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Cardiovascular Medicine, Research, Science, Stanford News

Scientists preferentially cite successful studies, new research shows

Scientists preferentially cite successful studies, new research shows

Say you’re a medical researcher. You slave over a project for months, even years, and you’re thrilled when a stellar journal agrees to publish it. That’s it, right? Well, no. Now, you need others to spot your work – and cite it in their studies. You can court citations just as you court Twitter followers: by producing high-quality content worthy of a bigger audience.

That said, sometimes bias creeps in. For example, studies by superstar scientists are cited more often than those by their junior colleagues — no surprise there. But now, Stanford medical resident Alex Perino, MD; cardiologist Mintu Turakhia, MD, MAS; and colleagues have shown that studies documenting higher success rates of a certain procedure are more likely to be cited than studies of the same procedure with lower success rates.

“This is an indication that we as clinicians and investigators need to be mindful of how we present the data,” Turakhia told me.

In a study released yesterday in Circulation: Cardiovascular Quality and Outcomes, Perino, Turakhia and other colleagues examined research papers on catheter ablation for atrial fibrillation, a treatment with widely varying success rates. For example, among the examined studies, the success of a single treatment varied between 10 and 92 percent. The variation is perfectly understandable, Turakhia said. Atrial fibrillation, an irregular heart rhythm, can be caused by a variety of underlying conditions and can vary in severity, he explained. The procedure itself, which uses energy to destroy tissue in key areas of the left atrium, can also vary, Turakhia said.

That’s why ablation for atrial fibrillation was an apt treatment to examine. The team included 174 studies with 36,289 patients published since 1990. They found that for every 10 point increase in reported success rate, there was an 18 percent increase in the mean citation count. The citation bias remained significant even when accounting for time since publication, the journal’s impact rating, sample size and study design.

The bias is important when considering the efficacy of new and evolving treatments, Turakhia said: “We just wanted to make sure the totality of evidence is being presented fairly and completely to readers of the medical literature, which may be clinicians, scientists, insurance companies and policy makers. However, in this case, we found that ablation could be perceived to be more effective than the totality of evidence would suggest.”

Turakhia said he hopes this study prompts other researchers to examine bias in other treatments and specialties.

Previously: Re-analyses of clinical trial results rare, but necessary, say Stanford researchers, John Ioannidis discusses the popularity of his paper examining the reliability of scientific research, A discussion on the reliability of scientific research, U.S. effect leads to publication of biased research, says Stanford’s John Ioannidis

Cardiovascular Medicine, Patient Care, Pediatrics, Stanford News

A nurse puts heart into her work at Adult Congenital Heart Program

A nurse puts heart into her work at Adult Congenital Heart Program

heart_sillman_560A few decades ago, if a child was diagnosed a serious heart defect it was essentially a death sentence, but thanks to recent advances in neonatal heart surgery, most patients now live well into adulthood. And at least one of them has gone on to care for other people with congenital heart defects.

Christy Sillman, RN, is the nurse coordinator for Stanford’s Adult Congenital Heart Program and is profiled in the most recent issue of Inside Stanford Medicine. Although most people who were treated for heart defects as children don’t require continued surgical interventions as adults, doctors now know that they have other challenges that require ongoing care. Sillman went through this firsthand. After being told as a teenager that she was “cured” and going a decade without care, she learned she was suffering from cardiomyopathy, a deterioration of the heart muscle. From the article:

“At that point, my frustration with the medical care of people with congenital heart defects was elevated,” Sillman recalled. “I wouldn’t have been in such bad shape had I gotten the right care earlier. This motivated me to get more involved.”

That involvement was huge. Sillman talked with many people who shared similar stories, which inspired her to become an advocate for patients like herself. When a position was available with the program at Stanford in 2013, Sillman jumped at the chance and was hired.

“I don’t want any teenager to go through what I went through,” Sillman said. “Being told you’re cured and finding out that’s not really true? That should never happen.”

Sillman’s personal experiences are not unusual for a congenital cardiac patient of her generation, but it influenced her professional choices and now, she says, she enjoys bringing “a patient’s perspective” to her work.

Previously: Patient is “living to live instead of living to survive,” thanks to heart repair surgery
Photo by Norbert von der Groeben

Bioengineering, Cardiovascular Medicine, Neuroscience, Research, Stanford News, Stroke

Targeted stimulation of specific brain cells boosts stroke recovery in mice

big blue brainThere are 525,949 minutes in a year. And every year, there are about 800,000 strokes in the United States – so, one stroke every 40 seconds. Aside from the infusion, within three or four hours of the stroke, of a costly biological substance called tissue plasminogen activator (whose benefit is less-than-perfectly established), no drugs have been shown to be effective in treating America’s largest single cause of neurologic disability and the world’s second-leading cause of death. (Even the workhorse post-stroke treatment, physical therapy, is far from a panacea.)

But a new study, led by Stanford neurosurgery pioneer Gary Steinberg and published in Proceedings of the National Academy of Sciences, may presage a better way to boost stroke recovery. In the study, Steinberg and his colleagues used a cutting-edge technology to directly stimulate movement-associated areas of the brains of mice that had suffered strokes.

Known as optogenetics – whose champion, Stanford psychiatrist and bioengineer Karl Deisseroth, co-authored the study – the light-driven method lets investigators pinpoint a specific set of nerve cells and stimulate only those cells. In contrast, the electrode-based brain stimulation devices now increasingly used for relieving symptoms of Parkinson’s disease, epilepsy and chronic pain also stimulate the cells’ near neighbors.

“We wanted to find out whether activating these nerve cells alone can contribute to recovery,” Steinberg told me.

As I wrote in a news release  about the study:

By several behavioral … and biochemical measures, the answer two weeks later was a strong yes. On one test of motor coordination, balance and muscular strength, the mice had to walk the length of a horizontal beam rotating on its axis, like a rotisserie spit. Stroke-impaired mice [in which the relevant brain region] was optogenetically stimulated did significantly better in how far they could walk along the beam without falling off and in the speed of their transit, compared with their unstimulated counterparts. The same treatment, applied to mice that had not suffered a stroke but whose brains had been … stimulated just as stroke-affected mice’s brains were, had no effect on either the distance they travelled along the rotating beam before falling off or how fast they walked. This suggests it was stimulation-induced repair of stroke damage, not the stimulation itself, yielding the improved motor ability.

Moreover, levels of some important natural substances called growth factors increased in a number of brain areas in  optogenetically stimulated but not unstimulated post-stroke mice. These factors are key to a number of nerve-cell repair processes. Interestingly, some of the increases occurred not only where stimulation took place but in equivalent areas on the opposite side of the brain, consistent with the idea that when we lose function on one side of the brain, the unaffected hemisphere can step in to help restore some of that lost function.

Translating these findings into human trials will mean not just brain surgery, but also gene therapy in order to introduce a critical light-sensitive protein into the targeted brain cells. Steinberg notes, though, that trials of gene therapy for other neurological disorders have already been conducted.

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, BE FAST: Learn to recognize the signs of stroke and Light-switch seizure control? In a bright new study, researchers show how
Photo by Shutterstock.com

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Cardiovascular Medicine, Health and Fitness, Medicine and Society, Research

Study questions safety of excessive exercise for heart attack survivors

Study questions safety of excessive exercise for heart attack survivors

Scope runningA recent article in PsychCentral highlighted findings published in the Mayo Clinic Proceedings offering more evidence that extreme exercise for heart attack survivors could put them at a higher risk for a cardiovascular event.

Paul Williams, PhD, staff scientist for the Life Sciences Division of Lawrence Berkeley National Laboratory, and Paul Thompson, MD, a cardiologist at Hartford Hospital, conducted a long-term study looking at the relationship between exercise and cardio-disease related death in about 2,400 physically-active heart attack survivors. The study reported on data taken from the National Walker’s and Runners’ heath studies at Lawrence Berkeley Laboratory.  From the piece:

“These analyses provide what is to our knowledge the first data in humans demonstrating a statistically significant increase in cardiovascular risk with the highest levels of exercise,” say Williams and Thompson.

“Results suggest that the benefits of running or walking do not accrue indefinitely and that above some level, perhaps 30 miles per week of running, there is a significant increase in risk.

Competitive running events also appear to increase the risk of an acute event.”

However, they point out that “our study population consisted of heart attack survivors and so the findings cannot be readily generalized to the entire population of heavy exercisers.”

On the other end of the spectrum, the journal also included research from Spain related to mortality in elite athletes. The investigation included over 42,000 top athletes, of which 707 were women, and examined the beneficial health effects of excessive exercise, particularly in decreasing cardiovascular disease and cancer risk. Senior investigator Alejandro Lucia, MD, PhD, said in the article, “What we found on the evidence available was that elite athletes (mostly men) live longer than the general population, which suggests that the beneficial health effects of exercise, particularly in decreasing cardiovascular disease and cancer risk, are not necessarily confined to moderate doses.”

With the majority of Americans still at risk for obesity, cardiovascular disease and diabetes, regular moderate exercise is still recommended by these researchers. As Hippocrates, the father of medicine, once said, “Everything in excess is opposed to nature.”

Previously: Study reveals initial findings on health of most extreme runners, The exercise pill: A better prescription than drugs for patients with heart problems?, Examining how prolonged high-intensity exercise affects heart health and Study reveals initial findings on health of most extreme runners
Photo by: Matthias Weinberger

Jen Baxter is a freelance writer and photographer. After spending eight years working for Kaiser Permanente Health plan she took a self-imposed sabbatical to travel around South East Asia and become a blogger. She enjoys writing about nutrition, meditation, and mental health, and finding personal stories that inspire people to take responsibility for their own well-being. Her website and blog can be found at www.jenbaxter.com.

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From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Cardiovascular Medicine, Research, Stanford News

Study highlights increased risk of death among patients with atrial fibrillation who take digoxin

Study highlights increased risk of death among patients with atrial fibrillation who take digoxin

After a decade of focusing on treatments for heart failure and heart attacks, it’s atrial fibrillation’s turn in the spotlight, said Mintu Turakhia, MD, MAS,  assistant professor of cardiology and director of cardiac electrophysiology for Palo Alto VA Health Care System.

“It’s a huge cost to society and one of the most common inpatient diagnoses,” Turakhia said.

Atrial fibrillation is an irregular and rapid heart rate — caused by spasms of the heart’s upper chambers — that afflicts more than 3 million Americans, increasing their risk of stroke and heart failure. Turakhia and his team planned to dig beneath the surface of atrial fibrillation using data from more than 122,000 patients with recent atrial fibrillation diagnoses in the U.S. Department of Veterans Affairs (VA) health-care system.

They started by examining the efficacy of digoxin, a generic drug derived from the plant foxglove. The results were striking: Patients who received digoxin were 3 percent more likely to die than similar patients.

“The take-home point is to question whether people should really be on this drug,” Turakhia said in a release. “These data challenge the current guidelines.”

Both doctors and patients assumed digoxin was safe because derivatives of foxglove had been used for centuries, not because it had been proven safe or effective, Turakhia said. He said there are many other preferable treatments for atrial fibrillation and he plans to work to standardize treatment for atrial fibrillation in coming years.

“Can we be smarter about how we deliver atrial fibrillation care so it’s delivered efficiently with less variation?” Turakhia asked.

The study will be published in the Aug. 19 issue of the Journal of the American College of Cardiology, which appears online today.

Becky Bach is a former park ranger who now spends her time writing, exploring, or practicing yoga. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Hybrid procedure helps treat difficult cases of atrial fibrillation and Newly approved drug appears to provide more cost-effective stroke prevention than warfarin

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Cardiovascular Medicine, Patient Care, Stanford News, Technology, Videos

“Liberated from LVAD support”: One patient’s story

“Liberated from LVAD support”: One patient’s story

One of the first things I noticed about Donna Jackson — 68 years old when I met her in 2011 — was her decisive nature. She had a schedule filled with activity, and regardless of how many people (many of her children, grandchildren, great-grandchildren, in-laws and friends live very near at hand) came to visit in her modest home in Central California, she was a certain force of calm. She was also someone who did not like restrictions on what she could do.

Back then, she was just a few months out from surgery at Stanford Hospital to implant a mechanical pump, a left ventricular assist device or LVAD, on her heart. She knew it had saved her life, but she chafed at the battery, back-up battery and controller she had to wear at all times. Before the surgery, she had been a regular at a water aerobics class, and she loved to swim with her grandchildren. Even in those early months, Jackson was leaning on her Stanford doctors to find a way to get her back in the water. She asked her cardiologist, Dipanjan Banerjee, MD, to consider allowing her to swim in a wetsuit.

Banerjee did her one better. It had become apparent to him that she could be one of that small percentage of LVAD recipients whose heart recovers after the rest that the LVAD gives it and who no longer need the device. (He had been waiting, he said, to find a patient “who can be liberated from LVAD support.”) By Spring 2013, a little less than three years after her LVAD implantation, Banerjee and Jackson’s surgeon, Richard Ha, MD, put Jackson in an even smaller percentage. She became the first person to have her LVAD deactivated by catheter in the most minimally invasive approach yet.

The challenge set by Jackson for her Stanford team — and its groundbreaking procedural response — appears today in the August issue of the Annals of Thoracic Surgery. The lead author of the paper is Sanford Zeigler, MD, a cardiothoracic surgery resident.  Ha, surgical director of the hospital’s Mechanical Circulatory Support Program is the paper’s senior author, and Banerjee, medical director of Mechanical Circulatory Support Program, is a co-author. As they explain in the paper, Jackson, nearing 71,  was a high surgical risk for complete removal of the implant — that would have required them to crack open her ribs again — a procedure that’s followed typically by a long and sometimes painful recovery.  So, her doctors instead threaded a slim plastic tube through a small incision to her femoral artery in the groin and up to her aorta, allowed them to plug the flow of blood to the LVAD. Then, they cut, cleaned and capped the wiring powering the LVAD so it no longer emerged from an opening in her abdomen. (The LVAD remains inside Jackson’s chest.)

The new catheter-based deactivation of the LVAD has value beyond Jackson’s way of life, as the paper explains. She inspired the team to begin research on how to predict which LVAD patients might be like her and reach a point where they no longer need the LVAD. “If we can find out which patients are going to recover sooner, we can be more aggressive with them so they can be liberated from the LVAD,” said Banerjee, “and many of these patients will not want or be able to tolerate a complete removal of the LVAD.”

Continue Reading »

Cardiovascular Medicine, Research, Videos

Researchers capture detailed three-dimensional images of cardiac dynamics in zebrafish

Researchers capture detailed three-dimensional images of cardiac dynamics in zebrafish

The stunning video above depicts a reconstructed beating heart of a zebrafish embryo with the muscle layer shown in red and the endothelium highlighted in blue. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics in Germany created the video using a new three-dimensional imaging technique, which holds the promise of leading to a better “understanding of congenital heart defects as well in future experiments on cardiac function and development”. As explained in a release:

[Researchers] developed a high-speed, selective plane illumination microscope that manages to do just that. By gently illuminating the fish heart with a thin light sheet and observing the emitted fluorescence with a fast and sensitive camera the researchers have achieved fast, non-invasive imaging of labelled heart tissue. The process involves taking multiple movies, each covering individual planes of the heart (movie stacks), then using the correlations between the individual planes to generate a synchronised, dynamic 3D image of the beating heart.

“These renderings allow us to further follow characteristic structures of the heart throughout the cardiac cycle,” says Michaela Mickoleit, PhD student who performed the experiments in [Jan Huisken's] lab.

Via Medgadget
Previously: An advancement in optogenetics: Switching off cells with light now as easy as switching them on and New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics

Cardiovascular Medicine, Genetics, Research, Stanford News

Stanford patient on having her genome sequenced: “This is the right thing to do for our family”

Stanford patient on having her genome sequenced: "This is the right thing to do for our family"

genomicsImagine you were diagnosed, seemingly out of the blue, with hypertrophic cardiomyopathy, a condition that is caused by mutations in genes involved in the heart’s muscle cells and is the most common cause of sudden death in young people. If given the chance, would you have your entire genome analyzed to understand more about your genetics and the condition? That’s the decision Julie Prillinger faced and, in the end, she embraced the opportunity to untangle the mystery of her DNA. “This is the right thing to do for our family – and our friends and family have been very supportive,” she said in a Stanford Medicine News story.

As described in the piece, Prillinger’s genome was among the first to be sequenced through a pilot program of the new Clinical Genomics Service at Stanford Hospital & Clinics. The pilot phase of the service is limited to specific patient groups, including: children with mystery diseases, patients with unexplained hereditary cancer risk, patients with inherited cardiovascular or neurological disease and those with severe, unexplained drug reactions. More details about the service from the article:

Stanford’s service will apply a highly integrated approach that includes professional genetic counseling, the most advanced genome sequencing technology available, and expert interpretation by molecular genetic pathologists and other physicians with expertise in this emerging and complex field.

The new service will be tied closely to other diagnostic genetic testing programs currently offered at the two hospitals. Those programs, which include molecular genetic pathology, cytogenetics and clinical biochemical genetics, have an outstanding record of compliance with the extensive regulatory requirements for diagnostic genetic testing.

In addition to providing Prillinger and her family with crucial information about their personal health, the results could reveal undiscovered information related to the condition encoded in the human genome, which may enable the expansion of current tests.

Previously: Using genetic testing to enhance students’ knowledge of personalized medicine, Ask Stanford Med: Genetics chair answers your questions on genomics and personalized medicine and Direct-to-consumer genetic testing: A commentary

Cardiovascular Medicine, Genetics, Patient Care, Pediatrics, Research, Stanford News

When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn

When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn

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It’s an ‘edge-of-your-seat’ story: The newborn’s heart had stopped multiple times in the hours since her birth. Her doctors at Lucile Packard Children’s Hospital Stanford had tried everything to help her, but her situation was dire.

The baby had an unusually severe form of an inherited cardiac condition called long QT syndrome. The syndrome, which is most often diagnosed in older children or adults, can be caused by a mutation in any of several genes; until the doctors knew exactly which genetic mutation was causing the condition they wouldn’t know what drug would be most likely to help. The stakes were high: by her second day of life she’d received an implantable defibrillator and several intravenous drug infusions.

As cardiologist Euan Ashley, MD, PhD, explained to me:

The team literally tried everything we could think of to help this child, including trying every drug that could possibly make a difference. It was a heroic effort by a very diverse group of professionals.

The clinicians and researchers, including pediatric cardiologist Scott Ceresnak, MD, who managed the baby’s clinical care, realized it was critically important to identify the baby’s disease-causing mutation to learn which drug would be best for her. To do so, they dropped everything else they were doing and sequenced her entire genome to pinpoint the culprit within just ten days – an unprecedented feat. Ashley, who directs Stanford’s new Clinical Genomics Service as well as its  Center for Inherited Cardiovascular Disease, and pediatric cardiology fellow James Priest, MD, recently published the case study in the journal Heart Rhythm.

This is the future of genetic testing and we hope, the future of medicine.

Using customized commercial software and tools developed at Stanford, the researchers were able to zero in on a mutation in a gene called KCNH2 known to be associated with long QT. They also found another, novel mutation in a gene involved in determining the structure of the heart during development.

As Priest explained in an e-mail to me:

Whether it is a CT scan, x-ray, or genetic test, we work hard to make a diagnosis as quickly as possible when there is a critically-ill baby under our care. Whole genome sequencing returned this diagnosis in days instead of weeks. We were able to turn the raw sequence data into a diagnosis in about 12 hours.

Continue Reading »

Cardiovascular Medicine, Genetics, In the News, Research, Science, Stanford News

A simple blood test may unearth the earliest signs of heart transplant rejection

A simple blood test may unearth the earliest signs of heart transplant rejection

2123984831_b7d09079a4_oIs there an organ more precious than a donated heart? Heart transplant recipients would likely say no. But, in order to keep their new heart healthy, they have to identify any signs of rejection as early as possible. Unfortunately (and ironically), the gold standard procedure to detect rejection – repeated heart biopsies – involves snipping away and analyzing tiny bits of tissue from the very organ they waited so long to receive. The procedure is also uncomfortable, and can cause complications.

Now, Stanford bioengineer Stephen Quake, PhD, and his colleagues have found that a simple blood test that detects donor DNA in the bloodstream of the recipient can detect signs of rejection far earlier than biopsy. Their results were published today in Science Translational Medicine.

From our release:

The study of 65 patients (21 children and 44 adults) extends and confirms the results of a small pilot study completed in 2011 by the Stanford researchers. Whereas the earlier study used stored blood samples and medical histories from seven people, the new study followed patients in real time before and after transplant. The researchers directly compared the results of simultaneously collected biopsies and blood samples, and tracked how the values changed during the rejection process.

The blood test takes advantage of the fact that dying heart cells release genetic material into the recipient’s blood. Any increase beyond a normal baseline level indicates a possible attack by the immune system on the donated organ. As described in our release:

In the pilot study of 2011, the researchers first used the presence of the Y chromosome to track the donor DNA when a woman received a heart from a male donor. Then they hit upon using differences in SNPs instead; this method doesn’t require a gender mismatch between donor and recipient. They found that, in transplant recipients not experiencing rejection, the donor DNA accounted for less than 1 percent of all cell-free DNA in the recipient’s blood. During rejection episodes, however, the percentage of donor DNA increased to about 3 or 4 percent.

In the new study, the researchers monitored 565 samples from the 65 patients to assess the assay under real-time clinical conditions. They found they were able to accurately detect the two main types of rejection (antibody-mediated rejection and acute cellular rejection) in 24 patients who suffered moderate to severe rejection episodes, one of whom required a second transplant. They were also able to detect signs of rejection up to five months before the biopsies indicated anything troubling.

The test will still need to be optimized for regular clinical use. However, cardiologist Kiran Khush, MD, a co-senior author of the study, explained what the advance could mean to heart transplant recipients:

This test has the potential to revolutionize the care of our patients… It may also allow us to conduct several diagnostic tests simultaneously. For example, we could also look for microbial sequences in the blood sample to rule out infection or other complications sometimes experienced by transplant recipients. It could allow us to determine whether shortness of breath experienced by a patient is due to an infection or the start of a rejection episode. It could be a one-stop shop for multiple potential problems.

Full disclosure: Stanford has applied for a patent relating to the test described in this study. Quake is a consultant for and holds equity in CareDX Inc., a molecular diagnostics company that has licensed a patent from Stanford related to a method used in the study and is developing it for clinical use.

Previously: ‘Genome transplant’ concept helps Stanford scientists predict organ rejection, Stanford study in transplant patients could lead to better treatment and New techniques to diagnose disease in a fetus
Photo by Desi

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