Forrest, who has been involved with the PROMIS initiative since 2009. “It’s how you feel about yourself and your life, what you can do in life, and then your ‘beings’ is what you become — your personal growth and development. You cannot get that information unless you ask somebody, and what we’ve done through the National Institutes of Health PROMIS program is standardize the methodology.”

For example, “In the past seven days, I fell asleep during school,” is one of the PROMIS items being considered to measure wakefulness and sleep-related impairment. A section of questions on sleep practices includes, “In the past seven days, what time did you go to bed on school nights?”

Once the set of PROMIS pediatric sleep health measures are developed, the idea is for the questionnaires to be offered on tablets, computer kiosks, or paper forms in physicians’ waiting rooms. Two versions will be available for child self-report (ages 8 and up) and parent-proxy (children ages 5 and up).

At CHOP, efforts are underway to eventually incorporate answers to the sleep bank items and other patient-reported outcomes measures as part of the electronic health record. In addition to giving clinicians a standardized way to assess sleep quality and address pediatric sleep concerns as they change over time, the sleep health measures could be used as clinical trial endpoints.

“A medical treatment ought to make kids feel better, but they are not fully recovered until they are able to do things better, like go to school, interact with friends, have sleepovers,” Dr. Forrest said. “Those tend to be the kinds of concerns that families have, but often they don’t get brought up at conventional medical encounters.”

An innovative facet of how the pediatric sleep health item banks are being created is the project’s engagement model. Twenty individuals from five stakeholder groups — parents, youth, advocates, clinicians, and researchers — help to design and oversee the research. One leader from each group plus the project staff make operational decisions.

The team already has accomplished a substantial part of the groundwork. They have interviewed sleep experts, parents, and children, as well as conducted a literature search to identify pediatric sleep measures that were developed previously. Based on the information that they gathered, they generated a preliminary list of 180 pediatric sleep measures. Their next step is to test and validate the questions by surveying about 4,000 children and parents from across the country. They will be recruiting children from CHOP’s Sleep Center, and another group of children with autism being treated at CHOP have agreed to participate in the research.

Dr. Forrest expects the PROMIS pediatric sleep measures will be narrowed down to about 100 items that will be ready for the engagement team to disseminate within the next two years. The final set of measures will be posted on the PROMIS website for free access.

“In addition to publishing papers, we will want to make known across the country through advocacy groups, through scientific communities, and clinical societies that these measures are available,” Dr. Forrest said. “Our hope is that they get used by thousands of researchers and tens of thousands of clinicians and patients.”

Dr. Forrest also serves as the principal investigator of PEDSnet, which is part of the PCORnet  national patient-centered research network established by PCORI to reduce the time and effort needed to launch new studies and focus research on questions and outcomes especially useful to patients and those who care for them.

Permanent link to this article: http://www.research.chop.edu/blog/researchers-developing-reliable-measures-childrens-sleep-health/

Feb 06 2015

Project Increases Flu Vaccination in Pediatric Patients With Cancer

vaccinationWhile influenza vaccination is important for all children, it is critical that pediatric patients with cancer get a flu shot because their weakened immune systems leave them especially vulnerable to severe infections. A quality improvement project at The Children’s Hospital of Philadelphia used simple strategies and cues for families and clinicians to ensure that these children did not leave outpatient clinics or inpatient units without any protection from the insidious virus.

Influenza hospitalizes and kills more people in the U.S. than any other vaccine-preventable disease. Because strains of influenza virus that circulate can differ from one season to the next, new influenza vaccine is available each September. The Centers for Disease Control and Prevention recommend that all children at least 6 months old should get the flu vaccine each year, as soon as it is available in their community. Healthy children can opt for a nasal spray version of the vaccine, but children who have cancer and are immunocompromised receive the flu shot, which does not contain live virus.

“Historically at CHOP, about 53 to 56 percent of patients with cancer were getting the flu vaccine,” said Jason L. Freedman, MD, MSCE, an attending physician in the Division of Oncology at CHOP. “Some parents fear: My child has cancer, why would I give them a vaccine on top of this? They may not realize that the ramifications of being unvaccinated are much worse. If you’re immunosuppressed and can’t fight the virus, it could be fatal.”

Dr. Freedman and colleagues decided to improve the Division of Oncology’s track record for flu vaccinations by implementing a multifaceted quality improvement initiative. Between September 2012 and March 2013, they focused on five overlapping interventions that took advantage of multiple opportunities during outpatient visits to identify patients who needed an annual flu shot and communicate the importance of early vaccination.

They started by boosting family education. Informational handouts and posters in physician waiting rooms encouraged patients to ask their physicians about flu vaccination. The next critical piece was working with the CHOP health informatics team to generate from the electronic health record a color-coded daily list of outpatients due for vaccination. As patients had their vital signs taken, the triage staff and nurses would ask, “Did you get the flu vaccine?” Patients who still needed flu shots received bright yellow colored wristbands as an alert to clinicians to order the vaccine. The study team provided education for clinicians during staff meetings on how to order the vaccine correctly and document any refusals or contraindications.

“On the inpatient side, we also saw discharge as an opportunity for vaccination,” Dr. Freedman said. “We built in an order for the flu vaccine into their admission order set. So when clinicians are admitting a child for chemo, there is already a prompt to order the flu vaccine for when they go home, which was a huge area of missed opportunity.”

The interventions were implemented in tandem, so while the research team is unable to pinpoint which interventions made the most difference, overall they increased the complete flu immunization rate by 20.1 percent to 64.5 percent. The proportion of patients receiving at least 1 dose of vaccination went up by 22.9 percent to 77.7 percent. In 2013, the oncology team continued to reinforce the process changes that they implemented during the study period, and they were able to sustain those rates, Dr. Freedman said.

“We augmented the opportunity for vaccination,” Dr. Freedman said. “The key to the success of this initiative is it was multifaceted and multidisciplinary. It has become part of our culture in clinic, and everyone has a sense of comradery about catching someone falling through the cracks.”

Other pediatric healthcare institutions could easily adapt this project to their settings with little expense or upkeep, Dr. Freedman pointed out. He also anticipates that similar approaches could be used within future quality improvement efforts to increase vigilance in other areas of pediatric cancer care, such as facilitating adherence to medication.

“This study shows that putting together new process changes, while it requires attention, education, and people who are invested, is feasible, doable, and affordable,” Dr. Freedman said.

The results of this study appeared online Jan. 12 in Pediatrics.

Permanent link to this article: http://www.research.chop.edu/blog/project-increases-flu-vaccination-pediatric-patients-cancer/

Feb 04 2015

CHOP Invited to President Obama’s Precision Medicine Announcement

precision medicineAt the invitation of the White House, last week The Children’s Hospital of Philadelphia sent two special guests to President Barack Obama’s announcement of the Precision Medicine Initiative: Steven M. Altschuler, MD, CHOP’s chief executive officer, and 9-year-old CHOP patient Emily Whitehead, who is cancer-free thanks to a personalized treatment called T cell therapy developed at CHOP.

The Precision Medicine Initiative, which President Obama first announced in his 2015 State of the Union speech, calls for new funding to build a national infrastructure to help sophisticated biomedical data flow from health clinics to DNA sequencing labs and back again as innovative treatments.

Precision medicine offers “one of the greatest opportunities for new medical breakthroughs that we have ever seen,” President Obama said.

The National Institutes of Health, Food and Drug Administration, and the Office of National Coordination for Health Information Technology will be involved in this program, which would allow researchers to custom-design more effective therapies based on a patient’s individual genetic profile.

“I am thrilled that President Obama recognizes the promise of our nation’s research efforts by making this investment. This announcement signifies his commitment to bringing this issue to the forefront of our national agenda,” said Dr. Altschuler.

Emily Whitehead, of Philipsburg, Pa., was diagnosed with acute lymphoblastic leukemia (ALL) at the age of four. After multiple relapses, she was out of standard treatment options. In 2012, she became the first child to enroll in the clinical trial for T cell therapy, which bioengineers a patient’s own immune cells to hunt down and eliminate cancer cells. The custom-designed cells then remain in a patient’s circulation to guard against the cancer’s resurgence. Today, Emily has been cancer-free for more than two years. She is active in school and loves playing with her dog, Lucy.

Emily has appeared prominently in many news stories since her doctors announced dramatic findings during a December 2012 scientific meeting. Shortly after the Precision Medicine Initiative was announced, Emily’s story was even highlighted in a White House blog post about Americans whose lives have been changed by precision medicine.

“If you didn’t know what happened to her, and you saw her now, you would have no idea what she has been through,” said Emily’s mother Kari Whitehead in the White House post.

And just last month, CHOP researchers and colleagues announced continuing promising results. In 39 children with ALL treated with T cell therapy in ongoing clinical trials, 36 had no evidence of cancer one month after treatment. The Food and Drug Administration has officially designated this approach as a Breakthrough Therapy, helping to expedite its progress into broader clinical trials.

“As a world leader in precision medicine, The Children’s Hospital of Philadelphia has made significant investment in its Center for Applied Genomics with the goal of diagnosing and curing pediatric disorders,” Dr. Altschuler noted. “We have already made strides harnessing this technology to better understand and treat cancer, autism, asthma, diabetes and many other childhood illnesses. Emily Whitehead’s personal story is a testament to the real impact this groundbreaking research can make in saving lives.”

To learn more about T Cell therapy at CHOP, see the Hospital’s website.

Permanent link to this article: http://www.research.chop.edu/blog/chop-invited-president-obamas-precision-medicine-announcement/

Feb 02 2015

Research Collaborative Aims to Advance Understanding of Preterm Birth

preterm birth

One in nine babies in the U.S. is born prematurely, according to the March of Dimes.

What causes preterm birth and how to prevent it remains a perplexing riddle in medical science. One in nine babies in the U.S. is born prematurely, according to the March of Dimes, and this rate has barely budged despite years of investigation.

Finding the solutions will require the ingenuity of researchers and physicians at The Children’s Hospital of Philadelphia who are part of a transdisciplinary team established by the new March of Dimes Prematurity Research Center at the Perelman School of Medicine at the University of Pennsylvania. They will apply sophisticated technology and methodology in molecular biology and genomics to help better understand the basis for preterm birth and eventually diminish the leading cause of newborn death in the U.S.

Babies born before 37 weeks are considered to be premature, and because their bodies and organ systems have not matured completely, they often need help breathing, eating, fighting infection, and staying warm. They can have long-term health problems, including cerebral palsy, cognitive impairments, and sensory disorders.

The March of Dimes announced in November that it will invest $10 million over the next five years to create the Prematurity Research Center, which is one of four launched by the foundation since 2011. The new center involves more than 40 investigators who will focus on three research themes that aim to generate important new discoveries regarding preterm birth: bioenergetics and genetics, cervical remodeling, and placental dysfunction.

“This kind of cooperation and collaboration is on a different scale than has ever been developed for preterm birth,” said Rebecca A. Simmons, MD, the project leader for the bioenergetics and genetics theme and an attending neonatologist at CHOP and the Hospital of the University of Pennsylvania. “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.”

The other transdisciplinary prematurity research centers include Stanford University School of Medicine in California; a partnership of Ohio research centers in Cincinnati, Columbus, and Cleveland; and Washington University in St. Louis.

At CHOP, the March of Dimes is particularly interested in researchers’ expertise in mitochondrial biology and biochemistry. Mitochondria are organelles often described as the body’s cellular power plants because they systematically extract energy from nutrient molecules (substrates) that is necessary to perform cells’ most basic and critical functions. Along with Marni Falk, MD, director of the Mitochondrial-Genetic Disease Clinic at CHOP, and Neal Sondheimer, MD, PhD, an attending physician at CHOP, Dr. Simmons will investigate how impaired cellular metabolism could result in power shortages in the reproductive tract that contribute to preterm labor.

“Reproductive tissues — the placenta, the uterus, the cervix — require a huge among of energy,” Dr. Simmons said. “But if for some reason the mitochondria aren’t able to utilize substrates normally, those reproductive tissues may not function properly.”

The study team will look at reproductive tissues from mice and humans with preterm birth to identify any patterns of mitochondrial dysfunction and then see if these disturbances interfere with the tissues’ ability to maintain bioenergetics and metabolic stability during pregnancy.

The Prematurity Research Center’s second theme ties into this hypothesis by exploring how the microbiome may influence cervical remodeling, which is a dynamic process during delivery that transforms the cervix from a rigid structure into a pliable passageway for a baby. The microbiome is a community of bacteria that normally inhabit the vagina and cervix. Preliminary studies suggest that the microbiome is different in women who experience preterm birth. The researchers will explore if abnormal bacteria cause mitochondrial distress and inflammation that accelerates cervical remodeling.

Michal Elovitz, MD, associate professor of Obstetrics and Gynecology and director of the Maternal and Child Health Research Program at the University of Pennsylvania, will lead the theme two projects. Samuel Parry, MD, associate professor of Obstetrics and Gynecology and chief of the Division of Maternal-Fetal Medicine at the University of Pennsylvania, is the project leader for theme three, which also will focus on mitochondrial deficiencies and an unhealthy microbiome as possible factors that disrupt metabolic processes in the placenta and lead to early labor.

“If we do find changes in the microbiome, those are targets for therapeutics that can be developed,” Dr. Simmons said. “We’ll look for strategies to either change the composition of the microbiome or change how the microbiome is functioning.”

Some of the answers to the medical mystery of preterm birth also may lie within complex gene-environment interactions that new research approaches could help to unravel. The study teams will explore the evolving field of epigenetics, which is the study of mechanisms that change how genes are expressed without altering the underlying DNA sequence.

They expect to gain insights into the multiple pregnancy-related risk factors — biological, behavioral, social, physical, and environmental — that could cause epigenetic modifications. For example, Dr. Simmons will explore in theme one how any abnormalities in the genes and biochemical pathways that regulate mitochondrial metabolic function could have a role in preterm birth.

“We think that if we can identify novel metabolic pathways, we can certainly design future interventions,” Dr. Simmons said.

As the Prematurity Research Center moves from the discovery phase to targeting and developing therapeutics, the researchers hope that their findings along the way will spark additional preterm birth studies. The Center will offer a series of pilot grants to investigators to encourage them to tackle this important health challenge. Dr. Simmons expects the first request for grant proposals to be issued in February.

Deborah A. Driscoll, MD, the Luigi Mastroianni Jr. Professor and Chair of the Department of Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania, is the director of the Prematurity Research Center, and Dr. Simmons, the Hallam Hurt Professor of Pediatrics, and Dr. Parry are the principal investigators.

Permanent link to this article: http://www.research.chop.edu/blog/research-collaborative-aims-advance-understanding-preterm-birth/

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