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Autism, Parenting, Pediatrics, Research, Stanford News

Parents can learn autism therapy in groups to improve kids’ verbal skills, Stanford study shows

Parents can learn autism therapy in groups to improve kids' verbal skills, Stanford study shows

HoldingHandsAutism is more than twice as common than it was 15 years ago. But the number of clinicians who treat the developmental disorder is growing more slowly than the number of new cases, prompting caregivers to look for novel ways to share their expertise as widely as possible.

One possible approach: Teach groups of parents an autism therapy they can deliver at home. A new study from Stanford and Lucile Packard Children’s Hospital Stanford, published today in the Journal of Child Psychology and Psychiatry, found that small groups of parents could learn to deliver a scientifically validated autism treatment to their own children in a short series of classes.

The therapy, called pivotal response training, which has been validated in several prior studies, was targeted to kids’ language skills. The therapy gives parents a structured method for nurturing children’s verbal skills during everyday interactions.

The approach of having parents give treatment is meant to complement, not replace, one-on-one therapy with autism professionals. But it can still be valuable to children and their families, as our press release explains:

“There are two benefits: The child can make progress, and the parents leave the treatment program better equipped to facilitate the child’s development over the course of their daily routines,” said study co-author Grace Gengoux, PhD, clinical assistant professor of psychiatry and behavioral sciences and a psychologist specializing in autism treatment at the hospital. “The ways that parents instinctually interact with children to guide language development may not work for a child with autism, which can frustrate parents. Other studies have shown that learning this treatment reduces parents’ stress and improves their happiness. Parents benefit from knowing how to help their children learn.”

… To use the treatment for building language skills, parents identify something the child wants and systematically reward the child for trying to talk about it. For instance, if the child reaches for a ball, the parent says, “Do you want the ball? Say ‘ball.’”

“The child might say ‘ba,’ and you reward him by giving him the ball,” [lead author Antonio] Hardan, MD, said. “Parents can create opportunities for this treatment to work at the dinner table, in the park, in the car, while they’re out for a walk.”

The researchers are now following up with studies that will give them more information about which children and families are most likely to benefit from this therapeutic approach.

Previously: Using Google Glass to help individuals with autism better understand social cues, Using theater’s sensory experience to help children with autism and “No, I’m not ready yet”: A sister’s translation for her brother with autism
Photo by Wilson X

Cancer, Genetics, Medicine and Society, Research, Stanford News, Women's Health

Screening could slash number of breast cancer cases

Screening could slash number of breast cancer cases

dna-163466_1280Should every newborn baby girl be genetically screened to prevent breast cancer? Obviously, that isn’t cost-effective — yet. But if it were, would it be worthwhile?

A previous study said no. But research published today in Cancer Epidemiology, Biomarkers & Prevention by Stanford researchers suggests otherwise.

Led by senior author Alice Whittemore, PhD, the team examined 86 gene variants known to increase the chances of breast cancer. They created a model that accounted for the prevalence of each variant and the associated risk of breast cancer. Each possible genome was then ranked by the likelihood of developing breast cancer within a woman’s lifetime.

“It was quite a computational feat,” Whittemore told me.

Working with Weiva Sieh, MD, PhD; Joseph Rothstein, PhD; and Valerie McGuire, PhD, the team found that women whose genomes ranked within the top 25 percent of risk include 50 percent of all future breast cancers. Those women would then have the opportunity to get regular mammograms, watch their diets and make childbearing and breast-feeding decisions with the awareness of their higher risk. Some women might even select, as Angelina Jolie did quite publicly, to have their breasts removed.

“The main takeaway message is we can be more optimistic than previously predicted about the value of genomic sequencing,” Whittemore said. “But we still have a way to go in preventing the disease.”

“Our ability to predict the probability of disease based on genetics is the starting point,” Sieh said. “If a girl knew, from birth, what her inborn risk was, she could then make more informed choices to alter her future risk by altering her lifestyle factors. We also need better screening methods and preventative interventions with fewer side effects.”

“We want to focus on those at the highest risk,” Whittemore said.

Previously: Despite genetic advances, detection still key in breast cancer, NIH Director highlights Stanford research on breast cancer surgery choices  and Breast cancer awareness: Beneath the pink packaging 
Photo by PublicDomainPictures

Biomed Bites, Genetics, Research, Stanford News, Videos

DNA architecture fascinates Stanford researcher – and dictates biological outcomes

DNA architecture fascinates Stanford researcher - and dictates biological outcomes

It’s time for the next edition of Biomed Bites, a weekly feature that highlights some of Stanford’s most innovative research and introduces Scope readers to groundbreaking researchers in a variety of disciplines. 

It’s a puzzle that would delight puzzle master Will Shortz: How do you pack 2 meters of DNA into a container (the nucleus) only .000005 meters wide? Precisely, and according to plan, it seems. Stanford biophysicist Will Greenleaf, PhD, studies the architecture of the genome, building on the knowledge that DNA’s shape effects how a gene is expressed.

In the video above, Greenleaf, now an assistant professor of genetics, explains: “The genes have to be unpacked to be expressed. The mechanics of that are really fascinating.”

Greenleaf is a physics guy, earning a PhD in applied physics at Stanford to build on his undergraduate Harvard physics degree. He has also studied computer science and chemistry, bringing all of this knowledge to bear on demystifying the structure of DNA, and its RNA offshoots. Greenleaf and his team also develop new instruments needed to measure, see and manipulate DNA structure.

This is important for many reasons, but most directly to treat chromatinopathies, or diseases caused by the improper folding or structure of DNA and its associated proteins.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving forward biomedical innovation here.

Previously: Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using, “Housekeeping” protein complex mutated in about 1/5 of all human cancers, say Stanford researchers and Mob science: Video game, EteRNA, lets amateurs advance RNA research

Cardiovascular Medicine, Chronic Disease, In the News, Research, Science, Stanford News

How best to treat dialysis patients with heart disease

How best to treat dialysis patients with heart disease

523392_4923732760_zKidney failure patients on dialysis often have other chronic diseases – heart disease topping the list. They’re prescribed an average of 12 pills a day by physicians, according to Stanford nephrologist Tara Chang, MD, and they spend three-to-four hours at a treatment center three times a week connected to an artificial kidney machine.

For Chang, this makes it all the more important that any medication she prescribes for a patient on dialysis is both essential and effective.

The problem is, particularly in the case of treating kidney patients with heart disease, evidence-based treatment guidelines just aren’t available. Kidney doctors are left making best guesses based on guidelines written for the general population.

“Our patients might be different from patients not on dialysis,” said Chang. “Dialysis patients have a lot of heart disease, yet rarely does a cardiology study enroll patients on dialysis, so we just don’t know.”

This was part of the motivation behind Chang’s most recent study examining the use of anti-platelet drugs such as clopidogrel, one of the most commonly prescribed drugs for kidney patients. The researchers looked at the use of anti-platelet medications such as clopidogrel as treatment following stenting procedures to unclog arteries in the heart in 8,458 dialysis patients between 2007 and 2010. The data suggests that longer-duration of drug use may be of benefit to patients on dialysis who get drug-eluding stents but not those who get bare metal stents. Chang told me:

We found that for those who got drug-eluting stents who took the drug for 12 months compared to those who had stopped the drug at some earlier time point, there was a non-statistically significant trend towards lower risks of death and heart attacks. So for this group, following the same guidelines as for the general population may be appropriate. However, we found no indication of benefit with longer duration of anti-platelet drug use for patients on dialysis who got bare metal stents.

About half of the 400,000 patients in the U.S. on dialysis also have coronary artery disease, as referenced in the study. The number of those getting stents inserted to unclog arteries also has increased 50 percent in the past decade, the study states. The results of the study, while not definitive as to exactly how long doctors should prescribe the drug, does stress the need for more clinical research on patients with kidney failure to provide guidance on treatment strategies for heart disease.

“Because our study was not a randomized trial,” said Chang, “we tried to be very measured in how we interpreted the results. What it does point to is the fact that we can’t assume that what works in non-dialysis patients works in dialysis patients. Hopefully our study will help convince researchers to include our dialysis patients in their studies.”

The paper was published this week in the Journal of the American Heart Association.

Previously: Keeping kidney failure patients out of the hospitalStudy shows higher rates of untreated kidney disease among older adults and Study shows daily dialysis may boost patients’ heart function, physical health.
Photo by newslighter

Big data, Research

Using supercomputers to spot drug reactions

Using supercomputers to spot drug reactions

sierraSupercomputer[1]Remember the drugs Avandia and Vioxx? Avandia, an anti-diabetic drug released in 1999, worked wonderfully against diabetes. But it was also shown to increase users’ risk of heart attacks – a devastating side effect that slashed its sales. And Vioxx, an anti-inflammatory drug, was also linked to an increased risk of heart attacks and stroke, leading manufacturer Merck & Co. to withdraw it from the market.

These are just the drugs that grabbed the headlines. Other side effects from drugs kill more than 100,000 patients a year, according to a study in the Journal of the American Medical Association.

To slash that number, researchers at Lawrence Livermore National Laboratory put their supercomputers to work. They developed a program that determines whether a drug will form a bond with any of hundreds of proteins found in the human body. The research, published recently in the journal PLOS One, found that modeling based on the protein’s 3-D structure can pinpoint reactions more quickly than current methods.

From the LLNL release:

“We have discovered a very viable way to find off-target proteins that are important for side effects,” said Monte LaBute, PhD,  a LLNL researcher and the paper’s lead author. “This approach using high-performance computers and molecular docking to find adverse drug reactions never really existed before.”

The team’s findings provide drug companies with a cost-effective and reliable method to screen for side effects, according to LaBute. Their goal is to expand their computational pharmaceutical research to include more off-target proteins for testing and eventually screen every protein in the body.

“If we can do that, the drugs of tomorrow will have less side effects that can potentially lead to fatalities,” Labute said. “Optimistically, we could be a decade away from our ultimate goal. However, we need help from pharmaceutical companies, health care providers and the FDA to provide us with patient and therapeutic data.”

Previously: Mining data from patients’ charts to identify harmful drug reactions, Medical journal wins award for reporting on problems with Medtronic bone product and New research scrutinizes off-label drug use
Photo by Lawrence Livermore National Laboratory

Health Costs, Health Policy, Medicine and Society, Public Health, Research, Stanford News

Competition keeps health-care costs low, Stanford study finds

Competition keeps health-care costs low, Stanford study finds

The term market competition usually sparks a mental image of business suits and ties, not white coats and stethoscopes. Yet even the health-care system plays by the rules of the economic market place.

A new study, conducted by Stanford researchers Laurence Baker, PhD; M. Kate Bundorf, PhD; and colleagues, provides important evidence that less competitive health-care markets are more likely to charge higher prices for office visits. The article was published today in The Journal of the American Medical Association.

There’s a push through the private sector and through Medicare to encourage the formation of larger practices, which could improve the efficiency of the health-care system, said Bundorf.  The researchers sought to understand what effect these larger practices have on health-care spending.

To make the comparisons, the researchers used a database to establish the prices paid by PPOs for the most commonly billed office visits within 10 physician specialties. Next, they adapted a standard economic competition measure to calculate physician practice competition for different U.S. regions.

As I wrote in a release today:

Studying a measure that averaged prices across multiple types of office visits, in their most conservative model, being in the top 10 percent of areas with the least competition was associated with 3.5 to 5.4 percent higher mean price. The researchers point out that in 2011, privately insured individuals in the United States spent nearly $250 billion on physician services. In that context, these small percentage increases could translate to tens of billions of dollars in extra spending.

The study’s findings show the importance of developing policies that will encourage a balance between the quality of care and health-care spending. As Baker explained, “Sometimes it can be tempting to say our goals for the health care system should be only about taking care of patients and doing it as well as possible – we don’t want to worry about the economics. But the truth is we do have to worry about the prices because the bill does come even if you wish it wouldn’t.”

Previously: What’s the going rate? Examining variations in private payments to physicians

NIH, Research, Science Policy, Stanford News

Shake up research rewards to improve accuracy, says Stanford’s John Ioannidis

Shake up research rewards to improve accuracy, says Stanford's John Ioannidis

currencyLab animals such as mice and rats can be trained to press a particular lever or to exhibit a certain behavior to get a coveted food treat. Ironically the research scientists who carefully record the animals’ behavior really aren’t all that different. Like mice in a maze, researchers in this country are rewarded for specific achievements, such as authoring highly cited papers in big name journals or overseeing large labs pursuing multiple projects. These rewards come in the form of promotions, government grants and prestige among a researcher’s peers.

Unfortunately, the achievements do little to ensure that the resulting research findings are accurate. Stanford study-design expert John Ioannidis, MD, DSci, has repeatedly pointed out serious flaws in much published research (in 2005 he published what was to be one of the most highly-accessed and most highly-cited papers ever in the biomedical field “Why most published research findings are false”).”

Today, Ioannidis published another paper in PLoS Medicine titled “How to make more published research true.” He explores many topics that could be addressed to improve the reproducibility and accuracy of research. But the section that I found most interesting was one in which he argues for innovative, perhaps even disruptive changes to the scientific reward system. He writes:

 The current system does not reward replication—it often even penalizes people who want to rigorously replicate previous work, and it pushes investigators to claim that their work is highly novel and significant. Sharing (data, protocols, analysis codes, etc.) is not incentivized or requested, with some notable exceptions. With lack of supportive resources and with competition (‘‘competitors will steal my data, my ideas, and eventually my funding”) sharing becomes even disincentivized. Other aspects of scientific citizenship, such as high-quality peer review, are not valued.

Instead he proposes a system in which simply publishing a paper has no merit unless the study’s findings are subsequently replicated by other groups. If the results of the paper are successfully translated into clinical applications that benefit patients, additional “currency” units would be awarded. (In the example of the mice in the maze, the currency would be given in the form of yummy food pellets. For researchers, it would be the tangible and intangible benefits accrued by those considered to be successful researchers). In contrast, the publication of a paper that was subsequently refuted or retracted would result in a reduction of currency units for the authors. Peer review and contributions to the training and education of others would also be rewarded.

The concept is really intriguing, and some ideas would really turn the research enterprise in this country on its head. What if a researcher were penalized (fewer pellets for you!) for achieving an administrative position of power… UNLESS he or she also increased the flow of reliable, reproducible research? As described in the manuscript:

[In this case] obtaining grants, awards, or other powers are considered negatively unless one delivers more good-quality science in proportion. Resources and power are seen as opportunities, and researchers need to match their output to the opportunities that they have been offered—the more opportunities, the more the expected (replicated and, hopefully, even translated) output. Academic ranks have no value in this model and may even be eliminated: researchers simply have to maintain a non-negative balance of output versus opportunities. In this deliberately provocative scenario, investigators would be loath to obtain grants or become powerful (in the current sense), because this would be seen as a burden. The potential side effects might be to discourage ambitious grant applications and leadership.

Ioannidis, who co-directs with Steven Goodman, MD, MHS, PhD, the new  Meta-Research Innovation Center at Stanford, or METRICS, is quick to acknowledge that these types of changes would take time, and that the side effects of at least some of them would likely make them impractical or even harmful to the research process. But, he argues, this type of radical thinking might be just what’s needed to shake up the status quo and allow new, useful ideas to rise to the surface.

Previously: Scientists preferentially cite successful studies, new research shows, Re-analyses of clinical trial results rare, but necessary, say Stanford researchers  and John Ioannidis discusses the popularity of his paper examining the reliability of scientific research
Photo by Images Money

Immunology, Infectious Disease, Microbiology, Public Health, Research, Stanford News

Paradox: Antibiotics may increase contagion among Salmonella-infected animals

Paradox: Antibiotics may increase contagion among Salmonella-infected animals

cattleMake no mistake: Antibiotics have worked wonders, increasing human life expectancy as have few other public-health measures (let’s hear it for vaccines, folks). But about 80 percent of all antibiotics used in the United States are given to livestock – chiefly chickens, pigs, and cattle – at low doses, which boosts the animals’ growth rates. A long-raging debate in the public square concerns the possibility that this widespread practice fosters the emergence of antibiotic-resistant bugs.

But a new study led by Stanford bacteriologist Denise Monack, PhD, and just published in Proceedings of the National Academy of Sciences, adds a brand new wrinkle to concerns about the broad administration of antibiotics: the possibility that doing so may, at least  sometimes, actually encourage the spread of disease.

Take salmonella, for example. One strain of this bacterial pathogen, S. typhimurium, is responsible for an estimated 1 million cases of food poisoning, 19,000 hospitalizations and nearly 400 deaths annually in the United States. Upon invading the gut, S. typhimurium produces a potent inflammation-inducing endotoxin known as LPS.

Like its sister strain S. typhi (which  causes close to 200,00o typhoid-fever deaths worldwide per year), S. typhimurium doesn’t mete out its menace equally. While most get very sick, it is the symptom-free few who, by virtue of shedding much higher levels of disease-causing bacteria in their feces, account for the great majority of transmission. (One asymptomatic carrier was the infamous Typhoid Mary, a domestic cook who, early in the 20th century, cheerfully if unknowingly spread her typhoid infection to about 50 others before being forcibly, and tragically, quarantined for much of the rest of her life.)

You might think giving antibiotics to livestock, whence many of our S. typhi-induced food-poisoning outbreaks derive, would kill off the bad bug and stop its spread from farm animals to those of us (including me) who eat them. But maybe not.

From our release on the study:

When the scientists gave oral antibiotics to mice infected with Salmonella typhimurium, a bacterial cause of food poisoning, a small minority — so called “superspreaders” that had been shedding high numbers of salmonella in their feces for weeks — remained healthy; they were unaffected by either the disease or the antibiotic. The rest of the mice got sicker instead of better and, oddly, started shedding like superspreaders. The findings … pose ominous questions about the widespread, routine use of sub-therapeutic doses of antibiotics in livestock.

So, the superspreaders kept on spreading without missing a step, and the others became walking-dead pseudosuperspreaders. A lose-lose scenario all the way around.

“If this holds true for livestock as well – and I think it will – it would have obvious public health implications,” Monack told me. “We need to think about the possibility that we’re not only selecting for antibiotic-resistant microbes, but also impairing the health of our livestock and increasing the spread of contagious pathogens among them and us.”

Previously: Did microbes mess with Typhoid Mary’s macrophages?, Joyride: Brief post-antibiotic sugar spike gives pathogens a lift and What if gut-bacteria communities “remember” past antibiotic exposures?
Photo by Jean-Pierre

Chronic Disease, Health Costs, Infectious Disease, Research

Despite steep price tag, use of hepatitis C drug among prisoners could save money overall

Despite steep price tag, use of hepatitis C drug among prisoners could save money overall

pills-384846_640There’s nothing free about the revolution that’s shaking up hepatitis C treatment. A slew of newer drugs, including sofosbuvir, are nearly eliminating the virus with fewer side effects than the old standbys, pegylated interferon and ribavirin, which had limited effectiveness and caused fatigue, nausea and headaches. But at a cost of $7,000 a week, it seems obvious they are more expensive.

Not necessarily, however, says Jeremy Goldhaber-Fiebert, PhD. Working with colleagues including former Stanford graduate student Shan Liu, PhD, Goldhaber-Fiebert developed a model that examines the overall costs and benefits of treating hepatitis C with sofosbuvir rather than the traditional drugs in prisons. Prisoners are more likely than those in the general population to be infected with hepatitis C, a virus that attacks the liver, because it can be transmitted through intravenous drug use and unclean tattoos.

The researchers found that the high upfront cost saves money in later years by reducing the number of liver transplants and other more invasive treatments needed. In accordance with standard practices, this  study examined the overall societal cost without accounting for the source of the money. For example, the prison system’s are more likely to spend more money upfront, although savings might be recouped by Medicaid or other private insurers several decades later. From our release:

“Overall, sofosbuvir is cost-effective in this population, though its budgetary impact and affordability present appreciable challenges,” said Goldhaber-Fiebert,who is also a faculty member at Stanford’s Center for Health Policy/Center for Primary Care and Outcomes Research, which is part of the university’s Freeman Spogli Institute for International Studies.

Goldhaber-Fiebert called hepatitis C a “public health opportunity.”

“Though often not the focus of health-policy research, HCV-infected inmates are a population that may benefit particularly from a highly effective, short-duration treatment,” he said.

The research appears in this week’s Annals of Internal Medicine.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, A primer on hepatitis C and For patients with advanced hepatitis C, benefits of new drugs outweigh costs
Photo by stevepb

Patient Care, Research, Stanford News

Fewer transfusions means better patient outcomes, lower mortality

Fewer transfusions means better patient outcomes, lower mortality

blood transfusionBlood transfusion has been cited by the American Medical Association as one of the top five most overused therapies in the United States. Moreover, studies have shown that when there are fewer transfusions in a hospital setting, patients generally do better, as they’re not exposed to potential transfusion risks.

With that in mind, Stanford Health Care has made a concerted effort since 2009 to effectively reduce the number of patients who receive transfusions. Since that time, patient outcomes have improved, including lower mortality rates and length of stay in the hospital. Moreover, blood costs have been markedly reduced, a new study finds.

Between 2009 and 2013, the number of red blood cell units transfused annually at Stanford Health Care fell almost 24 percent – from 29,472 to 22,991. At the same time, mortality rates and length of stays decreased overall among hospital patients. The decline occurred despite the fact that the volume of patients receiving treatment was higher and patients came in with more complex medical problems, according to the researchers, led by Lawrence Goodnough, MD, a professor of pathology and medicine and director of the hospital’s transfusion service.

Goodnough helped implement a program that uses the hospital’s electronic medical record system to alert clinicians to blood-use guidelines and relevant medical literature whenever they request a transfusion. The physician is asked to explain the reason for the transfusion, prompting him or her to reconsider whether it is also needed. As a result, the overall percentage of patients transfused dropped from 21.9 percent in 2009 to 17 percent in 2013, the researchers reported.

The researchers more closely analyzed outcomes for 3,622 patients transfused before implementation of the system and some 10,500 patients who received transfusions after the change. In this group, mortality rates fell from 5.5 percent to 3.3 percent. Patients also spent less time in the hospital (down from 10 to 6.2 days) and were less likely to be readmitted within 30 days.

In the process, the hospital has saved some $1.62 million annually in costs over each of the four years, not including indirect costs, such as patient testing and administration of blood, the researchers calculated.

A similar 2011 study conducted at Lucile Packard Children’s Hospital Stanford found that the automated alerts saved the children’s hospital 460 unnecessary red blood cell transfusions and $165,000 in one year, while patients who needed transfusions still received them.

“For health care institutions, improved blood utilization is accompanied by improved quality of care as measured by decreased patient exposure to unnecessary red blood cell transfusions, decreased blood transfusion-related costs and improved patient outcomes,” authors of the latest study, which appears in the current issue of the journal Transfusion, concluded.

Previously: Stanford Hospital trims use of blood supplies and New issue of Stanford Medicine magazine asks, What do we know about blood?
Related: Against the flow: What’s behind the decline in blood transfusions?
Illustration by Jonathon Rosen

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