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December 5, 2002

RESEARCH NOTES

Mood does not usually influence smoking habits

In what is believed to be the first study of its type regarding ongoing smoking, a team of Pitt researchers has concluded that cigarette smoking might not be as directly related to the smoker's mood as previously thought.

The study, "Immediate Antecedents of Cigarette Smoking: An Analysis From Ecological Momentary Assessment," can be found in the November 2002 edition of the Journal of Abnormal Psychology. The researchers, led by Saul Shiffman, professor of psychology, recruited 304 heavy smokers who had enrolled in a smoking cessation program. Each participant was trained to use a handheld computer or electronic diary (ED) to record data. Smokers were required to push a button on the ED to keep a record of every time they smoked a cigarette.

In addition, about four or five times a day the ED would randomly assess the circumstances surrounding a person's smoking, posing questions on the handheld device for the smoker to answer. The smokers were asked to enter information about their mood, their urge to smoke, their location and their activity at the time.

Participants also were randomly "beeped" by the ED four or five times a day and asked to enter information about times when they were not smoking. Thus, the study used technology and novel methodology to assess smoking in real time, in the smokers' natural environment. At the end of a one-week period, the EDs had calculated equations and contrasted 10,084 instances of smoking with 11,155 nonsmoking situations.

The study found that smoking was strongly related to smoking urges and that people were more likely to smoke when they drank coffee, ate food, were around other smokers or were engaged in leisure activities. But smoking was not related to positive or negative mood or arousal. At the time participants were moved to smoke, they felt neither better nor worse than they did when they were not smoking.

"We have long believed that smoking was triggered by negative moods, based on smokers' own beliefs," said Shiffman. "However, this more direct and valid research method shows that smoking is not usually related to mood. This should make us reevaluate our basic models of smoking behavior."

Shiffman's team also concluded that:

* While overall mood was not associated with smoking, restlessness showed a modest association, reflecting, the authors believe, the influence of nicotine withdrawal that smokers experience in the interval between cigarettes.

* Social cues influenced smoking, making it more likely the participants would smoke when they were around other people who were smoking.

* Participants were more likely to smoke when they had been eating or drinking.

* Participants seemed to smoke more often during breaks from their daily routine.

The study was funded by a grant from the National Institute on Drug Abuse.

Shiffman's team included Department of Psychology researcher Kenneth Liu and former graduate students Chad Gwaltney, Mark Balabanis, Jean Paty, Jon Kassel, Mary Hickcox and Maryann Gnys.

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Physicians not applying new, life-saving findings in ICU

Though most critical care doctors are aware of new life-saving clinical trial results published in leading medical journals, many do not apply these results in their own intensive care units (ICUs), according to findings from an expert symposium held at the 68th annual International Scientific Assembly of the American College of Chest Physicians last month.

The findings were compiled by electronic survey of more than 200 attendees of "Best Critical Care Medicine: Are We or Are We Not Putting It Into Practice?" sponsored by Pitt's School of Medicine.

"There is a potentially dangerous disconnect between the publication of solid, immediately usable data and putting those findings to work clinically," said Derek C. Angus, a Pitt medical school faculty member and chair of the symposium. "A fundamental tension exists between the desire to 'first do no harm,' and the need to incorporate new advances into practice. Doctors tend to be cautious about new advances until they are 'proven.' But failing to change practice on the basis of established, high-level evidence is essentially practicing out-of-date medicine."

Three symposium speakers each reviewed a medical technique demonstrated to save lives in large clinical studies recently published in The New England Journal of Medicine.

Each speaker discussed the results of the trials, as well as the available evidence regarding current practice patterns. In addition, they polled the audience about their knowledge and practice regarding these techniques.

The audience reported using some of these therapies in less than 10 percent of indicated patients. Reasons for this slow adoption included: the lack of proper education of medical staff; the reluctance of physicians to alter practicing habits; the failure of doctors to recognize acute lung infections, sepsis or other serious morbidities; physician apathy; cost and hospital financial constraints; too few incentives and penalties; the absence of quality assurance, and the lack of coordination between staff and departments that care for the critically ill.

With the ICU as the place where one in five Americans currently dies, the need for guidelines to overcome these barriers to innovations in care is crucial.

Among the solutions proposed during the symposium were: implementing institutional quality assurance programs to evaluate sepsis patients before they present to the ICU; instituting ongoing professional education efforts to help physicians keep current on medical advances for sepsis and other critical morbidities, and standardizing ICU and emergency department capabilities. In addition, however, much time and discussion were focused on raising the awareness among doctors and other health care professionals of the need to become agents for change — to recognize the dangers of slow adoption of new evidence and take a leading role in trying to overcome resistance.

The symposium's conclusions are in alignment with findings from a federal report released Oct. 30 by the National Academy of Sciences' Institute of Medicine, which also stated grave concern over widespread failure to adhere to new standards of care based on high-quality evidence.

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Dental school unveils simulation clinic

When first-year students at Pitt's School of Dental Medicine are introduced to their first patient they won't have to worry about the patient being scared of the dentist — the patient is a mannequin.

These mannequins, or patient simulators, along with two rooms full of state-of-the-art computer and audio-visual technology, are part of the school's new $2.6 million Simulation Clinic, which opened Nov. 21.

The clinic comprises two simulation labs with 80 workstations, each equipped with a patient simulator as well as standard dental instruments. The simulator has a removable jaw that replicates life-like jaw movements and can be positioned like a patient reclining in a dental chair.

From flat screen monitors placed at each station, students are able to view the professor, who teaches from an elevated platform at the front of the room. A movable camera offers students close-up views of the instructor performing a procedure on his or her own simulator. The teaching station also can broadcast slides, radiographs, video and/or transparencies on the monitors, and can tape classroom activities.

KaVo, a company in Lake Zurich, Ill., designed the patient simulators and laboratory equipment. ProCom, located in Oakland, maintains the computer systems.

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Innovative wheelchair allows users to operate on two wheels

The U.S. Food and Drug Administration recently approved the sale of a new wheelchair that enables users to operate on two wheels, allowing them to better negotiate obstacles like stairs and uneven pavement.

Research conducted at Pitt's School of Health and Rehabilitation Sciences (SHRS), in cooperation with Independence Technology, a Johnson & Johnson company, contributed to the FDA's approval.

"This device has the potential to significantly improve mobility for the two million Americans who use wheelchairs," said Rory Cooper, professor and chair of the Department of Rehabilitation Science and Technology and co-principal investigator of the trial.

Researchers at SHRS completed the second phase of a clinical trial that tested the device known as the INDEPENDENCE IBOT. The IBOT is an advanced gyro-balanced system that is designed to operate on four wheels or two wheels, stabilizing the user by instantly and automatically adjusting and balancing itself. In its two-wheel position, it allows a seated user to move about at standing eye-level. Its rotating four-wheel base allows the user to climb over street curbs and travel over uneven and hilly terrain.

Michael Boninger, director of UPMC's Center for Assistive Technology and co-principal investigator of the trial, said: "For the first time, people who use wheelchairs will be able to do things they never thought possible."

Phase two of the clinical trial consisted of 14 study subjects — 10 unimpaired non-wheelchair users and four expert wheelchair users, all of whom tested the device in their own homes and throughout their daily routine.

Powered by a rechargeable battery that can operate up to a full day on a single charge, the wheelchair uses an integrated system of electronic, sensor and software components to automatically adjust itself according to the seat's movement and the user's center of gravity. These components are accompanied by a backup system to ensure the safety of the user.

The wheelchair was invented by Dean Kamen, founder of DEKA Research and Development Corp.

Johnson & Johnson has been partnering with Kamen.

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Professor wins award for experimental therapeutics

William C. de Groat, a professor in Pitt's pharmacology department, has been named the winner of the Pharmacia-ASPET (American Society for Pharmacology and Experimental Therapeutics) Award for Experimental Therapeutics.

The award is given annually to recognize and stimulate outstanding research in pharmacology and experimental therapeutics/basic laboratory or clinical research that has had, or potentially will have, a major impact on the pharmacological treatment of disease.

De Groat, a Pitt pharmacology faculty member since 1968, will receive his award at the experimental biology 2003 meeting in April.

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Genetic connection found between two juvenile onset renal diseases

Pitt geneticists have identified mutations in a gene that are responsible for two heritable kidney diseases.

The discovery of four novel gene mutations in the uromodulin (UMOD) gene that are responsible for medullary cystic kidney disease 2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN) proves that these two diseases are actually the same condition, according to a study from the team of researchers led by the Pitt School of Dental Medicine.

These findings, published in the December issue of the Journal of Medical Genetics, will allow physicians to more effectively test patients for this condition.

Geneticists from Pitt studied DNA from members of several large families with multiple members having progressive kidney failure and gout. The research group, led by Thomas Hart, associate professor of oral pathology and medicine at Pitt's dental medicine school, was able to identify a small genetic change in the UMOD gene in all affected family members. The product of this gene, a protein called uromodulin, is the most common protein in normal urine.

Despite its being so common, the precise role of uromodulin is unknown. This study presents the first discovery of genetic defects in this gene, making the role of uromodulin more apparent. The identification of mutations in the UMOD gene will allow testing of clinically unaffected family members to identify those with the gene defect, permitting treatment intervention before significant pathology has occurred.

"If we are able to test children and siblings of individuals already diagnosed with this condition, we can diagnose and treat the disease early, possibly preventing the progression of kidney disease in these patients," Hart said.

Prior to the findings in this study, it was known that both MCKD2 and FJHN were heritable renal diseases that share common symptoms such as progressive renal failure, hyperuricemia (an excess of uric acid in the blood), gout and polyurea (the passage of large amounts of urine at one time). Before this discovery, the basic defect in these conditions was not known. Primary clinical features of the two diseases varied in presence and severity that made diagnosing patients complicated.

Working with Anthony Bleyer of Wake Forest University School of Medicine, the researchers obtained samples from four families, three with FJHN and one with MCKD2. The Pittsburgh group then conducted genetic linkage and mutational analysis tests on the samples and determined that four mutations in the UMOD gene were responsible for both diseases, making them the same disease. This discovery will allow physicians to develop a genetic test to diagnose this condition, which previously was very difficult to diagnose.

"Understanding the role of uromodulin in normal kidney function as well as in disease may provide valuable insights for the diagnosis and treatment of renal disease and gout. Currently there are approximately 350,000 people on dialysis, and 1 million suffering from kidney failure. An estimated 25 percent have no diagnosed cause of renal disease. This new genetic test will allow us to give some of these patients a diagnosis and determine the frequency of the disease in the population," said Hart.

Other members of the Pitt team include Michael Gorry, Suzanne Hart, Brian Shirts, Linda Xu and Michael Barmada. The study was funded in part by a U.S. Public Health Service grant from the National Institute of Diabetes and Digestive and Kidney Diseases.


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