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Big data, Cardiovascular Medicine, Chronic Disease, Research, Science, Stanford News, Videos

Big data approach identifies new stent drug that could help prevent heart attacks

Big data approach identifies new stent drug that could help prevent heart attacks

Ziad Ali, MD, PhD, was a cardiovascular fellow at Stanford with a rather unique skill when a 6-year study published today online in The Journal of Clinical Investigation first began.

The multi-talented physician-scientist – who is now associate director of translational medicine at Columbia University Medical Center – had figured out a way to put tiny little stents into mice with clogged arteries as a PhD student.

The skill would become key as he and colleagues set out to find a better pharmaceutical for the drug-eluting stents that are used in combination with angioplasty to treat coronary artery disease. In order to prevent stent disease, the often serious medical problem caused by stents themselves, chemotherapy drugs were added to bare metal stents. But these drug-eluting stents have their own problems: The drugs work like “hitting a pin with a sledgehemmer,” as Ali describes it, often damaging the lining of the arteries which can lead to heart attacks. As a result, patients are required to take blood thinners for up to a year after the procedure to prevent clots.

“A lot of our patient population is on the elderly side with bad hips or diabetes,” Ali told me. “Once you get a drug-coated stent, you can’t have surgery for a year. And if you stop the blood thinners for any reason, you’re at risk of a stent clotting off. And that actually causes a heart attack. Stent thrombosis has a high mortality rate.”

By using a “big data” computational approach, learning about the genetic pathways involved in coronary artery disease, then testing the new theories on mice models in the lab, researchers were able to pinpoint a potential new treatment for patients: Crizotinib, a pharmaceutical approved by the FDA for treatment in certain cases of lung cancer.

“This could have major clinical impact,” Euan Ashley, MD, PhD, senior author of the study, who discusses the work alongside Ali in the video above, said.

Previously: Euan Ashley discusses harnessing big data to drive innovation for a healthier world, New computing center at Stanford supports big data, Trial results promising for new anti-clotting drug and A call to use the “tsunami of biomedical data” to preserve life and enhance health
Photo in featured entry box by Mark Tuschman

Chronic Disease, Imaging, Immunology, Neuroscience, Research, Stanford News

Patients' reaction to ME/CFS coverage in Stanford Medicine magazine

Patients' reaction to ME/CFS coverage in Stanford Medicine magazine

me-cfs-brain-zeineh

In the last few weeks, Stanford published two articles on chronic fatigue syndrome, a.k.a. myalgic encephalomyelitis, and the outpouring of positive feedback from ME/CFS patients has been tremendous. In my long-form Stanford Medicine story and video, I describe a young woman’s seven-year battle with the disease and the groundbreaking research being done by her physician, José Montoya, MD, and immunologist Mark Davis, PhD, to identify the biomarkers and root causes of ME/CFS. My colleague Bruce Goldman followed up with an elegantly written article describing the distinct differences between the brains of ME/CFS patients with those of healthy people, in a newly released study from this same research team.

While our primary job as medical science writers is to explain new research accurately, it’s a bonus to know that we captured the patient experience in a compassionate way, and that we have in some way eased their suffering with hope.

Here is a sampling of a few of these letters from around the world:

From British Columbia, Canada:
Thank you for an article that is very well done. I will be printing it for my MD and forwarding it to family and a few close friends because it captures this devastating illness so well. I will keep a copy for myself to remind me (on those dark days) that Dr. Montoya is in my corner.

From Sweden:
I would like to thank you for your very informative and interesting article! This kind of information of what research is going on at Stanford, etc., is very important for us patients with ME all over the world! There is a lot of disinformation coming out about this disease and I therefore very much appreciate your article and especially Dr. Montoya’s passionate engagement with this disease.

From Cali, Colombia:
Here in Cali, Colombia, the city of birth of Dr. Montoya, I feel very happy reading your excellent article, and learning the marvelous and difficult investigation performed by these brilliant scientists. I was moved to tears. Thank you.

From the San Francisco Bay Area:
I want to thank you very much for the powerful piece you wrote about ME/CFS. You tell the story in a very engaging way, which is so compelling. It’s not the usual doom/gloom/dark room story which my daughter and I have encountered frequently in what people write about ME/CFS. Family and friends with whom I have shared the article are appreciative of your writing so descriptively and articulately about all aspects of ME/CFS: the science, the inequity of research funding, the personal experience of a patient, the work of Drs. Montoya/Mark Davis/Holden Maecker.

From India:
Today I have gone through your article about Erin’s story. How she recovered from CFS had given me a ray of hope as I am also suffering from such an ailment for the last 6-8 years.

From Atlanta, Georgia:
I just read your beautifully written article on Immune System Disruption. First soccer caught my eye, then “swimming in the primordial soup of creative disruption” locked me in. I read every word … and I am going to spend the rest of the night in Atlanta copying [my internal medicine doctor] on the article.

From Australia:
Just wanted to thank you for your excellent article. It could really make a difference in raising awareness and I appreciate the quality of your writing. I have suffered from CFS/ME for many years in Australia and find the research project and your understanding very encouraging.

From the blogosphere:
I just wanted to thank you for taking the time to write such an in-depth, accurate article on our oft-ignored illness. Dr. Montoya is a hero within the ME/CFS community, but I didn’t know about the others at Stanford also working on ME/CFS — that gives me some hope for a better future! I plan to share your article on my ME/CFS blog and in several Facebook groups for ME/CFS that I belong to.

Previously: Some headway on chronic fatigue syndrome: Brain abnormalities pinpointedUnbroken: A chronic-fatigue patient’s long road to recovery, Deciphering the puzzle of chronic-fatigue syndrome and Stanford Medicine magazine traverses the immune system
Image, showing white matter differences between a ME/CFS patient sample an a healthy control, by Michael Zeineh/Stanford

Ask Stanford Med, Chronic Disease, Events, Health and Fitness

Examining the role of exercise in managing and preventing diabetes

Examining the role of exercise in managing and preventing diabetes

zumba

More than 29 million adults and children in the United States are living with diabetes, and it’s estimated (.pdf) that an additional 86 million Americans ages 20 years or older have prediabetes, putting them at increased risk of developing the disease.

The good news is that lifestyle modifications can be an effective method for managing or preventing diabetes. In recognition of National Diabetes Month, I reached out to Baldeep Singh, MD, a clinical professor at Stanford who focuses on chronic disease management, to discuss the importance of regular physical activity for patients diagnosed with diabetes and those working to limit their risk of developing the disease. This Thursday, Singh will explore the topic more in-depth during a Stanford Health Library event at the Arrillaga Alumni Center on campus, where attendees can also have their blood glucose checked. The discussion will also be webcasted for those unable to attend in person.

In this Q&A, Singh highlights scientific evidence showing that staying active has a beneficial effect on insulin sensitivity, and discusses the potential of exercise, in combination with other behavioral changes, to induce partial, or full, remission of type 2 diabetes.

How does regularly exercising help in preventing or delaying type 2 diabetes?

The benefit of exercise in preventing diabetes has been demonstrated in several studies. A meta-analysis of 10 studies of physical activity and type 2 diabetes reported a lower risk of developing diabetes with regular moderate physical activity, including brisk walking, compared with being sedentary

Additionally, in a subsequent prospective cohort study in men, either weight training or aerobic exercise for at least 150 minutes per week was associated with a lower risk of developing type 2 diabetes compared to those with  a control group who did no physical activity.

Why is engaging in physical activity important in managing type 2 diabetes?

In patients with type 2 diabetes, studies show that short-term exercise training improves insulin sensitivity just as it does in non-diabetics. In patients with type 2 diabetes treated with medication, exercise tends to lower blood glucose concentrations.

Exercise improves glycemic control in patients with type 2 diabetes, as illustrated by the findings of several meta-analyses of trials examining the effect of exercise on glycemic control in patients with type 2 diabetes. Exercise training reduces glycosylated hemoglobin (A1C) values by approximately 0.5 to 0.7 percentage points compared with control participants.

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Chronic Disease, Obesity, Parenting, Pediatrics

Getting a handle on screen time: tips for parents

Getting a handle on screen time: tips for parents

child watches TV

Most parents know that they should keep screen time to a minimum, but how much is too much? Moreover, with the advent of many educational apps for tablets and smartphones, it’s easy as a parent to get confused about managing their childrens’ use of televisions, computers and tablets. Watching “Frozen” for the hundredth time is clearly entertainment, but what about playing with a Dora the Explorer app that teaches vocabulary? Should that count against a child’s screen time “budget?”

The Lucile Packard Children’s Hospital Stanford blog, Healthier, Happier Lives, had a post earlier this week that offers concrete tips from Thomas Robinson, MD, MPH, director of Packard’s Center for Healthy Weight. Robinson notes that educational screen time doesn’t need to count toward entertainment screen time, which he recommends keeping to less than an hour a day. But he cautions that parents should distinguish between real educational programs and entertainment disguised as education.

He also says that it’s easier to get kids to follow screen-time rules if parents are judicious about their own screen use (this includes time in front of a computer or with a smart phone, as well as TV time). One of the key reasons to turn off the TV (and other screens) is to avoid bad habits associated with screen time like eating high-fat, high-sugar snacks, especially while in front of a TV or computer. Another is simply to get kids to move more and be more active.

The bottom line? Robinson says:

More than anything else, just having family rules about how much, what, when, where, and with whom is the most important step in making screen time and technology work for your family, instead of against it.

Previously: Examining the effects of family time, screen time and parenting styles on child behavior, Childhood obesity expert to parents: Reduce your child’s screen time and Study: Too much TV, computer could hurt kids’ mental health
Photo by Vidmir Raic

Aging, Chronic Disease, Clinical Trials, Immunology, Research, Stanford News

Is osteoarthritis an inflammatory disorder? New thinking gets clinical test

Is osteoarthritis an inflammatory disorder? New thinking gets clinical test

SM arthritis imageOsteoarthritis sort of comes with the territory of aging. If you live long enough, you’ll probably get it.

For those fortunate enough not to have a working acquaintance with the disease, I describe its onset in a just-published Stanford Medicine article, “When Bones Collide”:

You start to feel some combination of pain, stiffness and tenderness in a thumb, a knee, a hip, a toe or perhaps your back or neck. It takes root, settles in and, probably, gets worse. And once you’ve got it, it never goes away. Eventually, it can get tough to twist off a bottle cap or to get around, depending on the joint or joints affected.

All too many of us, of course, are perfectly familiar with the symptoms of osteoarthritis. An estimated 27 million people in the United States have been diagnosed with it. By 2030, due mainly to the aging of the population, the number will be more like 50 million. Anything so common is all too easy to look at as inevitable: basically, the result of the same kind of wear and tear on your joints that causes the treads on a commuter car’s set of tires to disappear eventually.

But Stanford rheumatologists Bill Robinson, MD, PhD, and Mark Genovese, MD, think that just may not be the way it works. Almost four years ago I wrote about Robinson’s discovery that osteoarthritis is propelled by a sequence of inflammatory events similar to ones associated with Alzheimer’s disease, cardiovascular disease, and type-2 diabetes. That discovery and a steady stream of follow-up work in his lab have spawned a clinical trial, now underway and led by Genovese, to see if a regimen of anti-inflammatory medicines that’s been shown to roll back osteoarthritis’s progression in mice can do the same thing in people.

That’s the kind of progress most of us could live without.

Previously: New thinking about osteoarthritis, older people’s nemesis and Inflammation, not just wear and tear, spawn arthritis
Illustration by Jeffrey Decoster

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

Autoimmune Disease, Chronic Disease, Immunology, Stanford News, Videos

Unbroken: A chronic fatigue syndrome patient’s long road to recovery

Unbroken: A chronic fatigue syndrome patient’s long road to recovery

“Fatigue is what we experience, but it is what a match is to an atomic bomb,” said Laura Hillenbrand, the author of Unbroken, about how it feels to live with chronic fatigue syndrome.

I recently finished a Stanford Medicine story and video (above) about another CFS patient, “Erin,” who asked that her real name not be used. After an acute illness in rural Mexico, Erin went from being an elite soccer player to one of the 17 million people worldwide who suffer from the condition.

Most people who acquire hit-and-run infections go back to their normal lives after a few days. But these patients don’t. They become virtual shut-ins, prisoners of a never-ending cycle of flu-like symptoms, many of them bedridden for years. CFS, also called myalgic encephalomyelitis or ME/CFS, has no known cause or cure, frustrating both patients and physicians.

What makes Erin’s CFS story somewhat rare is its happy ending. With the help of Stanford infectious disease expert José Montoya, MD, and cardiac electrophysiologist Karen Friday, MD, Erin is back to working fulltime and playing soccer.

“Dr. Montoya and doctors like him are heroes for taking up an unpopular disease and patients that most doctors shun,” said Lori Chapo-Kroger, a registered nurse and CEO of the patient charity, PANDORA Org. “He combines his medical expertise and a creative approach with a truly caring heart for suffering patients.”

Dr. Montoya is also collaborating with immunologist Mark Davis, PhD, on the Stanford Initiative on Infection-Associated Chronic Diseases, a research project using cutting-edge technologies to identify the biomarkers and root causes of ME/CFS. Working at the Human Immune Monitoring Center, team members are searching 600 blood samples for infectious microbes, inflammation-related molecules and genetic flaws. In addition, they’re conducting brain scans and physical exams to look for physical abnormalities among these patients.

Early results are promising — the team has discovered a number of measurable biological markers that indicate that ME/CFS patients may be suffering from out-of-control inflammation.

The team’s goal: To find out what is wrong with the immune systems of patients with infection-triggered diseases such ME/CFS and Lyme disease, then figure out how to help them get better.

Previously: Deciphering the puzzle of chronic fatigue syndrome

The HIMC is partially funded by Spectrum, Stanford’s NIH Clinical and Translational Science Award.

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

Big data, Chronic Disease, Immunology, Research, Stanford News

Out of hiding: Found lurking in public databases, type-2 diabetes drug passes early test

Out of hiding: Found lurking in public databases, type-2 diabetes drug passes early test

lurking 3Way too often, promising-looking basic-research findings – intriguing drug candidates, for example – go swooshing down the memory hole, and you never hear anything about them again. So it’s nice when you see researchers following up on an upbeat early finding with work that moves a potential drug to the next peg in the development process. All the more so when the drug candidate targets a massively prevalent disorder.

Type 2 diabetes affects more than 370 million people worldwide, a mighty big number and a mighty big market for drug companies. (Unlike the much less common type 1-diabetes, where the body’s production of the hormone insulin falters and sugar builds up in the blood instead of being taken up by cells throughout the body, in type-2 diabetes insulin production may be fine but tissues become resistant to insulin.) But while numerous medications are available, none of them decisively halt progression, much less reverse the disease’s course.

About two-and-a-half years ago, Stanford data-mining maven Atul Butte, MD, PhD, combed huge publicly available databases, pooled results from numerous studies and, using big-data statistical methods, fished out a gene that had every possibility of being an important player in type 2 diabetes, but had been totally overlooked. (For more info, see this news release.) Called CD44,  this gene is especially active in fat tissue of insulin-resistant people and, Butte’s study showed, had a strong statistical connection to type-2 diabetes.

Butte’s study suggested that CD44’s link to type-2 diabetes was not just statistical but causal: In other words, manipulating the protein CD44 codes for might influence the course of the disease. By chance, that protein has already been much studied by immunologists for totally unrelated reasons. The serendipitous result is that a monoclonal antibody that binds to the protein and inhibits its action was already available.

So, Butte and his colleagues used that antibody in tests they performed on lab mice bioengineered to be extremely susceptible to type-2 diabetes, or what passes for it in a mouse. And, it turns out, the CD44-impairing antibody performed comparably to or better than two workhorse diabetes medications (metformin and pioglitazone) in countering several features of type 2 diabetes, including fatty liver, high blood sugar, weight gain and insulin resistance. The results appear in a study published today in the journal Diabetes.

Most exciting of all: In targeting CD44, the monoclonal antibody was working quite differently from any of the established drugs used for type-2 diabetes.

These are still early results, which will have to be replicated and – one hopes – improved on, first in other animal studies and finally in a long stretch of clinical trials before any drug aimed at CD44 can join the pantheon of type-2 diabetes medications. In any case, for a number of reasons the monoclonal antibody Butte’s team pitted against CD44 is far from perfect for clinical purposes. But refining initial “prototypes” is standard operating procedure for drug developers. So here’s hoping a star is born.

Previously: Newly identified type-2 diabetes gene’s odds of being a false finding equal one in 1 followed by 19 zeroes, Nature/nurture study of type-2 diabetes risk unearths carrots as potential risk reducers and Mining medical discoveries from a mountain of ones and zeroes
Photo by Dan-Scape.co.uk

Chronic Disease, Pediatrics, Public Health, Stanford News

Diabetes self-management program helps at-risk teens and their families make healthier choices

Diabetes self-management program helps at-risk teens and their families make healthier choices

Diabetes_coaches_classThe prevalence of Type 2 diabetes among Americans ages 12 to 19 has grown from nine percent to 23 percent in less than a decade. In an effort to reduce U.S. adolescents’ diabetes risk, researchers at Stanford developed a school-based program where medical residents train healthy at-risk teens to be self-management coaches for family members diagnosed with Type 2 diabetes.

Researchers tested the initiative, called the Stanford Youth Diabetes Coaches Program, over the course of a year at three Bay Area high-schools serving primarily ethnic minority youth of low socioeconomic status. The study involved 97 adolescents – 49 student coaches and 48 non-participant students. Student coaches participated in an eight-week training course that was taught by family medicine residents and modeled after the Stanford University Diabetes Self-Management Program for adults. All participants completed pre- and post-study questionnaires and a select group of student coaches and family members gave in-depth interviews.

The program emphasized communication skills, problem solving and setting achievable goals using action plans. Beyond providing basic diabetes knowledge, the program also included guidance on nutrition, healthy meal planning, physical activity, weight management and stress management and on developing relationships with health-care providers. Student-coaches engaged with their family members during weekly 30-minute sessions where they shared information about topics they learned in class, discussed their relatives’ experiences and goals and helped them make an action plan for the week. In discussing their findings, study authors’ wrote:

The results of the study indicate that the Stanford Youth Diabetes Coaches Program increases knowledge and psychosocial assets of participant youth … Youth participants also reported positive changes in their own lives as the coached family members, and family members emphasized the importance of student coaches’ role in encouraging healthy behaviors. Additionally youth participants reported high program satisfaction.

These results substantiate current work suggesting that school-based programs benefit adolescents and that children have potential to support the self-management of family members with diabetes. Evidence strongly suggests that school-based programs hold promise to improve the health of at-risk adolescents.

“This study really speaks to the question of: How do you engage teens about their health?,” said first author Liana Gefter, MD, a research associate in Stanford’s Center for Research and Education in Family and Community Medicine. “The effectiveness of the program is rooted in the idea of empowering students to be a leader in a setting where they are traditionally only told what to do. A lot of the students really had a transformation during the eight-week course. Our findings demonstrated that after only eight weeks, compared to non-participants, students had significant increases in self-worth and belonging – assets that have been shown to be necessary precursors for adopting healthy behaviors. In this way, we believe the program could lay the foundation for sustainable health improvement.”

During interviews with researchers, student coaches and diabetes patients said the program inspired them to improve their diet and increase their regular physical activity. Additionally, they noted that the program strengthened their relationships with each other, and students reported their appreciation for having a physician come into their classroom.

In light of the program’s success, Gefter and colleagues Nancy Morioka-Douglas MD, MPH; Eunice Rodriguez, MPH, DrPH, and Lisa Rosas, MPH, PhD, are working to expand the program to underserved schools at other sites in California and around the country. Pilots are currently underway, or will begin, at campuses in Delaware, Georgia, Washington, Ohio and Michigan.

Previously: Sugar intake, diabetes and kids: Q&A with a pediatric obesity expert, Have you voted in the Healthy Living Innovation Awards?, Diabetes prevention program trains youth in chronic disease self-management and Stanford Diabetes Coaches Class selected as 2011 Healthy Living Innovation Awards finalist
Photo by Stanford Youth Diabetes Coaches Program

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