TAG: "Pediatrics"

Study finds significant cost savings in pediatric telemedicine consults

Rural emergency departments save money compared to telephone consults.

James Marcin, UC Davis

By Tricia Tomiyoshi, UC Davis

Researchers at UC Davis have conducted a comprehensive study to determine whether pediatric telemedicine consultations with rural emergency departments save money compared to telephone consults. The answer is a resounding yes. While telemedicine systems are expensive to install and maintain, they more than pay their way, saving an average $4,662 per use. The study was published in the journal Medical Decision Making.

“Our previous work showed that telemedicine was good for kids, families and providers, but we didn’t really address the cost issue,” said James Marcin, UC Davis interim head of pediatric critical care medicine. “Now we know, not only does it improve quality, safety and satisfaction, but it also saves money.”

Public health researchers worked closely with health economists to determine the actual costs of a telemedicine consult, as well as the potential savings. On one side of the ledger, hospitals must invest in equipment, software and IT support. In addition, urban hospitals must pay to have subspecialists on call to assist their rural colleagues. These and other costs averaged out to $3,641 per consultation.

However, the value of these consultations far exceeded these expenses. The study found that, compared to telephone, telemedicine consults produced extensive savings. In many cases, savings accrued from reduced transfers between hospitals. In particular, moving patients by air ambulance can dramatically increase the cost of care. Telemedicine consults reduced the number of patients being transferred by 31 percent.

To make these findings, the team reviewed the Pediatric Critical Care Telemedicine Program at UC Davis, tracking its interactions with eight rural emergency departments between 2003 and 2009. They collected detailed information on the costs of implementing and maintaining the telemedicine program and weighed those against the transfer logs at the eight hospitals, as well as the costs of ED visits. The team focused on five conditions: asthma, bronchiolitis, dehydration, fever and pneumonia. These diagnoses stand out because, with appropriate guidance, they can be treated at the rural hospitals.

Marcin and his team will continue to study the relationship between telemedicine and patient costs and are excited to share this information with payers, hospital administrators, physicians groups and other interested parties. Given its ability to both improve quality and reduce costs, Marcin believes telemedicine should play a larger role in health care.

“In California, physicians get paid for telemedicine consultations, but in many states they don’t,” says Marcin. “Given its ability to reduce medication errors and increase patient, family and physician satisfaction, as well as lowering costs, I think it makes sense to actually pay physicians a little more for this service to incentivize the model.”

Other authored included: Nikki H. Yang, Madan Dharmar, Byung-Kwang Yoo, J. Paul Leigh, Nathan Kuppermann, Patrick S. Romano and Thomas S. Nesbitt.

This study was funded by the Agency for Healthcare Research and Quality (AHRQ 1 K08 HS 13179-01); Emergency Medical Services for Children (HRSA H34MC04367-01-00); Office for the Advancement of Telehealth (HRSA 5R01HS019712);the California HealthCare Foundation (CHCF #02-2210); and the William Randolph Hearst Foundations.

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California children with health insurance, regular dental care show big gains

UCLA research shows significant increases over past decade, but disparities persist.

Photo by Elena Zhukova

By Venetia Lai, UCLA

An impressive 3 in 4 California children ages 2 to 5 had a regular dental checkup in 2012, including those from poorer households, according to a new policy brief by the UCLA Center for Health Policy Research.

A decade earlier, just half the children in low-income households made an annual visit to the dentist, along with 60 percent of those from higher-income households.

The findings are part of a comprehensive new study that tracked young children’s health in California from 2003 to 2012. The study found gains in many areas, including health insurance coverage and dental care, but showed a drop in preschool participation, perhaps because of the associated costs.

“These are really encouraging trends for the health and well-being of children in California,” said Sue Holtby of the Public Health Institute, who is lead author of the study. “But some beneficial services remain out of reach for low-income families. The challenge for policymakers is to continue to improve access to, and quality of, the care children receive.”

Using data from 10 years of California Health Interview Survey from 2003 to 2012, the report assessed trends in the health of young children in areas linked to health and school readiness. The report focused on Latino, white, Asian and African-American children ages 5 and younger. According to CHIS, more than 3 million children in that age range lived in the state in 2012.

The safety net expands

Much of the time period covered by the study took place during the recession from 2008 to 2012, when many families lost access to employer-funded health coverage. As more low-income families gained health coverage through two public programs — Medi-Cal and Healthy Families —  ––the share of children ages 5 and younger who had private health insurance plummeted, from 57 percent in 2003 to 44 percent in 2011–12. The change meant a bigger share of young children relied on public coverage: 1 in 2 overall, compared to 1 in 3 a decade earlier.

The dramatic improvements in dental care for young children during the time period may be attributable, in part, to expanded public support.  Specifically, the study notes that a $7 million grant from First 5 California, which funded the study, provided preventive dental health training and education for dental and medical providers at Women, Infants and Children and Head Start programs from 2004 to 2008, the same time period in which annual child dental visits increased. In addition, Medi-Cal and Healthy Families promoted greater awareness of dental benefits.

More parents reading to their children

Another bright spot: More families participated in activities that promote social skills and brain development in young children. The percentage of parents who sang or played music with their child every day rose from 64 percent in 2003 to 68 percent in 2011–12, and those who took their children out on an excursion increased from 32 percent to 37 percent. The biggest jump was in the share of parents who read to their children daily: from 53 percent in 2003 to 62 percent a decade later.

However, the report found the proportion of 3- and 4-year-olds going to preschool at least 10 hours a week dropped over the decade, from 37 percent to 30 percent.

“Parents have gotten the message that there’s a lot they can do for their children’s development at home,” said Elaine Zahnd, a faculty associate at the Center for Health Policy Research and co-author of the study. “But there is more work to do to help parents who want their children to go to preschool.”

Other findings from the report:

  • More young children had access to health care. Access to health care improved for poor children as the decade progressed: the rate of uninsured poor children dropped from 13 percent in 2003 to 8.9 percent in 2012.
  • There are disparities in the sources of medical care. In 2012, far more young Latino children (40 percent) obtained care at community clinics or public hospitals compared to white (14.6 percent) and Asian (20.1 percent) children. However, the share of white children who visited a private doctor’s office or an HMO declined 5.3 points over the decade to 82 percent.
  • Almost all young children (97 percent) had a usual source of medical care in 2012, with two-thirds being treated by private practice doctors and HMOs and the rest at community clinics and hospitals.

“Parents are getting coverage for their children, but can they access health care for their children when they need it?” asked David Grant, director of the California Health Interview Survey and co-author of the report. “As more children rely on the safety net, policymakers must ensure that the clinics and public hospitals that serve them are adequately funded.”

The report found noteworthy improvements in young children’s health over the decade — especially in closing the income gap in dental and health care. But authors say continued monitoring and further research are needed to understand what prompted negative changes in private insurance coverage and preschool enrollment.

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UC Davis Children’s Hospital launches Pediatric Early Mobility Program

Program to help improve recovery times, shorten patient stays among PICU patients.

By Tricia Tomiyoshi, UC Davis

Early mobility and exercise have been shown to help patients recover faster and decrease long-term effects of delirium, a common condition of pediatric patients admitted to the pediatric intensive care unit (PICU). UC Davis Children’s Hospital has today (May 19) launched a Pediatric Early Mobility Program to help improve recovery times, shorten patient stays, reduce pain and delirium among PICU patients.

Delirium  is a state in which a child may be confused, irritable or withdrawn and may be caused by illness or infection and certain medications. It is frequently associated with perceptual motor and behavioral problems, and delusional memories, which can trigger the occurrence of post-traumatic stress disorder.

The program follows PICU standard procedures known as the ABCDEF bundle, which includes protocol to combat the effects of potential effects of delirium. Early mobility and exercise is the “E” in the ABCDEF bundle.

“We look forward to implementing the Pediatric Early Mobility Program and helping to improve the quality of care and long-term effects of our pediatric patients,” said Cheryl McBeth, assistant manager for the UC Davis Pediatric Intensive Care Unit and the Pediatric Early Mobility Program lead.

In 2012, UC Davis Medical Center successfully implemented an Early Mobility program within the adult population. This program has demonstrated a decrease in ICU length of stay (LOS), ventilator days, overall hospital LOS and hospital costs without compromising patient or staff safety. Due to the success of the adult program, the project was extended to UC Davis Children’s Hospital.

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Maternal obesity compromises babies’ immune system at birth

Study investigates key innate and adaptive immune cells in umbilical cord blood samples.

Ilhem Messaoudi, UC Riverside

By Iqbal Pittalwala, UC Riverside

Almost 60 percent of women of childbearing age in the United States are overweight or obese. Obesity is a major public health issue, and has been linked to health problems like heart disease, cancer and hypertension. It can complicate pregnancy by increasing the mother’s risk of having gestational diabetes, preeclampsia, preterm birth or a baby with birth defects. Maternal obesity is also linked to several adverse health outcomes for the infant that can persist into adulthood, such as type-2 diabetes, heart disease and mortality.

But when exactly does the immune system of babies born to obese mothers get compromised? Very early in the baby’s life, according to a new study by a research team led by Ilhem Messaoudi of the University of California, Riverside.

The team analyzed umbilical cord blood samples of infants born to lean, overweight and obese mothers, and found that pre-pregnancy maternal weight has a significant impact on the immune system of the neonate, putting such children at risk for potential diseases such as heart disease and asthma.

The pilot study, performed on 39 mothers in Portland, Oregon, is published online in PubMed and will soon appear in the journal Pediatric Allergy and Immunology.

“A number of studies have linked maternal obesity – starting pregnancy with excess weight and gaining a lot of weight during pregnancy – to a higher incidence of cardiovascular disease and asthma in children,” said Messaoudi, an associate professor of biomedical sciences in the School of Medicine at UC Riverside. “Our study offers potential links between changes in the offspring’s immune system and the increased susceptibility and incidence of these diseases later in life.”

The researchers used established body mass index (BMI) categories to sort the mothers participating in the study, BMI being a number calculated from height and weight. A mother was considered overweight if her BMI was 25 to 29.9. A mother was considered obese if her BMI was 30 or higher.

The mothers were all non-smoking, had no diabetes and had an uncomplicated gestation at term. Each mother delivered just one baby. Eleven mothers were lean, 14 were overweight and 14 were obese. Thirty were white, three were Asian American/Pacific Islander, one was an American-Indian/Alaskan native and two were African American. The racial identity of three women was unknown.

“We found that very specific immune cells in circulation – monocytes and dendritic cells –isolated from babies born to moms with high BMI were unable to respond to bacterial antigens compared to babies born to lean moms,” Messaoudi said. “Such babies also showed a reduction in ‘CD4 T-cells.’ Both of these changes could result in compromised responses to infection and vaccination.”

Further, the researchers found that cells (eosinophils) that play a role in allergic response and asthma pathogenesis were significantly reduced in the umbilical cord blood of babies born to obese mothers. One potential explanation for these observations is that these cells have already moved into the lungs, which could explain the increased incidence of asthma observed later in life in children born to obese mothers.

The research is the first to show the link between maternal obesity during pregnancy and neonatal immune outcomes, and shows that changes in immunity are already detectable at birth and could persist for the lifetime of the child into adulthood.

“This could change how we respond to vaccination and how we respond to asthma-inducing environmental antigens,” Messaoudi said. “As we know, in the first two years of life, children typically receive plenty of vaccines. The questions that arise are: Are the responses to vaccines in infants born to obese moms also impaired in the first two years of life?  Should we change how often we vaccinate children born to obese moms? Should we change practices of how much and how often we vaccinate?”

Messaoudi sees the research paper as a launching point for further studies and a call to action.

“If you are thinking of becoming or are already pregnant, talk to your ob-gyn about weight management, weight gain and the ideal targets for weight gain,” she said. “When moms come in for prenatal visits, doctors tell them about smoking, recreational drug use and alcohol. But they should be talking also about weight and weight management. Obesity has serious repercussions for maternal health. It is associated with low fertility and success with pregnancy.  Rates of gestational diabetes, preeclampsia, placental abruption – all of these risks increase dramatically with weight gain and obesity. So it is important to talk to your doctor about ideal weight entering into pregnancy and throughout pregnancy.”

Messaoudi was joined in the study by Randall M. Wilson and Daniel R. Jeske at UCR; and Nicole E. Marshall, Jonathan Q. Purnell and Kent Thornburg at the Oregon Health & Science University, Portland, Oregon.

The research was supported by grants from the National Institutes of Health.

More information about obesity and pregnancy can be found here.

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Study explains how early childhood vaccination reduces leukemia risk

Chronic infections push ‘pre-leukemia’ cells, common in newborns, into malignancy.

By Juliana Bunim, UC San Francisco

A team led by UC San Francisco researchers has discovered how a commonly administered vaccine protects against acute lymphoblastic leukemia (ALL), the most common type of childhood cancer.

The Haemophilus influenzae Type b (Hib) vaccine not only prevents ear infections and meningitis caused by the Hib bacterium, but also protects against ALL, which accounts for approximately 25 percent of cancer diagnoses among children younger than 15 years, according to the National Cancer Society. The Hib vaccine is part of the standard vaccination schedule recommended by the Centers for Disease Control and is routinely given to children in four doses before 15 months of age.

Though the cancer protection offered by the Hib vaccine has been well established in epidemiological studies, it is not well-known among the public at large, and the mechanism underlying this effect has been poorly understood. Now, in work to be reported on today (May 18) in Nature Immunology, an international team led by UCSF researchers has shown that recurrent Hib infections can put certain immune-system genes into overdrive, converting “pre-leukemia” blood cells — which are present in a surprisingly large number of newborns — into full-blown cancer.

“These experiments help explain why the incidence of leukemia has been dramatically reduced since the advent of regular vaccinations during infancy,” said Markus Müschen, M.D., Ph.D., professor of laboratory medicine at UCSF and senior author of the study. “Hib and other childhood infections can cause recurrent and vehement immune responses, which we have found could lead to leukemia, but infants that have received vaccines are largely protected and acquire long-term immunity through very mild immune reactions.”

Many newborns carry oncogenes — genes that could potentially cause cancer — in their blood cells, but only 1 in 10,000 will eventually develop ALL. In the new study, the researchers tested the idea that chronic inflammation caused by recurrent infections might cause “collateral damage” — additional genetic lesions — in blood cells already carrying an oncogene,  promoting their transformation to overt disease.

Led by co-first authors Srividya Swaminathan, Ph.D., a former UCSF postdoctoral fellow now at Stanford University School of Medicine, and Lars Klemm, assistant research specialist at UCSF, the research team conducted experiments with mice that homed in on two enzymes known as AID and RAG as the drivers of this process.

AID and RAG introduce mutations in DNA that allow immune cells to adapt to infectious challenges, and these enzymes are necessary for a normal and efficient immune response. But in the presence of chronic infection, the group found, AID and RAG are strongly hyperactivated, and they cut and mutate genes randomly, including important gatekeepers against cancer.

By studying genetically engineered pre-leukemia cells lacking either AID or RAG, as well as cells lacking both enzymes, the team found that AID and RAG working together is critical to introduce the additional lesions that result in life-threatening disease.

Though the researchers focused on Hib, a bacterial infection, they believe that the same mechanisms may be at work in viral infections. The team is currently conducting experiments to determine if protection against leukemia is also provided by vaccines against viral infections, such as the well known MMR vaccine at the center of recent anti-vaccination controversies.

Mel F. Greaves, M.D., Ph.D., professor of cell biology at the Institute of Cancer Research, in London, is among the scientists who developed the theory that chronic and recurrent immune reactions during infancy promote cancer in children and one of the co-authors of the study. “The study provides mechanistic support for the hypothesis that infection or inflammation promotes the evolution of childhood leukemia and that the timing of common infections in early life is critical,” said Greaves.

Also participating in the research were scientists from the University of Freiburg; Cambridge University; the Wellcome Trust Sanger Institute; the University of Southern California; Heinrich-Heine-Universität Düsseldorf; the University of Ulm; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; and Yale School of Medicine.

The work was funded by the National Institutes of Health; the National Cancer Institute; the Leukemia and Lymphoma Society; the William Lawrence and Blanche Hughes Foundation; the California Institute for Regenerative Medicine; the Wellcome Trust; and Cancer Research UK.

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UC residency programs awarded grants to help primary care workforce

State grants will support internal medicine, pediatric residency training programs.

By Charles Casey, UC Davis

California’s Office of Statewide Health Planning and Development has awarded more than $600,000 in grants to UC Davis’ internal medicine and pediatrics residency training programs to boost primary health care workforce training in California. This is the first time the departments have received funding from what is known as the Song-Brown Program.

Song-Brown is designed to support education programs that will increase the number of underrepresented primary care practitioners, provide clinical training and education in underserved areas, and expand access to health care for the California’s underserved populations.

“We are one of only two internal medicine residency programs to be awarded two Song-Brown grants this year,” said Craig Keenan, a professor of internal medicine and principal investigator for the department’s grants. “This support allows us to build upon our track record of successful workforce training initiatives such as the Transforming Education and Community Health (TEACH) program. “Song-Brown funding helps ensure that UC Davis residency programs remain at the forefront of national efforts to meet the primary care needs of very diverse populations, enabling us to provide resident physicians with both clinical and culturally appropriate expertise.”

The grants are part of a $4 million augmentation in funding from California. Other recipients include UC Riverside, UC San Diego and UC San Francisco.

Health Data and Planning Fund to support both new and existing primary care physician residency slots via the Song-Brown Program.

Also receiving Song-Brown funding for residency training for the first time was the UC Davis Department of Pediatrics. It will receive more than $300,000 over the next three years to support pediatric resident education.

“This funding comes at an ideal time because it enables us to increase our residency program from 36 pediatric residents to 39 residents,” said Su-Ting Li, associate professor of pediatrics and the department’s residency program director. “It’s allowing us to train even more outstanding general pediatricians to provide care for underserved children and families in California.”

The Song-Brown Family Physician Training Act was passed by the California lawmakers in September 1973 to encourage newly trained physicians to practice in designated underserved areas of California. Historically, it supported training programs for family practice residents and primary care physician assistants, including many at UC Davis. This year was the first time the program specifically included internal medicine and pediatrics.

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UCSF, San Francisco community partner to address oral health epidemic

Plan aims to move toward making the city cavity-free.

A UCSF dental resident gives a free dental screening to a child during a Sunday Streets fair in the Bayview, one of several annual outreach events for the local community. (Photo by Cindy Chew)

By Scott Maier, UC San Francisco

In San Francisco, nearly 40 percent of children have experienced tooth decay by the time they reach kindergarten, and low-income kindergartners are eight times more likely to have untreated tooth decay, reports the San Francisco Children’s Oral Health Collaborative (SF COH).

Oral health disparities are specific to local neighborhoods, with the highest rates in Chinatown, where more than 50 percent of all kindergarteners suffer from cavities.

To inform and elicit community feedback about the importance of children’s oral health – and continue to learn why some ethnicities are more at-risk – the SF COH, which includes UC San Francisco, the SF Department of Public Health and community health providers and advocates, hosted a community stakeholder meeting on April 30 in Chinatown.

Attendees at the two-hour meeting at the Chinatown YMCA included San Francisco Supervisors Julie Christensen and Scott Wiener, and Health Commissioner Ed Chow.

“Good oral health is critical to the well-being of our city, and we need to expand access to dental care as well as healthy and nutritious food, particularly in our low-income communities,” Wiener said.

Similar stakeholder meetings are planned for Latino and African American communities in San Francisco.

“Because of this meeting, we were able to raise the level of awareness of children’s dental caries that is disproportionately affecting the Chinatown neighborhood,” said Lisa Chung, D.D.S., M.P.H., associate professor in the UCSF School of Dentistry Department of Preventive and Restorative Dental Sciences and SF COH co-director. “We were able to bring together local health and child care providers and organizations and engage in a spirited discussion about what could be causing these Chinatown disparities, existing barriers to addressing them, and how we can collaborate and move forward.”

A silent epidemic

Tooth decay and periodontal disease are the two biggest threats to oral health and among the most common chronic diseases in the United States. In fact, former U.S. Surgeon General Regina Benjamin called oral diseases a “silent epidemic.”

Children with untreated cavities may experience pain, dysfunction, school absences, difficulty concentrating and low self-esteem, according to the SF COH.

“It is better to prevent tooth decay than to provide extensive dental treatment for a very young child,” said Dr. Steven Ambrose, director of dental services for the San Francisco Department of Public Health, a co-leading agency of the Children’s Oral Health Collaborative. “If we can help parents understand how to keep their babies’ teeth healthy, we can prevent unnecessary disease and pain, and promote and protect our children’s oral health in a far easier and cost effective manner.”

Dental caries is largely preventable through dental sealants, fluoride varnish, healthy eating habits, daily oral care at home and routine dental visits. However, many parents, medical providers and even dental providers do not fully understand their critical roles in preventing this disease.

Plan to make San Francisco cavity-free

A cross-sector initiative designed to improve the health and wellness of all San Franciscans, the San Francisco Children’s Oral Health Collaborative coordinated the San Francisco Children’s Oral Health Strategic Plan 2014-2017 toward making the city cavity-free. The plan identifies the most effective, evidence-based actions each group can take to make the most impact. Target groups are children under 10, pregnant women, low-income communities of color, recent immigrants and other populations most at risk.

“Involving the community and collaborating with its members are essential in efforts to improve public health, and is at the core of SF HIP’s Children’s Oral Health Collaborative,” Chung said. “We prioritized this first meeting in Chinatown on public and private health professionals and Chinatown program planners, community leaders, and school administrators as they are working closest with the target population – young children and their caregivers. We look forward to working to have similar community briefings throughout San Francisco.”

The San Francisco Children’s Oral Health Collaborative is supported by the Hellman Foundation. The Chinatown community stakeholder meeting was sponsored by the Chinatown YMCA, the Asian Pacific Islander Health Parity Coalition, APA Family Support Services, NICOS Chinese Health Coalition and API Council.

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Intervention pioneered at UC Davis helps mothers address depression

Motivating our Mothers program relies on pediatricians for diagnosis.

Erik Fernandez y Garcia, UC Davis

By Tricia Tomiyoshi, UC Davis

Researchers at UC Davis have developed a new intervention that identifies potentially depressed mothers and encourages them to seek treatment. The Motivating our Mothers (MOM) program takes a unique approach, relying on pediatricians rather than the mother’s doctor for diagnosis. In the study, mothers were given a short survey to assess whether they needed additional care. Those who identified depression symptoms were then coached by a research assistant to seek further help.

The program had a remarkable impact. Nearly 74 percent of mothers in the intervention group sought additional help, compared to around 54 percent in the control group. The research was published recently in the journal Academic Pediatrics.

“This is one of the first studies to take on the role of the pediatrician in not only identifying depression in mothers but also helping them take the next step,” said Erik Fernandez y Garcia, associate professor of clinical pediatrics and lead author on the study. “The hope is that once we’ve refined the intervention and presented it to pediatricians, they will feel more comfortable about addressing depression with mothers of their patients.”

The study targeted English-speaking mothers, with children between 0 and 12 years, who were given a simple, two-question survey about the core symptoms of depression. Mothers who showed symptoms received targeted education that focused on removing the stigma associated with depression and how treatment could improve their children’s health. They also received follow-up calls two days later to reinforce the message.

The researchers set a high bar for success, using an active control group that was also screened for depression and given depression education and advice. However, the control intervention lacked the targeted messaging designed to destigmatize depression and link treatment to improved child health.

Pediatricians may be the ideal conduits to help depressed mothers seek care, according to Fernandez y Garcia. Many young mothers rarely visit their own physicians but make frequent trips to the pediatrician’s office – multiple times during a child’s first two years and once a year after that.

In addition to having more opportunities, pediatricians may also be more effective at broaching the subject, as they can better explain how seeking treatment improves children’s health.

“Pediatricians are in a position to talk to moms about the effects of depression on their children and use that as a motivation to get their symptoms evaluated,” said Fernandez y Garcia.

In some ways, the MOM intervention was even more effective than the researchers had expected. For example, many mothers sought care from a number of different sources simultaneously, including spiritual counselors and mental health and medical practitioners.

The next step is to refine the program and conduct a similar study including Spanish-speaking mothers.

“If I can give pediatricians an efficient intervention to implement in their practices, we can really increase our ability to identify women with depression,” said Fernandez y Garcia. “We can help them feel better and the kids will have better outcomes as well, so it has a positive effect on everybody’s well being.”

Other UC Davis authors were Jill Joseph, Machelle Wilson, Ladson Hinton, Gregory Simon, Evette Ludman, Fiona Scott and Richard Kravitz.

This study was funded by the National Center for Advancing Translational Sciences, grants UL1 TR000002 and 1K23MH101157-01A1 and by a grant from the UC Davis Department of Pediatrics Children’s Miracle Network, as well as the UC Davis Office of the Dean and 5K24MH07275605.

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Hollywood stars, street artists help raise $2M for pediatric research

The Kaleidoscope Ball was a success for Mattel Children’s Hospital UCLA.

Actress Halle Berry speaks after receiving the “Kaleidoscope Award” during the Mattel Children’s Hospital UCLA Kaleidoscope Ball. (Credit: Alex J. Berliner, ABImages)

By Amy Albin, UCLA

The Children’s Discovery and Innovation Institute at Mattel Children’s Hospital UCLA raised more than $2 million this past weekend for pediatric research at its 3rd annual Kaleidoscope Ball.

“The funding raised at the Kaleidoscope Ball will be used to support critical research that benefits children around the world,” said Dr. Sherin Devaskar, physician-in-chief of Mattel Children’s Hospital UCLA and executive director of the UCLA Children’s Discovery and Innovation Institute. “We are very grateful to all of our sponsors and supporters who made this evening an incredible success.”

During the sold-out event, which 750 guests attended at 3LABS in Culver City on May 2, actress Halle Berry received the hospital’s “Kaleidoscope Award” from actress Goldie Hawn.

“I know, as a mother of two, how important children are,” Berry said upon receiving her award, which was established to recognize members of the arts and entertainment community who professional achievements and humanitarianism improve children’s lives. “And they are the most important, the most vulnerable, the most valuable assets that we have on our planet.”

Kelvin Davis, a senior partner at TPG Capital, received the “Philanthropic Leadership Award,” and actress Halston Sage received the “Young Luminary Award.” Actor Chris O’Donnell, proudly presented the “Extraordinary Children’s Award” to his young friend, Charlie Croxall, who was a patient at UCLA.

Actress Poppy Montgomery helped host the evening and guests enjoyed a performance by Grammy-nominated artist Aloe Blacc and music from DJ Michelle Pesce.

World-renowned street artists came together and curated a selection of art pieces that were auctioned off in celebration of the evening’s theme, “Los Angeles: An Art-Full City.” Award winning street artist, Mr. Brainwash, collaborated on a piece with Harry Winston that paid tribute to Winston as “Jeweler to the Stars.”

The evening also featured work from notable artists including Robert Vargas, who painted live at the event. Special pieces were donated by internationally acclaimed artists PichiAvo, Shepard Fairey, Roy Lichtenstein, James Rosenquist, Ed Ruscha, William Wegman, Charles Arnoldi, Enrique Martinez Celaya, Mike Stilkey, Billy Al Bengston, Sage Vaughn, Charming Baker and others.

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Breakthrough in understanding Canavan disease

UC Davis findings could help find a way to treat devastating genetic disorder.

David Pleasure, UC Davis

By Charles Casey, UC Davis

UC Davis investigators have settled a long-standing controversy surrounding the molecular basis of an inherited disorder that historically affected Ashkenazi Jews from Eastern Europe but now also arises in other populations of Semitic descent, particularly families from Saudi Arabia.

Through a series of elegant experiments, the researchers uncovered the biochemical underpinnings of Canavan disease, a type of leukodystrophy that is an incurable and progressively fatal neurological condition. The UC Davis team identified an abnormally high buildup of the second most common molecule in the brain, N-acetylaspartate (NAA), as the culprit that causes the syndrome’s destructive effect.

The findings, which are now available online, appear in the May issue of the journal Annals of Neurology in an article titled, “Ablating N-acetylaspartate prevents leukodystrophy in a Canavan disease model.”

“By finally identifying the biochemical basis for this terrible disorder, we are hopeful that it can lead to an effective treatment,” said David Pleasure, a UC Davis Distinguished Professor of neurology and pediatrics, and principal investigator of the study.

Leukodystrophies comprise a number of rare genetic disorders of the central nervous system that involve disrupted development of the myelin sheath that grows around neurons, which is essential for normal nerve conduction. Canavan disease usually becomes apparent in infancy with poor muscle tone and abnormal head enlargement, and rapidly progresses to mental retardation, paralysis, blindness, hearing loss and usually death by age 10. There is currently no treatment.

Canavan disease is inherited in an autosomal recessive pattern, meaning that if both parents carry the mutation, each child has a 1 in 4 chance of developing the condition. Although the disease occurs worldwide, the most frequent carriers of the mutation are Ashkenazi Jews from Eastern Europe. Because of widespread genetic counseling in that population, most cases of the disease now arise in families from other backgrounds, especially in Saudi Arabians.

It has been well understood for years that the critical mutation that leads to Canavan disease is of the gene that codes for an enzyme called aspartoacylase (ASPA), which breaks down NAA into acetate and aspartate. Without a working ASPA enzyme, NAA – which provides multiple important functions in the brain — builds up, resulting in a shortage of the two byproducts. Knowing this led to two hypotheses of what is responsible for the manifestation of Canavan disease – it might either be a problem of too much NAA or too little availability of the byproducts. Because acetate is an essential component of myelin synthesis, the “too little byproduct” hypothesis had a good theoretical basis and led to attempted treatments that stymied investigators because of their ineffectiveness.

Pleasure’s group used mice engineered with specific genetic mutations to prove that the “too much NAA” theory is the correct one. Mice that were genetically unable to produce NAA exhibited normal myelination, indicating that not having acetate available from this pathway cannot be responsible for poor myelin development. Furthermore, these same mice, if also given the ASPA mutation of Canavan disease, did not develop signs of the syndrome.

It has been suggested that one of NAA’s functions is to preserve the essential water and salt balance in the brain. It is this possible function that Pleasure believes is likely to be the primary problem in Canavan disease. Children with the disease have enlarged fluid-filled areas in the brain evident in magnetic resonance imaging studies, possible evidence of a water-salt imbalance. According to this theory, dysmyelination occurs secondarily to the problems caused by fluid imbalance.

Attempts to treat Canavan disease have taken several directions. Supplementing acetate has been unsuccessful, which according to the new findings is to be expected. Combating the mutation directly by implanting a working ASPA gene using a viral vector has worked well in mouse models of the disease but is technically unfeasible so far in humans.

This current research points to a new avenue of treatment: blocking the production of NAA. However, NAA, being such a common molecule in the brain, must have essential functions, according to Pleasure. Mice that are genetically engineered to be unable to synthesize NAA have been reported to have abnormal social interactions. One child has been identified in the literature who was unable to produce NAA because of a genetic mutation. The child had neurodevelopmental retardation.

“Reducing NAA without eliminating it completely may be the most promising direction of treatment,” said Pleasure, whose laboratory is based in Sacramento at Shriners Hospitals for Children Northern California. “Our goal is to find a method to reverse the process in children with the disease – that will be the most useful to families with this heartbreaking condition.”

Research for this study was funded by Shriners Hospitals for Children and the European Leukodystrophy Association.

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Prenatal stem cell treatment improves mobility issues caused by spina bifida

Lower-limb paralysis associated with the birth defect may be effectively treated before birth.

Fetal surgeon Diana Farmer (front), stem cell bioengineer Aijun Wang (behind her) and their research team are testing placental stem cells as a treatment for the paralysis associated with spina bifida.

By Karen Finney, UC Davis

The lower-limb paralysis associated with spina bifida may be effectively treated before birth by combining a unique stem cell therapy with surgery, new research from UC Davis Health System has found.

The study, conducted in an animal model, was led by Diana Farmer, the fetal surgeon who helped pioneer in utero treatment for spina bifida — a congenital birth defect that occurs when the spinal cord does not close properly, leading to lifelong cognitive, urological, musculoskeletal and motor disabilities. Farmer’s chief collaborator was Aijun Wang, co-director of the UC Davis Surgical Bioengineering Laboratory.

“Prenatal surgery revolutionized spina bifida treatment by improving brain development, but it didn’t benefit motor function as much as we hoped,” said Farmer, chair of the UC Davis Department of Surgery and senior author of the study, published online today (April 24) in Stem Cells Translational Medicine.

“We now think that when it’s augmented with stem cells, fetal surgery could actually be a cure,” said Wang.

Farmer and Wang are the first to combine fetal surgery with a placental stem cell treatment to reduce the effects of spina bifida, which in children can range from barely noticeable to severe. The most common and disabling form of the disorder, called myelomeningocele, causes the spinal cord to emerge through the back, often pulling brain tissue into the spinal column and causing cerebrospinal fluid to fill the interior of the brain. Permanent shunts are required to drain the extra fluid.

Farmer was senior author of the landmark Management of Myelomeningocele Study (MOMS), which showed that prenatal surgery could improve cognitive outcomes for the 1,500 children born each year in the U.S. with spina bifida. A majority of treated children in the study, however, were unable to walk independently at 30 months of age.

For the current research, lambs with myelomeningocele received fetal surgery to return exposed tissue to the spinal canal. Human placenta-derived mesenchymal stromal cells (PMSCs) — known for their neuroprotective qualities — were preserved in hydrogel and applied to the site of the lesion. A scaffold was placed on top to hold the hydrogel in place, followed by surgical closures to complete the repair.

Six animals that received the stem cell treatment were able to walk without noticeable disability within a few hours following birth, while six control animals that received just the hydrogel and scaffold were unable to stand.

“We have taken a very important step in expanding what MOMS started,” said Wang. “Next we need to confirm the safety of the approach and determine optimal dosing.”

Farmer and Wang will continue their efforts with funding from the California Institute for Regenerative Medicine. With additional evaluation and FDA approval, the new therapy could be tested in human clinical trials.

“Fetal surgery provided hope that most children with spina bifida would be able to live without shunts,” Farmer said. “Now, we need to complete that process and find out if they can also live without wheelchairs.”

Additional authors were Erin Brown, Lee Lankford, Benjamin Keller, Christopher Pivetti and Nicole Sitkin of UC Davis, and Michael Beattie and Jacqueline Bresnahan of UC San Francisco. Their study — titled “Placental Mesenchymal Stromal Cells Rescue Ambulation in Ovine Myelomeningocele” — was funded by the UC Davis Department of Surgery. It is available online at http://stemcellstm.alphamedpress.org/content/early/recent.

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In utero exposure to extreme morning sickness may result in neurological deficit

UCLA study suggests nutritional deficiency early in pregnancy may play a role.

By Kim Irwin, UCLA

Women who experience extreme morning sickness during pregnancy are three times more likely to have children with developmental deficits — including attention disorders and language and speech delays — than women who have “normal” nausea and vomiting, a UCLA study found.

The research was the first to look specifically at the relationship between in utero exposure to extreme morning sickness, also known as hyperemesis gravidarum or HG, and childhood neurologic developmental outcomes, said Marlena Fejzo, the study’s first author, and an associate researcher at the David Geffen School of Medicine at UCLA.

Fejzo said the correlation was especially apparent in women whose HG symptoms began very early, prior to five weeks gestation.

“These findings show that it is vital to take HG seriously so these pregnant women can get nutritional support right away,” Fejzo said. “An encouraging finding is that we did not find any association with medications to treat this disorder and neurodevelopmental delays, so I speculate that the neurodevelopmental outcomes are more likely caused by nutrient deficiency early in pregnancy rather than medication.”

The study was published online by the European Journal of Obstetrics and Gynecology and Reproductive Biology.

HG is the condition that the former Kate Middleton, Duchess of Cambridge, has experienced during both of her pregnancies. Its cause is unknown and the symptoms are intense — including continuous nausea and vomiting so violent that it can cause detached retinas, blown eardrums, cracked ribs and torn esophagi, Fejzo said. The symptoms can last for a month or two or for the entire pregnancy.

This study looked at 312 children born between 2007 and 2011 to 203 mothers with extreme morning sickness, and 169 children born to 89 mothers who did not have the disorder. Children born to women with HG had attention and sensory disorders, and learning, speech and language delays. Fejzo said the researchers do not yet know the mechanism that causes abnormal neurologic development in children of women with hyperemesis gravidarum.

The women in the study who had HG experienced nausea and vomiting so severe that they lost at least five pounds and needed intravenous fluids. Children exposed in utero to HG were 3.28 times more likely than the others to have neurodevelopmental delays, Fejzo said.

“There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea and vomiting decreases that risk of neurodevelopmental delay,” she said.

Fejzo said HG is diagnosed in up to 2 percent of pregnant women worldwide, and it accounts for more than 285,000 hospitalizations in the U.S. every year.

Previous studies have shown that HG is associated with low birth weight babies, small size for gestational age and preterm births. Fejzo showed previously that children born to mothers who had extreme morning sickness were 3.6 times more likely to have behavioral or emotional disorders as adults.

Fejzo and her team are investigating the genetic basis of HG, and they hope to determine whether earlier treatment in women with symptoms limits or prevents the adverse outcomes identified in the study.

“A significant increase in neurodevelopmental and behavioral disorders in children exposed to
HG in utero was demonstrated which suggests HG may be linked to life-long effects on the exposed fetus,” the study states. “The cause for this is unknown, but may be due to maternal stress, abnormal hormone levels during fetal development and/or maternal-newborn bonding after birth, or malnutrition and vitamin deficiency.”

The study was conducted at UCLA and the University of Southern California, and it was funded in part by the Hyperemesis Education and Research Foundation.

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