University Times

Phone-based care helps those with panic, anxiety disorders

A better life for people with general anxiety and panic disorders may only be a phone call away, according to a Pitt study published in the December issue of the Archives of General Psychiatry.

The researchers report that telephone-based care for people with generalized anxiety disorder and panic disorder significantly improves both their symptoms of anxiety and depression and their mental health-related quality of life. The Pitt researchers also found the intervention results in fewer missed workdays and lower levels of emergency room usage.

This study, funded by the National Institute of Mental Health, is among the first to evaluate the efficacy of a telephone-based collaborative care intervention for anxiety disorders in a primary care setting, garnering results that could have far-reaching impact on how patients in all types of communities — urban, suburban and rural — can be helped.

“Collaborative care” involves care managers who teach patients about their illnesses and treatment options. They also teach self-management techniques and promote adherence with recommended treatments according to evidence-based guidelines. The care managers work under the direction of the patients’ primary care physicians and specialists.

“There has been a surge of interest in treating anxiety disorders and depression in the primary care setting, but we had few time-efficient and cost-effective ways to treat these disorders,” said Bruce L. Rollman, associate professor of medicine and psychiatry at the School of Medicine and lead author of the study. “We found that having non-mental health specialty care managers provide patients with information and support over the phone in collaboration with patients’ primary care physicians was indeed a very effective way of improving patients’ symptoms, quality of life and patterns of employment. Perhaps most importantly, this method can be used in a variety of settings and could prove extremely beneficial to underserved populations.”

Researchers enrolled 191 adults between the ages of 18 and 64 years who presented with panic and/or generalized anxiety disorder at one of four UPMC-affiliated primary care practices in the Pittsburgh area.

Patients were randomized to receive either their primary care physician’s usual care for panic and generalized anxiety disorder or the telephone-based care management intervention.

The telephone-based intervention used care managers who provided participants with psychoeducation about their anxiety disorders, discussed the participants’ treatment preferences, monitored treatment response and relayed this information to the patients’ primary care physicians via an electronic medical record system. Intervention patients received a median of 12 telephone contacts from their care managers over the course of 12 months.

At the 12-month follow-up, those who participated in the telephone intervention were more likely to experience a decline in anxiety and depressive symptoms, less likely to visit the emergency room, less likely to miss work and better able to work more hours than those receiving conventional care.

Co-authors of the study are Bea Herbeck Belnap of the Department of Medicine and Center for Research on Health Care, Charles F. Reynolds III, M. Katherine Shear and Patricia R. Houck of the Department of Psychiatry; Sati Mazumdar and Fang Zhu of the Department of Biostatistics; William Gardner of the Ohio State University Department of Pediatrics and Herbert C. Schulberg of Cornell University’s Weill Medical College Department of Psychiatry.

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NIH grant funds study of stress, substance abuse

Timothy Blackson, a research associate professor in the School of Pharmacy, has been awarded a three-year grant of $376,363 by the National Institutes of Health. The award will fund his project “Acute and Chronic Stress, Neurobehavior and Drug Abuse,” which will evaluate the effects of acute stress in the development of substance use disorders among 19- to 25-year-old adults. Defining the role of stress in substance abuse may lead to the development of new prevention and treatment strategies, Blackson stated.

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Who gives first does matter

Whether writing a check to a favorite charity or dropping a few dollars into the Salvation Army kettle, the end of the year is the time for many to make donations. But what prompts people to give? Does it help if a person of high status gives first?

Pitt professor of economics Lise Vesterlund has researched charitable giving to better understand the motivations behind donations. Her study, “The Effect of Status on Charitable Giving,” shows that when a person of high status gives first to a specific charity, others are apt to follow. In addition to helping to establish that the charity is reputable, a famous donor can help elicit other acts of generosity.

“The standard theory would be that if a well-known philanthropist gave first, people would think they wouldn’t have to give. But what we’re seeing instead is that if a renowned individual has given up front, it can trigger a lot of subsequent contributions. This actually gives high-status donors a greater incentive to give first, because they know their contributions will get everyone else going,” said Vesterlund.

In a study conducted in Pitt’s Experimental Economics Laboratory, which can be configured to run a wide variety of computerized experiments in controlled economic environments, Vesterlund divided Pitt students into what she called a high-status group and a low-status group. When those in the low-status group donated first, they didn’t give much, and the high-status group that followed with a donation gave even less. But when those in the high-status group gave first, they gave a larger amount, and contributions from the low-status group almost doubled.

“In our study, the net effect is that total contributions increase by more than 80 percent when high-status participants contributed first,” said Vesterlund. “It’s not that members of the high-status group are generally more generous. They’re only generous if they contribute first.”

Vesterlund said the study shows that fundraisers can benefit from using sequential solicitation strategies and that it is optimal for them to first solicit those who hold a higher social ranking.

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Stents reopen totally blocked carotid arteries

Pitt researchers report a high level of effectiveness in re-opening completely blocked internal carotid arteries (ICA) using stents as late as two to three days after acute stroke symptoms. The study by the School of Medicine’s Department of Neurology and the UPMC Stroke Institute is reported in the November issue of Stroke, a peer-reviewed publication of the American Heart Association.

“This report breaks new ground in that it contradicts the conventional wisdom that a completely blocked or occluded carotid cannot be opened,” said the study’s lead author, Tudor Jovin, assistant professor of neurology and neurosurgery at Pitt’s School of Medicine and co-director of the Center for Endovascular Therapy at UPMC.

Jovin’s team from the UPMC Stroke Institute retrospectively studied 25 patients with acute carotid occlusion who underwent angiography with the intent to revascularize the occlusion from January 2002 to March 2005.

Researchers concluded that recanalization, or re-opening of the artery, was successful in 23 of the 25 patients, and that the procedure was done safely.

“The main finding of the report was that endovascular revascularization of occluded ICA in the setting of acute or subacute ischemic stroke carries a high-revascularization rate and is safe in selected patients,” Jovin reported.

“Management of stroke because of acute internal carotid artery occlusion continues to represent a challenge because it may result in significant disability in 40 percent and death in 20 percent of cases,” Jovin said. “Our results are significant because they offer an opportunity for patients who may need more aggressive treatment. Future prospective studies are necessary to determine which patients are most likely to benefit from this form of therapy.”

Jovin added that early restoration of flow in the occluded ICA may improve the symptoms of acute stroke, prevent worsening and reduce long-term stroke recurrence risk.

The study also demonstrated that ideal candidates for endovascular ICA revascularization would be patients with a small area of tissue irreversibly compromised and a large area of tissue that is viable but threatened to undergo infarction.

Michael B. Horowitz, associate professor of neurosurgery and radiology and director of the UPMC Center for Neuroendovascular Therapy, also participated in the study along with Rishi Gupta, fellow, Department of Neurology; Ken Uchino, assistant professor of neurology; Lawrence R. Wechsler, professor of neurology and director, UPMC Stroke Institute; Maxim D. Hammer, assistant professor of neurology, all from the School of Medicine; and Charles A. Jungreis, professor of radiology and chair of radiology at Temple University Hospital.

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Can they take the heat?

Research into the way superconductors interact with magnetic fields by Pitt professor of physics and astronomy Yadin Y. Goldschmidt and former Pitt postdoctoral associate Eduardo Cuansing may aid in the discovery of superconductors that can function at higher temperatures. Their findings were published in the Oct. 21 issue of the journal Physical Review Letters.

Superconductors are materials with no electrical resistance that are used to make strong magnets. To maintain their superconductivity, they must be kept extremely cold.

The researchers used computer simulations of the melting process to discover direct evidence of new vortex patterns that form when a superconductor is exposed to a magnetic field. The vortices arrange themselves into patterns and melt as the material’s temperature increases.

“This melting transition of the vortices is important, because it usually causes superconductivity to disappear,” said Goldschmidt. “It is thus beneficial to delay the full melting as much as possible.

“Once physicists understand these melting mechanisms, they may be able to design materials that remain superconductors at higher temperatures,” Goldschmidt said.

High temperature to a superconductor is approximately -300°F.

The research was funded by the U.S. Department of Energy. Computations were performed using the Pittsburgh Supercomputing Center, a joint effort of Pitt and Carnegie Mellon University together with Westinghouse Electric Co.

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Mechanical chest compression study called off

A multi-center study testing and comparing the effectiveness of a mechanical chest compression device versus manual chest compressions for out-of-hospital sudden cardiac arrest has been terminated after analysis of preliminary data suggested that some patients treated with the mechanical device may fare worse than those receiving manual chest compressions.

The AutoPulse Assisted Prehospital International Resuscitation Trial (ASPIRE) was coordinated by the University of Washington, with participating centers at UPMC, the University of Calgary, University of British Columbia and Ohio State University.

Beginning in September 2004, emergency medical service personnel performed either manual cardiopulmonary resuscitation (CPR) or used the FDA-approved AutoPulse CPR assist device to deliver chest compressions to adults during cardiac arrest outside of hospital settings.

Patients had a 50-50 chance of being treated with manual CPR or the AutoPulse.

The study had planned to enroll 1,800 patients and monitor the survival of both patient groups for four hours, starting from the time of their 911 call. Patients who survived to be discharged from the hospital were followed for three months.

Although the 111 eligible patients enrolled at UPMC did not follow the overall trend and fared better with the mechanical chest compressions than with manual chest compressions, an independent data board that monitored the overall safety and efficacy of the study recommended suspending patient enrollment in all sites after a preliminary analysis of outcomes suggested a potential negative effect in the patients treated with the AutoPulse.

After further analysis of the 1,071 enrolled subjects, the ASPIRE investigators terminated the study early.

Overall, the study analysis showed minimal differences between the two groups of patients and their four-hour survival rates following the 911 call; after four hours, 24.7 percent of patients treated with manual CPR survived while 26.4 percent of patients treated with AutoPulse CPR survived. However, 9.9 percent of the manual CPR patients survived to hospital discharge compared to 5.9 percent of the AutoPulse-treated patients.

Among Pittsburgh patients, 13.7 percent treated with manual CPR survived for four hours following the 911 call while 21.6 percent of patients treated with AutoPulse survived. Of the Pittsburgh enrollees, 1.9 percent of the manual CPR patients survived to hospital discharge compared to 6.7 percent of the AutoPulse-treated patients.

Investigators have been unable to determine the reason for these outcomes, but AutoPulse maker ZOLL Circulation, which sponsored the study, continues to evaluate the data for possible explanation.

Vincent N. Mosesso, Pitt associate professor of emergency medicine, medical director of UPMC Prehospital Care and principal investigator of the Pittsburgh study site, said: “The overall results of this first multi-center study of the AutoPulse device were unexpected and disappointing. However, we remain optimistic that with further modifications of the device and how it is used, it may prove to be an effective treatment for sudden cardiac arrest, which is a leading cause of death in the United States with a mortality rate of more than 90 percent.”

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Broccoli may inhibit ovarian cancer

Researchers Sivakumar Loganatan, Ruifen Zhang and Sanjay K. Srivastava of the University of Pittsburgh Cancer Institute and Ian Humphreys of Pitt presented research that indicates a compound found in cruciferous vegetables may help prevent ovarian cancer.

The team exposed human ovarian cancer cells to a concentration of phenethyl isothiocyanate (PEITC) that could be achieved through dietary intake of cruciferous vegetables such as broccoli. They found PEITC inhibited the proliferation of the cancer cells.

“Based on our findings it is logical to speculate that PEITC will find its place as a novel dietary agent for the prevention and/or treatment of ovarian cancer,” the study concluded.

The findings were presented as part of an ovarian cancer symposium held last month at the UPMC Cancer Pavilion.

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GSPH research examines black women & cancer screening trials

Do African-American women who join a screening trial for cancer differ from those who do not join? Researchers at the Graduate School of Public Health (GSPH) sought to answer this question by surveying African-American women who were invited to join the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, a randomized, community-based longitudinal study evaluating the effectiveness of cancer screening tests on site-specific mortality.

The results, published in the Dec. 1 issue of the Journal of Clinical Oncology, indicate that African-American women who decided to join PLCO held significantly different beliefs regarding the benefits and risks of participation than those who did not join.

The majority of those who joined were much more likely to report that African Americans benefit as much as whites from participating in clinical trials. The study also found that none of the women surveyed had reported learning about clinical trials from their doctors or other health care providers.

“By interviewing women who joined the PLCO as well as those who did not, we were able to analyze their responses and suggest a strategy for improving the recruitment of African-American women to cancer clinical trials,” said Jeanette Trauth, lead author of the study and GSPH associate professor of behavioral and community health sciences.

The researchers interviewed 299 African-American women between the ages of 55 and 74 who were eligible for the PLCO. Of those, 230 decided not to participate in PLCO (non-joiners) and 69 decided to participate in PLCO (joiners). The investigators found that joiners had a better understanding of cancer and the role of early detection and screening, and appeared to be motivated to join a trial by the experience of having a loved one with cancer. Joiners also tended to seek out information more than non-joiners and were willing to take the next step and take part in a study of a new treatment for a health problem that they perceived was important, especially if they or one of their loved ones had the problem.

Although there were differences between the groups, there also were similarities. The two groups had similar attitudes about cancer and their susceptibility to PLCO cancers. Most joiners and non-joiners alike, 73 and 72 percent respectively, agreed that if meant to get cancer, a woman would get it regardless of what she did to prevent it. However, they did not think having cancer was automatically a death sentence. The majority of both groups also reported that they would be unlikely to get lung, colon or ovarian cancer during their lifetimes.

One of the most striking findings was that none of the participants in the study reported their doctors had talked to them about joining a clinical trial. “This represents a major missed opportunity to impart vital educational information and to recruit African-American women more successfully into clinical trials,” said Trauth.

To increase recruitment of African-American women to cancer clinical trials, Trauth suggests first providing women a health benefit that they want and need. She also suggests creating registries of African-American women interested in participating in clinical trials from current or former participants; informing physicians about the importance of talking to their patients about clinical trial opportunities; engaging African-American women in a dialogue about their perceptions of clinical trials and providing them with the tools they need to make informed decisions.

The study was funded by a grant from the National Cancer Institute. Co-authors of the study include Jan Jernigan, Laura Siminoff, Donald Musa, Derietra Neal-Ferguson and Joel Weissfeld.

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Mycobacteria biofilm protein identified

Howard Hughes Medical Institute (HHMI) researchers at Pitt and the Albert Einstein College of Medicine have identified a gene that enables mycobacteria — the cause of tuberculosis (TB) and leprosy — to form biofilms. Bacterial biofilms help mycobacteria resist treatment.

But the researchers found that when mycobacteria closely related to the TB and leprosy pathogens lack one key protein, mature biofilms fail to form. Interrupting the gene that produces this protein, known as GroEL1, could help treat or prevent these diseases.

To decipher the protein’s role in biofilm construction, Pitt HHMI professor Graham F. Hatfull collaborated with HHMI investigator William R. Jacobs Jr. at Einstein. They discovered that GroEL1 oversees the production of a particular set of fatty acids called mycolic acids, which are necessary for biofilm growth. Their study is reported in the Dec. 2 issue of the journal Cell.

“We’ve defined one of the first genes and mechanisms through which mycobacteria form biofilms,” said Hatfull, who also is Eberly Family Professor of Biotechnology and chair of the Department of Biological Sciences at Pitt. “Understanding biofilms is important because bacteria in biofilms are tolerant to most antibiotics, and this tolerance is a major problem in controlling TB infections.”

TB infects one in three people worldwide and kills thousands each day in underdeveloped countries. Infections can persist undetected for a lifetime. “Biofilms could play an important role in how TB itself can hunker down and protect itself from drugs and immune effector killing mechanisms. Perhaps TB hangs out in a biofilm somewhere in the body,” suggested Jacobs, who also is professor of microbiology and immunology and of molecular genetics at Einstein. “If so, an understanding of biofilm formation will provide novel ways to develop more effective drugs to fight TB and other mycobacterial infections.”

Jacobs and Hatfull’s current study began with the unexpected observation by Hatfull’s postdoctoral fellow, Anil Ohja, that a virus-infected strain of Mycobacterium smegmatis could not form proper biofilms. The virus integrates its DNA into the middle of the mycobacterium’s GroEL1 gene, disrupting production of the GroEL1 chaperone protein, which helps the mycobacteria construct mature, textured biofilms.

To find out how a chaperone protein might influence different growth phases, Ohja compared proteins made by mycobacteria strains with and without GroEL1. The group showed that without the chaperone, the cells were lacking a key part of their fatty acid synthesis machinery. Then the group compared the fatty acids profiles of the two strains. The bacteria without GroEL1 made less fatty acid in general and none of the mycolic acids required to produce a biofilm.

“These studies emphasize that fatty acid synthesis is a highly regulated process that depends on the physiological growth state of the cells,” said Hatfull. Researchers must do further study to find out how the chaperone causes the change in mycolic acid production, he said, but it is likely that it throws a molecular switch in the synthesis machinery.

Mycobacterium tuberculosis has a GroEL1 protein that is 90 percent identical to the M. smegmatis GroEL1. Even though there is no direct evidence yet that M. tuberculosis forms biofilms, Hatfull and Jacobs say it is highly likely that its proteins act in similar ways to change mycolic acid synthesis — a hypothesis they plan to test.

Mridula Anand of Pitt also contributed to the study.