MURDOCK COPD Study enrolls 300th participant

December 19, 2017 – MURDOCK COPD investigators led by the DCRI’s Scott Palmer, MD, hope to enroll 850 patients.

The first time Joseph Griggs met Nellie Griggs, he made a bold prediction.

“You’re going to be my wife,” Joseph told Nellie in August 2001 while they chatted in a New York City park.

Nellie wasn’t so sure.

“I told him he was crazy,” she said, as the couple reminisced in their Kannapolis home. “But after that, we became inseparable.”

The New York natives moved to Kannapolis in 2002 and were married at the Cabarrus County Courthouse. Fifteen years later, they remain nearly inseparable and share a common goal: They hope to improve the health of future generations by joining the MURDOCK COPD Study, managed by the Duke Clinical and Translational Science Institute (CTSI) in Kannapolis at the North Carolina Research Campus.

Nellie recently became the 299th participant in the study, and Joseph enrolled the next day as No. 300. The Duke team aims to enroll 850 people in the study and follow their health for up to five years. To qualify, participants do not need to have COPD, which stands for chronic obstructive pulmonary disease, but they must have smoked.

Duke researchers are studying the severity of smoking-related symptoms in participants and following the progression of their lung function to better understand the disease. The study could help doctors provide better care for their patients and more effective treatments in the community setting, according to Scott Palmer, MD, director of respiratory research for the DCRI and principal investigator for the study.

“I think it’s wonderful,” Joseph said. “It will help people later on if researchers can understand COPD. I want them to know more about what’s going on, because I have it. If we can help them by joining the study, then we feel like we’ve done our part.”

Chronic lower respiratory diseases, which include COPD, are the third-leading cause of death in the United States.

MURDOCK COPD 300th patientParticipation in the study by people like Nellie and Joseph, who started smoking as teenagers, provides a way for researchers to compare the current system for classifying the stages of COPD to disease development and progression in a real-world setting.

“Much of what we have learned about COPD to date has been gathered from research done in large academic medical centers,” said Jamie Todd, MD, assistant professor of medicine in the DCRI and co-principal investigator of the study. “But for this study, we have the unique opportunity to work with the MURDOCK Study to better understand the progression and management of COPD in a community setting.”

Joseph, 57, coughs and tires easily now, but growing up in Brooklyn, he played baseball and football, drove a truck, and worked as a mechanic. A former boxer and chef, Joseph had to quit sports and his job when he suffered a stroke in 2010.

Nellie, 51, grew up in the Bronx with 10 siblings and worked for the City of New York in a variety of jobs, including helping people who received public assistance find work. She suffered kidney failure last year and receives dialysis three days a week while awaiting a kidney transplant.

“I would like to give her one of mine,” Joseph said, “but I am not a match.”

Nellie and Joseph moved back to New York a few years ago to care for their ailing mothers. They returned to Kannapolis in 2016, drawn by the mild winters and lower cost of living. Without a car, they call a cab or have friends shuttle them to health care appointments. For errands, Nellie walks and Joseph uses a motorized scooter.

Sixteen years after Joseph asked Nellie if he could buy her a Pepsi on a hot summer day, the couple count their blessings daily, despite their many health problems. They are intrigued by the transformation of Kannapolis into a research hub, and proud that they have contributed by joining the MURDOCK COPD Study.

“I like the idea of Kannapolis being about research,” Joseph said. “Helping sick people, that’s what we need to do.”

“We feel good about being in the study,” Nellie added. “We are blessed.”

Current or former smokers who are at least 40 years old could qualify to join the MURDOCK COPD Study. No geographic restrictions apply. During study follow-up, Duke CTSI in Kannapolis will contact participants every six months to measure changes to their health.

To learn more, call 704-250-5861, send an email to murdock-study@duke.edu or visit www.murdock-study.org/COPD. Participants will be offered compensation for each in-person visit.

The MURDOCK Study, DCRI, and Boehringer Ingelheim Pharmaceuticals Inc. are collaborating on the study.

DCRI investigators receive PCORI award

December 18, 2017 – The award will fund research into the prevention and reduction of opioid abuse in patients with chronic pain.

Li-Tzy WuRowena Dolor, MD (pictured far left), and Li-Tzy Wu, RN, ScD, MA (pictured near left), have received an award from the Patient-Centered Outcomes Research Institute (PCORI) to support research on health services to reduce opioid use in patients with chronic pain.

In recent years, opioid use in America has become an epidemic. According to a 2015 study by the American Society of Addiction Medicine, nearly 10 percent of Americans suffer from a substance abuse disorder involving prescription pain relievers. But for one-third of the American population that suffers from chronic noncancer pain (CNCP), opioids are a primary treatment method.

“Physicians are trying to learn how to safely prescribe opioids,” Dolor said. “Any trial that can teach people to self-manage pain without relying solely on opioid pain relievers is important.”

The study, “Integrated Health Services to Reduce Opioid Use While Managing Chronic Pain,” will examine two approaches to CNCP management. The first approach, shared decision making, will involve patients working with trained clinicians to reach a decision on whether to continue with or reduce the dose of opioid therapy. The second approach, motivational interviewing and cognitive behavioral therapy (MI+CBT), will feature patients working with clinicians in group settings to develop alternative techniques for dealing with chronic pain symptoms which may reduce their reliance on opioid therapy.

For this study, Dolor and Wu will be working with RTI International, the University of North Carolina Health System, and the Vanderbilt University Health System, as well as Duke Primary Care and Duke Pain Clinic clinicians. Researchers will be working with 1,060 patients for one year, with half the patients receiving the shared decision making approach and half receiving MI+CBT. Enrollment is projected to begin in fall 2018.

The research team is part of the Mid-South Clinical Data Research Network in the National Patient-Centered Clinical Research Network (PCORnet), a PCORI initiative. PCORnet is designed to make it faster, easier, and less costly to conduct clinical research than is now possible by harnessing the power of large amounts of health data and patient partnerships. In addition, Dolor is the director of the Duke Primary Care Research Consortium (PCRC), and both resources have helped drive the study forward.

“The ability to work with an established practice-based and clinical data research network strengthens the proposal,” Dolor said.

This award has been approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract.

Eric Peterson named one of nation’s top cardiologists

December 5, 2017 – The list, published by Forbes, was compiled by an algorithm created by medical technology company Grand Rounds.

DCRI Executive Director Eric Peterson, MD, MPH, has been named one of the nation’s top 27 cardiologists, as chosen by the medical technology company Grand Rounds.

The list was published online today by Forbes.

Grand Rounds uses a database of approximately 700,000 physicians, 96 percent of the U.S. total, and merges it with insurance-claims data and biographical information to evaluate doctors based on the quality of their work. Using this information and a proprietary algorithm, the company then matches patients to the best available physician.

In addition to Peterson, the list included the University of Cincinnati’s Richard C. Becker, MD, formerly of the DCRI, as well as physicians from the Cleveland Clinic, the Mayo Clinic, Johns Hopkins University, and other institutions.

Only 1 in 4 adults receive recommended statins for high cholesterol

December 5, 2017 – Among patients who are on statins, less than half receive the recommended dosage.

Many physicians who prescribe statins for hyperlipidemia, or elevated cholesterol levels, are not in line with the most recent guidelines, according to a new study by DCRI researchers.

High levels of low-density lipoprotein (LDL), or “bad” cholesterol, can lead to greater risk of heart disease and stroke. Approximately 71 million Americans have elevated LDL levels, and only 1 in 3 adults with high LDL have the condition under control.

In 2013, the American Heart Association (AHA) and American College of Cardiology (ACC) issued new guidelines for the treatment of high LDL. These guidelines represented a change from previous recommendations, placing an emphasis on cardiovascular risk assessment to determine who is eligible for treatment and pushing for use of high-dose statins rather than a treat-to-target strategy.

The Patient and Provider Assessment of Lipid Management (PALM) registry was designed to determine how closely current clinical practice reflects the AHA/ACC guidelines. PALM’s primary results were published recently in the American Heart Journal.

“While there’s been a lot of focus on people who are not any statin, there has been less emphasis on whether they are on the right recommended dose of statin,” said the DCRI’s Ann Marie Navar, Ann Marie NavarMD, PhD, who led the study.

PALM enrolled more than 7,900 patients from 138 sites across the United States. These patients included adults on statins, adults at high risk of atherosclerotic cardiovascular disease (ASCVD), and adults with prior ASCVD. The researchers collected information from patient surveys, core laboratory lipid panels, and other medical records to assess current lipid-lowering therapy in high-risk groups.

Navar and her colleagues found that while 74.7 percent of eligible adults were on statins, only 57 percent of those on statins were on guideline-recommended intensity. Overall, only 42.4 percent of adults were on a statin at the recommended dose. ASCVD patients were more likely to be on a statin than other patients (83.6 percent versus 63.4 percent) and were also more likely to receive guideline-recommended therapy (47.3 percent versus 36.0 percent). Men were more likely than women to be prescribed the recommended intensity for both primary and secondary prevention.

In primary prevention, increasing age, diabetes, obesity, hypertension, and lower 10-year ASCVD risk were associated with increased odds of receiving the recommended intensity. Among ASCVD patients, those with coronary artery disease were more likely to be on recommended intensity than cerebrovascular or peripheral vascular disease patients, as were those seen by cardiologists. Median LDL levels were highest among patients not on statins and slightly higher among those on lower-than-recommended intensity compared with recommended-therapy recipients.

These findings, Navar said, illustrate the need to identify both high-risk patients not currently on statin therapy, as well as patients currently on a statin who could benefit from more intensive treatment.

“People on a low or moderate dose of a statin should ask their doctor if they are eligible for a higher dose,” Navar said. “This can further lower their cholesterol and their risk of heart attack and stroke.”

In addition to Navar, the study’s other DCRI authors included Tracy Y. Wang, MD, MHS, MSc; Shuang Li, MS; and Eric D. Peterson, MD, MPH.

Study suggests digital treatment through a video game could improve attention in ADHD

December 4, 2017 – The full results of the study will be submitted to a peer-reviewed journal.

Attention-deficit hyperactivity disorder (ADHD) affects 11 percent of school-aged children in the U.S. and often leads to behavioral, academic and social challenges. A new study suggests a digital treatment in the form of a video game specifically designed to improve attention could hold potential as a future treatment for the condition.

Scientists from the DCRI designed and led the 20-site, 350-patient study to determine whether children ages 8 to 12 with ADHD benefited from the treatment from Akili Interactive Labs, Inc., in which users race through a course, dodge obstacles and capture rewards to advance to the next level.

The company publicly disclosed initial data on Dec. 4. An initial analysis shows that children who received the treatment performed better on an attention test after four weeks compared to children who played a game designed as a comparative control. The company announced it plans to submit the digital treatment, currently titled AKL-T01, to the U.S. Food and Drug Administration for review as an approved medical device to treat ADHD in children.

“Software or game companies have marketed products they say can improve attention, but to date, none of these products have gone through the rigorous testing required by the FDA to become an approved treatment for ADHD,” said principal investigator Scott Kollins, PhD (pictured), a member of the DCRI and director of the ADHD program at the Duke University School of Medicine.

“This study represents, to my knowledge, the largest and most rigorous evaluation of a digital medicine,” he said. “Continued work on this approach could mean that in a few years, doctors could be prescribing a therapeutic video game to improve a patient’s ADHD symptoms.”

Although initial results are promising, the full study data require in-depth analyses, which researchers plan to present at an upcoming scientific conference and submit to a peer-reviewed medical journal, Kollins said.

AKL-T01, delivered on a tablet children could use at home, requires quick reaction time and decision-making and increases in difficulty in response to the player’s skills. According to designers, it targets parts of the prefrontal cortex that assist in cognitive control and are believed to be deficient in ADHD.

Children who underwent treatment showed a statistically-significant improvement compared to a control group on the Test of Variables of Attention (T.O.V.A.®), an FDA-cleared test to measure attention and impulse control. Participants, who were not receiving drugs or other therapies, took the test before using the device and again after four weeks. One participant withdrew from the study early, while 11 others reported the side effects of headaches and frustration, but no serious adverse events were reported.

Participants were also evaluated using other methods to detect improvements in their attention and behavior, but differences between treatment and control groups on these measures were not statistically significant, the researchers said.

“This study demonstrates just how fast medical care and clinical research are changing,” said Eric Peterson, MD, MPH, executive director of the DCRI. “While digital medicine represents a promising approach to treat many conditions, these treatments need to be rigorously tested and proven, just like other drug and device therapies.”

Currently, pharmaceutical drugs and behavioral therapy for families are the only evidence-based treatments available for ADHD, but these treatments may not be effective for all patients and access to providers can be limited. An innovative digital treatment could fill these gaps for many families, Kollins said.

“However, future testing of digital technologies is needed to better define in whom they can work best and how long they are needed to gain their maximal effect,” Kollins said.

Families seeking information on future clinical trials for children and adults with ADHD can find resources on the Duke Health website.

Disclosures: Scott Kollins serves as a consultant to Akili Interactive Labs, Inc.

Lesley Curtis to lead Duke’s new Department of Population Health Sciences

November 30, 2017 – Curtis has served as interim chair of the department since its inception in July of this year.

Lesley Curtis, PhD, has been named to serve as the first chair of the Department of Population Health Sciences at the Duke University School of Medicine.

Curtis has been interim chair of the new department since July 2017, when creation of the department was approved by the Duke University Board of Trustees. From 2016-2017, Curtis served as director of the Center for Population Health Sciences, which was a launching pad for the new department.

Lesley Curtis

“I couldn’t be more pleased about this appointment,” said Mary E. Klotman, MD, dean of the School of Medicine. “Dr. Curtis is an outstanding scientist and a visionary leader. She was a key driver and instrumental in the creation of this new department and will be the impetus for the department’s future growth and success.”

The Department of Population Health Sciences engages faculty members from a variety of disciplines — including epidemiology, health services research and policy, health economics, health measurement and behavior, and implementation science — who work to answer complex questions about the drivers of health in large populations.

A health services researcher by training, Curtis has spent her career advancing the health of patients with cardiovascular disease, eye disease, and other chronic conditions. An expert in the use of Medicare claims data for health services and clinical outcomes research, she has been a leader in using Medicare claims data along with large clinical registries and epidemiological cohort studies, including the Framingham Heart Study and the Cardiovascular Health Study.

In addition to her role as chair, Curtis is director of the Center for Pragmatic Health Systems Research in the Duke Clinical Research Institute (DCRI). She also leads the Distributed Research Network Operations Center for PCORI’s National Clinical Research Network (PCORnet), is co-principal investigator of the National Institutes of Health’s Health Care Systems Collaboratory, and co-leads the Data Core for the FDA’s Sentinel Initiative.

DCRI faculty among world’s most-cited researchers

November 29, 2017 – Eight DCRI faculty members were included in Clarivate Analytics’ list of the most-cited researchers in 21 fields of science and social science.

A new list of the world’s most-cited researchers includes 33 Duke faculty members, 8 of whom are DCRI faculty.

The list, compiled by Clarivate Analytics, comprises 3,400 researchers in 21 fields of science and social science from around the world. The data used in the analysis and selection of the new Highly Cited Researchers came from Essential Science Indicators (ESI), 2005-2015, which included 134,832 Highly Cited Papers. Each of these papers ranked in the top 1 percent by total citations according to their ESI field assignment and year of publication.

The DCRI members included in the list are Robert Califf, Christopher Granger, Richard S.E. Keefe, Kristin Newby, E. Magnus Ohman, Manesh Patel, Michael Pencina, and DCRI Executive Director Eric Peterson. Many of these researchers were also included in Clarivate’s lists from previous years.

“This list illustrates how our faculty are fulfilling our mission to share knowledge that improves patient care,” Peterson said. “None of this work, however, would be possible without the vital collaboration of our operations team and partners around the world. That spirit of cooperation is what makes the DCRI unique among our peers in both academia and industry.”

New blood pressure guidelines to bring substantial changes for patients, physicians

November 27, 2017 – DCRI Executive Director Eric Peterson, MD, MPH, recently weighed in on the impact of the new guidelines in a recent editorial in JAMA.

New blood pressure guidelines issued this month by the American College of Cardiology (ACC) and the American Heart Association (AHA) represent the best of the current thinking surrounding hypertension, but also present a challenge for physicians looking to translate them into clinical practice.

That is the conclusion of an editorial by DCRI Executive Director Eric Peterson, MD, MPH, and Philip Greenland, MD, of Northwestern University’s Feinberg School of Medicine. The editorial was published this month in JAMA.

The guidelines, the first comprehensive new high blood pressure guidelines in over a decade, lower the threshold for high blood pressure to 130/80 mm Hg, rather than 140/90 mm Hg. With the previous definition, 1 in 3 American adults were defined as having high blood pressure (32 percent). Under the new guidelines, 46 percent of the U.S. adult population is classified as having high blood pressure or hypertension.

The new ACC/AHA guidelines also propose more aggressive thresholds and goals for treatment based on an individual’s underlying cardiovascular disease (CVD) risk, and place more emphasis on out-of-office blood pressure measurements using ambulatory or home monitoring.

“This is a welcome change, as there is clearly strong evidence to suggest that knowing the blood pressure of an individual outside the clinic setting is more predictive of outcomes than their clinic pressure and brings the U.S. guidelines more in line with those used already in Europe,” Peterson and Greenland write. “For many patients and clinicians, however, these recommendations will be new and will require a substantial change in patient education, practice organization, performance measurement, and follow-up approaches.”

“A huge challenge for clinicians will be to translate these guidelines into clinical practice. Only approximately half of patients classified as having hypertension under the previous guidelines had their blood pressure controlled, and the proportion at the new goals will be even lower. Thus, the ‘pressure’ is on to more effectively treat blood pressure at individual and population levels.”

AHA 2017: Innovative therapy investigated in prevention of heart muscle damage after heart attack

November 15, 2017 – A recent study of the ability of cell therapy derived from cardiac tissue to regenerate heart muscle and reduce scar tissue showed some signals of efficacy, but was terminated due to futility.

The amount of heart muscle damage – as measured by the scar tissue or infarct size – is a strong predictor of prognosis after a heart attack, or acute myocardial infarction (MI). Such scar tissue is not able to contract, placing the remaining heart muscle under a greater burden, and potentially leading to heart failure and other complications.

A recent phase II clinical trial aimed to investigate the ability of cardiac cell therapy to regenerate heart muscle and reduce scar tissue after heart attack. The ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) trial was a randomized, placebo-controlled, double-blind study designed to evaluate the safety and efficacy of an allogeneic cardiosphere-derived cell product candidate, CAP-1002, on post-MI left ventricular dysfunction.

The results of ALLSTAR were presented today at the 2017 American Heart Association (AHA) Scientific Sessions in Anaheim, California.

The cells were obtained from heart tissue from an allogeneic source, and were infused into the infarct-related artery 1 to 12 months after myocardial infarction. Patients assigned to the control group were treated with infusion of cell medium.

In an earlier study, the Intracoronary CArdiosphere-Derived aUtologous StemCElls to reverse ventricUlar dySfunction (CADUCEUS) trial, similar cells obtained from biopsies from the patients themselves reduced the amount of scar tissue, apparently helping to regenerate lost heart tissue.

The ALLSTAR trial aimed to enroll 260 ST-elevation myocardial infarction (STEMI) patients in the randomized cohort, but the trial was halted due to the low probability that a treatment effect would be observed in the primary analysis at 12 months as determined by a pre-specified interim analysis performed when 134 patients had been enrolled.

In addition, while the trial was supposed to assess the impact of the treatment at both 6 and 12 months, complete assessments were only available on the entire cohort at 6 months due to the early cessation of the study.  The change in scar size at 6 months was not significantly different between the arms, but there were signals of efficacy, including trends for improvement in left ventricular end-diastolic volume (LVEDV) and N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of congestion and an important prognostic indicator of outcome.

“There are important lessons to learn from this study, including the difficulty of carrying out studies of patients with acute MI, due to changing treatment paradigms,” said the DCRI’s Thomas J. Povsic, MD, PhD, associate professor of medicine, study steering committee member, and an author on the presentation. “Although the study was unable to provide definitive answers, there were signals that these progenitor cells may improve left ventricular remodeling in patients with a significant MI. Importantly, all the endpoints trended in favor of cell therapy.”

AHA 2017: Unclear if Botox can treat atrial fibrillation, researchers say

November 15, 2017 – Duke and DCRI researchers followed up on a Russian study that reported a 70 percent drop in atrial fibrillation episodes among patients who received botulinum toxin.

From temporarily softening wrinkles to easing migraines, botulinum toxin has become a versatile medical remedy because of its ability to block nerve signals that can become bothersome or risky.

But could the toxin also quell heart flutter, known as atrial fibrillation, after cardiac surgery? That question was at the root of a study led by Duke University researchers, who report today at the Scientific Sessions of the American Heart Association meeting that the answer is … maybe.

Researchers at the DCRI and Duke’s Department of Anesthesiology launched their inquiry after a study from Russian scientists reported a 70-percent drop in atrial fibrillation episodes among a small cohort of heart surgery patients who were treated with strategic injections of botulinum toxin (commonly marketed as Botox).

Nathan WaldronBouts of irregular heartbeat are a common complication after cardiac surgery, affecting up to 40 percent of patients and increasing the risk of stroke and death.

“The results from Russia were very interesting, but needed to be replicated on a larger and more medically complex group of patients,” said lead author and DCRI Fellow Nathan Waldron, MD.

Waldron and colleagues enrolled 130 patients who were slated to undergo a coronary artery bypass grafting procedure, valve surgery, or both. During their surgeries, roughly half the patients were randomly assigned to receive shots of botulinum toxin in the fat pads around their heart where the fibrillation is known to arise; the other half received harmless saline. The medical teams did not know which injection the patients received.

Afterward, the patients were monitored continuously by electrocardiogram to pick up signs of atrial fibrillation. Among the patients who received injections of botulism toxin, 36.5 percent had atrial fibrillation, compared to 47.8 percent of those who had the saline placebo.

The researchers also found that patients who received the botulinum toxin had shorter initial bouts of atrial fibrillation, but there were no significant differences in the length of hospital stays or post-operative complications.

“Unfortunately, while there was a numerically lower risk of atrial fibrillation among the Botox patients, it did not meet statistical significance,” said Jonathan P. Piccini, MD, a member of the DCRI and senior author of the study. “What we observed was a modest positive effect on preventing atrial fibrillation, so a larger trial is something that is needed to provide a clearer picture.”

The study received funding from the American Heart Association and the Foundation for Anesthesia Education and Research.

In addition to Waldron and Piccini, study authors include Mary Cooter, John C. Haney, Jacob N. Schroder, Carmelo A. Milano and Joseph P. Mathew.