Early physical therapy could reduce opioid dependence for pain patients

December 14, 2018 – New research points to evidence that a nonpharmacological treatment option could reduce opioid use in patients with musculoskeletal pain.

Early physical therapy could lead to fewer pain patients becoming dependent on opioids, according to new research co-authored by the DCRI’s Steven George, PhD.

George worked with Stanford University’s Eric Sun, PhD, MD, and other DCRI faculty members, including Chad Cook and Adam Goode, to analyze a proprietary database that pulls from insurance claims and other data recorded during routine patient visits. The team, whose research was published today in JAMA Network Open, reports that when patients with low back, shoulder, knee, or neck pain sought physical therapy early, their subsequent opioid use for the following year was reduced by approximately 10 percent.

Stephen George cropped photoGeorge, the DCRI’s director of musculoskeletal research, said he initially became interested in the association between physical therapy and opioid use because of the patients he saw in his clinical practice as a physical therapist, which suggested that nonpharmacological treatments for back pain patients could have protective effects against long-term opioid use.

The most recent study expanded beyond previous research in back pain to determine whether the protective effect would also apply to patients with neck, knee, and/or shoulder pain.

“Because the CDC guidelines and the American College of Physicians guidelines are pushing toward early non-drug options for patients, this was an opportunity for us to look at a real-world data set to see what one of the non-drug options looked like across the four most common musculoskeletal pain conditions,” George said.

There is no standard definition for what constitutes early physical therapy, George said, but the new study focused on patients who received physical therapy within 90 days of their index date. The study also only included patients who were opioid naïve, meaning that they had not used opioids within a year before their index date. The researchers examined data from almost 89,000 patients with back, neck, knee, or shoulder pain between 2007 and 2015.

In all four pain categories, patients who received early physical therapy were found to use opioids for a shorter length of time than those who did not. In a sensitivity analysis, the researchers found that early physical therapy may be most likely to limit chronic opioid use in patients with back or knee pain. When patients did continue to use opioids, those who received early physical therapy took a smaller amount of opioids in terms of dosages.

The exception for dosage was patients with neck pain, as results for this group were not statistically significant. George said there could be several reasons why the neck pain group did not show the same results as the other pain groups. Neck conditions could be more resistant to physical therapy, or could initially be prescribed higher dosages of opioids.

Although research suggests that early physical therapy is potentially beneficial, there are still time delays and barriers for patients looking to access this type of treatment. For example, many insurance providers still require patients to see a primary care provider first and get a referral to a physical therapist — and while seeing a physician can be beneficial for many reasons, it does delay physical therapy, George said.  High co-payments can also be a barrier — often, the co-payment for a one-month opioid prescription is less than the co-payment for a single session with a chiropractor or physical therapist.

George acknowledges that to further expand use of nonpharmacological treatments, health care systems will need to change established delivery patterns. “Because the system is set up to deliver prescriptions, it’s a lot easier for it to do that than deliver nonpharmacological interventions,” he said. “However, the opioid crisis has led to awareness that the system needs to improve in delivering on these interventions if we are going to successfully reduce unnecessary exposure to opioids for pain relief.”

DCRI to lead new study of treatments for patients with diabetes and heart disease

December 13, 2018 – The COORDINATE-Diabates trial will analyze how different interventions affect guideline-recommended therapies among caregivers and patients.

The DCRI is leading a new clinical study to optimize care for people with type 2 diabetes and cardiovascular disease through evaluation of a multidisciplinary approach at cardiology clinics across the U.S. The research program, COORDINATE-Diabetes (COOrdinating CaRDIology CliNics RAndomized Trial of Interventions to Improve OutcomEs), will be funded by Boehringer Ingelheim and Eli Lilly and Company.

“The public health impact of type 2 diabetes and cardiovascular disease in the U.S. is immense,” said the DCRI’s Christopher Granger, MD, lead researcher for COORDINATE-Diabetes. “While highly effective evidence-based treatments have been developed, these treatments are not consistently used, and thus preventable death and disability are occurring. Our goal with COORDINATE-Diabetes is to better understand the effectiveness of specific interventions at cardiology clinics to achieve best practices for improving patient health.”

People with diabetes are up to four times more likely to develop cardiovascular disease than those without diabetes, and cardiovascular disease ranks as their leading cause of death and disability despite available treatments. To help improve these striking statistics, COORDINATE-Diabetes will examine the impact of multifaceted interventions involving guideline-based therapies among cardiologists, endocrinologists, primary care providers and patients, including the recommendations outlined in the American Diabetes Association (ADA) 2018 Standards of Medical Care in Diabetes and the American College of Cardiology (ACC) Expert Consensus Decision Pathway on novel therapies for cardiovascular risk reduction in adults with type 2 diabetes and atherosclerotic cardiovascular disease.

The trial will include 46 cardiology clinics in the U.S. and aims to enroll 30 patients at each site. The clinics will be randomized to a basic education arm (in which patients will be treated by clinicians who receive only basic information about guideline-based therapy) or an intensive intervention arm (that focuses on coordinating care between cardiologists and endocrinologists to develop and implement an integrated, multidisciplinary care pathway). The care teams at the intervention sites will be encouraged to communicate with patients’ primary care physicians to facilitate a well-rounded, multidisciplinary approach to patient care. The trial will measure the impact of the intervention on the sites’ use of guideline-recommended therapies after 12 months.

“We are pleased to support evidence-based research to understand how to best manage risks and optimize care for patients with type 2 diabetes and cardiovascular disease in a real-world, clinical setting,” said Thomas Seck, MD, senior vice president, Medicine and Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “Although there are treatments with proven cardiovascular benefits recommended by the ADA and other organizations, many healthcare providers are not prescribing them to all their patients who may benefit. We look forward to learning more about how healthcare providers can work together to improve adherence to these treatment guidelines in the quest to reduce patients’ cardiovascular risk.”

The trial will also leverage the power of electronic health record data from a consortium of health systems across the U.S. that have curated their data to support research and improve outcomes. Researchers will begin enrolling clinics and patients for the study in 2019 with the goal of sharing the main results by 2021.

“Few rigorous studies have tested the effectiveness of a multidisciplinary approach to improving care among this vulnerable patient population,” noted Sherry Martin, MD, vice president, Medical Affairs, Lilly. “Given the serious cardiovascular complications associated with type 2 diabetes, it is important for cardiologists and endocrinologists to work collaboratively to help improve care for people with type 2 diabetes and cardiovascular disease.”

Age is the biggest risk for heart disease, but lifestyle and meds have impact

December 11, 2018 – Understanding what modifications can work will help improve adherence to guidelines, researchers say.

Of all the risk factors for heart disease, age is the strongest predictor of potential trouble.

While no one can stop the march of time, making healthy lifestyle choices or adhering to medication regimens for conditions such as high cholesterol, hypertension or diabetes can substantially reduce the risk of heart disease.

Michael Pencina

Understanding which risk factors modifications are actually effective, and by how much, is increasingly important for doctors and patients to understand in light of new blood pressure and cholesterol guidelines that drive medical care.

In a study published online Dec. 7 in the journal Circulation, a research team led by the DCRI provided a statistical analysis that answers the question of what works to lower heart disease risk, and by how much.

“Guidelines of who to treat for cardiovascular disease depend on risk, so we need to accurately estimate that risk,” said lead author Michael Pencina, PhD, vice dean for Data Science and Information Technology at the Duke School of Medicine and member of DCRI.

“Although taken individually, each modifiable risk factors contributes only modestly to the heart disease risk model performance,” Pencina said. “But our analysis indicate that eliminating or controlling these factors can lead to substantial reductions in serious cardio-vascular events.”

Pencina and colleagues analyzed key modifiable heart disease risk factors, including lipids/cholesterol, systolic blood pressure, diabetes and smoking. Each of those factors was assessed for associations with major heart events such as myocardial infarction, angina or cardiac arrhythmia.

Using pooled participant-level data from four National Heart, Lung and Blood Institute studies that included more than 22,000 people aged 45-85, the researchers found that:

  • Age, sex, and race account for about 80 percent of the predictive power of cardiovascular risk models, with age being the main predictor.
  • Adding either systolic blood pressure, high cholesterol, diabetes, or smoking to a model with other risk factors only minimally increases the ability of the model to determine who will suffer heart disease events.
  • Lowering blood pressure to current recommendations (systolic measurement of less than 130) and lowering low-density lipoprotein cholesterol by 30 percent could reduce the 10-year coronary heart disease risk by as much as a third.

Pencina said there are two ways to achieve lower blood pressure and cholesterol: Never acquire the adverse conditions by maintaining a healthy weight and exercising, or manage them with appropriate lifestyle modifications and medications. The better of the two approaches is, not surprisingly, not developing risk factors.

“Our models suggest that when making individual treatment decisions, clinicians and patients should consider not only the 10-year risk of coronary heart disease, but also the expected benefit from the intervention,” Pencina said. “We are moving from models that focus either on the causes or the risks, to a model that combines both and focuses on potential risk reduction.”

In addition to Pencina, study authors include Ann Marie Navar, Daniel Wojdyla, Robert J. Sanchez, Irfan Khan, Joseph Elassal, Ralph B. D’Agostino, Eric D. Peterson and Allan D. Sniderman.

Clinical trial sheds new light on potential risk associated with intravenous iron treatment

December 6, 2018 – A new clinical trial finds that many patients who were treated for iron deficiency anemia with ferric carboxymaltose showed persistent hypophosphatemia five weeks after receiving the treatment.

Results from a new clinical trial may shed new light on hypophosphatemia, a condition caused by a drop in phosphate levels in the blood that has emerged as a common side effect of a widely used intravenous iron treatment for iron deficiency anemia.

Although the first line of treatment for iron deficiency anemia is often oral iron, many patients who experience adverse effects require intravenous iron as an alternative treatment. A recent study led by Myles Wolf, MD, MMSc, of the DCRI (pictured) compared the risk of hypophosphatemia in two intravenous iron treatments – ferric carboxymaltose (Injectafer®), which is currently the most widely used on the market, and ferumoxytol (Feraheme®).

The study’s results were published today in the journal JCI Insight.

The FIRM trial was a randomized, double-blind trial that investigated 1,997 patients over a period of five weeks. Roughly half of the patients received a total of 1,500 mg of ferric carboxymaltose, while the other half received 1,020 mg of ferumoxytol. Each group received the first half of their treatment at baseline and the second half one week later. Hypophosphatemia is listed as a common side effect on the label for ferric carboxymaltose, but it has generally been considered a benign and transient condition, Wolf said. However, recent case reports and the results from the FIRM trial suggest otherwise.

“In the trial we saw that patients who were treated with ferric carboxymaltose were more likely than patients who received ferumoxytol to experience severe or extreme hypophosphatemia,” said William E. Strauss, MD, executive director of medical affairs at AMAG, the company that manufactures ferumoxytol. “These patients were also more likely to have severe hypophosphatemia that persisted at the end of the five week long study.”

The FIRM trial results were as follows, for ferric carboxymaltose and ferumoxytol recipients respectively:

  • 50.8 percent versus 0.9 percent had severe hypophosphatemia, defined as phosphate levels less than 2.0 mg/dL
  • 10.0 percent versus 0.0 percent had extreme hypophosphatemia, defined as phosphate levels below 1.3 mg/dL
  • 29.1 percent versus 0.0 percent had persistence of severe hypophosphatemia at the end of the five-week study period

Wolf said these results suggest hypophosphatemia is not always as transient as once thought. He added that recent case reports have shown instances of persistent hypophosphatemia that led to osteomalacia, bone fractures, and other musculoskeletal disorders. Other literature has found that some patients who take a single dose of ferric carboxymaltose have experienced fatigue and shortness of breath.

Researchers were also able to determine which patient populations were at higher risk because of the large study population. Results showed that both women with abnormal uterine bleeding and black patients were high-risk populations. Because kidney failure is associated with reduced ability to excrete phosphate, patients with healthy kidneys are more likely to develop intravenous iron-induced hypophosphatemia. This phenomenon, Wolf said, is a serious concern.

“This problem is slipping through the cracks in the health care system,” Wolf said. “Nephrologists often administer intravenous iron, and they focus on phosphate because they treat people with kidney failure who frequently develop hyperphosphatemia,” he said. “But they rarely see hypophosphatemia in response to iron because kidney diseases reduces the risk. In contrast, other practitioners who frequently administer intravenous iron to patients at high risk for hypophosphatemia do not think about phosphate levels, and phosphate levels are not measured in standard lab panels.

“Meanwhile patients feel poorly because of their lower phosphate levels, but it is easy to misattribute their symptoms to the original iron deficiency they are being treated for or the underlying disease that caused iron deficiency. If we don’t raise clinicians’ awareness of hypophosphatemia, it’s going to get missed, and grave consequences can ensue.”

DCRI researcher receives 2018 Carolinas Collaborative Grant

December 5, 2018 – Melissa Daubert, MD, will collaborate with researchers at UNC-Chapel Hill to study how to optimize cardiovascular care in women with hypertensive disorders of pregnancy.

The DCRI’s Melissa Daubert, MD, has received one of four 2018 Carolinas Collaborative Grant awards to examine the postpartum care received by pregnant women with hypertensive disorders.

“From retrospective studies, we know that hypertensive disorders during pregnancy put women at higher risk for cardiovascular events later in life,” Daubert said. “If we screen for these early markers for future disease and treat them appropriately, we have the potential to change the trajectory for these patients.”

The $50,000 grant, administered by the North Carolina Translational and Clinical Sciences Institute, calls for applicants to collaborate with researchers from other institutions to use resources from the Carolinas Collaborative. The Collaborative harmonizes electronic health record data across Duke, the University of North Carolina at Chapel Hill, the Medical University of South Carolina, and Wake Forest University.

Daubert, the principal investigator, will work with co-investigators in cardiology and obstetrics-gynecology at Duke (the DCRI’s Tracy Wang, MD, and Thomas Price, MD) and UNC-Chapel Hill (Rachel Urrutia, MD, MS, and Paula Miller, MD). The team will study women with hypertensive disorders of pregnancy who received treatment from Duke and UNC between January 2007 and June 2018. Preliminary results show that over 10,000 women have experienced a hypertensive disorder of pregnancy, which is about 14 percent of all pregnancies that received care at Duke and UNC-Chapel Hill during this time period.

“The national average for the proportion of pregnancies in which the mother has a hypertensive disorder is 10 percent, so these complications are particularly prevalent in our region,” Daubert said. “That makes this study especially important to figure out how best to care for this high-risk population of women and devise interventions to reduce their future cardiovascular risk.”

In North Carolina, many patients transition between Duke and the University of North Carolina Health Care Systems for their primary and specialty care needs. The collaborative nature of the study is also important, Daubert said, because if the research team looked at records from only one institution, there would be a high likelihood of missing follow-up care or treatment for women who saw providers at both Duke and UNC. Because the Carolinas Collaborative has coded electronic health records so that they can be viewed simultaneously across institutions, she said, it was the perfect opportunity to answer this research question.

Guidelines from the American Heart Association advise that women who have hypertensive disorders during pregnancy should be screened six to 12 months after giving birth. Daubert and her team will look at how consistently this screening is being carried out, as well as which types of providers are conducting the screening. They will also compare outcomes of women who received screenings and women who did not.

“While there is growing awareness that these hypertensive disorders increase risks down the road, this correlation is still often unrecognized by patients and providers,” Daubert said. “There is also a misconception that the cardiovascular events will occur decades later, but in reality, up to 45 percent of women who have hypertensive disorders during pregnancy will develop overt hypertension that needs treatment within five years of giving birth.”

Daubert said her team will also be considering how providers in different specialty areas can have the most impact, as well as how care for these patients should be distributed.

“Not only will this lay the groundwork for future studies, but it will also help us identify gaps in care and determine where therapeutics interventions could be implemented in clinical practice,” she said.

The project also recently received a $20,000 DCRI Innovation Award.

DCRI faculty make “highly cited” list again

November 28, 2018 – Ten DCRI faculty members are listed in a new ranking of the world’s most influential researchers.

Once again, several DCRI faculty members are included in the 2018 Highly Cited Researchers list compiled by Clarivate Analytics and Web of Science.

A high citation rate is an indication that a researcher’s work is influential in their field. In both 2016 and 2017, Duke was the fifth-highest cited U.S. institution.

The DCRI researchers listed on this year’s list are Robert Califf, Lesley Curtis, Pamela Douglas, Christopher Granger, Richard S.E. Keefe, L. Kristin Newby, E. Magnus Ohman, Manesh Patel, Michael Pencina, and Eric Peterson. Pencina, the school of medicine’s vice dean for data science and information technology, appears on the list in two separate categories. Several of this year’s researchers also appeared on previous year’s lists.

This year’s list of 6,078 names recognizes world-class researchers for their production of multiple highly cited papers that rank in the top one percent by citations for their field and over the past decade (2006 to 2016), based on Web of Science data. Clarivate’s website allows users to explore the data further.

“The Highly Cited Researchers 2018 list helps to identify the researchers who are having the greatest impact on the research community as measured by the rate at which their work is being cited by others and that contributes so greatly to extending the frontier and gaining knowledge and innovations for society,” said Annette Thomas, CEO of the Scientific and Academic Research group at Clarivate Analytics.

The DCRI’s Sheng Luo on the benefit of biostatistics

November 27, 2018 – DCRI biostatisticians play a key role in many of the organization’s projects.

When the Duke Department of Anesthesiology recently re-applied for a research grant from the National Institutes of Health (NIH), it invited DCRI’s Sheng Luo, PhD, to contribute his biostatistical expertise. The NIH grant would be for a study related to chronic pelvic pain affecting reproductive-aged women.

Sheng LuoThe trial was a multi-site, randomized, double-blinded trial to compare the efficacy of individualized treatments in alleviating pain and improving outcomes for patients suffering from vestibulodynia (VBD). Investigators hoped the study’s findings would help patients, their partners, and their clinicians make more informed decisions about pain management related to VBD. The study design was longitudinal, with patients followed over a period of time and returning for follow-up visits.

“Because data will be collected at each visit,” Luo said, “it was especially important to add a statistical section in the proposal on how we analyze that kind of longitudinal data and what model the study will use. We want to plan for many variables and outcomes of interest.”

A major challenge in all clinical studies is patient enrollment and retention, and especially the probability of patient dropout, according to Luo.

“We want to be ready to handle that with the right statistical analysis plan,” he said. “A study could see as much as a 10 to 20 percent dropout rate, greatly reducing the chances of statistically and clinically significant results. So we use a whole set of criteria to assess how to increase sample size from the beginning to compensate for dropout.”

In general, he said, when preparing a grant application, “it’s ideal to have a statistician join the conversation as early as possible to tackle a wide range of challenges and issues. When properly designed, the study’s data should have sufficient power to show that therapies do or do not work. This is what we looked at with the VBD study.”

DCRI biostatisticians also help predict whether investigators can meet study targets on time, according to Luo, and if patients will be randomized and blinded properly. “The NIH is very concerned about these issues, which can create huge red flags. When studies are properly designed with enough patients and power to produce usable results, time and money will have been well-spent.”

Working with data related to living organisms, DCRI biostatisticians both crunch numbers and help design studies where enough data and the right kind of information are collected. Along the way, they analyze, evaluate, and interpret results while accounting for biases, and missing data, and other relevant issues.

Luo said that including biostatisticians as part of a study team during the grant application process can help boost the chances for a winning proposal. Thanks in part to Luo’s contributions, this fall the Department of Anesthesiology received the five-year NIH grant for its VBD study. Luo also credited Kevin Anstrom, the DCRI’s Director of Biostatistics, for his assistance in applying for the grant.

“Whether a clinical trial is for government or industry,” Luo said, “biostatistics should always play a major role. We’re glad to be brought into the process as early as possible to provide investigators with feedback on the protocol. The sooner the better, really.”

AHA 2018: Plasma proteins may be biomarkers for cardiovascular disease risk in persons living with HIV

November 12, 2018 – A DCRI substudy identified proteins that may differentiate diastolic dysfunction in HIV patients from non-HIV individuals.

As antiretroviral therapy has transformed HIV from a potentially fatal disease to a chronic one, persons living with HIV (PLHIV) may develop more cardiovascular risk factors and CV-related morbidity and mortality, even with viral suppression, than those not infected by HIV.

“Antiretrovirals have shifted the epidemiology of heart failure in HIV from systolic to diastolic dysfunction (DD), putting PLHIV at a higher risk for cardiovascular disease,” said the DCRI’s Svati Shah, MD, MHS. “The question has been what are the mechanisms?”

On Monday at the American Heart Association’s Scientific Sessions 2018 in Chicago, Shah presented her research on proteomics that identify inflammatory, lipid, and cell proliferative pathways in diastolic dysfunction in HIV. Her presentation was a substudy of the CHART (Characterizing Heart Function on Antiretroviral Therapy) clinical trial that recently enrolled 195 healthy PLHIV through the National Heart, Lung, and Blood Institute’s Heart Failure Network.

“With a goal of looking deeply at these patients, we used proteomic profiling technologies to test CHART blood samples and locate the novel biomarkers and potential mechanisms underlying DD in PLHIV,” Shah said. “Both cardiac fibrosis and inflammation have been proposed as key mechanisms in PLHIV underlying cardiovascular disease and heart failure with preserved ejection fraction (HFpEF), but those mechanisms had not been well understood.”

After assaying 977 unique protein biomarkers, Shah and her colleagues determined that cardiac fibrotic pathways (as represented by extracellular matrix proteins) rather than inflammatory pathways were the strong differentiators of DD in PLHIV. “We believe these biomarkers can help identify those PLHIV who have DD and are at risk of developing HFpEF or diastolic heart failure.”

Shah’s team also used STRING bioinformatics tools to analyze which pathways may be “overrepresented” in the data. The extra cellular matrix, which is the core component of cardiac fibrosis, was overrepresented in the significant proteins, Shah said.

“This reinforces other findings that it is not just one protein but several proteins in that pathway that are significant in the development of DD in PLHIV,” she said. “The beauty of these relatively new technologies is the ability to measure so many proteins in very small amounts of blood. It’s like a liquid biopsy, and with such high specificity that we can be confident of what we are measuring.”

“Basically, we are measuring the stiffness of the heart, which is, at a simple level, what DD is,” Shah said. “These proteins essentially show us how cells talk to each other and how they become stiff and cause cardiovascular disease. Going forward, we plan to compare these results to a non-HIV infected group and to perform longitudinal assessments.”

Shah said this may be the first time anyone has been able to look at this many plasma proteins at one time.

“We may also be the first to use high throughput large-scale proteomic profiling to get this comprehensive and unbiased view of the diverse biological pathways underlying DD in PLHIV,” she said.

In addition to Shah, DCRI contributors included Lydia Coulter Kwee, Steven McNulty, and Adrian Hernandez.

AHA 2018: DCRI founder Robert Califf honored with Braunwald Mentoring Award

November 11, 2018 – The award is given to physicians who demonstrate excellence in mentoring young academic clinicians.

The American Heart Association (AHA) has awarded DCRI founder and former FDA Commissioner Robert M. Califf, MD, the 2018 Eugene Braunwald Award for Academic Mentoring. The award, which is given to physicians who demonstrate a consistent track record of outstanding mentorship of young academic physicians, was presented to Califf Sunday at the AHA’s annual meeting in Chicago.

For Califf, who is currently the director of Duke Forge, vice chancellor for health data science, and Donald F. Fortin Professor of Cardiology at the Duke University School of Medicine, the award recognizes a commitment to teaching and mentoring that has been a recurring theme throughout a four-decade career as a cardiologist, researcher, teacher, and public servant.

With the exception of an internal medicine residency at the University of California – San Francisco and two years serving as Deputy Commissioner and then Commissioner of the FDA, almost all of Califf’s career, including his time as an undergraduate and medical student, has been spent at Duke University. But despite his long association with Duke, Califf remains keenly aware that learning and mentoring are to be found in many places.

“Mentoring is a two-way street,” said Califf, noting that some of the most profound lessons of his career have been imparted outside of academia.

Although perhaps best known as a leading figure in cardiovascular clinical trials and as the founding director of the DCRI, Califf also taught and mentored multiple generations of academic physicians at Duke, incorporating continuous learning and teaching into the fabric of the institution he helped create. In addition to mentoring individual learners, Califf also contributed to the creation of innovative training curricula, including the DCRI Research Fellowship Training Program and the University of North Carolina-Duke Collaborative Postdoctoral Training Program.

“Without question, he is the single most important influence in my professional development as both a cardiovascular clinician and a cardiovascular clinical researcher,” said Robert Harrington, MD, chair of the Department of Medicine at Stanford University and incoming AHA president. Harrington, who spent more than two decades at Duke as a cardiologist and clinical researcher, first met Califf in 1990 upon arriving at Duke to begin a cardiology fellowship.

“He has an amazing ability to push people into areas where they are not yet accomplished, to step back and let them run a bit on their own, but to always be available when things don’t work out,” Harrington continued, noting that Califf’s mentoring style helped trainees to grow into true colleagues.

His extensive contributions as mentor at Duke were honored in 2012 with the Duke Clinical Research Mentoring Award, and the DCRI’s award given to faculty for outstanding mentorship of fellows is named in honor of Califf. Among the numerous clinicians and researchers, and academic leaders that Califf mentored are Harrington and the Chair of the 2018 Scientific Sessions, Eric Peterson, MD, MPH, – both of whom also followed Califf in the role of director of the DCRI.

During Califf’s remarks at the award presentation, he also issued a call to service. Noting that amid deep cultural and political division the United States is currently experiencing significant health challenges that threaten to erode hard-won gains in life expectancy and quality of life, he challenged his audience to continue to engage with the wider world outside of academic medicine.

“Keeping our heads down in our respective academic or clinical foxholes will not solve the daunting problems that we face both as health professionals and as members of society,” Califf said. “We must work together to re-envision and change the ways that we work to achieve better health outcomes.”

AHA 2018: Female patients significantly less likely to receive statin therapy compared with male patients

November 11, 2018 – A DCRI analysis of patient data from the PALM Registry examines possible reasons for the treatment gap.

While the safety and efficacy of statin therapy for the prevention of atherosclerotic cardiovascular disease is well-established, female patients have historically received less aggressive lipid management than males, according to the DCRI’s Michael Nanna, MD. The reasons for those differences, he said, have been poorly understood.

To investigate this discrepancy, Nanna and his colleagues examined patient data from the PALM (Patient and Provider Assessment of Lipid Management) Registry. Their findings were presented Saturday at the American Heart Association annual meeting in Chicago.

“In looking at why statins are underutilized in eligible women,” Nanna said, “we concluded that they were more likely to never be offered a statin, to decline a statin, and to discontinue a statin than men, even when meeting a treatment indication. This was also after adjusting for patient beliefs, demographics, provider type, and other factors.”

The investigators identified nearly 6,000 adult patients (43 percent female) potentially eligible for primary or secondary prevention statins at 138 U.S. cardiology, primary care, and endocrinology practices in 2015 in the PALM Registry. PALM data and patient surveys showed that 36.7 percent of female patients were on statin treatment and guideline-recommended statin intensity compared to 45.2 percent of male patients, and that these results were consistent across levels of education and income as well as type of treating physician.

Nanna’s study used the 2013 American College of Cardiology and the American Heart Association guidelines on the treatment of blood cholesterol to identify patients eligible for guideline-recommended statin treatment.

“I was surprised to find that such differences persist in contemporary practice and the degree to which they do so,” Nanna said. “Another surprising insight was the difference in beliefs and perception between female and male patients — women were more worried about heart attacks and strokes, for example, but less likely to believe in the association between cholesterol and their heart attack risk.”

Nanna’s study also showed that about 50 percent of female and 43 percent of male patients currently on statins reported adverse effects associated with statin use and that nearly 7.8 percent of women versus 3.6 percent of men reported stopping their statin use as a result. In addition, female patients who were formerly on statins and those that were never on statins were both less willing to try a statin compared with males.

The study had several limitations, according to Nanna. The researchers were unable to specifically capture reasoning for statin prescribing and did not have access to longitudinal data on statin dosing.

“We feel that we can begin to close this treatment gap through better education and communication, especially from clinicians,” he said. “Statins are an important medication for cardiovascular risk reduction, especially for those with existing cardiovascular disease.”

In addition to Nanna, DCRI researchers contributing to the study included Tracy Wang, Qun Xiang, Eric Peterson, and Ann Marie Navar. The study was funded by a National Institutes of Health (NIH) training grant and by Sanofi and Regeneron Pharmaceuticals.