New physician scientist already conducting pioneering research in neonatology

As a recently recruited young physician scientist on CHOC’s neonatal intensive care unit (NICU), Dr. Grant Shafer is maintaining a busy clinical schedule while settling into a new life in Southern California.

And Dr. Shafer, who joined CHOC on Sept. 1 after finishing a fellowship at Texas Children’s Hospital (TCH), arrives here with some pioneering result already under his belt – with more to come.

Dr. Grant Shafer, CHOC neonatologist

In one of the first such large studies of its kind in neonatology, Dr. Shafer is researching the prevalence of diagnostic errors and the ethical responsibilities of providers to disclose such errors to families of impacted NICU patients. 

“Studying and quantitating diagnostic errors is a relative new science in the field of neonatology,” said Dr. Vijay Dhar, medical director of CHOC’s NICU, and division chief, Neonatology, at CHOC/UCI. “Grant has been an outstanding addition to our growing young faculty in the division.”

In March 2020, Dr. Shafer, with a TCH colleague, authored the paper “The Ethics of Disclosing Diagnostic Errors: What is the Researcher’s Duty?” that was published in JAMA Pediatrics, a monthly peer-reviewed medical journal of the American Medical Association.

And in late October, Dr. Shafer was one of eight former distinguished fellows who spoke on a panel before a global international audience at the Society to Improve Diagnosis in Medicine’s (SIDM) Diagnosing Errors in Medicine 13th Annual International Conference.

“To me, this research is interesting because it’s about how we provide the care we provide,” Dr. Shafer said. “It’s the kind of research that I really enjoy. Some people enjoy benchwork, some people enjoy working in the lab, some enjoy clinical studies.

“I really enjoy research that looks at the systems in which we practice medicine and how that impacts the care we provide, and diagnostic errors encapsulates all of that,” he added. “But it’s a field that we really haven’t studied yet. There’s just not a lot of information out there. All the data we’re finding is new to everyone.”

Earned a master’s in English Literature before becoming a doctor

Dr. Shafer, whose parents are from Hawaii, grew up in Denver. His mother, Andrea, is a retired school administrator and his father, Duane, worked in finance. He has a younger sister who runs a CrossFit gym in Kansas City with her husband.

Dr. Shafer earned bachelor’s and master’s degrees in English Literature from Wayne State University in Detroit. He went on to earn his medical degree from the University of Cincinnati College of Medicine and completed his pediatrics residency at University of Texas Southwestern.

At Baylor College of Medicine at TCH, Dr. Shafer completed a neonatal-perinatal medicine fellowship and, over the last year, also completed a second research fellowship in diagnostic excellence through SIDM.

In his JAMA Pediatrics paper, Dr. Shafer and co-author Dr. Frank X. Placencia probed the duty of a researcher performing retrospective medical reviews to disclose diagnostic errors. They concluded that because researchers are outside the patient-clinician relationship, the researcher is not ethically obligated to disclose a diagnostic error directly to a patient with whom they have no formal relationship.

However, Drs. Shafer and Placencia concluded, there is potentially a responsibility to discuss the error with the treating clinician, who then assumes the responsibility of contacting the patient.

Elaborating on this ethical framework during his SIDM panel presentation, Dr. Shafer noted many researchers feel uncertain how to proceed when they come across a diagnostic error that potentially could cause harm to a patient. Because of the sensitive nature of the information, Dr. Shafer recommended that it be delivered to the clinician in a structured setting.

Dr. Shafer said with hard numbers about diagnostic errors in NICUs still years away, a lot of research remains to be done.

“It’s widely acknowledged that diagnostic errors occur in the NICU, but we don’t know how often or how much harm they are causing, which means we can’t try to make things better,” he said.

And making things better – building on CHOC’s already sterling reputation in the field of neonatology — is the whole point, he added.

“I think this is the right place and right time to really push this research forward,” Dr. Shafer said. “I’m humbled and excited to have the opportunity to provide clinical care to babies here in the NICU at CHOC as well as research how we can continue to improve the diagnostic care we provide moving forward.”

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Collaborative effort involving milestone procedure saves premature baby with complex heart disease

Baby Hope looked into her mother’s eyes and gurgled.

Four days short of turning 9 months old, wearing a white onesie with the words “Best Gift Ever” on the front, she made more baby talk.

“You’re always a big chatterbox – what are you saying?” her mother, Elizabeth “Becca” Wyneken, said as she smiled and stared into Hope’s blue eyes.

Becca and Hope endured a lot to get to where they are now — a happy and very grateful mom and a relatively healthy 9-month-old baby girl whose light-brown hair is just starting to fill in.

The odds were stacked against Hope when she was born prematurely at 31 weeks and five days, weighing just 2 pounds, 3 ounces. Today, Hope is alive thanks to a team of doctors, nurses and others who cared for her throughout a four month stay on CHOC’s neonatal intensive care unit (NICU) and cardiovascular intensive care unit (CVICU).

Born with a complex heart disease, as well as only one kidney and defects on her right leg and foot, Hope’s cardiac neonatologist, Dr. Amir Ashrafi, pegged her chances of survival at between 20 and 30%.

When Becca first set eyes on Hope a couple of days after she was born, she was very concerned about her baby’s health.

“Don’t worry, Mom,” Dr. Ashrafi told Becca that day. “I think we can help her.”

It would take an extensive collaboration between highly regarded cardiovascular interventionalists, some of whom were consulted at hospitals as far away as London, to do so.

And it would involve a high-risk procedure never performed on a baby so small at CHOC.

Dr. Amir Ashrafi, neonatologist at CHOC

Grim news at 20-week scan

At 18 weeks pregnant, Becca, a teacher’s aide, went in for a checkup. Blood tests showed her baby had a high risk for Down syndrome and spina bifida.

Two weeks later, a scan of her baby’s anatomy revealed other potential problems.

Her baby had no kidneys, Becca was told. She appeared to have no bladder, no right leg, no lungs, issues with her bowels, and a heart defect.

“I don’t think I stopped crying for the rest of the day,” Becca recalls. “It was horrible.”

She couldn’t drive home from the clinic. A friend had to pick her up. That night, Becca had dinner with her mother and aunt.

Later, lying beside her mother, Becca cried.

“I can’t believe this is happening,” she said.

She felt a poke in her belly.

“Over and over again, when I got upset, she would poke me,” Becca said.

At that moment, she decided on a name for her baby.

“Hope,” Becca told her mother.

Second opinion reveals true complications

Becca got a second opinion about her unborn baby’s condition.

Her baby was missing a kidney and had a leg defect, she was told. Most seriously, Becca was told, she had a defect on her right ventricle, the chamber within the heart responsible for pumping oxygen-depleted blood to the lungs.

Hope’s aorta and pulmonary artery that carry blood away from the heart hadn’t developed properly. She had a hole in her heart as well as one in her left superior vena cava, a vein that helps circulate deoxygenated blood back to the heart. These holes caused blood to drain incorrectly; Hope would need a team of doctors to correct the blood flow.

“Being very small with complex heart disease, your options are very limited with what you can do and the timing of any procedures,” said Dr. Ahmad Ellini, Hope’s primary pediatric cardiologist.

There were lots of sleepless nights as Hope’s team of doctors and nurses monitored her closely. Becca was beside her nearly every night.

Dr. Ashrafi and Dr. Ellini consulted with two outside experts, San Francisco-based Dr. Mohan Reddy, who specializes in complex heart disease in small newborns, as well as renowned thoracic and cardiac surgeon Dr. Glen Van Arsdell of Ronald Reagan UCLA Medical Center on the best course of action.

The team of physicians determined that a stent needed to be inserted under a pulmonary artery that was becoming too narrow, making it hard for blood to flow through it. Such a procedure is risky, especially on a baby so small.

“In Hope’s case, the idea was if we could open up the area below the valve while not injuring the valve, that would be a home run,” said Dr. Sanjay Sinha, a CHOC pediatric cardiologist who put the stent in Hope’s heart. “Two things made this difficult: she was very small, and we had no stents this size.”

A vendor was able to secure the small stent needed a day before Hope’s surgery.

Assisting Dr. Sinha during the procedure was Dr. Michael Recto, medical director of CHOC’s Cardiac Catheterization Lab.

Observing the recently developed procedure, known as valve-sparing RVOT (right ventricular outflow tract) stent placement, were several cardiologists, from CHOC and other pediatric hospitals.

“In some patients, there is very little room for a stent. Hope had just enough room for the stent to be placed,” Dr. Sinha explained, “We knew we had the technical skills and ability to do this, but this had never been done before at CHOC on a baby this size.”

A very scary moment

After the surgery, Hope got seriously ill with a viral infection. At one point, Dr. Ashrafi said, her heart stopped but the team was able to revive her.

In cases like Hope’s, where a newborn’s state of health is fragile, members of her clinical team often must pivot in an instant, making their work schedules long and unpredictable.

Hope was at CHOC for four months before she was able to go home. After that, physicians at another hospital removed the stent, closed the hole in her heart, and corrected her left superior vena cava.

Dr. Ellini, who continues to see Hope at her check-ups, is very pleased with her progress.

“She basically has a normal circulation,” he said. “She needed a pacemaker. Overall, she’s doing great. She’s only on one medication and is gaining weight.”

In fact, she’s up to 13 pounds.

Baby Hope

Dr. Ellini said he’s proud of the extensive collaboration that was involved in Hope’s care at CHOC.

“We try to really foster a collaborative team approach in our interventional lab, and this is a great example of that,” he said. “Having a dedicated neonatal cardiac intensive team of physicians and nurses who are really experts in what they do really was paramount in making sure she did well.”

Becca can’t praise Hope’s team at CHOC enough. “They’re totally lifesavers,” she said. “It was a roller coaster — heartbreaking and exiting. I was pretty much afraid all the time, but they treat you like you are family.”

Investigational Drug Study Leads to FDA Approval for Fenfluramine in Treatment for Dravet Syndrome

Children who experience seizures associated with Dravet syndrome have a new medication option, thanks to research at CHOC Children’s that helped gain the recent approval of the U.S. Food and Drug Administration (FDA).

Dravet syndrome is a sodium channelopathy that causes an intractable, difficult-to-control form of epilepsy beginning in the first year of life, as well as significant developmental and motor impairments. Many patients with this rare and severe type of epilepsy experience prolonged and unrelenting seizures and are at risk for SUDEP (sudden unexpected death in epilepsy).

Dravet syndrome is difficult to treat with the antiepileptic medications currently available in the United States, but the FDA has recently approved FINTEPLA® (fenfluramine) for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older. Dr. Mary Zupanc, pediatric epileptologist and co-medical director of the CHOC Children’s Neuroscience Institute, was a key investigator in one of the two international drug studies that led to U.S. FDA approval.

Dr. Mary Zupanc
Dr. Mary Zupanc, pediatric epileptologist and co-medical director of the CHOC Children’s
Neuroscience Institute

“The drug we recently trialed, fenfluramine, showed a significant reduction in convulsive seizures and overall seizures, which helped improve the quality of life not only for patients with Dravet but for their families as well,” Dr. Zupanc said.

Study 1 trialed 0.2 mg/kg/day or 0.7 mg/kg/day. The patients on the higher dose had a 70% reduction relative to placebo in monthly convulsive seizure frequency. And 70% of the patients on the higher dose had at least a 50% reduction in their monthly convulsive seizures compared to 7.7% of patients on placebo. Patients on the lower dose of fenfluramine had a 31.7% reduction relative to placebo in monthly convulsive seizure frequency, and 34.2% of patients on the lower dose had at least a 50% reduction in their monthly convulsive seizures.

In addition to reducing the monthly convulsive seizure frequency in patients whose seizures were not adequately controlled on one or more antiepileptic drugs, most study patients responded to treatment with fenfluramine within three to four weeks, and the effects remained consistent over the treatment period. Dr. Zupanc remarked that fenfluramine’s effectiveness could be “life-changing” for patients with Dravet.

Fenfluramine — used on its own and also paired with phentermine in the popular weight-loss combination known as “fen-phen” — was withdrawn from the U.S. market in 1997 after reports of heart valve disease and continued findings of pulmonary hypertension. Due to these risks, subjects received frequent EKGs and echocardiograms throughout the investigational trial. No valve disease or hypertension was found, but a decrease in appetite and some observations of a minor increase in irritability were noted.

Dr. Zupanc is optimistic about fenfluramine’s application for Dravet, but advised that it is only part of an overall treatment plan. “If a physician has a patient with Dravet syndrome, I would make sure the patient gets referred to a Level 4 epilepsy program, the highest designation for epilepsy centers,” Dr. Zupanc said. “CHOC is a level 4 epilepsy center, which means we do investigational drug studies, vagus nerve stimulation, epilepsy surgery, ketogenic diet and provide a full-service epilepsy program with six epileptologists with board-certification in epilepsy. Because we have participated in these [investigational] studies, we are on the ground floor and know how to dose these drugs and adjust these medications.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the neurology/neurosurgery specialty.

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

CHOC recognized as one of nation’s best children’s hospitals

CHOC Children’s is one of a select group of pediatric facilities nationwide to have been ranked today as a best children’s hospital by U.S. News & World Report.

The following CHOC specialties are honored in the 2020-21 Best Children’s Hospitals rankings: neonatology; cancer; diabetes and endocrinology; neurology and neurosurgery; orthopaedics; pulmonology; and urology. Both orthopaedics and diabetes and endocrinology earned a “Top 20” spot.

“At CHOC, we are committed to the highest standards of care, safety and service – and this honor reflects that unwavering dedication,” said Dr. James Cappon, CHOC’s vice president, chief quality and patient safety officer and interim chief medical officer. “Not only does this recognition of our excellence in these subspecialties, including two on the top 20 lists, validate our efforts, but it also offers our patients and families additional assurance of our commitment to their health and safety.”

The Best Children’s Hospitals rankings were introduced by U.S. News in 2007 to help families of children with rare or life-threatening diseases find the best medical care available. Only the nation’s top 50 pediatric facilities are distinguished in 10 pediatric specialties, based on survival rates, nurse staffing, procedure and patient volumes, reputation and additional outcomes data. The availability of clinical resources, infection rates and compliance with best practices are also factored into the rankings.

The U.S. News Best Children’s Hospitals rankings rely on clinical data and on an annual survey of pediatric specialists. The rankings methodology factors in patient outcomes, such as mortality and infection rates, as well as available clinical resources and compliance with best practices.

Learn more about Best Children’s Hospitals rankings.

CHOC recognized as one of nation’s best children’s hospitals

CHOC Children’s is one of only 50 pediatric facilities in the nation to earn recognition as a best children’s hospital by U.S. News & World Report. The following CHOC specialties are honored in the 2019-20 Best Children’s Hospitals rankings: diabetes/endocrinology, cancer, neonatology, neurology/neurosurgery, pulmonology and urology. Cancer ranked in the “top 20.”

“The national recognition for CHOC’s cancer program is well-deserved. There’s nowhere else I’d rather have gone through treatment than CHOC,” says 17-year-old Sydney Sigafus, CHOC patient and cancer survivor. “Everyone who works at CHOC cares about you as a person, not just a patient. I was included in every decision and conversation about my care.”

The Best Children’s Hospitals rankings were introduced by U.S. News in 2007 to help families of children with rare or life-threatening diseases find the best medical care available. Only the nation’s top 50 pediatric facilities are distinguished in 10 pediatric specialties, based on survival rates, nurse staffing, procedure and patient volumes, reputation and additional outcomes data. The availability of clinical resources, infection rates and compliance with best practices are also factored into the rankings.

“We understand how scary it can be for parents whose children are dealing with life-threatening illnesses or injuries. That’s why we are committed to the highest standards of care, safety and service,” says Dr. James Cappon, CHOC’s chief quality officer. “While we are proud of our accolades, including being named a best children’s hospital, we remain focused on preserving the magic of childhood for all kids, whether they are seriously ill or healthy, or somewhere in between.”

More information about the Best Children’s Hospitals rankings can be found here.