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March 5, 2015

Research Notes

Pitt to lead national back pain trial

Lower back painThe University will lead a $14 million clinical trial to determine how well an intervention that helps people better understand their back pain early on works toward promoting recovery and keeping the pain from becoming chronic.

UPMC will be the first in the trial to offer the intervention, followed by four other academic medical centers nationwide.

The five-year award from the Patient-Centered Outcomes Research Institute (PCORI) is the 13th and largest to come to the Comparative Effectiveness Research Center (CERC) housed in the University’s Health Policy Institute.

This center bridges Pitt’s Schools of the Health Sciences and UPMC, providing a multidisciplinary platform and research infrastructure for patient-centered comparative effectiveness research across all of the health sciences.

The Pitt-led study will examine the transition from acute lower back pain to chronic lower back pain, and compare two approaches that can be delivered in a primary care office.

The first approach allows physicians to do what they think is best, which is termed “usual care.”

The second approach teams physicians with physical therapists to deliver cognitive behavioral therapy, a specialized therapy designed to help patients put their lower back pain in perspective, allowing them to identify and overcome barriers to recovery.

Said lead investigator Anthony Delitto, chair of the Department of Physical Therapy in the School of Health and Rehabilitation Sciences: “Certain patients are more inclined to worry that when their back hurts they are further harming it, causing them to become inactive. That can seriously impede recovery, cause further damage and lead to chronic back pain.

“Once the problem becomes chronic, the effects are magnified, even causing some people to lose their jobs and have prolonged difficulty with most daily activities. Chronic lower back pain is clearly something we would like to avoid.”

Lower back pain accounts for about $86 billion in health care expenditures every year, according to a study in the Journal of the American Medical Association. A major focus of the Affordable Care Act is mandating studies to examine pain as a public health problem and look for solutions.

Said Sally C. Morton, director of CERC and chair of the Department of Biostatistics in the Graduate School of Public Health: “Our Comparative Effectiveness Research Center was created to provide the infrastructure to support these larger, pragmatic studies. We built the necessary methodological expertise and data environment to allow researchers to answer the questions facing our health system that are important to patients. Ultimately, these taxpayer investments through PCORI will improve outcomes and inform national policy and practice. ”

Delitto’s study will recruit 60 primary-care clinics affiliated with UPMC, Intermountain Healthcare, Johns Hopkins Hospital and Health System, Boston Medical Center and The Medical University of South Carolina. At each site, 12 primary-care clinics will be randomly assigned to one of two study arms: the usual care their physician would prescribe for lower back pain or primary care coupled with physical and cognitive behavioral therapy.

Across the five regional sites, the team expects to recruit 2,640 patients with acute lower back pain, which is defined as pain they feel less than half the time and have had for less than six months. These patients will be evaluated with a standardized test that characterizes their response to pain and their predisposition to psychosocial characteristics that cause them to avoid pain out of fear.

The study will compare a patient-centered outcome that asks how well the patients perform activities that typically bother people with lower back pain, such as sitting, standing, walking, lifting, traveling and sleeping. Finally, the research team will measure the number of X-rays, MRIs, surgeries and other lower back-related medical procedures for all patients enrolled in the study.

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

Stem cells from wisdom teeth can become corneal cells

Clean healthy teeth on blue backgroundStem cells from the dental pulp of wisdom teeth can be coaxed to turn into cells of the eye’s cornea and could one day be used to repair corneal scarring due to infection or injury, according to researchers at the School of Medicine.

The findings, published online in Stem Cells Translational Medicine, indicate they also could become a new source of corneal transplant tissue made from the patient’s own cells.

Corneal blindness, which affects millions of people worldwide, typically is treated with transplants of donor corneas.

Said senior investigator James Funderburgh, ophthalmology faculty member and associate director of the Louis J. Fox Center for Vision Restoration, a joint program of UPMC Eye Center and the McGowan Institute for Regenerative Medicine: “Shortages of donor corneas and rejection of donor tissue do occur, which can result in permanent vision loss. Our work is promising because using the patient’s own cells for treatment could help us avoid these problems.”

Experiments conducted by lead author Fatima Syed-Picard, also of ophthalmology, and the team showed that stem cells of the dental pulp, obtained from routine human third molar, or wisdom tooth, extractions performed at the School of Dental Medicine, could be turned into corneal stromal cells called keratocytes, which have the same embryonic origin.

The team injected the engineered keratocytes into the corneas of healthy mice, where they integrated without signs of rejection. They also used the cells to develop constructs of corneal stroma akin to natural tissue.

Said Syed-Picard: “Other research has shown that dental pulp stem cells can be used to make neural, bone and other cells. They have great potential for use in regenerative therapies.”

In future work, the researchers will assess whether the technique can correct corneal scarring in an animal model.

Pitt co-authors include Yiqin Du, Kira L. Lathrop, Mary M. Mann and Martha L. Funderburgh. The project was funded by the National Institutes of Health (NIH), Research to Prevent Blindness and the Eye and Ear Foundation of Pittsburgh.

Detox medicine may help late-life resistant depression

Researchers at the School of Medicine and Western Psychiatric Institute and Clinic are testing a unique drug, often used to treat both opioid addiction and severe pain, to determine if it can help people suffering from late-life treatment-resistant depression (LL-TRD).

Researchers will assess the clinical effects of buprenorphine in treating LL-TRD while also determining optimal dosing strategies. This type of depression is a common condition that has serious consequences including worsened medical conditions, increased caregiver burden, higher mortality rates and suicide.

Said Jordan F. Karp, faculty member in psychiatry, anesthesiology, and clinical and translational science and principal investigator of the study: “We observed that buprenorphine improved symptoms of depression for people who were taking the drug for other reasons. While it is unusual to use a narcotic to treat depression, we are hopeful that using a low dose of this drug will greatly improve the lives of people who are suffering from this difficult disorder and have not responded to other medications.”

Individuals age 50 or older, currently in an episode of major depression and not abusing alcohol or narcotics, may be eligible to participate in this clinical trial. Participation involves a brain MRI. Participants receive all interventions at no cost to them or their insurance.

For more details regarding the study, call 412/246-6021.

Popular YouTube videos portray drunkenness positively

The 70 most popular videos depicting drunkenness on YouTube account for more than 330 million views, with little portrayal of the negative outcomes of excessive alcohol consumption, according to an analysis led by the Center for Research on Media, Technology and Health.

The popularity of such videos on YouTube could be an opportunity for public health interventions aimed at educating teenagers and young adults about the negative consequences of intoxication, the researchers suggest in an article published in Alcoholism: Clinical and Experimental Research.

Said lead author Brian A. Primack, director of the center and assistant vice chancellor for health and society in the Schools of the Health Sciences: “While we know that some viewers may be savvy enough to skeptically view music videos or advertisements portraying intoxication as fun, those same viewers may be less cynical when viewing user-generated YouTube videos portraying humorous and socially rewarding escapades of a group of intoxicated peers.”

Primack’s team mined YouTube for five terms synonymous with alcohol intoxication — drunk, buzzed, hammered, tipsy and trashed — winnowing their findings down to the most relevant.

There were 333,246,875 views for all 70 videos combined.

Humor was juxtaposed with alcohol use in 79 percent of the videos.

Motor vehicle use was present in 24 percent.

Although 86 percent of the videos showed active intoxication, only 7 percent contained references to alcohol dependence.

An average of 23.2 “likes” were registered for every “dislike.”

While 89 percent of the videos involved males, only 49 percent involved females.

A specific brand of alcohol was referenced in 44 percent of the videos.

“These statistics should be valuable in guiding interventions,” said Primack, who also is a practicing physician. “For example, we know that men tend to report more frequent binge drinking than women and that alcohol use is perceived as more socially acceptable for men. Because they are portrayed more frequently in YouTube videos, it may be useful to target men with future interventions debunking alcohol-related myths propagated on social media.”

Additional authors on this research are Jason B. Colditz and Kevin C. Pang of Pitt, and a colleague from Brown University.

This research was funded by ABMRF/The Foundation for Alcohol Research.

Teen brains’ decision-making often “overruled”

Teenage exploration and risk taking could be explained by dramatic changes in the brain that allow elaborate planning and are driven by the need for immediate reward, according to a neuroscientist who presented her research at the American Association for the Advancement of Science annual meeting.

Using a model in which eye movements, or saccades, reveal insight into executive brain function, Beatriz Luna, Staunton Professor of Psychiatry and Pediatrics in the School of Medicine, has studied hundreds of volunteers to examine brain development during the transition between childhood and adulthood.

Said Luna: “Our studies are beginning to challenge the traditional concept that the teenage brain can’t plan because of an immature prefrontal cortex. Our findings indicate that the teen prefrontal cortex is not much different than in the adult, but it can be easily overruled by heightened motivation centers in the brain. You have this mixture of newly gained executive control plus extra reward that is pulling the teenager toward immediate gratification.”

In the experiments, volunteers are instructed to immediately look away from a small light that randomly appears on a screen in front of them. This “anti-saccade” test shows if the brain is able to engage the planning centers of the prefrontal cortex to overcome the impulse to look toward the light rather than away from it. Luna’s team has found in previous studies that children succeed in about half their tries, teens in about 70 percent of tries and adults in about 90 percent of tries. People with mental illnesses typically struggle with the task.

The study team had volunteers do the same tasks while scanning their brains with functional MRI. They found that much of the architecture of the mature brain is in place by adolescence, but the ability of the networks to talk to one another and integrate information is still a work in progress.

“Further enhancement of this network integration is likely why adults can switch and very quickly adapt their behavior to changing circumstances, which is more difficult for adolescents,” Luna explained.

She added that while parents and teachers sometimes find bewildering the choices teens might make, their brains are perfectly adapted to explore and take some chances as they become independent adults.

“Across societies and species, we know that adolescence is a period of increased sensation seeking that can lead to risk taking, which increases mortality rate. Also, we often see during this period the first signs of mental illnesses such as schizophrenia, depression and eating disorders. All of these have a neurobiological basis, so if we know how the brain is changing, we might be able to figure out a way to intervene earlier in life.”

Luna teamed with researchers from the Children’s National Medical Center in Washington, D.C., Columbia University Medical Center and the University of California-Berkeley.

Reducing adverse drug outcomes in mental illness

Geneticists at the Graduate School of Public Health will provide their scientific expertise to a new initiative aimed at preventing and reducing the adverse effects of medications in people with mental illnesses.

The research project will take a personalized medicine approach to managing drug therapy by analyzing each patient’s genetic makeup to determine potential adverse reactions to medications. Funded by the Polk Foundation, it will be led by NHS Human Services, one of the nation’s largest providers of human services, in collaboration with Pitt’s public health school; CareKinesis, a medication therapy management services provider, and Coriell Life Sciences, a pharmacogenomics testing vendor.

Said Dietrich Stephan, chair of the Department of Human Genetics at the public health school: “An individual’s genetic makeup defines how many common drugs are processed by the body and who is at risk for an adverse drug response from such therapies. Individuals can suffer immensely from the very drugs that are meant to improve their health if given drugs they cannot tolerate, often resulting in increased emergency room visits and elevated health care costs.”

For example, some people are genetically predisposed to metabolize certain drugs faster than the average person, causing them to have a stronger, more immediate response to medication. Such responses can cause unexpected and potentially dangerous drug interactions.

“The people at highest risk, such as the aged and mentally ill, often are prescribed a multitude of drugs with no insight into their genetic susceptibilities,” said Stephan, who also is associate director of the Institute for Personalized Medicine, a collaboration between Pitt and UPMC.

“In this study, we aim to systematically implement comprehensive genetic testing in these populations and develop the evidence around improved outcomes and reduced costs that allows such testing to be broadly delivered to the general population and reimbursed by insurers.”

Stephan serves as chair of the clinical advisory panel for the 28-month, $350,000 initiative.

Study oversight will be provided by Robin Grubs, director of Pitt’s genetic counseling program, and by Lisa Parker of the Center for Bioethics and Health Law, who also provides oversight for the National Human Genome Research Institute.

—Compiled by Marty Levine


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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