Category: Health

How Precision Medicine is Reshaping Epilepsy Research

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on multiple interviews with the investigators.

Excerpt:

The little girl’s epilepsy was so debilitating that she was virtually nonresponsive. Traditional antiseizure medicines could not reduce the five to 20 seizures she experienced daily when she first came to The Children’s Hospital of Philadelphia.

Trying a new approach, her neurologist, David Bearden, MD, prescribed a drug that targeted a molecular pathway involved in her seizures, and within a month, she was seizure-free for the first time since a few days after her birth.

This success excited hope among epilepsy researchers worldwide that other such successful strategies could soon follow. The case exemplifies the popular concept of precision medicine, which is barreling ahead in cancer but not yet common practice in neurologic disorders such as epilepsy.

“Most drugs for epilepsy work like treating pneumonia with a cough suppressant: It may stop the symptom but doesn’t treat the underlying problem,” said Ethan Goldberg, MD, PhD, a CHOP neurologist and neuroscientist who was senior author of a case report about the little girl’s treatment (of which Dr. Bearden was first author) in Annals of Neurology in 2014. Her treatment, while not yet analogous to an antibiotic, was more precisely targeted to the underlying mechanism of her seizures than most treatments.

The future need for precision medicine is one that epilepsy researchers are approaching with conscious attention to the field’s strengths and unmet challenges. Dr. Goldberg was a presenter at a precision medicine scientific symposium during the American Epilepsy Society annual meeting in December. His colleague, Dennis Dlugos, MD, MSCE, a CHOP pediatric neurologist, was among the major contributors to an international consortium of researchers who authored a roadmap for precision medicine in epilepsy published in The Lancet Neurology this fall.

New Collaboration Uncovering a Mitochondrial Mystery

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on an interview with the investigator.

Excerpt:

Mistakes happen. Inside every cell, the functions of life rely on the basic process of building proteins. But, about half the time, cells make errors when building proteins and have to recycle the pieces and start again. One important player in the cell’s recycling process, an enzyme called N-glycanase 1 (NGLY1), is at the center of a new, fundamental biological mystery that researchers at The Children’s Hospital of Philadelphia are setting out to solve.

Two young patients brought this mystery to the team’s attention. Both children arrived within a short time of each other with symptoms of suspected mitochondrial disease at CHOP’s Mitochondrial-Genetic Disease Clinic, which Marni Falk, MD, directs. Mitochondria are the organelles inside of cells that act as the cell’s energy generator, and diseases of mitochondria can have wide-ranging effects across every organ system and commonly include neurological and cardiac complications.

“There are a lot of areas of mitochondrial biology that are still not known at all,” said Dr. Falk, an attending physician at CHOP. “We’ve been so intrigued with this project because, every time we asked a question, three more questions followed.”

Dr. Falk and her team found that, instead of a primary mitochondrial disease, these two children had an extremely rare genetic disorder that was only recently identified, caused by an inherited deficiency in the protein-recycling enzyme, NGLY1. This was fundamentally weird. There was no evident logical reason for a disease of NGLY1 dysfunction to so closely resemble diseases of mitochondrial dysfunction because the proteins in mitochondria do not require NGLY1’s services, or so says conventional wisdom.

Baby Poop Study to Link Infant Microbiome and Obesity

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on an interview with the investigator.

Excerpt:

New parents who find themselves surprisingly attentive to their babies’ poop are in good company. Researchers at The Children’s Hospital of Philadelphia and the University of Pennsylvania are beginning the second phase of a study that is exploring whether baby poop is an important data source to learn how the risk of obesity develops early in life.

The research team is focused on the miniscule but mighty passengers in baby poop: the gut microbiome. The collection of bacteria and other microorganisms that live within the digestive tract and contribute to processing food could reveal a lot about early excess weight gain.

Speeding Up Success with Precision Medicine Cancer Trial

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on an interview with the investigator, following up on a CHOP press release.

Excerpt:

An innovative new clinical trial launching this year at The Children’s Hospital of Philadelphia may not only help patients who have no further proven treatment options for neuroblastoma, a high-risk cancer, but may also be a model for how precision medicine clinical trials can spur better and faster cancer therapy discoveries in the future.

The trial uses a dynamic design, which allows researchers to quickly translate findings from the lab based on the evolving individual characteristics of each patient’s tumor. It is the first time such a strategy is being applied to a prospective clinical trial in children with cancer. Known as the NExt-generation Personalized NEuroblastoma THErapy (NEPENTHE) trial, it is moving forward with a new $1.5 million grant from Alex’s Lemonade Stand Foundation (ALSF), announced in December.

“The novelty of this trial could be viewed on numerous levels,” said principal investigator Yael Mossé, MD, a CHOP pediatric oncologist and assistant professor at the Perelman School of Medicine at the University of Pennsylvania. “It’s based on rigorous preclinical data, understanding the molecular drivers that are important in this disease. It’s combining multiple novel drugs, not just one at a time. And it’s bringing that to the clinic and assigning patients to therapy based on what their tumor genetics are teaching us at the time that they meet us with relapsed or refractory cancer.”

Palliative Care Experts Study Grieving Siblings’ Psychological Welfare

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on interviews with the investigators.

Excerpt:

The experience of grieving for a dying brother or sister during childhood is something that the surviving siblings carry with them for the rest of their lives. Research conducted at The Children’s Hospital of Philadelphia suggests that the experience itself is not a source of serious psychological problems, despite many parents’ concerns that their healthy children could suffer lasting harm from the loss of their sibling. .

“The study comprises a small number of children, but indicates that kids honestly do OK,” said first author Lisa Humphrey, MD, medical director of palliative care at Nationwide Children’s Hospital, who performed the study during her fellowship at CHOP. “When we share this information with parents, this gives them a little glimmer of hope.”

Teens’ Rising Risk of Kidney Stones: Four Things to Know

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this original article based on a CHOP press release and an interview with the investigator.

Excerpt:

Who is at the most increased risk of kidney stones: Teen girls.

The highest rate of increase in kidney stones was among adolescent females, Dr. Tasian’s team found. In any given year, stones were more common among females than males age 10 to 24 years. After age 25, kidney stones became more common among men.

Between 1997 and 2012, the risk of kidney stones doubled during childhood for both boys and girls, while there was a 45 percent increase in the lifetime risk for women.

Among African-Americans, the incidence of kidney stones increased 15 percent more than in whites within each five-year period covered by the study.

Why it matters for children’s health: Pediatric providers may not be prepared to optimally test, identify, and treat youth with kidney stones.

“The emergence of kidney stones in children is particularly worrisome, because there is limited evidence on how to best treat children for this condition,” Dr. Tasian said. “The fact that stones were once rare and are now increasingly common could contribute to the inappropriate use of diagnostic tests such as CT scans for children with kidney stones, since healthcare providers historically have not been accustomed to evaluating and treating children with kidney stones.”

In addition, Dr. Tasian noted that the increased incidence among adolescent girls is concerning because kidney stones are associated with a higher risk of chronic kidney disease, cardiovascular and bone disease, particularly among young women.

How Children’s Hospitals Can Gain Social Awareness Via ACOs

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this original article based on an interview with the investigator.

Excerpt:

Five-year-old Jasmine’s family hears from her pediatrician’s office a lot more often than they used to, and they discuss topics ranging far beyond Jasmine’s health and development. That is because Jasmine (a fictional example) sees a doctor in a health network that has a different kind of contract with her insurance provider, designating it as an Accountable Care Organization (ACO), and as a result it takes a broader view of its role in preventive care than most.

Health policy experts anticipate that ACOs will improve population health under the Affordable Care Act, but demonstrating the value of pediatric ACOs remains a challenge. Policy researchers at The Children’s Hospital of Philadelphia are among those leading a public conversation about how pediatric hospitals and health systems can address social factors affecting health within ACO structures, now that some of the first research on the effect of pediatric ACOs on the use and costs of healthcare resources has begun to emerge.

Tall Man Lettering Falls Short as Error Prevention Strategy

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this original article based on an interview with the investigator.

Excerpt:

A new study spells out shortcomings of an error prevention strategy known as Tall Man lettering, a visual display method for written prescription orders intended to prevent mixing up drugs whose names are easily confused.

“When thinking about patient safety, even great ideas may not work,” said Chris Fuedtner, MD, PhD, MPH, director of the Department of Medical Ethics and director of Research for the Pediatric Advance Care Team and the Integrated Care Service at The Children’s Hospital of Philadelphia. “We always have to be on guard so that we don’t simply follow the fad. We would like to see what is most effective so we can allocate the resources we have to effective safeguards.”

Tall Man lettering entails using capital letters to highlight and distinguish differences in look-alike sound-alike (LA-SA) drug names, such as cefUROXime and cefOTAXime. Several authoritative sources thought it was a good idea; the Food and Drug Administration adopted Tall Man lettering by 2001, and it has since been endorsed by multiple safety regulatory and accreditation bodies in the U.S. and globally. Many hospitals adopted the method after the Joint Commission recommended it as part of its National Patient Safety Goals in 2007.

Yet there is no apparent evidence that Tall Man lettering has reduced LA-SA errors in practice, according to a recent study led by Dr. Feudtner.

Going Back to the Future of Obesity and Osteoporosis

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this original article based on an interview with the investigator.

Excerpt:

In medicine, prevention costs a lot less than a time machine. Fifty to 60 years in the future, many of today’s healthy children and teens will develop later-onset chronic conditions including heart disease, cancer, and osteoporosis. But some of the factors that put them at risk are already beginning now. Prevention of these chronic diseases during childhood may be far more effective than treating them later in adulthood, particularly if we can predict today who will benefit most from these preventive efforts in the future.

This childhood prevention of adult disease is the pursuit of Jonathan Mitchell, PhD, an instructor of Pediatrics in the Division of Gastroenterology, Hepatology and Nutrition at The Children’s Hospital of Philadelphia. Dr. Mitchell was recently awarded a training grant from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health for a study of connections between sleep and obesity risk in teenagers as they transition from middle school to high school. Obese teens tend to become obese adults who face increased risk for heart disease and cancers, so there could be a major long-term public health benefit in understanding how sleep patterns, physical activity-related factors, and genetic factors influence obesity in early adolescence.

“I want to address the question of whether or not short sleep duration leads to the development of adolescent obesity, but we know that other factors, such as physical activity and genetics are also important,” Dr. Mitchell said.

Medicine’s Version of Santa’s Workshop: A Laboratory Medicine Q&A

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Originally published on Cornerstone, the CHOP Research Blog.

I conducted, transcribed, and edited this interview, and wrote the introduction.

Excerpt:

Laboratory medicine specialists in pediatrics have a lot in common with Santa’s elves. They are less visible and receive far less of children’s attention than the ones who directly deliver gifts or bedside care, but their behind-the-scenes contributions are essential for the whole enterprise to function correctly. Just think how often you and your family members of any age need to have blood drawn and wait for lab test results to receive the doctor’s diagnosis or a treatment decision.

Michael J. Bennett, PhD, FRCPath, FACB, chief of laboratory medicine at The Children’s Hospital of Philadelphia, is at the forefront of the professional group representing these essential experts in analyzing blood, tissue, chemicals, and cells. Dr. Bennett will serve on the board of the American Association for Clinical Chemistry (AACC) beginning in January 2016 as president-elect, then in 2017 as AACC president.

On the occasion of this new leadership role, Cornerstone sat down with Dr. Bennett, who is director of the Michael J. Palmieri Metabolic Laboratory at CHOP and a professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania to discuss his insights from 40 years of experience in clinical chemistry in pediatrics.