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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

Autism, In the News, Pediatrics, Research

Using theater’s sensory experiences to help children with autism

Using theater's sensory experiences to help children with autism

Gesamkunstwerk, my favorite German word and a term commonly associated with the operas of Richard Wagner, can be translated as a “total work of art” playing to many of the senses and synthesizing numerous art forms. The word came to mind as I read about a pilot study using theater as an environment for children with autism-spectrum disorders  to explore “communication, social interaction, and imagination skills – the ‘triad of impairments’ seen in autism,” a New Scientist piece notes, “engaging all the children’s senses at once.”

Twenty-two children ages 7-12 attended one weekly 45-minute session for 10 weeks involving improvisation exercises led by trained performers in enclosed make-believe environments such as a forest or outer space.

From the piece:

As well as looking at whether behaviours used to diagnose autism changed after the drama sessions, the researchers also assessed emotion recognition, imitation, IQ and theory of mind – the ability to infer what others are thinking and feeling. Subjective ratings were also gathered from parents and teachers and follow-up assessments were conducted up to a year later.

At the early assessments, all children showed some improvement. The most significant change was in the number of facial expressions recognised, a key communication skill. Nine children improved on this. Six children improved on their level of social interaction. The majority of these changes were also seen at the follow-up assessments.

The project’s lead psychologist, David Wilkinson, PhD, at the University of Kent, told New Scientist, ”It’s an opportunity for children to create their own narratives in an unconstrained, unfamiliar environment.” He continued, “They find this empowering, and we know from the psychology literature that individuals who are empowered enjoy increased attention skills and an improved sense of well-being.”

Previously: Making museums more inviting for autistic children and their familiesStanford study reveals why human voices are less rewarding for kids with autismDirector of Stanford Autism Center responds to your questions on research and treatment and A mother’s story on what she learned from her autistic son

Autoimmune Disease, Chronic Disease, Patient Care, Pediatrics

A wake-up call from a young e-patient: “I need to be heard”

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often chronic diseases share their unique stories. Our latest comes from 15-year-old Morgan Gleason, who lives with the autoimmune disease juvenile dermatomyositis. 

Before June 18, 2010, the day I was diagnosed, I knew the medical system the way that most kids do. I went to the doctor for immunizations, physicals, sore throats and bones that might be broken. Then, I developed a rash on my joints. I started sleeping more than normal, was very weak in my muscles, and experienced frequent stomachaches and headaches.

At the age of 11, after a year of these symptoms, I was diagnosed with a rare autoimmune disease called juvenile dermatomyositis. I suddenly was in a whole new medical system. I had to learn to swallow pills, wait for hours in doctors offices, spend nights in the hospital, worry about what was happening, deal with some not-so-nice doctors and nurses, and endure a lot of pain. I also watched my parents get frustrated with figuring out medical bills and trying to understand all of the claim statements and appeal denials.

Now I take 21 pills a day, get two infusions a month by an IV, and give myself an injection once a week. I have more specialists than my grandparents, and I spend a lot of time as a patient.

This January, I was hospitalized for the second time in four months for meningitis due to a reaction from a treatment I received. After four days of little sleep and an excruciating headache, I made a video about my hospital experience and posted it online. To my surprise, the video got a lot of attention. Forbes, Time, the Huffington Post and other outlets wrote about it. I believe that the video was popular because my experience was a common one and struck a nerve with others.

I am appreciative of the care I have been given. I love the hospital where I get my treatment, and I think it’s a great hospital. The medical students, residents, attending physicians, and specialists are great doctors. The nurses are also really great. This is not an issue with the individual people or hospitals. The issue is much bigger, and it’s the way the system as a whole is designed.

My video had a few main points. I was frustrated that I couldn’t get any rest in the hospital. The system is designed around the schedules of the doctors and the desire to discharge patients by noon instead of around the circumstances and needs of the patient. Second, the doctors come in individually instead of coming together and addressing all the concerns at one time. Third, when patients are awoken from deep sleep, they’re not going to be as engaged as they would be when they are alert and comfortable. Finally, patients, and even children and teenagers, appreciate having the doctor talk with them instead of having the doctors talk over them or away from them in the hallway.

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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

Autism, In the News, Pediatrics, Research, Stanford News

Inspired by his autistic son, a Stanford researcher works to understand the biochemistry of autism

Inspired by his autistic son, a Stanford researcher works to understand the biochemistry of autism

dolmetschIn a Q&A published today in the New York Times, Stanford neurobiologist Ricardo Dolmetsch, PhD, tells reporter Claudia Dreifus that his immediate reaction to learning his son was diagnosed with autism was, “We’re not going to leave any stone unturned to help him.”

Leaving no stone unturned included changing the focus of his research to better understand the biochemistry of autism and leading an effort to create a technique that involves reprogramming skin cells from autistic children into neurons. As reported previously on Scope, this approach allows scientists to better study brain function in children with autism.

Dolmetsch, who is currently on leave from Stanford and working at Novartis, tells Dreifus that his main goal is to develop new pharmaceutical therapies for autism. When she asked him how he identifies patients to participate in his research, he responded:

Through social media. We’re often interested in groups or families who have specific kinds of mutations. Some of them are rare — 5,000 people worldwide.

So we have a committee that decides what’s the next mutation we’re going to work on. Then we find children with it. It used to be we’d spend half of our budget locating people. Now, we go to the families with a Facebook page for people with X, Y, or Z mutation. Then I’ll post a call. Parents will come forward.

The aim is to develop a database of the mutations we think are causative of the neuropsychiatric diseases. If we can get samples through stem-cell-derived neurons and create a library of them, we could change the way the diseases are diagnosed.

Previously: Using stem cells to advance autism research, Stanford Magazine spotlights scientists’ efforts to untangle the root causes of autism and Research on autism is moving in the right direction
Photo by Steve Fisch

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, Global Health, Infectious Disease, Pediatrics, Stanford News

Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial

Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial

dollar bill 2Nearly every child in the world has been infected with rotavirus at least once by the age of five. But kids in poor countries get the worst of it. Rotavirus mortality is low in the developed world, but in low-income countries it’s a killer, accounting for 85 percent of the estimated 180,000 to 400,000 annual deaths caused by the pathogen.

The disparity exists for at least two reasons.

First, widespread malnutrition results in a different epidemiology. For example, 70 percent of rotavirus hospitalizations in India happen the first year of life, compared with 40 percent in high- and middle-income countries.

Second, price. Vaccination is second only to gaining access to potable water as a low-cost, high-payoff  strategy for ensuring children’s health. But many vaccines are far too pricey for families living on incomes in the neighborhood of $1,500 per year. As a result, most childhood deaths from vaccine-preventable diseases happen in low-income countries. India has the most rotavirus deaths in the world, estimated at about 75,000-122,000 per year (close to a quarter of the worldwide total.)

So it’s great news that a new rotavirus vaccine developed by Indians for Indians has leaped the safety and efficacy thresholds of a late-stage clinical trial, in which more than 6,500 Indian infants were inoculated, and will likely become available in that country for less than a dollar a dose. (The full immunization procedure requires three separate doses.)

The results appear in a study just published in The Lancet and co-authored by a team including veteran rotavirus-vaccine developer Harry Greenberg, MD. An accompanying perspective piece co-written by Greenberg, who also directs the Stanford Center for Clinical and Translational Research and Education, states:

[P]roof of the efficacy of the… vaccine against a disease that affects almost every child in India, leads to millions of clinic visits and hundreds of thousands of hospital admissions, and kills roughly one child in every 175-200 born in India before their fifth birthday is cause for celebration.

The new vaccine was the first to be fully tested for efficacy in a randomized, double-blind, placebo-controlled clinical trial in India. Interestingly, its development began with the discovery, by an Indian pediatrician, that newborns were getting rotavirus infections in the hospital but not getting sick. The strain they were infected with turned out to be an attenuated mutant virus that turns on the body’s immune response without causing symptoms: in short, the ideal vaccine candidate.

Ultimately spearheaded by a young Indian biotechnology company, Bharat Biotech, the effort to capitalize on this promising episode of serendipity drew financial support from the Bill & Melinda Gates Foundation and technical assistance from the Government of India’s Department of Biotechnology, the United States’ Centers for Disease Control and Prevention, and Stanford, among others.  This international team of collaborators then spent more than 15 years turning the promise into a reality.

Previously: Trials, and tribulations, of a rotavirus vaccine
Photo by David Guo

Parenting, Patient Care, Pediatrics, Stanford News

Children’s hospital volunteers snuggle infants to soothe tiny patients and reassure their parents

Children's hospital volunteers snuggle infants to soothe tiny patients and reassure their parents

Calling all cuddlers! As previously written about here and in the most recent  Stanford Medicine Newsletter, volunteers Pat Rice and Claire Fitzgerald have been holding and soothing infants at Lucile Packard Children’s Hospital Stanford for 16 years, providing comfort both to the tiny patients and their parents. Rice and Fitzgerald, Ronald Cohen, MD, and sweet babies were featured on ABC’s World News with Diane Sawyer in the segment above.

Previously: Paying kindness forward through infant-cuddling“I opened the doors:” A look back at two special babies and Neonatologist celebrates 50 years of preemie care

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