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Autism, Behavioral Science, Pediatrics, Stanford News

Home videos could help diagnose autism, says new Stanford study

Home videos could help diagnose autism, says new Stanford study

Autism is more complex to diagnose than many other childhood conditions. There’s no physical sign or lab test; rather, making the diagnosis requires careful observation for clues such as poor language and social skills or repetitive behaviors. Standard diagnostic tests take several hours of a professional’s time, and families may wait months to see someone who can assess their child.

But new research from Stanford and Harvard Medical School suggests that faster diagnoses might become possible. The research team, whose findings appear today in PLOS ONE, tested whether short home videos could be harnessed to speed the process. Using a scoring system that was pared down from the “gold standard” diagnostic test, they assessed kids’ behavior in 100 short videos pulled from YouTube. About half of the videos showed children with autism; the rest did not. The scoring system classified 97 percent of the videos accurately.

The system is unlikely to replace traditional diagnostic methods, but could help relieve the diagnostic bottleneck, study author Dennis Wall, PhD, explained in our press release:

“For instance, we could use this system for clinical triage, as a way to channel traffic so that children can get the kind of attention they need as early as possible,” Wall said. Children who clearly have autism might be diagnosed primarily with videos and quickly started on therapy, freeing clinicians to spend more time evaluating children whose diagnosis is less clear-cut.

Home videos also provide information that is otherwise unavailable to those making the diagnosis, Wall said:

Another potential advantage of using video for diagnosis is that young children often behave differently in a doctor’s office than at home.

“Clinical settings are often stark, artificial and can elicit behaviors that are abnormal,” Wall said. “The odds are stacked against the diagnostic professional because the child is in an unknown environment with strangers.”

The researchers plan to explore whether the same method could also be used for making other behavior-based diagnoses, such as detecting attention-deficit hyperactivity disorder or adult-onset neurologic conditions such as Alzheimer’s or Parkinson’s disease.

Previously: Using Kinect cameras to automate autism diagnosis, Director of Stanford Autism Center responds to your questions on research and treatment and New imaging analysis reveals distinct features of the autistic brain

Global Health, Pediatrics, Public Safety, Research, Stanford News, Women's Health

Empowerment training prevents rape of Kenyan girls

Empowerment training prevents rape of Kenyan girls

Adolescent girls in the slums of Nairobi, Kenya, are frequent targets of sexual harassment and assault: Nearly one in five of them is raped each year. When these crimes are perpetrated against Nairobi’s teen girls, they’re often expected to react with shame and silence.

But a small non-governmental organization, No Means No Worldwide, has a strategy to change that. The co-founders, Jake Sinclair, MD, and Lee Paiva, an American husband-and-wife team, developed a curriculum of empowerment training to teach girls that it’s OK to say “no” to unwanted sexual advances. The training also gives girls specific verbal and physical skills to defend themselves, as well as information about where to go for help after a rape or other sexual assault.

The results are impressive. Stanford researchers who work with Sinclair and Paiva report today in Pediatrics that the empowerment training cut annual rates of rape by more than a third. Among the group of 1,978 girls trained during the study, more than half used their new knowledge to fend off attempted rape, and 65 percent stopped instances of harassment, halting hundreds of incidents.

From our press release about the research:

“Clearly, girls should never be placed in these situations in the first place,” said Clea Sarnquist, DrPH, the study’s lead author and a senior research scholar in pediatrics at Stanford. Changing males’ attitudes and behavior about assault is an important area for the team’s current and future work, she said. “But with such a high prevalence of rape, these girls need something to protect them now. By giving them the tools to speak up and the knowledge that ‘I have domain over my own body,’ we’re giving them the opportunity to protect themselves.”

The video above, one of a series of testimonials that No Means No Worldwide has collected from Nairobi girls, shows the power of that sense of domain over one’s body. In the video, a schoolgirl named Catherine tells how she stopped a male student from harassing her. When the video begins, it’s impossible not to notice how young and vulnerable she seems. But then she recounts how, when this boy followed her and demanded sex, she remembered her self-defense classes.

“I stood and maintained eye contact,” she says in the video. “I warned him that day and told him he should never in his life dare follow me.”

As she says the words, her demeanor transforms: She draws herself up straight, looks directly in the camera, and raises her index finger in a gesture of commanding attention.

Maryanne Wangui, a young Kenyan woman who recorded many of the testimonials, said something to me that resonates with Catherine’s account and sticks in my mind: “If you give girls the right skills, they know what to do. It doesn’t matter the age of the girl or the size of the girl; they’re all powerful inside.”

Previously: Self-defense training reduces rapes in Kenya
Video courtesy of No Means No Worldwide

Clinical Trials, Dermatology, Pediatrics, Research, Stanford News

Using Viagra to treat a rare childhood deformity: A research update

Using Viagra to treat a rare childhood deformity: A research update

Researchers at Lucile Packard Children’s Hospital Stanford are investigating a surprising treatment for a rare and potentially dangerous childhood deformity. As I’ve described previously, pediatric dermatologist Al Lane, MD, and his colleagues are studying the drug sildenafil – better known by its trade name, Viagra – as a treatment for lymphangioma. The condition, an overgrowth of the body’s lymph vessels, can cause disfigurement and even threaten children’s lives if the deformity impinges on essential body structures such as the airway.

“It can be lethal in 10 percent of people or more, and the problem is, we don’t know what’s the best treatment,” Lane told me.

Other treatments, such as surgery and sclerotherapy, are less effective than doctors would like: Afterward, the deformity often grows back.

A new publication from Lane’s team appeared this week in the Journal of the American Academy of Dermatology, reporting on the first seven patients to have their lymphangiomas treated with sildenafil. Though the idea of giving this drug to children might seem startling, it has a good safety profile and is already used in kids who have a form of high blood pressure in the lungs called pulmonary arterial hypertension. Lane realized that the medication might work for both PAH and lymphangioma when he treated a child with both conditions who was receiving the drug.

The new study shows mixed results. Six of the seven children responded to the medication, though not all responses were equally strong. One child’s deformity became worse while taking the drug. The team is now planning a larger, placebo-controlled, blinded study to investigate why they saw these differences.

“If we can identify which patients respond to sildenafil, we may get a better idea for the molecular mechanism of how it helps, and that could help us understand the disease more,” Lane said.

His team has applied for an orphan disease grant through the National Institutes of Health and the U.S. Food and Drug Administration and will find out in the fall if they’ve been funded.

Previously: Viagra may treat rare childhood deformity

Genetics, Ophthalmology, Pediatrics, Research, Stanford News

Crying without tears unlocks the mystery of a new genetic disease

Crying without tears unlocks the mystery of a new genetic disease

LittlePackardGirlSometimes one tiny clue holds the key to a baffling medical mystery. That was the case for a San Francisco Bay Area child whose family and doctors struggled for the first three years of her life to pinpoint the cause of her developmental delays and neurologic, muscle, eye and liver problems. The essential clue? Grace Wilsey doesn’t make tears when she cries.

Grace’s combination of symptoms didn’t fit any known condition. Her team of caregivers at Lucile Packard Children’s Hospital Stanford, led by pediatric geneticist Gregory Enns, MB, ChB, strongly suspected that she had an as-yet-undiscovered genetic disease. Several genetics experts at Stanford helped sequence her genome, then came up with a list of eight mutated genes that might be responsible for her symptoms. They ranked the genes in order of likelihood that each was involved and began working down the list to try to pinpoint the culprit.

At the bottom of the list was a gene called NGLY1, which normally codes for N-glycanase 1, a housekeeping enzyme that helps cells break down and recycle mis-folded proteins. Part way through the investigation of the list of eight suspect genes, Grace’s parents, Matt and Kristen Wilsey, contacted a team at Baylor College of Medicine that had also previously performed whole genome sequencing on Grace and consulted on Grace’s case. A postdoctoral associate there, Matthew Bainbridge, PhD, reran Grace’s raw sequence data against the latest algorithms. NGLY1 jumped to the top of the candidate list of what was causing Grace’s underlying condition. As a next step, Dr. Bainbridge searched the scientific literature and found something so new that the Stanford researchers hadn’t yet run across it: a report of one child with suspected NGLY1 deficiency. From our press release about the discovery:

Bainbridge read in the medical literature of another child, studied at Duke University, whose caregivers there suspected his unusual symptoms were tied to an NGLY1 gene defect. But without a second patient for comparison, they weren’t sure.

As part of his detective work, Bainbridge emailed Kristen Wilsey to ask if Grace produced tears when she cried. Wilsey replied that although Grace’s eyes were moist, she never really made tears. Bainbridge wrote back, “I think I have it.”

“My heart jumped out of my chest,” Wilsey said. The first patient identified with NGLY1 deficiency, it turned out, also did not make tears, and the same characteristic has since been observed in seven of the eight children with NGLY1 gene defects whom the researchers have identified.

The scientific implications of the diagnosis are profound: Researchers can start looking for treatments or a cure. So far, the way that malfunctioning N-glycanase 1 causes the children’s symptoms is not understood, so unraveling the connection is a large area of focus for scientists.

They can also look for variants of the disease, Enns told me. “We are likely detecting the most severe form of NGLY1 deficiency – ascertainment bias – and it is quite possible that more mild forms of the disease exist,” he said. The first eight children found with NGLY1 deficiency are described in a new scientific paper publishing today in Genetics in Medicine; Enns and Bainbridge are both primary authors. Of the children, six have the same mutation in their NGLY1 gene and (probably not coincidentally) also share a very severe manifestation of the disease. Two children, including Grace, have different NGLY1 mutations and also have less severe disease, a finding that hints that other children with as-yet-unexplained developmental delays may also have less-severe variants of NGLY1 deficiency.

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Obesity, Parenting, Pediatrics, Research

Feeding practices and activity patterns for babies vary with families’ race and ethnicity, study shows

Feeding practices and activity patterns for babies vary with families' race and ethnicity, study shows

4361756526_774638516a_zWhen and how does childhood obesity begin? The question is a big challenge for researchers, who have observed that more than a quarter of US children aged 2 to 5 are now obese. That’s worrying because of links between obesity, heart disease and diabetes.

To help find answers, a new study is following babies and their parents from age 2 months to 2 years, tracking the babies’ growth and the families’ habits around feeding and activity for their little ones. Researchers at four centers around the country have recruited more than 800 baby-parent pairs to participate. The subjects are ethnically diverse and come mostly from low-income households, with 86 percent receiving Medicaid.

Today in Pediatrics, the scientists report the first findings from the project, an analysis of baseline data collected when the babies were 2 months old. The researchers found striking differences in feeding practices and activity patterns along racial and ethnic lines, suggesting that perhaps future efforts to prevent childhood obesity should be culturally tailored for different groups. Stanford’s Lee Sanders, MD, is one of the authors of the new paper, though none of the data was collected at Stanford.

Among the findings, Hispanic parents were more likely to encourage babies to finish a bottle and reported less tummy time than white parents; black parents were more likely to put babies to bed with a bottle, prop a bottle in front of a baby with a blanket (instead of holding it as the baby ate), and reported more TV watching for their babies than white parents. The differences persisted after the data was adjusted for possible confounding factors such as family income. It’s not clear whether all of these behaviors will be connected to higher obesity rates, but later reports from the same study will give more information about that.

In the study’s discussion, the researchers write:

If these behaviors are truly “obesogenic,” however, families from all races and ethnicities studied need early counseling, and the findings here also underscore the likely need for culturally sensitive health behavior counseling during early infancy. Particularly actionable are the specific behaviors that may be most sensitive to culturally adapted interventions: (1) infant exposure to television and other visual media; (2) breastfeeding initiation and exclusivity; and (3) encouraging infants to finish bottles.

Previously: Childhood obesity a risk for imminent heart problems, research shows, Sugar intake, diabetes and kids: Q&A with a pediatric obesity expert and Nutrition and fitness programs help East Palo Alto turn the tide on childhood obesity
Photo by dogs & music

Clinical Trials, Immunology, Pediatrics, Research, Stanford News

Simultaneous treatment for several food allergies passes safety hurdle, Stanford team shows

Simultaneous treatment for several food allergies passes safety hurdle, Stanford team shows

milk and eggsLiving with one food allergy is a challenge; living with more than one can make ordinary activities such as eating at a restaurant feel downright impossible.

That’s because the standard medical advice for the 4 million Americans with food allergies is to avoid all of your allergy triggers, all the time – and, by the way, make sure you always carry injectable epinephrine in case you accidentally eat something contaminated with a food that triggers anaphylactic shock.

So it will be welcome news to these food-allergy sufferers to hear that a Stanford team is making progress on a new way to help them. In research published today in the journal Allergy, Asthma & Clinical Immunology, a team led by Kari Nadeau, MD, PhD, found that an experimental treatment already being widely tested for single food allergies, called oral immunotherapy, could be modified so that patients can be desensitized to multiple food allergens at the same time. The results now being reported are the products of a pair of phase-1 safety trials.

In our press release about the findings, Nadeau explained why she wanted to develop the new therapy:

“Parents came up to me and said things like, ‘It’s great that you’re desensitizing children to their peanut or milk allergies, but my daughter is allergic to wheat, cashews, eggs and almonds. What can you do about that?’” said Kari Nadeau, MD, PhD, associate professor of pediatrics at the medical school and an immunologist at Stanford Hospital & Clinics and Lucile Packard Children’s Hospital Stanford. Nadeau is the senior author of the new study.

… [O]ral immunotherapy is still experimental and quite slow: In prior studies, patients took as long as three years to become desensitized to one food. Being desensitized to several foods, one at a time, could prospectively take decades. Yet Stanford researchers succeeded in safely desensitizing patients to several food allergens at once and were able to speed up desensitization by supplementing oral immunotherapy with injections of omalizumab (brand name Xolair).

With omalizumab, patients were desensitized to up to five of their allergens in a median of 18 weeks; without the medication, the same process took a median of 85 weeks, the research team found. The published results add weight to the anecdotal findings from three of Nadeau’s patients who participated in the trial and shared their experience in a story in the New York Times magazine last spring.

The researchers stress that the treatment is still experimental and must be performed in a hospital setting, but they are excited by the next step in the process: a phase-2 trial to evaluate the therapy more rigorously in a larger number of patients. The phase-2 trial will be conducted at Stanford, where recruitment of new patients has already begun, and at four other centers across the country, which will begin recruiting patients in the coming months. Individuals who are interested in learning more about participating in the new studies can check the federal clinical trials website for opportunities in their region.

Previously: Researchers show how DNA-based test could keep peanut allergy at bay, A mom’s perspective on a food allergy trial and Searching for a cure for pediatric food allergies
Photo by Logan Brumm Photography and Design

Patient Care, Research, Stanford News, Technology

Automated safety checklists prevent hospital-acquired infections, Stanford team finds

Automated safety checklists prevent hospital-acquired infections, Stanford team finds

inserting central line - smallPilots, astronauts and workers in other high-risk industries follow rigorous safety checklists to help them avoid hazards. Checklists have shown potential to reduce risk in health care, too, but the challenge is figuring out how to incorporate them into physicians’ and nurses’ work flow.

A Stanford team has built a solution: an automated checklist that pulls data directly from patients’ electronic medical records and pushes alerts to caregivers. The checklist, and a dashboard-style interface they used to interact with it, caused a three-fold drop in the rates of a serious type of hospital-acquired infection, the team found. The work has just been published in Pediatrics.

From our press release about the study:

“Electronic medical records are data-rich and information-poor,” said Natalie Pageler, MD, the study’s lead author. Often, the data in electronic medical records is cumbersome for caregivers to use in real time, but the study showed a way to change that, said Pageler, who is a critical care medicine specialist at the hospital and a clinical associate professor of pediatrics. “Our new tool lets physicians focus on taking care of the patient while automating some of the background safety checks.”

Working in the pediatric intensive care unit at Lucile Packard Children’s Hospital Stanford, the researchers focused on bloodstream infections that occur via central lines, which are catheters inserted in major veins. The automated alerts were designed to help physicians and nurses follow an established set of best practices for caring for central lines. For example, alerts were generated when the dressing on a patient’s central line was due to be changed.

The drop in the rate of central line infections – from 2.6 to 0.7 infections per 1,000 days of central line use – not only protected patients from harm; it also saved money. The team estimated that the savings in the pediatric intensive care unit were about $260,000 per year.

Next, the researchers hope to adapt the automated checklists to other uses, such as helping to guide the recovery of patients who have received organ transplants.

Previously: More than a manual: Stanford’s crisis checklist helps those working in the OR, What health-care providers can learn from the nuclear industry and Sully Sullenberger talks about patient safety
Photo by Jocelyn Augustino/FEMA Photo Library

Pediatrics, Public Health, Stanford News

Stanford physician leading efforts to track emerging polio-like illness in California children

Stanford physician leading efforts to track emerging polio-like illness in California children

Sofia JarvisJessica Tomei remembers the exact moment her daughter’s arm stopped functioning.

It had been a rough week. Sofia Jarvis, Tomei’s then-two-year-old, had been sick with a respiratory illness. Tomei and Sofia were leaving the pediatrician’s office with a pneumonia diagnosis and a prescription for antibiotics when, on the way out, Sofia reached for a toy.

“Her left arm, in mid grasp, stopped working,” Tomei said.

The next day, when Sofia was still not using her arm, Tomei and husband Jeff Jarvis took her back to the doctor. An MRI showed a lesion in Sofia’s spinal cord. At first, she was diagnosed with transverse myelitis, a form of paralysis from which some patients recover. But when the family eventually found their way to pediatric neurologist Keith Van Haren, MD, at Lucile Packard Children’s Hospital Stanford, he had bad news.

“Dr. Van Haren immediately said, ‘She probably will not get back the function of her arm,’” Tomei recalled.

Sofia’s case fit into a pattern that Van Haren and other neurologists around California had begun to observe: Since late 2012, about 20 children in the state have developed sudden-onset, permanent paralysis that looks similar to polio. Van Haren is the primary author of an abstract that describes five of the cases, which will be presented at the annual meeting of the American Academy of Neurology, April 26 to May 3 in Philadelphia.

From an AAN press release about the abstract:

“Although poliovirus has been eradicated from most of the globe, other viruses can also injure the spine, leading to a polio-like syndrome,” said case report author Keith Van Haren, MD, with Stanford University in Palo Alto, Calif. and a member of the American Academy of Neurology. “In the past decade, newly identified strains of enterovirus have been linked to polio-like outbreaks among children in Asia and Australia. These five new cases highlight the possibility of an emerging infectious polio-like syndrome in California.”

All five of the children in the report, including Sofia, had been immunized against polio. Two others in addition to Sofia had respiratory symptoms before the paralysis began. In two of the children, the physicians found evidence of infection with enterovirus-68, which is from the same family as polio virus. Although the team suspects this form of paralysis is infectious, they have not completely excluded other causes such as autoimmune disease. They are asking other physicians to report similar cases to the California Department of Public Health so that the cause of the disease can be pinpointed.

One concern, Van Haren added, is that physicians who have not heard of the new disease may make the same misdiagnosis of transverse myelitis that Sofia received, giving affected children and their families unrealistic expectations about the likelihood of recovery.

“The MRI can look similar but the clinical exam is very distinct,” he said. “There’s a knee-jerk reaction to just call it transverse myelitis. This is something else, and it’s quite bad.”

The good news is that the disease is very rare and likely to remain so. “There have been similar reports in Southeast Asia for many years, and the disease has rarely reached epidemic proportions there,” Van Haren said. “We want to temper the concern about this. It is not a massive epidemic.”

Meanwhile, families like Sofia’s will be watching closely to see what is uncovered by the upcoming research.

“We really want to know what caused this,” Tomei said, adding that the disease and a string of attempted treatments have been difficult for Sofia to go through. Now four, Sofia is generally healthy, but her arm is still paralyzed and the muscles have begun to atrophy.

Still, the family is keeping a positive outlook. Said Tomei, “We’re lucky it was just her left arm.”

Photo courtesy of Jessica Tomei and Jeff Jarvis

Pediatrics, Research, Stanford News

Stanford brain tumor research featured on “Bay Area Proud”

Stanford brain tumor research featured on “Bay Area Proud”

Stanford physician-scientist Michelle Monje, MD, PhD, conducts research on a particularly heartbreaking form of brain tumor. Diffuse intrinsic pontine glioma, a brain cancer of school-aged children, has a five-year survival rate of just one percent. The prognosis has not improved in decades, in part because the tumor is rarely biopsied in living patients, making tumor samples that scientists might study very scarce.

However, for the last five years, Monje’s lab has been culturing cancer cells from tumors donated by the families of recently deceased patients. The cell cultures, which Monje has been sharing with scientists around the country, could give valuable information about how the cancer grows and what drugs might work to fight it.

Today, NBC Bay Area featured a Gilroy family who just donated their daughter’s tumor. After 6-year-old Jennifer Kranz passed away earlier this week, Monje’s team began working to grow the tumor cells.

“If I can stop another mother, another grandmother, another aunt from feeling the way I do right now, I will,” said Jennifer’s mother, Libby Kranz, in the NBC story.

“I think it is the definition of selfless to donate tissue in this way,” Monje told NBC.

Previously: Emmy nod for film about Stanford brain tumor research – and the little boy who made it possible, Big advance against a vicious pediatric brain tumor and New Stanford trial targets rare brain tumor

Cancer, Infectious Disease, Pediatrics, Public Health, Research, Sexual Health

Girls don’t have riskier sex after the HPV vaccine

Girls don't have riskier sex after the HPV vaccine

HPV vaccineWhen the first vaccines were introduced against the human papillomavirus, some people worried that this anti-cancer vaccine would give young women the wrong idea. The vaccines, which protect against common cancer-causing strains of HPV, don’t guard against other sexually transmitted infections or unwanted pregnancies. But some parents and physicians thought that vaccine recipients might forgo condoms more often, have more sexual partners or otherwise engage in riskier sexual behaviors than women who were not vaccinated.

However, a study published today in Pediatrics says that’s not the case. According to the new research, young women don’t change their sexual behaviors after receiving the HPV vaccine. The researchers asked more than 300 girls and women, aged 13 to 21, about their risk perception and their sexual behaviors when they received their first dose of the HPV vaccine. They followed the group over time, repeating the questions 2 and 6 months later, when the vaccine’s booster shots were delivered.

“Most participants in this study did not perceive that they had a lower risk for STIs other than HPV, and most believed that safer sexual behaviors were still important,” the study’s authors wrote. Later, they add, “These findings contribute to the growing literature suggesting that HPV vaccination is unlikely to alter sexual risk behaviors in young women.”

I asked Stanford’s Sophia Yen, MD, for her take on the results. Yen provides HPV vaccinations in her role as an adolescent medicine specialist at the Teen and Young Adult Clinic at Lucile Packard Children’s Hospital Stanford. “The findings are not surprising and re-emphasize what other studies have shown,” she told me, adding that she hopes the study will be repeated in males, since boys have now begun receiving the HPV vaccine, too.

In the meantime, Yen plans to continue using this and other scientific evidence to reassure parents about the value of the vaccine. “I hope that the findings of this study and its many other predecessors will become widely known to parents and other non-adolescent medicine specialists who see adolescents, and to policymakers,” she said. “Let’s prevent STDs and cervical cancer together.”

Previously: Study shows racial disparities in HPV vaccination, Packard Children’s adolescent and young-adult specialist offers tips for college-bound students, HPV-associated cancers are rising, HPV vaccination rates still too low, new national report says and Only one-third of teenage girls get HPV vaccine to prevent cervical cancer
Photo by wintersoul1

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