Mar 25 2015

Technology Helps Overcome Barriers to Vaccination

vaccinationElectronic health records (EHRs) hold promise as tools to trigger reminders to clinicians and families to support on-time vaccination. Making sure that a child is immunized at the right time helps to provide the best defense against dangerous childhood diseases.

Pediatricians capture vaccine data and share these records with immunization information systems, formerly known as registries, which have been implemented in all 50 states to track vaccine receipt by children across practices. With the widespread use of EHRs, practices can use an EHR interface to populate these immunization records, and then the data can be used to expedite efforts to improve health outcomes.

In a recent editorial, Alexander Fiks, MD, MSCE, a faculty member at PolicyLab and the Center for Pediatric Clinical Effectiveness at The Children’s Hospital of Philadelphia, commented about a study appearing in the same issue of JAMA Pediatrics that described an approach to using health information technology to increase vaccination coverage. Allison Kempe, MD, MPH, of the Children’s Hospital Colorado, led the study team that conducted the randomized pragmatic trial.

The researchers targeted families of more than 18,000 children, comparing traditional practice-based vaccine reminders through telephone or mail versus multiple telephone and mail reminders delivered centrally by health departments working in collaboration with practices and using the Colorado Immunization Information System (CIIS) as a data source.

They found that those who received the collaborative centralized reminder not only had higher rates of vaccination, but also lower costs per child vaccinated. Of importance, vaccination rates were higher when reminder messages were specifically endorsed by a child’s practice.

In certain settings where the interests of the practice and public healthcare systems coincide, collaboration with health departments or other outside groups may prove effective, especially if they are built on existing relationships between families and clinicians, according to the JAMA Pediatrics commentary.

“With nearly 80 percent of pediatric practices now capturing data in EHRs, a remarkable opportunity exists to use these data to improve health outcomes,” Dr. Fiks wrote.

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Mar 24 2015

Babies’ BMI May Predict Childhood Obesity

childhood obesityA new study from The Children’s Hospital of Philadelphia shows body mass index (BMI) during infancy may help to predict if a child will be obese by age four. In work focused on the infant BMI-childhood obesity relationship in a cohort with a majority of African-American children, Children’s Hospital researchers say a better understanding of infant growth patterns may lead to more effective early efforts at obesity prevention.

“Given the public health importance of obesity-related medical problems, we investigated whether BMI in infants could be used as a tool to identify children at increased risk of future obesity, in order to develop better prevention strategies,” said the study’s leader, Shana E. McCormack, MD, a pediatric endocrinologist at CHOP. “We also analyzed ancestry-based differences in growth patterns, and found differences that were apparent at as early as nine months of age were ultimately related to childhood obesity risk.”

As a measure that includes both weight and height, BMI is an approximation of body fat content. BMI increases after birth, reaching its peak in infancy, usually between eight and nine months of age.

The current study, published in the Journal of Clinical Endicronology and Metabolism, analyzed the electronic health records of healthy Philadelphia-area infants, as part of a larger study conducted by the Center for Applied Genomics. Sixty-one percent of the children in the study were African-American, a population that has shown high rates of obesity and diabetes in adulthood. Investigators hope that more reliable, early identification of all infants at increased risk for obesity will offer a unique opportunity to develop and implement targeted interventions.

The research team identified significantly different growth trajectories between African-American infants and white infants. Peak infant BMI occurred around 12 days earlier in African-American children, and was about 3 percent higher in magnitude than others in the study, who were primarily of European ancestry. Overall, African-American infants appeared to have more than twice the risk of obesity at age four compared to infants of primarily European ancestry.

However, the study team performed statistical analyses to distinguish the effects of ancestry and infancy BMI, while also accounting for other factors such as birth weight and socioeconomic status. Their conclusion was that infancy BMI played a more important role than ancestry in determining the risk of childhood obesity. In addition, socioeconomic factors, inferred from geographic and insurance data, played a role in infancy BMI.

In children under age two, there is currently no consensus definition of obesity, said Dr. McCormack.

“In the absence of an accepted, valid definition of obesity in infancy, we struggle both as researchers and clinicians with how to best individualize recommendations for infants to prevent childhood obesity,” she added. “Our findings suggest that infant BMI pattern could be one additional tool. In addition, infant BMI may be an early metric to use in evaluating the impact of public policy interventions.”

To read more, see the full press release about this study.

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Mar 23 2015

View Amazing Images in Honor of Brain Awareness Week

Brain Awareness WeekNeuroscientists worldwide celebrated the 20th Anniversary of Brain Awareness Week, March 16-22. The outreach campaign aims to educate the public about the brain and the promise of brain research. Future therapies for brain-related diseases such as Alzheimer’s, Parkinson’s and epilepsy depend on a better understanding of the brain and neuroscientists’ innovation.

At The Children’s Hospital of Philadelphia, researchers in the Division of Neurology are looking at the cellular and molecular mechanisms underlying the development of epilepsy. They use sophisticated imaging technology to view and characterize alterations occurring in the epileptic brain at a circuit level. Epileptic seizures emanate from a burst of electrical signals in dysfunctional brain circuits, which are complex collections of interconnected neurons that process information.

Neuroscience researcher Hajime Takano, PhD, who works in Douglas Coulter, PhD’s, epilepsy research laboratory at CHOP, is investigating which specific neurons could be inciting the neural network. Here are some amazing images from Dr. Takano’s work. He modified the original scientific micrographs for the artistic effect:

Brain Awareness Week

Left Image: Interneuronal network in the dentate gyrus captured by two-photon excitation fluorescence microscopy. Image Courtesy of Hajime Takano, Christopher Dengler, Ethan Goldberg, Douglas Coulter (Translational Epilepsy Research Program)
Right Image: Hippocampal neurons with the genetically encoded calcium indicator captured by two-photon excitation fluorescence microscopy. Image Courtesy of Hajime Takano, Fu-Chun Hsu, Douglas Coulter (Translational Epilepsy Research Program)

Brain Awareness Week

Left Image: Fluorescence micrograph of a hippocampal slice expressing red fluorescent protein in dentate gyrus granule cells. Image Courtesy of Hajime Takano and Douglas Coulter (Translational Epilepsy Research Program)
Right Image: Fluorescence micrograph of CA3 hippocampal neurons stained with calcium indicator dye and color coded activity map of individual neurons captured by high speed confocal microscopy. Image Courtesy of Hajime Takano and Douglas Coulter (Translational Epilepsy Research Program)


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Mar 20 2015

Researchers Honored for Using Video to Better Understand Alarm Fatigue

Christopher_Bonafide_0139ECRI Institute selected an innovative study conducted by patient safety researchers at The Children’s Hospital of Philadelphia who aimed to objectively measure alarm fatigue as a finalist for its 9th Annual Health Devices Achievement Award. The award recognizes an outstanding initiative undertaken by an ECRI Institute member healthcare institution that improves patient safety, reduces costs, or otherwise facilitates better strategic management of health technology.

When healthcare workers experience alarm fatigue, they become overwhelmed, distracted by, or desensitized to the numbers of alarms that monitors activate, which can lead to delayed response times or missed alarms. Addressing alarm fatigue is one of the key factors to improving the management of clinical alarm systems, according to the Joint Commission’s National Patient Safety Goal on alarm safety.

CHOP pediatrician and patient safety researcher Christopher Bonafide, MD, MSCE, submitted the entry, “Using Video to Evaluate Physiologic Monitor Alarm Characteristics and Nurse Responses to Alarms.” It described how the study team used a video-based approach to gather data on staff response times and false alarm rates.

After obtaining permission from nurses and patients’ parents or guardians, the team mounted cameras strategically in patient rooms to capture simultaneous views of the patient room, a close-up view of the patient, a full view of monitor screens and ventilator displays, and views of the caregivers responding to the alarms. Additional software generated a time-stamped list of alarms that occurred during the video sessions.

The team performed 40 video sessions and then analyzed the data generated by 4,962 alarms. They determined that caregiver response times increased as the number of false, or nonactionable, alarms increased. In the intensive care unit, 86.7 percent of alarms in heart and lung failure patients were characterized as false. In the general wards, 99 percent of alarms were false.

An article published in the ECRI’s online journal Health Devices described how Dr. Bonafide and a multidisciplinary team of biomedical engineers, physicians, nurses, researchers, and administrators designed and conducted the study.

“Studies such as these can help drive and inform interventions to reduce alarm burden and fatigue, thereby improving system and staff performance and ultimately improving the quality of care,” the article states.

Dr. Bonafide shared his reaction to the runner-up award: “Our team was thrilled to hear that the ECRI Institute selected our project for this tremendous honor. We are committed to using the findings of this study to inform new initiatives to eliminate alarm fatigue and improve the outcomes of hospitalized children.”

The National Heart, Lung, and Blood Institute recently awarded a five-year career development award to Dr. Bonafide, who is also an assistant professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, to learn more about the science behind alarm fatigue and discover new ways to combat it.

See a PDF of the Health Devices article describing the CHOP initiative that was selected as a finalist for the 2014 Health Devices Achievement Award.

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Mar 18 2015

Vaccinating Against Diseases, Without a Vaccine

vaccineOn the heels of his being consulted about a novel study led by the Scripps Research Institute’s Michael Farzan, PhD, the work of The Children’s Hospital of Philadelphia’s Philip R. Johnson, MD, was highlighted in a new The New York Times article about immunoprophylaxis by gene transfer (IGT), a technology spearheaded in part by Dr. Johnson.

Last month, Dr. Farzan published a study in Nature that describes his team’s creation of a new molecule that prevents monkeys from being infected with simian/human immunodeficiency virus. That research builds on Dr. Johnson’s work with simian immunodeficiency virus (SIV) to develop proteins that act like antibodies called immunoadhesins. These proteins, which Dr. Johnson and his team delivered via recombinant adeno-associated virus (rAAV) vectors, successfully blocked SIV infection.

As The New York Times article notes, this approach “is altogether different from traditional vaccination.” Instead, it is more akin to gene therapy, for in the case of HIV the AAV-delivered antibodies “can latch onto many different strains of the virus and keep them from infecting new cells.”

“The new study reinforces the potential promise of the AAV-mediated immunoprophylaxis approach as an alternative to vaccination to prevent HIV infection,” said Wayne C. Koff, chief scientific officer of the International AIDS Vaccine Initiative (IAVI), after Dr. Farzan’s study was published. “We look forward to further studies that will show how well any of these approaches can work in humans and will bring us all closer to a world without HIV/AIDS.”

Following that, Children’s Hospital last year partnered with IAVI to launch a clinical trial to study the safety of the rAAV vector carrying the broadly neutralizing antibody PG9, which has been shown to protect against HIV. The study team hopes to collect data later this year.

“For Dr. Johnson,” the Times article notes, “the growing interest in IGT is gratifying. ‘It’s catching on, but it’s certainly not mainstream,’ he said. That seems likely to change, and soon.”

“The sky’s the limit,” said Dr. Farzan.

Read the whole thing at The New York Times.

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Mar 17 2015

Researchers Look for Factors Underlying Disparities in Diabetes Care

diabetesChildren with type 1 diabetes are not able to produce insulin on their own, which puts them at risk for long-term complications involving their eyes, nerves, circulation, kidneys, and heart. One way that they can prevent these problems is by using insulin pump therapy to help control the levels of sugar (glucose) in their blood. These systems can be programmed to imitate the body’s normal release of insulin and allow some children with diabetes to avoid daily insulin injections.

A study published in Pediatrics and written by Steven Willi, MD, director of the Diabetes Center for Children at The Children’s Hospital of Philadelphia, took a close look at health care practitioners’ prescribing practices for insulin pumps. The study team investigated potential racial and ethnic disparities in insulin treatment approaches and health outcomes among 10,704 participants from 2010 to 2012 in the T1D Exchange (T1DE) Clinic Registry. CHOP is the largest pediatric member of the T1DE, which includes 60 pediatric diabetes sites across 31 states.

“We had a sense that there were subtle differences in prescribing practices and that insulin pump therapy, in particular, was not being prescribed as often to children from ethnic minorities,” Dr. Willi said. “We recognized that there was controversy in the literature about whether these disparities exist, and if so, why. Since the T1DE is the largest collection of patients with type 1 diabetes in the U.S., we thought the data would allow us to examine those questions. We were quite surprised by the disparities that we uncovered.”

The study’s results showed that fewer black children were receiving insulin pump treatment than Hispanic or white children, regardless of socioeconomic status. White children were 3.6 times more likely to receive insulin pump therapy than black children, and 1.9 times more likely than Hispanics. The researchers also found that even in high-income families, black children were less likely to be on a pump, and they had much higher glucose levels, which suggest that black children tend to have poorer diabetes control.

“What I found quite remarkable is that you were more likely to have an insulin pump if your parents had a high school education and you were white than if your parents were educated at the level of a master’s degree and you were black,” Dr. Willi said. “I would not have predicted that finding, as previous studies have suggested that socioeconomic status was the primary determinant of insulin pump use.”

It raises the question, he continued, of how much prescribing practices are being influenced by personal bias. For example, if practitioners harbor preconceived notions about who may be more or less likely to respond to an insulin pump, then they may be more reluctant to introduce the treatment method as an option to patients.

To counteract this possible bias, diabetes teams should try to objectify the prescription of these devices, Dr. Willi said. Objective criteria, a checklist for example, could be used to identify patients who might benefit from insulin pump therapy. It also is important, he said, for practitioners to recognize that previous research has shown that patients of all backgrounds can successfully undergo training to use an insulin pump.

“We would like for this to serve as a wake-up call for diabetes practices to open their minds to the idea that insulin pumps can be safely prescribed and that we shouldn’t allow our biases to determine who is a ‘good’ pump candidate,” Dr. Willi said.

The study team concluded that further research is needed to identify the barriers to optimal diabetes management in all racial, ethnic, and socioeconomic status groups and to determine the reasons why practitioners may not prescribe insulin pumps as frequently in certain minority children with type 1 diabetes. The research team also has a study underway that aims to explain some of the health outcomes disparities that have been found among ethnic groups. They will explore how glycated hemoglobin (HbA1c) may be influenced by genetics, as some research has suggested that HbA1c may be lower in whites than blacks, even when they have the same blood sugar levels.

At CHOP, insulin pump prescribing practices have increased dramatically over the last decade, according to Dr. Willi, and insulin pump therapy classes are available to all patients interested in incorporating the technology into their diabetes care plan.

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Mar 16 2015

NPR Story Highlights CHOP Childhood Adversity Study

childhood adversityA recent All Things Considered story touched on an innovative, potentially transformative project by The Children’s Hospital of Philadelphia’s Roy Wade Jr., MD, PhD, MPH. Since last year, Dr. Wade has been working to add children’s voices and language feedback to tools used to assess and respond to childhood adversity.

Dr. Wade’s work builds on the CDC’s Adverse Childhood Experiences (ACEs) Study, conducted from 1995 to 1997. Designed to assess associations between adverse childhood experiences and health later in life, the study’s findings “suggest that certain experiences are major risk factors for the leading causes of illness and death as well as poor quality of life in the United States,” according to the CDC site.

Dr. Wade’s research — funded in part by a grant from the Stoneleigh Foundation — seeks to add to the original ACEs by adding youth voices to build a concise, effective, youth-informed measure of childhood adversity.

“If you only have five minutes with a kid, what would be the five most relevant questions that you would need to ask in order to assess that kid’s adversity? You don’t have time to ask twenty questions or ten questions,” said Dr. Wade in the NPR piece. Arming clinicians with an assessment of a child’s ACEs, Dr. Wade, says, could help physicians “address an array of different problems in a family.”

As the NPR story reiterates, “research has shown that the stress of a tough childhood can raise your risk for later disease, mental illness, and addiction.”

To read and listen to the entire story, check out the NPR site. And to read about Dr. Wade’s work in greater detail, see CHOP Research’s Bench to Bedside.

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Mar 13 2015

VEPTR Inventor Dr. Robert Campbell Honored by Pennsylvania Bio

VEPTRWe’re so pleased to announce that Children’s Hospital’s Robert M. Campbell, MD, was honored with Pennsylvania Bio’s Patient Impact Award at the organization’s annual dinner last night! Dr. Campbell, a professor of Orthopaedic Surgery at the University of Pennsylvania’s Perelman School of Medicine, is the inventor of the vertical expandable prosthetic titanium rib (VEPTR), the first device approved by the FDA to treat thoracic insufficiency syndrome (TIS), a rare condition affecting children in which the thorax cannot support regular growth or breathing.

Pennsylvania Bio’s Patient Impact Award “recognizes a company or organization that has made a significant contribution to the quality of healthcare or length of life of patients in 2014.” Last year, the University of Pennsylvania and CHOP were jointly given the award for their groundbreaking immune therapy research.

Dr. Campbell led a recent Journal of Pediatric Orthopaedics study that showed VEPTR treatment improved Jeune syndrome (a severe form of TIS) patients’ survival to nearly 70 percent, compared to a 70 to 80 percent mortality rate without treatment. To learn more about this inspirational work, check out the video below, the first on CHOP Research’s new YouTube channel!

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Mar 13 2015

Study of Rare Disease Reveals Gene Crucial to Immune Defense

rare disease

“This discovery fits well with the ‘precision medicine’ concept that is currently in its infancy but represents the future of genomic medicine,” said Dr. Hakonarson.

Genomics researchers from the Center for Applied Genomics (CAG) at The Children’s Hospital of Philadelphia investigating a serious, rare disease called common variable immunodeficiency (CVID) have discovered a gene linked to immune defense. Children with the challenging disorder have difficulty fighting off infections.

CVID affects one in 25,000 to one in 50,000 people worldwide, and they may start experiencing signs and symptoms of the disorder anytime between childhood and adulthood. Researchers suspect that mutations in the genes associated with CVID result in a shortage of antibodies that leaves the body vulnerable to infections from bacteria and viruses. Recurrent respiratory infections can lead to chronic lung disease, and patients also may have joint inflammation, stomach and bowel disorders, and a higher risk of cancers.

The study team performed an association analysis that focused on immune-related genes in a cohort of 360 CVID patients and 21,610 healthy controls. They compared regions of the genome using a genotyping chip specialized to search for gene variants previously implicated in autoimmune and inflammatory diseases.

The researchers found 11 single nucleotide polymorphisms (SNPs) associated with CVID on the 16p11.2 locus of chromosome 16. SNPs are changes in a single DNA building block (A,T, C, or G), compared to the more typical sequence in a certain stretch of DNA. Of particular interest, the study team found variants in the gene ITGAM, which carries codes for an integrin protein that regulates cellular contact and adhesion.

“This association is of high biological relevance because ITGAM plays an important role in normal immune responses,” said Hakon Hakonarson, MD, PhD, director of the CAG, who led the study team. “Other researchers have shown that mice in which this gene has been knocked out have immune deficiencies.”

The new findings may promote better understanding of ITGAM’s functional role and eventually lead to targeted therapies for patients with CVID. Dr. Hakonarson added that the research may have broader implications for other patients who do not have these novel gene variants because the integrin protein affects many important pathways in immune function.

“This discovery fits well with the ‘precision medicine’ concept that is currently in its infancy but represents the future of genomic medicine,” said Dr. Hakonarson, who is also on the faculty of Perelman School of Medicine at the University of Pennsylvania.

The study team reported their findings in the Journal of Allergy and Clinical Immunology. Funds from the National Institutes of Health, the Kubert Estate Foundation, and CHOP’s Institute Development Fund supported this research.

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Mar 11 2015

Technology Focuses on Acne Evaluation, Management

acneIt is challenging for clinicians who are treating a patient with acne to accurately measure disease activity from visit to visit. Often, they must rely on personal memory and the patient’s perspective to determine if the skin problem is improving, which can be an imprecise and time-intensive process.

In the U.S., it is estimated that 60 million people have acne, and one-fourth will seek out medical services; however, pediatric dermatology services are particularly difficult for patients to access with referral wait periods that can exceed more than three months.

Albert Yan, MD, Section Chief of the Division of Dermatology at The Children’s Hospital of Philadelphia and associate professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and co-developers Elena Bernardis, PhD, and Jianbo Shi, PhD, are creating a software program using sophisticated computer vision algorithms that will expedite clinical visits for acne and allow physicians to spend more valuable time on patient education.

“We are excited about this project because of the great potential to streamline the efficiency of primary care management of this disease in a way that adheres to accepted evidence-based guidelines and reduces unnecessary referrals of less severe disease to specialists,” Dr. Yan said.

Learn more about this exciting program in the Research Annual Report.

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