Clot removal reduces mortality in stroke

Researchers at the School of Medicine have completed an international, randomized, controlled trial showing that a clot-retrieval procedure, known as endovascular treatment (ET), can dramatically improve patient outcomes after an acute ischemic stroke. The study, in which the University enrolled more participants than any other American site, also shows a dramatic reduction in deaths from stroke. The results were published in the New England Journal of Medicine and will be presented at the American Heart Association’s international stroke conference.

Overall, positive outcomes for patients increased from 30 percent to 55 percent. In many cases, instead of suffering major neurological disability, patients went home to resume their lives. Led by researchers at the University of Calgary, the study found that overall mortality rate was reduced from 20 percent for standard treatment of care to 10 percent – a 50 percent reduction with ET.

Said Tudor Jovin, neurology and neurological surgery faculty member, director of the UPMC Stroke Institute and leader of the Pitt arm of the study: “These results mean we are on the verge of a revolution in stroke care. This is a devastating condition from the standpoint of death and disability. Finally, we are able to offer these patients a treatment that really works.”

Ischemic stroke is caused by a sudden blockage of an artery to the brain, which deprives the brain of critical substances, such as glucose and oxygen. Currently, the international standard of care based on Canadian, U.S. and European guidelines is to administer a “clot buster” drug called tPA to attempt to dissolve the blood clot.

In this trial, known as ESCAPE (Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times), 316 patients who fit the criteria for ET and arrived for treatment within 12 hours of their stroke were assigned randomly to receive either standard medical care, which included tPA where appropriate, or standard medical care plus ET.

ET is performed by inserting a thin tube into the artery in the groin through the aorta and into the brain vessels to the clot using X-ray-guided imaging. A retrievable stent opens the blocked vessel to restore blood flow and then is withdrawn, pulling the clot out with it.

Endovascular treatments were developed in the 1990s, but ET has been technically possible only recently. The ESCAPE team says the success of the trial can be credited to very fast treatment and the use of brain and blood vessel imaging. On average, researchers were two hours faster in opening the blocked blood vessels than in previously reported trials.

ESCAPE is the second ET trial that demonstrates the efficacy of the treatment and the first trial to demonstrate reduced mortality. The previous trial was published in the New England Journal of Medicine in December 2014.

ESCAPE included 22 sites worldwide and patients in the U.S., U.K., Ireland and South Korea. Canada had 11 participating hospitals and enrolled two-thirds of the patients.

Said co-investigator Lawrence Wechsler, Henry B. Higman Professor and chair of neurology and the institute’s founding director: “This was a trial that was very carefully designed to tell us for certain whether endovascular therapy should play a role in the treatment of stroke patients … and we encourage our patients to take advantage of the opportunity to participate in important clinical trials like this one.”

The study was funded by The Heart and Stroke Foundation of Canada, Alberta Innovates-Health Solutions, Medtronic and the Calgary Stroke Program.

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Amputees may feel with prosthetic limb

Rehabilitation experts in medicine hope one day to give people with an arm amputation a prosthetic limb that not only moves like a natural one, but “feels” like it, too. They expect such sensation will improve dexterous control of the device and give users greater intuition about what they are doing with their prosthetic.

Robert Gaunt, faculty member in the Department of Physical Medicine and Rehabilitation (PM&R), with a multidisciplinary research team from Pitt, West Virginia University and Ripple LLC, will begin developing the technology with the aim of being able to test it in patients’ homes within four years.

Said Gaunt: “Advanced prosthetic limbs that behave like the hand and arm they are replacing have been an unrealized promise for many years largely because until recently, the technologies to really accomplish this goal simply haven’t been available. To make the most of these new capabilities, we have to integrate the prosthetic into the remaining neural circuitry so the patient can use it like a regular hand that, for example, can pick up a pen, gently hold an egg or turn a stuck doorknob.”

In the first phase of the project, the team will recruit five volunteers to try to demonstrate that stimulation of the sensory portion of the spinal cord nerves, which normally would innervate the hand and forearm, can cause the amputee to feel distinct sensations of touch and joint movement in the “phantom” hand and wrist.

They also plan to insert fine-wire electrodes into the forearm muscles of able-bodied volunteers to collect and interpret muscle signals to guide movement of a virtual prosthetic hand to control hand opening and closing, as well as thumb movement. Eventually, the team aims to devise a fully implantable system for home use.

Michael Boninger, PM&R chair, will co-direct the project with Gaunt.

The project will be conducted by a multidisciplinary team of engineers, scientists and clinicians from PM&R, plastic surgery and neurological surgery in the School of Medicine, and occupational therapy and rehabilitation science and technology in the School of Health and Rehabilitation Sciences. Key aspects of the system will be designed by researchers at West Virginia University. Ripple, in Salt Lake City, will develop all the implantable system components.

Funding for the research was made possible by the White House’s BRAIN Initiative and the Defense Advanced Research Projects Agency hand proprioception and touch interfaces program.

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New drug tested for smoking cessation

Investigators in the School of Medicine and at the Western Psychiatric Institute and Clinic are testing a novel compound, originally developed to prevent decline in cognitive function, to determine if it can help people quit smoking.

As Kenneth A. Perkins, faculty member in psychiatry, epidemiology and psychology and principal investigator of the study noted, withdrawal symptoms include problems with concentration and short-term memory. These cognitive difficulties and other symptoms lead to relapse in the majority of smokers who try to quit.

The experimental compound, developed by Janssen and known as JNJ, acts at specific nicotine receptors in the brain involved in cognitive function, and researchers will assess whether limiting decline in cognitive problems may decrease motivation for tobacco and lessen the withdrawal symptoms, making it easier to quit altogether.

Study participants will try to quit briefly during each of two weeklong periods in which they receive JNJ during one and placebo during the other. The difference in their ability to quit will be compared between the JNJ and placebo periods.

Said Perkins: “Many smokers desperately want to quit, but often have a hard time with loss of concentration, focus and short-term memory. This compound is different than other cessation drugs and we are excited to see if it can aid more smokers to quit successfully.”

All participants will be offered counseling and the FDA-approved cessation medication bupropion (Zyban) at no cost to help them permanently quit once they have completed study testing. They also will be compensated for attending study visits. Smokers already planning to quit soon can find out more information by calling 412/246-5306 or visiting www.smokingstudies.pitt.edu.

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TissuGlu provides alternative to stitches, stapling

The Food and Drug Administration (FDA) has approved a surgical glue known as TissuGlu, making it the first tissue adhesive approved for internal use. TissuGlu was developed by Cohera Medical, a company spun out of Pitt in 2006.

TissuGlu is a biodegradable, biocompatible product that provides surgeons with an alternative to stapling, stitching or less-effective surgical wound sealants currently used to close large tissue flaps resulting from abdominoplasties (tummy tucks) and other surgical procedures.

Chemical engineering faculty member Eric Beckman and oral and maxillofacial surgeon Michael Buckley (formerly of the School of Dental Medicine) developed the adhesive technology in collaboration. In 2006, they founded Cohera Medical — with help from the Office of Enterprise Development and Office of Technology Management that are now part of the Innovation Institute — to develop and market TissuGlu.

Said Beckman, the George M. Bevier Professor of Engineering in the Swanson School of Engineering: “The original collaboration between Michael and myself was targeted at an entirely different technology and clinical issue, where we essentially stumbled upon the potential to create a biocompatible adhesive. Clinicians have lacked internal adhesives that are both strong and safe, and it’s exciting that TissuGlu is the first internal tissue adhesive to be approved by the FDA.”

TissuGlu completed European clinical trials in 2010 and received a CE mark certifying its conformity with European Union health standards in July 2011; Cohera Medical launched its first products in September of that year in Germany.

Surgeons use TissuGlu by using a hand-held applicator to apply drops of TissuGlu liquid. After applying the drops, the surgeon positions the abdominoplasty flap in place. Water in the patient’s tissue starts chemical reactions that bond the flaps together and cure the adhesive into a flexible solid.

The surgeon then proceeds with standard closure of the skin using sutures. Compared to other options, TissuGlu seals large-flap wounds more effectively, reducing fluid buildup and potentially the need for drains and offering a number of other advantages, including a lower risk of postoperative complications arising from drain use.

The FDA’s review of TissuGlu included data from a clinical study of 130 participants undergoing elective abdominoplasty. Half of the participants received surgical drains while the other half received TissuGlu and no drains. The study results showed that 73 percent of participants who received TissuGlu required no postoperative interventions to drain fluid that had accumulated between the abdominoplasty tissue flaps. Those who did require intervention, however, were more likely to require another operation to insert surgical drains.

Participants who received TissuGlu without surgical drains generally were able to return to most daily activities such as showering and climbing stairs sooner than those who had surgical drains. There was no difference between the two groups in reported levels of pain or discomfort due to the surgery.

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Grant to train PT researchers

With the first-ever grant to train future researchers and scientists in the physical therapy field, Pitt’s School of Health and Rehabilitation Sciences (SHRS) and Health Policy Institute will partner with Brown and Boston universities on a five-year, $2.5 million program that, at Pitt, will focus on generating pilot studies.

The Foundation of Physical Therapy awarded the grant to Brown to establish the Center on Health Services Training and Research. CoHSTAR will offer multi-institutional research and a training program where each university will focus on specific areas of health services: Brown on large database analysis; Boston on outcome measurement, and Pitt on quality assurance and implementation.

Tony Delitto, chair of the Department of Physical Therapy in SHRS and faculty member Kelley Fitzgerald will serve as co-directors overseeing the pilot studies core. There are three funded pilot studies expected to start as soon as this summer, and Delitto and Fitzgerald said they plan to fund three new pilot projects each of the remaining four years of the grant, with base funding of $100,000 total per year. The amount of funding Pitt receives will vary according to its number of fellows, trainees and projects.

Three pilot programs will be launched this summer, with one headquartered at Pitt. James Irrgang, faculty member and director of clinical research in the medical school’s Department of Orthopaedic Surgery, with Fitzgerald among his co-investigators, will develop and pilot test a nationwide registry of patients receiving care for non-operative knee pain. Such a database could affect trials, research, care and insurance policymaking.

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Primary care-based program increases physical activity

Getting help from the family doctor may be a better way for overweight, middle-aged women to increase their physical activity, rather than trying to go it alone, according to a trial led by researchers in the School of Medicine and funded by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). Obesity and physical inactivity are significant risk factors for cardiovascular disease in middle-aged women.

The results, published online in the Journal of General Internal Medicine, show that obese, middle-aged women who participated in an exercise program based at their primary care doctor’s office were more likely to continue to exercise over several months compared with those who were self-guided.

Said Molly Conroy, faculty member in medicine, epidemiology, and clinical and translational science: “Women who participated in programs in their doctor’s office had a structured environment allowing them to focus on their lifestyle habits like eating and exercising, and make changes.”

The Healthy Bodies Healthy Hearts investigators enrolled 99 inactive, overweight women ages 45-65 at three UPMC primary care offices at UPMC Montefiore, UPMC Shadyside and Magee-Womens Hospital. The women were separated randomly into two groups: one in which they participated in 12 weekly sessions at their primary care physician’s office consisting of 30 minutes of discussion and 30 minutes of moderate-intensity exercise, and a self-guided group that received a manual for independent use.

After three months, assessments showed that the women in the interventionist-led group had significantly higher levels of physical activity, such as walking at a moderate pace, with improvements equal to about 90 minutes per week, compared to the self-guided women who improved by only about 30 minutes per week.

After a year, both groups reduced their level of activity. The self-guided participants returned to pre-intervention activity levels; however, the interventionist-led women still were more active than they had been before participation by about 60 minutes of exercise per week.

“These outcomes imply that primary care-based interventions can be very beneficial to keep sedentary women motivated for several months,” said Conroy.

Pitt study collaborators were Dana Tudorascu, Irna Karpov, Bobby L. Jones, Andrea M. Kriska and Wishwa N. Kapoor. Other co-authors were from Heartchange and Chatham.

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Contraceptive counseling improves knowledge of acne drug

Providing women who take an acne drug with a fact sheet about contraception while visiting the dermatologist can significantly improve their awareness of the most effective birth control options and may prevent unintended pregnancies and birth defects that can be caused by the drug, according to a study published in JAMA Dermatology.

Isotretinoin, formerly marketed as Accutane, is an effective drug for acne, but is considered a teratogen, or a drug that can cause birth defects. Because of this, the FDA strictly regulates the distribution of the drug to women of childbearing age. Through the FDA’s iPLEDGE program, women who are prescribed the drug must pledge to use two forms of contraception, in addition to taking regular pregnancy tests and online tests to make sure they understand the dangers of getting pregnant while taking the drug.

Despite the regulations, 122 pregnancies affected by isotretinoin were reported in the U.S. during the first year of the iPLEDGE program. Pitt researchers have been studying this and found gaps in patients’ knowledge about the most effective forms of contraception.

Said Carly A. Werner, UPMC resident in the Department of Obstetrics, Gynecology and Reproductive Sciences in the School of Medicine and lead author on the study: “While contraceptive counseling isn’t something a dermatologist has to do on a daily basis — like an obstetrician or gynecologist would — it does matter for young women using these drugs.”

In the study, researchers surveyed 100 women from a single dermatology clinic between April and May 2014. Prior to viewing the contraceptive fact sheet, 75 percent overestimated the effectiveness of condoms, while 51 percent did the same for oral contraceptives.

Thirty-four percent of women said they had never heard of contraceptive implants and 16 percent had never heard of IUDs (intrauterine contraceptive devices), despite their effectiveness being much higher than that of condoms and oral options.

Researchers surveyed those women again after they had reviewed the fact sheet and found significant improvement in knowledge of contraceptives.

Said Laura Ferris, director of clinical trials for UPMC’s Department of Dermatology and a study co-author: “This shows us that dermatologists can make a difference by providing women who take this drug more education regarding effective forms of contraception.”

The researchers recommended that study is needed to determine how much the information provided was retained and if it does reduce the risk of medication-induced birth defects.

Other Pitt collaborators were Melissa J. Papic and Eleanor Bimla Schwarz.

The study was funded in part by the FDA.

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ALS research center established here

The Live Like Lou Center for ALS Research has been created with the pledge of O’Hara Township couple Neil and Suzanne Alexander to raise half of its initial funding. The center will focus both on developing treatments and, ultimately, a cure for amyotrophic lateral sclerosis (ALS) and on improving the quality of life for people who are now living with the progressive, degenerative neurological condition, also known as Lou Gehrig’s disease.

The Alexanders established Live Like Lou at the Pittsburgh Foundation in 2011, soon after Neil Alexander was diagnosed with ALS at age 46. They have pledged to raise $2.5 million over five years. Pitt has matched the contribution as part of an effort to raise $10 million for the new research center.

ALS causes progressive paralysis and eventually makes swallowing and breathing difficult, if not impossible, while sensation and cognitive function remain unaffected. Patients with ALS live two years after diagnosis, on average, with about 10 percent surviving for 10 years or longer.

Neil Alexander said that he is inspired by the dignity and perseverance shown decades ago by legendary Yankees first baseman Lou Gehrig, who died from ALS in 1941.

The center will:

• Recruit an expert in the neurobiology of ALS.
• Develop a nonhuman primate model of the disease.
• Create a prototype of a “smart house” to test neuro-technologies and neuro-prostheses in a real-life home setting.
• Explore brain-computer interface technology to foster patient independence.
• Support clinical trials to slow or reverse the progression of ALS.
• Award annual innovator grants to catalyze novel research approaches.

—Compiled by Marty Levine

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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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