EXSCEL Contributes to New Discoveries via Secondary Manuscripts

January 15, 2020 – The EXSCEL trial, which explored the impact of exenatide on major cardiovascular events in patients with Type 2 diabetes, has also published nearly a dozen secondary manuscripts on a range of topics.

The study team on the EXSCEL trial, which was co-led by the DCRI and Oxford University’s Diabetes Trial Unit (DTU), continues to draw insights and share knowledge through impactful secondary manuscripts nearly three years after the conclusion of the trial.

EXSCEL logoEXSCEL, which was sponsored by Amylin Pharmaceuticals, a subsidiary of AstraZeneca, was a global trial run over the course of eight years. The study assessed whether patients with Type 2 diabetes who were given once-weekly exenatide experienced fewer major adverse cardiovascular events than those on placebo. Although the results from the exenatide group did not meet statistical significance for superiority in reducing cardiovascular events as compared to placebo, a prespecified analysis suggested that all-cause mortality was lower for patients taking exenatide. Primary results from the trial were published in 2017 in the New England Journal of Medicine.

Since then, data from EXSCEL have been leveraged to publish 11 secondary manuscripts. In the fall and winter of 2019 alone, members of the DCRI contributed to six EXSCEL publications in topics ranging from heart failure to medical costs.

“Initial results from EXSCEL answered an important question about the safety and efficacy of treating patients with Type 2 diabetes with once-weekly exenatide,” said the DCRI’s Adrian Hernandez, MD, MHS, who served as a co-principal investigator of EXSCEL. “We are also pleased to see how many additional questions this dataset has been able to answer via a robust set of secondary manuscripts. Because of the work of these investigators, EXSCEL has had an even broader impact on patient care.”

Read below to see a sampling of recently published studies that used EXSCEL data to answer research questions.

How Are Patients with Heart Failure Affected by Exenatide?

A DCRI-led group of researchers examined EXSCEL data to determine the associations of once-weekly exenatide with secondary endpoints in patients with and without heart failure. The researchers were also interested in determining associations with recurrent hospitalization for heart failure.

Although exenatide was safe for both patients with and without baseline heart failure, there was evidence that those who did have heart failure saw less benefit from the treatment. Patients without heart failure were more likely to see a decrease in rates of all-cause death and hospitalization for heart failure as compared to those with baseline heart failure.

Adrian Hernandez, MD, MHSThe results were published online in Circulation in September 2019. Former DCRI fellow Marat Fudim, MD, served as the lead author, with the DCRI’s Robert Mentz, MD, as the senior investigator. Additional DCRI faculty contributors included Neha Pagidipati, MD, MPH; Renato Lopes, MD, PhD; Yuliya Lokhnygina, PhD; and Hernandez. Jennifer White, MS provided staff statistical support for this publication.

How Do Different Classes of Diabetes Medications Interact and Affect Cardiovascular Outcomes?

Hernandez (pictured left) and Mentz worked with researchers from other institutions and with representatives of the study’s sponsor to study the 8.7 percent of participants who also received an SGLT2 inhibitor either with or shortly after their assigned treatment of exenatide or placebo. A post-hoc analysis suggested that combining SGLT2 inhibitor therapy with exenatide may benefit cardiovascular outcomes and mortality.

The findings were published in October 2019 in Cardiovascular Diabetology.

How Does Exenatide Affect Patients with Peripheral Artery Disease?

Researchers also analyzed EXSCEL data to take a closer look at peripheral artery disease (PAD). The investigators were interested in determining the association between baseline PAD at the trial’s outset with rates of subsequent major adverse cardiovascular events and lower extremity amputation. They also assessed the effects of exenatide in patients both with and without PAD.

The results showed that trial participants with PAD had higher rates of all-cause mortality and amputation than participants without PAD. However, patients treated with exenatide or placebo had similar rates of major adverse cardiovascular events and lower extremity amputation, regardless of whether they had PAD.

Duke’s Anish Badjatiya, MD, served as lead author on this paper, which was published in Circulation: Cardiovascular Interventions in November 2019. The DCRI’s Schuyler Jones, MD, was senior investigator. Other DCRI contributors to this paper included Pagidipati; Manesh Patel, MD; Hernandez; and Mentz.

How Does Exenatide Affect Outcomes In Patients of Differing Renal Function?

Investigators on this study evaluated the microvascular and cardiovascular outcomes of trial participants after separating them into groups based on their baseline renal function. Results showed that exenatide had no impact on unadjusted retinopathy or renal outcomes.

Angelyn Bethel, MD, previously at the DTU and now at Eli Lilly and Company, served as the lead author for this paper, which was published in Diabetes Care in November 2019. DCRI faculty contributors included Mentz, Lopes, Hernandez, and Lokhnygina. Peter Merrill, PhD, provided staff statistical support for this publication.

Does Exenatide Help Alleviate Health Care Costs?

A study led by the DCRI’s Shelby Reed, PhD, followed patients enrolled in the EXSCEL trial for an average of 3.3 years to analyze medical resource use and costs for each arm of the trial.

Overall medical costs, including diabetes medications other than the study drug, exenatide, were lower in the group receiving exenatide. However, when the cost of branded exenatide was factored in, the total costs were lower in the placebo arm.

Other DCRI contributors to this study included Mentz, Pagidipati, and Hernandez. The paper was published in Diabetes Care in December 2019.

Is There A Relationship Between Severe Hypoglycemic Events and Cardiovascular Events?

A study sought to determine whether there was a bidirectional association between severe hypoglycemic events and cardiovascular events, and to characterize individuals who are at risk for both.Robert Mentz, MD

Although severe hypoglycemic events were uncommon in the EXSCEL trial, fully adjusted models showed that these events were associated with an increased risk of all-cause mortality, cardiovascular death, and hospitalization for heart failure. Certain cardiovascular events, such as heart attack, stroke, and hospitalization for acute coronary syndrome or heart failure, were also associated with an increased risk of subsequent severe hypoglycemic events. These results confirm the bidirectional nature of the two adverse outcomes in patients with high comorbidity scores.

Eberhard Standl, PhD, of the Munich Diabetes Research Group e.V. at Helmholtz Centre, served as the lead author for the paper, which was published in Diabetes Care in December 2019. The DCRI’s Mentz and Hernandez also contributed to the study.

“EXSCEL has been a fascinating project to work on over the years as we continued to learn new insights and worked with colleagues around the world on new secondary manuscripts,” Mentz (pictured right) said. “Not only is this a great example of the ways in which DCRI shares knowledge, but the study has also provided exciting breakthroughs in the cardio-metabolic space as we care for patients with an increasingly wide spectrum of comorbidities.”

With Huge Opportunities for Cardiovascular Secondary Prevention, Better Adoption Strategies will be Critical

January 8, 2020 – In response to a recent study that found the majority of cardiovascular patients are eligible for at least one of 12 novel secondary prevention therapies, representatives from the DCRI urge a focus on implementation of these therapies into clinical practice.

The wide range of new therapies for cardiovascular secondary prevention raises questions about the best way to use these therapies in clinical practice and underscores the need for novel approaches to implement these therapies into routine patient care, according to a recent editorial in JAMA Cardiology written by DCRI fellow Michael Nanna, MD, (pictured left), and DCRI’s Eric Peterson, MD, MPH (pictured right).

Michael Nanna, MDThe editorial, titled “Translating the Secondary Prevention Therapeutic Boom Into Action,” accompanied a study by Martin Bodtker Mortensen, MD, PhD, and colleagues, which examined a population of more than 8,000 patients to determine the proportion of patients who were eligible for 12 novel cardiovascular preventive therapies. Findings from the study were compelling, with 80 percent of patients with a prior myocardial infarction eligible to receive four or more new therapies.

These new therapeutic choices are daunting particularly because there is no evidence defining what the optimal combination of these therapies are. Implementation of these therapies into clinical practice is also a significant concern. “Despite the billions of dollars spent yearly by pharmaceutical companies on prescriber detailing and direct-to-consumer marketing, the scientific breakthroughs of the last decade remain unrealized for most eligible patients,” Nanna and Peterson write.Eric Peterson, MD, MPH

More work needs to be done to drive faster drug adoption.  “To date, multifaceted strategies that combine clinician education, real-time feedback, performance incentives, policy changes, and patient engagement strategies have proven most effective,” Nanna and Peterson write. They also note that future opportunities in this arena exist in using the electronic health record to identify patients who are eligible for treatments and alert clinicians of opportunities to improve care.

More Individualized Decision Making Needed in Treatment of Acute Ischemic Stroke

January 6, 2020 – The observational study found that amongst acute ischemic stroke patients treated with intravenous tissue plasminogen activator, patients who had experienced a previous stroke within the past two weeks were especially susceptible to symptomatic intracranial hemorrhage.

Recent findings from the DCRI published in Circulation Cardiovascular Quality and Outcomes shed new light on when it might be risky to use intravenous tissue plasminogen activator (IV tPA) as a treatment for acute ischemic stroke in patients with history of a previous ischemic stroke.

IV tPA has been an approved treatment for acute ischemic stroke since a large trial sponsored by the National Institute of Neurological Disorders and Stroke (NINDS) proved its safety in 1995. However, exclusion criteria for the trial eliminated patients who had experienced a stroke within the past 90 days. Because of the lack of safety data for this group, current guidelines recommend against use of IV tPA for these patients.

Shreyansh Shah, MDHowever, the DCRI’s Shreyansh Shah, MD, the lead author of the paper, explained, these guidelines are not always adhered to in clinical practice. As providers become more comfortable with using IV tPA, some have begun to use the treatment on types of patients not included in the original trial data. A group at the DCRI decided to conduct an observational study to determine the safety of this practice.

The study, funded by a grant from the American Heart Association to the DCRI’s Ying Xian, MD, PhD, examined a population of 31,987 patients that experienced an ischemic stroke and were treated with IV tPA, comparing a group of patients who had experienced a prior stroke within the past 90 days with a control group of patients with no prior history of stroke. The analysis found that the patients with recent history of stroke were more likely to have adverse outcomes of in-hospital mortality or discharge to hospice. This is likely because patients with previous stroke history have a poorer functional baselines, Shah said.

However, symptomatic intracranial hemorrhage, thought to be the primary risk associated with IV tPA when treating patients who had experienced a recent stroke, was not found at higher rates. The study team conducted a secondary analysis in an effort to further stratify the recent stroke population and identify which patients were truly at higher risk when treated with IV tPA. The secondary analysis found elevated rates of adverse outcomes in patients who experienced a prior stroke within the past 30 days. However, higher rates of symptomatic intracranial hemorrhage were only found in patients who experienced a prior stroke within the last two weeks.

“Beyond two weeks after a prior stroke, our analysis found the risk for intracranial hemorrhage to be similar for patients with history of stroke and patients without,” Shah said. “This analysis suggests that while IV tPA may still be harmful to some patients, that subset may be smaller than we originally thought. More individualized treatment decisions will be necessary in caring for patients who have experienced an acute ischemic stroke, with providers and patients weighing the potential risks and benefits together.”

The patients included in this study were drawn from the Get With the Guidelines-Stroke registry, for which the DCRI acts as a coordinating center. To enable additional analysis, the DCRI also Ying Xianhelped link the patients to their Medicare records. Shah said the ability to provide this linkage is one of the greatest strengths of the DCRI’s Outcomes Group, as it enables more longitudinal follow-up and communicates information about specific timing of the patients’ previous stroke.

“This study used real-world evidence to provide useful insights about how clinical practice differs from recommendations outlined by the guidelines,” said the DCRI’s Ying Xian, MD, PhD. “With these results, we can better understand when this derivation from the guidelines may be beneficial for the patient, as well as when it may pose a potential risk.”

Other DCRI contributors to the paper include Adrian Hernandez, MD, MHS; Eric Peterson, MD, MPH; and Li Liang, PhD (statistics). Barbara Lytle served as the DCRI project leader for this project.

DCRI-led Trial Leads to Coronary Device Approval in Japan

January 2, 2020 – The HARMONEE trial is part of the Harmonization by Doing program, which aims to create a uniform pathway for clinical development in the U.S. and Japan.

A DCRI-led trial that was the first to use a common protocol to study a device in patients in both the U.S. and Japan recently led to approval for a coronary device in Japan.

Mitchell Krucoff, MD

HARMONEE enrolled 572 patients with ischemic coronary disease and non-ST-elevation acute coronary disease across 50 sites in the U.S. and Japan to test the efficacy of a novel combo stent developed by OrbusNeich Medical. The DCRI’s Mitchell Krucoff, MD, (pictured left), was the international co-primary investigator, along with Shigeru Saito, MD, from Kamakura, Japan. The DCRI’s David Kong, MD, (pictured right), served as the primary investigator leading the operations team.

Because stents work by inserting a metal scaffold into the blood vessel to help open it, these devices can present a risk of blood vessel tears. The tears heal by developing scar tissue, which may result in blocked blood vessels—the same condition the stent was meant to treat.

To address this problem, producers of stents began to use chemotherapy agents to prevent scar tissue from growing. However, the drugs also prevented healing, which increased risk of blood clots leading to stent thrombosis.David Kong, MD

The combo stent tested in the HARMONEE trial seeks to prevent stent thrombosis by including an antibody that attracts progenitor cells in an effort to combat the negative effects of the chemotherapy drug, sirolimus.

The trial, which randomized patients to either a typical stainless steel stent, or the combo stent, completed dual regulatory objectives. In the U.S., it functioned as a feasibility study, while in Japan, it led to Shonin regulatory approval—the equivalent of pre-market authorization in the U.S.

Primary results from HARMONEE were presented as a late-breaking clinical trial at TCT 2017 and were published in American Heart Journal.

HARMONEE is a part of the “Harmonization by Doing” program, which is a collaborative effort between U.S. and Japanese academics, medical device industry collaborators, and the U.S Food and Drug Administration (FDA) and the equivalent regulatory body in Japan, the Pharmaceuticals and Medical Devices Agency (PMDA). The goal of the program, which has been running for over 15 years, is to create a uniform pathway for clinical development in the U.S. and Japan. DCRI founders and leaders of the program are Krucoff and John Alexander, MD, MHS (pictured bottom).

Working with Japan on device approvals is a great opportunity because it is such a large and important health care market, Alexander said. Additionally, both countries have learned from each other throughout the process.

John Alexander, MD, MHSA trial like HARMONEE takes coordination from many groups within the DCRI, including regulatory experts, statisticians, and operations staff. It also requires external collaboration with a Japanese contract research organization and Japanese regulators. The DCRI’s Clinical Events Classification (CEC) group also played a major role in this study, building a robust system for electronic data capture of clinical events. The group also built a quality control process, blindly resending events back through additional adjudicators and comparing the results to ensure consistency in the adjudication process. Lauren Arney served as the CEC project lead for the study, and Alicia Lowe served as the CEC coordinator. The DCRI’s Rajendra Mehta, MD, oversaw the work as the CEC principal investigator. Additional DCRI contributors to this project include Diane Joseph, the project leader; and Hussein Al-Khalidi, PhD, and Jyotsna Garg, MS, who served as senior statisticians.

“The DCRI’s ongoing partnership with clinical investigators in Japan is a good representation of the DCRI’s mission to conduct innovative clinical research and share knowledge that improves the care of patients around the world,” Alexander said. “Our faculty and operational staff collaborate with colleagues from many countries around the world.”

Certain Risk Factors Could Predict High Costs for Patients with Musculoskeletal Pain

December 31, 2019 – A new analysis from the DCRI showed that 35 percent of direct costs related to musculoskeletal pain were attributable to about 4 percent of patients who were persistent high-cost utilizers.

Health care delivery models that take into consideration risk factors such as physical and mental health may help alleviate the burden of high costs for patients with musculoskeletal pain, according to recent DCRI-led research.

An analysis led by the DCRI’s Trevor Lentz, PT, PhD, MPH, and recently published in PLOS One, examined health care utilization costs and other patient characteristics in a sample of nearly 13,000 patients with musculoskeletal pain drawn from Medical Expenditure Panel Survey data between 2008 and 2013. Because musculoskeletal pain can be a chronic condition, the study team wanted to find out which factors contributed to high health care costs over time.

Findings showed that 35 percent of direct costs related to musculoskeletal pain were attributable to about 4 percent of patients. Persistent high cost utilization was related to non-modifiable variables such as age, race, poverty level, geographic region, insurance status, diagnosis type, and total number of diagnoses. However, modifiable variables also contributed to risk of high costs, including higher number of days missed at work, greater pain interference, and higher use of prescription medication for pain. Conversely, those who reported to have better mental and physical health were less likely to become high-cost utilizers over time.

Trevor Lentz, PT, PhD, MPH“Because we now better understand the factors that are associated with persistently high health care costs, we may be able to prospectively identify the individuals who are at great risk of carrying this burden by looking at demographic and health information for our patients, as well as pain-related characteristics,” Lentz said. “We also may be able to decrease costs for some of these patients by addressing modifiable risk factors within our health care delivery systems.”

“This analysis adds to the conversation because it is, to our knowledge, the first study that examines persistence of high costs for musculoskeletal pain in the U.S,” said Steven George, PT, PhD, FAPTA, who also contributed to the study. “Studies have been conducted in other countries with single-payer systems, but those data do not always translate well to the U.S., where we know that socioeconomic status and insurance status can have a significant impact on health care costs. Further research is needed to be able to ascertain when these high costs are necessary for good musculoskeletal outcomes, versus when they are indicative of low-value care.”

Federal Awards Funds Collaborative Child Health Effort Among Duke, UNC, NC DHHS

December 23, 2019 – The initiative, which will be led by a DCRI pediatrician, aims to create a new care and services model for children in five North Carolina counties.

A federal funding award of up to $16 million to Duke University, in partnership with the University of North Carolina at Chapel Hill and the N.C. Department of Health and Human Services, will help establish an innovative approach to providing health and wellness services to children in five N.C. counties.

The model, called North Carolina Integrated Care for Kids, was one of eight nationally to be awarded funding from the Centers for Medicare & Medicaid Services.

The initiative aims to integrate a variety of services that children receive from different agencies and providers, including those for physical and behavioral health, housing, food, early care and education, child welfare, mobile crisis response services and juvenile justice and safety.

“The NC Integrated Care for Kids model is a tremendous opportunity for us to transform how we support the well-being of children and their families by breaking down siloes and working together across the many systems, including health care, schools, child welfare and early child care settings,” said the DCRI’s Charlene Wong, MD, executive director of the new initiative and an adolescent medicine pediatrician at Duke.

“Our goal is to build relationships, link data and develop new connections between all the different sectors that are currently working to improve the welfare of children,” Wong said. “We believe we can demonstrate that this approach can better serve the children we all seek to help.”

The initiative’s leaders hope improved integration of services will address some of the root causes of poor health, reduce avoidable out-of-home placements, prevent hospitalizations for children, and create innovative and sustainable pediatric alternative payment models under the state’s Medicaid program.

“Children’s health and wellbeing are shaped by so much more than visits to the doctor,” said Mandy K. Cohen, MD, Secretary of North Carolina Department of Health and Human Services. “Do they have enough food to eat? Do they have safe housing? Do they have nurturing caregivers? This model builds on our commitment to caring for the whole person and will help us achieve the bold goals set in our state’s early childhood action plan.”

The model will serve Medicaid- and CHIP-insured children from birth to age 21 in Alamance, Orange, Durham, Granville, and Vance counties, which includes an estimated 80,000 eligible children. The CMS funding allocation begins Jan. 1, 2020 and covers two years for planning and program infrastructure development, followed by five years of implementation beginning in 2022.

The NC Integrated Care for Kid Partnership Council will serve as the governing body. It will include representation from families, youth and Medicaid payers as well as service providers in health care as well as other core areas.

“As the lead organizations at Duke, UNC, and NC DHHS work in collaboration, we are excited to join with many other state and local entities to make this approach a success, and really improve the lives of children by better addressing all of the factors that impact their health,” said Mike Steiner, MD, medical director of NC Integrated Care for Kids and pediatrician in chief of UNC Children’s.

The project described is supported by Funding Opportunity Number CMS 2B2-20-001 from the U.S. Department of Health & Human Services, Centers for Medicare & Medicaid Services. The contents provided are solely the responsibility of the authors and do not necessarily represent the official views of HHS or any of its agencies.

Year in Review 2019: DCRI Continues Study Support and Knowledge Sharing

December 19, 2019 – As the year—and the decade—draws to a close, we take a look back at some of our accomplishments and the ways in which we shared knowledge in 2019.

Road with years on itAs detailed in our DCRI Annual Report, 2019 was a busy and productive year. Our faculty and operational staff published more than 1,300 scholarly articles in FY19—the highest number on record for the DCRI. In addition to publishing science in scholarly journals, DCRI representatives shared their knowledge and expertise in plenty of other avenues, including through writing editorials on seminal topics in their respective fields, contributing research that helped shape FDA guidance and other regulatory documents, and presenting at large conferences. Take a look through this article to view some of the year’s highlights.

Providing Wraparound Study Support: Our Services and Capabilities

The DCRI continues to provide capabilities that are critical to the future of efficient and well-designed clinical research, such as taking pragmatic approaches to clinical trials. This year, the DCRI’s pragmatic approach of identifying and recruiting patients through electronic health records resulted in ADAPTABLE successfully meeting its enrollment goal of 15,000 participants. The DCRI also continues its services in areas like adjudication of clinical events from its Clinical Events Classification group and partnering with patients to provide diverse perspectives in research through DCRI Research Together. New this year to the DCRI was the Behavioral Research Intervention Science Center (BRISC), which implements behavioral incentives into studies and provides evidence for what motivates patients and providers to change their behavior.  Additional services and capabilities provided by the DCRI are discussed in the following articles:

  • The DCRI Arrhythmia Core Lab, which has longstanding expertise in evaluation and adjudication of electrograms and electrocardiograms, is now set to work on more studies that involve wearable devices.
  • The DCRI provides advice on best practices via white papers. For example, through the Global Pediatric Clinical Trials Research Network, the DCRI worked directly with sponsors to identify pain points and challenges to pediatric clinical research, and subsequently released a white paper providing recommendations to address these challenges.
  • Along with groundbreaking studies, the DCRI also generates new evidence through registries, such as the cv-MOBIUS registry that seeks to enroll and follow 8,500 high-risk patients to understand how lipid management treatments are used in real-world practice.
  • The DCRI hosts quarterly DCRI Think Tanks, which are designed to convene diverse stakeholders to tackle the greatest challenges and largest gaps in clinical research. Recently, the DCRI published a paper sharing findings from a think tank on tech-enabled trials.

Sharing Our Expertise: Contributions to Regulatory Documents and Other Recommendations

The DCRI also delivers on our mission to share knowledge through contributing to regulatory documents and other recommendations widely recognized by their fields. This year, work from DCRI pediatrics researchers helped to shape FDA guidance on how to conduct studies in newborns. Several collaborations among the DCRI and other organizations have also helped the FDA to map its strategy and recommendations for using real-world evidence in research. Other key examples of DCRI faculty sharing their expertise to impact their fields include:

Conducting Innovative Research: New Studies and Study Milestones

DCRI teams continued to work diligently on their respective studies. Some teams launched new trials, such as the PREVENTABLE trial, which was awarded $90 million to study the effects of statins on the cognitive function of older adults. Others celebrated the achievement of milestones years in the making; for example, expansive childhood research program ECHO, for which the DCRI acts as a coordinating center, received IRB approval and has already initiated studies. Additional new studies and study milestones included:

Working Together to Make an Impact: Collaborations and Strategic Partnerships

In addition to new studies, the DCRI has also entered into new collaborations over the last year. Some of these strategic partnerships have been study-related, such as a partnership with Cerner, the world’s largest electronic health record company, to leverage real-world data in clinical research. Others have been related to a general area of expertise, such as the DCRI’s entry into the Digital Therapeutics Alliance. Additional collaborations and partnerships include:

Owning Our Perspective: Editorials and Discussion Pieces

From a Viewpoint in JAMA Cardiology from Ann Marie Navar, MD, PhD, which likened medical misinformation surrounding vaccines to fears surrounding statins, to an editorial from Michael Felker, MD, in Circulation that called for more data on the benefits of newer cardio-metabolic drugs, our faculty shared many perspectives this year. A sampling of DCRI stories that covered other editorials and discussion pieces published within the last year include:

Presenting New Discoveries: Attendance at Major Conferences

Many DCRI faculty and operations staff attended both the American College of Cardiology Annual Scientific Session, held in March in New Orleans, and the American Heart Association Scientific Sessions, held in November in Philadelphia. Science shared at these two major cardiology conferences included:

In addition to ACC and AHA, our cardiology faculty, fellows, and staff attended and presented at several other key cardiology related conferences throughout the year, including: the Cardiovascular Clinical Trialists Forum; European Society of Cardiology Congress; the 23rd annual meeting of the Heart Failure Society of America; the Society for Cardiovascular Angiography & Interventions Scientific Sessions; and the Transcatheter Cardiovascular Therapeutics Symposium.

Our conference attendance isn’t reserved for our cardiovascular therapeutics team only, however. DCRI faculty and operational staff also attended and presented at: The American Association for the Study of Liver Diseases; Digestive Disease Week; the Infectious Diseases Society’s IDWeek; the American Society of Nephrology’s Kidney Week; the American Urological Association’s 2019 Annual Meeting; the American Medical Informatics Association’s Informatics Summit and its Annual Symposium; the professional society for health economics and outcomes research (HEOR) annual ISPOR conference; the Society for Clinical Data Management’s SCDM 2019 conference; the Pediatric Academy Societies Meeting; the American Thoracic Society’s International Conference; and the International Stroke Conference.

Survey Finds Older Cardiac Patients Have Different Goals, Lower Risk Tolerance

December 18, 2019 – The survey focused on invasive cardiac care and measured patient knowledge, goals, and concerns related to these procedures.

Findings from a survey conducted by researchers at the DCRI sheds new light on how age plays a role in invasive cardiac care and further emphasizes the need to take individual patient preferences into account when determining a treatment plan.

The study, which was led by DCRI Fellow Michael Nanna, MD, and recently published in the American Heart Journal, surveyed 628 patients hospitalized with acute coronary syndrome. This group included 373 patients younger than 75 and 255 patients who were 75 or older.

The survey sought to determine:

  • Knowledge, preferences, goals, and concerns related to cardiac care;
  • Risk tolerance for coronary artery bypass grafting (CABG) surgery; and
  • Whether willingness to consider different types of invasive cardiac care corresponds with whether patients actually received the procedures.

Prior to this survey being conducted, systematic studies of the knowledge, beliefs, and preferences of older patients as these factors relate to invasive cardiac care had been lacking. There had also been no quantitative assessment of risk tolerance for this type of care.

The survey found that when compared with younger patients, older patients had less knowledge of acute invasive cardiac care and were less willing to consider cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass grafting (CABG). However, even in the older group, the majority of patients were willing to consider cardiac catheterization.

Even when they indicated they would not be willing to consider surgery, many patients across both groups did end up having a procedure done. Nearly half of those who wouldn’t consider cardiac catheterization did have the procedure, and 22 percent of patients who originally answered no underwent percutaneous coronary intervention or CABG.

To measure risk tolerance, the study team measured the patient’s highest risk prior to changing his or her preference away from CABG, a measure called a standard gamble score. Older patients were found to have lower risk tolerance (a median of 1 percent) than younger patients (a median of 20 percent).

Michael Nanna, MDBoth groups were concerned about the potential of death associated with invasive surgery, but other concerns varied between younger and older patients. For example, older respondents cited losing mental capacity as their top concern.

Goals for treatment also differed between the two groups. Younger patients were more likely to prioritize preserving life in the years to come, while older patients prioritized symptom relief. However, smaller proportions of older patients valued preserving life, while smaller proportions of younger patients valued symptom relief, indicating that it is important to consider individual preferences in treatment plans.

“These survey results are illuminating because they reveal the goals, concerns and priorities of older adults as they seek cardiac care later in life,” Nanna said. “While high quality evidence supports revascularization to improve chances of survival and quality of life, we know that one size does not fit all and that individualized treatment plans are important, especially when older adults were not included in many of the evidence-generating studies. Efforts to decrease the knowledge gap for older adults in regard to cardiac surgery have been successful, but more work can be done to ensure we are all well informed as we work together in shared decision-making.”

Other DCRI contributors to this study include Eric Peterson, MD, MPH; Karen Alexander, MD; Angie Wu, MS; Tina Harding, BSN; Anthony Galanos, MD; and Lisa Wruck, PhD.

ADHD Could Present Higher Risk for Nicotine Addiction

December 17, 2019 – A study showed that young adults with ADHD were more likely to self-administer nicotine in both relaxing and cognitively difficult scenarios.

Study results recently published in Neuropsychopharmacology indicate that young adults with ADHD are at higher risk of becoming addicted to nicotine after even the first exposure to the substance.

The study included 136 non-smokers between ages 18 to 25, about half of whom had a clinical diagnosis of ADHD. Participants were administered two different doses of nicotine and a placebo. Then, they were asked to choose a spray while engaged in two different scenarios: a relaxed setting and a setting in which they were asked to solve math problems.

Scott Kollins, PhDThe researchers hypothesized that participants with ADHD would be more likely to choose the nicotine while solving the math problems.

“We have known for a long time that nicotine does have some of the same properties that medicine used to treat ADHD has,” said the DCRI’s Scott Kollins, PhD, while discussing the findings in an interview with NPR. “It increases vigilance and attention.”

However, while participants without ADHD were more likely to choose nicotine when working on the math problems, those with ADHD were more likely to self-administer nicotine in both scenarios. Participants with ADHD were also more likely to report pleasurable effects from the nicotine.

Kollins, who was the lead author of the paper, said that these results indicate that young adults with ADHD could be at higher risk for nicotine addiction after only one exposure to the substance. Conversation, education, and prevention efforts surrounding nicotine use and addiction need to start early, he added.

Research Network Based at DCRI Awarded up to $102.5M for Work on Antibacterial Resistance

December 13, 2019 – The Antibacterial Resistance Leadership Group conducts clinical research to better understand how to diagnose, treat, and prevent antibacterial resistant infections.

 The Antibacterial Resistance Leadership Group (ARLG), a unique research network for which the DCRI acts as a coordinating center, received a federal award worth up to $102.5 million over seven years that will continue the ARLG mission to prioritize, design, and execute clinical research to reduce the public health threat of antibacterial resistance.

The funding, provided by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, supports the mission of the ARLG under award number UM1AI104681.

Antibacterial treatments are becoming less effective, resulting in an urgent threat to public health. A 2019 report from the Centers for Disease Control and Prevention estimates that antibiotic-resistant bacteria infect more than 2.8 million people annually, killing at least 35,000 in the U.S.

The ARLG, which received its inaugural funding from NIAID in 2013, is composed of more than 50 leading experts working together to innovate clinical trial design, inform guidelines, and improve clinical practice in infectious diseases.

The ARLG’s research team has collaborations in 19 countries and has initiated more than 40 clinical research studies involving more than 20,000 patients across more than 130 sites. Its three areas of research align with the CDC’s antibiotic resistance threats and include:

  • Infections caused by Gram-negative bacteria, such as Escherichia coli;
  • Infections caused by Gram-positive bacteria, such as Staphylococcus aureus; and
  • Diagnostics such as rapid point-of-care tests to detect drug resistance, guide antibacterial therapy, and support clinical trials.

Vance Fowler, MD, MHS“The renewal support from the NIAID will allow the ARLG to continue its collaborative work to advance science in antibacterial research, and to provide funding opportunities for the next generation of researchers dedicated to addressing this public health threat,” said Vance Fowler, M.D., ARLG co-principal investigator, member of the DCRI, and professor of medicine at the Duke University School of Medicine.

“We are delighted to be able to continue to support efforts to fight antibiotic resistance by generating data that is used to inform dosing guidelines and developing diagnostic testing for better detection and timely treatment,” Fowler said.

To learn more, read the news release from the NIAID.