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Breast Cancer Patients on Opioids Less Likely to Stick to Vital Treatment

A new study has found a troubling lack of adherence to a potentially lifesaving treatment regimen among breast cancer patients who take opioids to manage their pain.

The treatment, adjuvant endocrine therapy, commonly known as hormone therapy, is used to prevent the cancer from returning after surgery, chemotherapy or radiation therapy. Opioid use, however, was “significantly associated” with both failure to adhere to the hormone therapy and a higher risk of death, the study found.

Overall, the study found “really suboptimal” adherence to hormone therapy among the women on opioids, said researcher Rajesh Balkrishnan, PhD, of the University of Virginia School of Medicine’s Department of Public Health Sciences. “It’s not a big secret that the U.S. uses more opioids than any other country in the world,” he said. “Clearly there has to be better management of opioids in the elderly cancer population.”

One researcher cautioned that the opioid crisis sweeping the country may be causing doctors to become too cautious about prescribing the powerful drugs, even when appropriate and much needed. “A lot of doctors feel worried about prescribing them,” said researcher Leslie Blackhall, MD, a pain-management expert at the UVA Health System. “People feel judged for prescribing them.”

Appropriate Use of Opioids

Blackhall suggested that the lack of adherence to the adjuvant endocrine therapy, as seen in the study’s findings, may be due to the pain involved in the therapy, rather than because of the opioid use, as some might assume. The pain, she said, is why the patients need powerful opioids in the first place.

“The main problem is that these hormonal medications … have so many side effects that women do not want to take them. They can cause really severe joint and muscle pain in a significant number of women,” Blackhall said. “These women switch from one agent  to the other but still can't tolerate them. They are then given opioids for the pain, which may or may not help. The opioids may themselves add to the mortality, but we don't know. More data is needed.”

Breast Cancer and Opioids

Up to 60 percent of breast cancer survivors suffer chronic pain related to their treatment, the study notes. Survivors often face 10 years of adjuvant endocrine therapy to keep the cancer from coming back – a long time to comply with any treatment regimen, but especially if suffering poorly managed pain.

To better understand the relationship between opioid use and the hormone therapy, the researchers looked at treatment adherence among more than 10,000 women, with an average age of 72.3, using the National Cancer Institute’s expansive SEER database. They found that women who were younger, single and had more advanced cancer all were more likely to be on opioids, as were women with depression.

Women who received chemotherapy and breast cancer surgery were more likely to take opioids, but this was not the case for women receiving radiation therapy. This may be because of new, more targeted radiation therapy that causes less pain, the researchers hypothesized.

Using Opioids Safely

Researcher Virginia LeBaron, PhD, of the UVA School of Nursing, is a former medical oncology staff nurse and palliative care nurse practitioner. “These results underscore the importance of a balanced approach to the utilization of prescription opioid medications,” she said. “By balanced approach, I mean that it is critically important we ensure that prescription opioid medications are accessible to cancer patients who need them, but at the same time we must ensure we have appropriate systems in place to mitigate risk and reduce potential harms related to these medications.”

The researchers have published their findings in the scientific journal Breast Cancer Research and Treatment. Blackhall noted that the article is intended to foster dialogue and spur additional research. For example, clinical trials might compare opioids with non-opioids for managing cancer pain or identify patient subgroups that would most benefit from certain approaches to pain management.  “This study was really just a way to bring attention to the problem and the need to provide better care for patients,” she said.


UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

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  • Exercise Can Make Cells Healthier, Promoting Longer Life, UVA Finds

    Whether it’s running, walking, cycling, swimming or rowing, it’s been well known since ancient times that doing some form of aerobic exercise is essential to good health and well-being. You can lose weight, sleep better, fight stress and high blood pressure, improve your mood, plus strengthen bones and muscles.

    “Whether muscle is healthy or not really determines whether the entire body is healthy or not,” said Zhen Yan, PhD, of the University of Virginia School of Medicine. “And exercise capacity, mainly determined by muscle size and function, is the best predictor of mortality in the general population.”

    But why? Yan might have some answers. He and colleagues at UVa are peering inside the cell to understand, at a molecular level, why that workout, like it or not, is so vital to the body. They found that one important benefit involves the cellular power plant – the mitochondria – which creates the fuel so the body can function properly.

    Exercise Stresses Mitochondria

    Yan and colleagues have completed a study in mice that, for the first time, shows that just one bout of moderate to intense exercise acts as a “stress test” on mitochondria in muscles. They discovered that this “stress test” induced by aerobic exercise triggers a process called mitophagy, where the muscle disposes of the damaged or dysfunctional mitochondria, making the muscle healthier. Yan compares exercise-induced mitophagy to a state vehicle inspection that removes damaged cars from the streets.

    “Aerobic exercise removes damaged mitochondria in skeletal muscle,” Yan said. “If you do it repeatedly, you keep removing the damaged ones. You have a better muscle with better mitochondrial quality. We clean up the clunkers, now the city, the cell, is full of healthy, functional cars.”

    How Exercise Removes Mitochondria ‘Clunkers’

    For this study, Yan and colleagues assessed the skeletal muscle of a mouse model where they had added a mitochondrial reporter gene called pMitoTimer. The mitochondria fluoresce green when they are healthy and turn red when damaged and broken down by the cell’s waste disposal system, the lysosomes.

    The mice ran on a small treadmill for 90 minutes and Yan’s team observed mitochondrial stress (signs of “state inspection”) and some mitophagy (towing of the clunkers) at six hours after exercise. Yan explained that exercise in these mice also stimulated a kinase called AMPK, which in turn switched on another kinase called Ulk1. These chemical reactions appear to be important in control of the removal of dysfunctional mitochondria.

    “When its turned on, Ulk1 activates other components in the cell to execute the removal of dysfunctional mitochondria,” Yan said. “It’s analogous to a 911 call where a tow truck removes the clunkers. However, we still do not know how these activities are coordinated.”

    Some Mice Didn’t Benefit From Exercise

    Yan’s lab also deleted the Ulk1 gene in mouse skeletal muscle and found that, without the gene, the removal of damaged or dysfunctional mitochondria is dramatically inhibited, suggesting a new role for the Ulk1 gene in exercise and mitophagy.

    “Mice that were unable to do mitophagy did not have the benefit of exercise,” explained study co-author Joshua Drake, PhD, a postdoctoral fellow in the Yan lab. “Even though, from an exercise standpoint, they still were able to run just as far as normal mice, they didn’t benefit metabolically with training.”

    Drake pointed out that some people with type 2 diabetes don’t respond to exercise, which is a growing clinical problem. He hopes that continued research in the Yan lab will lead to new discoveries to help these non-responders.

    Findings Published

    The findings have been published online by the scientific journal Nature Communications.

    The study is the product of a collaboration among several laboratories at UVA, Brigham and Women’s Hospital and Harvard Medical School in Cambridge, Mass., and St. Jude’s Children’s Research Hospital in Memphis.

    The article is the work of Yan, Drake, Rhianna C. Laker, Rebecca J. Wilson, Vitor A. Lira, Bevan M. Lewellen, Karen A. Ryall, Mei Zhang, Jeffrey J. Saucerman, Laurie J. Goodyear and Mondira Kundu. 

    The research was made possible by grants from the National Institutes of Health and the National Institute of Musculoskeletal and Skin Diseases (R01-AR050429, ADA 1-16-PDF-030).


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • Doctors Can Now Predict the Severity of Disease Just by Measuring Molecules

    An international team of researchers has found a way to diagnose disease and predict patient outcomes simply by measuring unbelievably small changes in interactions between molecules inside the body. The simple new technique could offer vastly superior predictions of disease severity in a huge range of conditions with a genetic component, such as Alzheimer’s, autism, cancer, cardiovascular disease, diabetes, obesity, schizophrenia and depression.

    Measuring Gene Mutations

    Gene mutations that cause disease physically alter the interactions of molecules that cells use to communicate with each other. Until now, scientists have had no easy way to measure the incredibly subtle changes in these interaction forces. But researcher J. Julius Zhu, PhD, of the University of Virginia School of Medicine, and his collaborators have developed a method to accurately and efficiently calculate these tiny changes. It’s a feat that requires incredible precision: Force is typically measured in newtons – the amount of force needed to accelerate one kilogram of mass one meter per second squared – but Zhu’s technique measures on a scale of piconewtons – one trillionth of a newton.

    Zhu, of UVA’s Department of Pharmacology, and his colleagues have used the new technique to show that gene mutations responsible for mental-health diseases change molecular interactions by a few piconewtons. These small changes then have a tremendous ripple effect. The researchers found the molecular changes lead to harmful changes in how the cells communicate – and, ultimately, in cognitive ability. By measuring the molecular changes, the scientists could predict the resulting cognitive impairment. In essence, the researchers are directly linking these tiny molecular changes to big changes in human behavior.

    Diagnosing Disease

    Zhu’s approach represents a new use for a high-tech scientific instrument called “optical tweezers” that uses a highly focused laser to hold and move microscopic objects, much like regular tweezers might be used to grip and move a splinter. Using the optical tweezers, the scientists can measure the force required to break up intermolecular bonds between the signaling molecules inside the body, allowing them gauge the effects of gene mutations in patients. The researchers say the technique is simple to do and will dramatically improve our ability to diagnose mental illness and many other diseases.

    Findings Published

    The researchers have described their work in an article published online by the scientific journal Small. The team consisted of Chae-Seok Lim, Cheng Wen, Yanghui Sheng, Guangfu Wang, Zhuan Zhou, Shiqiang Wang, Huaye Zhang, Anpei Ye and Zhu. The researchers are from UVA, Peking University in China, Rutgers’ Robert Wood Johnson Medical School, Zhejiang University School of Medicine in China and Radboud University in the Netherlands.

    The work was supported by the National Research Foundation of Korea, the National Natural Science Foundation of China, the Chinese Ministry of Education Project 111 Program, the National Key R&D Program of China and the National Institutes of Health. (NIH grants NS065183, NS089578, NS053570, NS091452, NS094980 and NS092548.)

    To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • UVA Joins AVIA to Speed Innovation

    The University of Virginia Health System has joined AVIA, the nation’s leading network of health systems addressing pressing challenges by unlocking the power of digital solutions.

    UVA will work with AVIA to evaluate, select, and scale digital solutions to improve patient care, promote wellness and improve access to care. AVIA will work closely with Jeff Keller, named last year as UVA Health System’s first chief innovation officer, to harness technology to achieve these objectives.

    “At UVA, we are continuously seeking to apply new ideas and technology that can help us better carry out our missions of providing high-quality patient care, conducting research that improves the human condition and educating the next generation of healthcare providers,” Keller said. “By joining AVIA, we will collaborate with other leading health systems to find better ways to serve our patients and improve the care they receive.”

    AVIA brings together more than 20 action-oriented health systems from across the nation. AVIA and its members are building the digital answer key for initiatives such as convenient access and social determinants of health. AVIA members collaborate to find best-fit technology solutions, build strong business cases, develop best practice-based implementation plans, measure results, and develop benchmarks.

    “UVA has already established itself as a leader in medical research, telehealth, and healthcare innovation. By joining AVIA, UVA will collaborate with other health systems to transform care delivery through digital technology,” said Eric Langshur, AVIA CEO and co-founder. “We are excited to help UVA connect with its peers and achieve its ambitions.”

    About AVIA

    AVIA leads a network of health systems working together to innovate and transform. AVIA Innovator Network members solve pressing challenges with digital solutions that deliver financial and clinical results. AVIA provides strategic focus and a collaborative approach to accelerate innovation. Learn more at Follow us on LinkedIn and Twitter.


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • UVA, Foundation Radiology Group Partner to Expand Access to Specialized Medical Imaging

    To expand access throughout Virginia to specialized, high-quality medical imaging, University of Virginia Health System and Foundation Radiology Group have signed a radiology and medical imaging services partnership agreement.

    “There is no question that the rapid changes occurring in the health care environment are creating challenges for all radiology practices.  Academic medical centers, in particular, have the additional challenge of adjusting to these changes while continuing to optimize the educational experience of their trainees and pursue discovery and scholarly activities,” said Alan Matsumoto, MD, chair of the Department of Radiology and Medical Imaging at UVA Health System. “The innovative partnership between the University of Virginia and Foundation Radiology group will not only allow our Department of Radiology and Medical Imaging to better address our clinical, research and educational missions, but also create a radiology practice model that can more easily adapt to the changing needs of the patients and health systems we serve. One of the most exciting components of this new UVA-Foundation radiology team is that we will have a greater opportunity to positively impact the well-being of more patients across the Commonwealth.”

    “Support from Foundation’s team will bolster our teaching and research missions, and help us enhance the services we provide to patients in Charlottesville and throughout the Commonwealth,” said Dan Wassilchalk, chief operating officer for UVA Radiology. “Working together, UVA and Foundation will be able to advance and share knowledge to improve the health and well-being of the communities being served.”

    “As health systems shift to value-based care, having more subspecialty-trained radiologists both locally and remotely to support every service line and center of excellence is essential to deliver the future of radiology,” says Foundation’s Chief Executive Officer, Richard Vance, MD.

    Foundation’s proprietary IT platform fully integrates multiple hospitals across networks, allowing for a seamless workflow, image visualization, and data exchange. Six Sigma efficiency processes and quality measures are incorporated into all aspects of the radiology workflow. And, comprehensive reporting on service and quality inform each hospital’s strategic plan and drive progress toward goals and quality initiatives.

    “With 100 percent of critical findings delivered in less than 20 minutes with more accuracy, you are not merely supporting hospital centers of excellence, you are saving lives,” Vance said.


    About Foundation Radiology Group

    Foundation Radiology Group, based in Pittsburgh, PA, is one of the nation’s largest radiology groups and serves as a trusted advisor for academic medical centers, Integrated Delivery Networks (IDNs), community hospitals, and local radiologists. With over 30 referenceable clients across a 10-state region, our fully integrated radiology solutions platform combines onsite local radiologists and subspecialty services of a highly-trained physician team. Foundation’s more than 90 radiologists are all US-based providers. They offer expertise in every subspecialty.  Their radiology team is available for consults day and night, 24/7/365, and delivers over 1.8 million final reads annually. Foundation is the first multi-institutional radiology group accredited by The Joint Commission.

    Learn more at: WebsiteTwitter and Facebook.

    About UVA Radiology and Medical Imaging

    UVA Department of Radiology and Medical Imaging provides full-service subspecialty diagnostic imaging interpretations of more than 400,000 exams per year and image-guided peripheral and neurointerventional services inclusive of outpatient clinic visits and consultations. The department is a leader in research, consistently ranking as one of the top-funded departments within the School of Medicine. Many of the faculty members are nationally and internationally acknowledged as experts in their subspecialty areas of practice and research, having made impactful and significant contributions to clinical care, the education of trainees and innovative imaging research. The Department currently consists of 54 full-time Clinical Faculty, 14 Research Faculty, 40 Residents and 25 Fellows/Instructors in training. State-of-the-art imaging equipment is available in five convenient locations around the city of Charlottesville. 

    Learn more about Radiology & Medical Imaging at: WebsiteFacebook, Twitter, and Blog

    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • Antibiotics Found to Weaken Body's Ability to Fight Off Disease

     Adding another reason for doctors to avoid the overuse of antibiotics, new research shows that a reduction in the variety of microbes in the gut interferes with the immune system’s ability to fight off disease.

    Researchers at the University of Virginia School of Medicine have found that antibiotic use made neutrophils, a type of immune cell, less effective in fighting infections and weakened the intestinal barrier against invading bugs.

    “Neutrophils play an important role as a first-line ‘innate immune response’ when foreign pathogens invade,” said researcher Koji Watanabe, PhD. “We found that antibiotic disruption of the natural microbes in the gut prevented this from happening properly, leaving the gut susceptible to severe infection.”

    Antibiotics and the Microbiome

    The researchers were seeking to understand the role of the gut microbiome – the microorganisms that live within us – in amebic colitis, a potentially deadly parasitic infection common in developing countries. They analyzed stool samples collected from children in the urban slums of Dhaka, Bangladesh, and determined that children with more severe infections had less diversity in their gut microbiome. (Antibiotic use, the researchers note, is widespread in low- and middle-income countries, with children often getting more than two dozen treatments by age 2.)

    The researchers then used lab mice to determine how the decrease in natural intestinal flora might be worsening the disease. They found that antibiotics disrupted the mice’s gut microbiomes, decreasing the activity of neutrophils and blocking these important white blood cells from responding when needed. This left the gut insufficiently protected. In essence, the gut’s guards did not respond when called and the invaders could march right in.

    In addition, the intestinal barrier that protects against disease was compromised. The disruption of the microbiome reduced production of a key cellular protein vital to the barrier’s effectiveness.

    “I think the take-home is that this is another important reason not to use antibiotics unless they are clearly needed,” said researcher Bill Petri, MD, PhD, the chief of UVA’s Division of Infectious Diseases. “Unwise use of antibiotics not only increases the risk of multi-drug resistant bacteria and the risk of C. difficile infection but also impairs white blood cell function.”

    In addition to shedding light on the role of the microbiome in protecting our health, the work could prove important in the efforts to develop a vaccine for amebic colitis, also known as amebiasis. The discovery might offer a way to enhance the effectiveness of such a vaccine, the researchers noted.

    Findings Published

    The researchers have published their findings in the scientific journal PLOS Pathogens. The team consisted of Watanabe, Carol A. Gilchrist, Md Jashim Uddin, Stacey L. Burgess, Mayuresh Abhyankar, Shannon N. Moonah, Zannatun Noor, Jeffrey R. Donowitz, Brittany N. Schneider, Tuhinur Arju, Emtiaz Ahmed, Mamun Kabir, Masud Alam, Rashidul Haque (who led the Bangladesh efforts), Patcharin Pramoonjago, Borna Mehrad and Petri.

    The Bangladesh work represented a collaboration of UVA with icddr,b, a group based in Dhaka dedicated to solving public health problems in low- and middle-income countries through scientific research.

    The work was supported by the National Institutes of Health, grant R01 AI026649-28, and the Henske Foundation.


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

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