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May 27, 2004

Research Notes

People would trade longevity for quality end-of-life care

An overwhelming majority of people surveyed would trade a longer life span in order to receive better end-of-life care, according to Pitt researchers.
The study, published in the May issue of the journal Medical Care, used a sampling of 104 persons who took a survey based on six scenarios involving an 80-year old man who died after a one month stay in an intensive care unit (ICU).
“From our research, we found that people care a great deal about the quality of the death experience,” said lead author Cindy L. Bryce, assistant professor of medicine and a researcher at the Center for Research on Health Care at Pitt.
On average, interviewees were willing to trade seven months of healthy life just to ensure better quality of care in the final month of life.
“We tested the importance of good care at the end of life by measuring whether people would be willing to trade life expectancy and live a shorter life for better care at the end of life,” Bryce said. “The results were overwhelming, as 75 percent said they would trade some amount of healthy life to improve the quality of end-of-life care.”
According to Bryce, quantifying the value of end-of-life care is relevant for prioritizing care when resources are limited.
Efforts to set health care priorities might include something like a cost effectiveness analysis, which compares the costs and benefits of various health care services to determine which ones provides the most benefit relative to their costs, Bryce said.
“Typically, quality-adjusted life years are used as the measure of benefit. But, as our paper describes, quality-adjusted life years may not do a satisfactory job in measuring the benefits of end-of-life care, which could result in end-of-life services being rated as unimportant.”
Bryce said the study affirms that end-of-life care is important and that good end-of-life care includes both medical and non-medical considerations, including pain control and support for family members.
“We need to develop the right kind of measurement tools because it’s not enough to simply say ‘x, y and z’ are all important, which has always been true of all kinds of health services. Our study begins to assess how important ‘x, y and z’ are,” she said.
The research determines the importance of end-of-life care and improves upon previous measures such as quality-adjusted life years, which restrict the value placed on services and are therefore incapable of measuring the true importance of end-of-life care.
Other Pitt researchers involved in the study were medicine professor Robert M. Arnold; psychology professor Jonathan Schooler, and Derek C. Angus, professor of critical care medicine, medicine, and health policy and management and vice chair for research in Pitt’s Department of Critical Care Medicine. Faculty from Carnegie Mellon and the University of Toronto also were involved.

Life-saving procedures more effective when done individually

For patients in respiratory distress and in need of basic life support, it may be beneficial for them to receive rescue breathing, cardiopulmonary resuscitation (CPR) and automated external defibrillation (AED) through a more automated and precise system in order to receive optimal care, suggest emergency medicine researchers at Pitt.
Results of their study were presented May 19 at the Society for Academic Emergency Medicine Annual Meeting in Orlando, Fla.
This study examined the effectiveness of artificial ventilation by pre-hospital care providers using basic life support techniques, which is the basic level of care provided by first responders, paramedics and emergency medical technicians (EMTs).
“Through this study, we found that as resuscitation complexity increases, basic life-saving performance decreases,” said study author Jon Rittenberger, a second-year resident in the affiliated residency in emergency medicine at Pitt’s School of Medicine.
Using full-torso mannequins, 36 pre-hospital care providers were tested in pairs and randomly completed three sets of six-minute scenarios. These scenarios included a non-breathing patient with a pulse and a pulseless patient with and without an AED. The mannequins, which were programmed to generate a carotid pulse, were connected to a computer to record the number of ventilations, ventilation rates and capacity of air exchange, number of chest compressions and compression depth.
At the completion of the experiment, the researchers found that rescue breathing alone provided more correct ventilations than CPR or CPR plus AED. The researchers also noted that fewer ventilations were delivered during CPR and CPR plus AED. Eight pairs incorrectly treated the non-breathing patient by providing CPR instead of rescue breathing and were excluded from the ventilation analysis. More compressions were delivered with CPR alone versus CPR plus AED. The researchers suggest that further decrements might occur when advanced life-saving skills enter into resuscitation.
“This research is compelling in that it demonstrates how basic life-saving skills may need to be redefined in order for patients to receive the best possible care,” said Donald M. Yealy, professor and vice-chair of emergency medicine at Pitt’s medical school and president of the Society for Academic Emergency Medicine.
Rittenberger’s collaborators on the study have included Dave Hostler, Guy Guimond and Tom Platt, all from Pitt and Western Pennsylvania Center for Emergency Medicine.

Chemist gets grant for biomolecular modeling research

Ken Jordan, professor and chair of the Pitt chemistry department and director of the University’s Center of Molecular and Materials Simulations, has been awarded IBM’s Shared University Research (SUR) grant for his work in the computer modeling of biomolecules.
In 1999, Jordan also received an SUR grant, which was instrumental in establishing the molecular and material simulations center.
The IBM grant will support Jordan’s collaborative work with researchers at Iowa State University and IBM’s Life Sciences Group to enhance the use of grid computing through biomolecular modeling and simulation.
“IBM’s grant will advance our ability to craft complex computer models of biomolecular processes such as the folding of proteins of water,” said Jordan. “Ultimately such simulations will enable us to discover how diseases develop in the human body and aid in designing ways to prevent the occurrence of diseases.”
The SUR grant will provide high-performance computing equipment, specifically IBM p-series computers and grid-computing software, to Pitt and ISU research groups. These computers will be used for calculations of biomolecules in aqueous environments.

Study yields clue to why liver is less prone to organ rejection

Researchers from Pitt’s Thomas E. Starzl Transplantation Institute believe they have identified a mechanism that may help to explain why the liver enjoys privileged immunological status over other organs, making it the least vulnerable to rejection when transplanted.
Playing a central role in this mechanism is the dendritic cell, known for its ability to identify and present antigens, or foreign substances, to other immune system cells that are programmed to destroy the antigen.
When mature, dendritic cells signal T cells, the soldiers of the immune system, to attack a transplanted organ, for example. But dendritic cells that reside in the liver are relatively docile in nature. Why this is, according to the Pitt study, may be due to the fact that they express lower amounts of a certain molecule that serves as a switch for the maturation process.
Reporting in a plenary session at the American Transplant Congress, the joint scientific meeting of the American Society of Transplant Surgeons and the American Society of Transplantation, Pitt research associate An de Creus identified the key molecule as a Toll-like receptor known as TLR-4.
Toll-like receptors are like night watchmen that look for suspicious activity characterized by unusual patterns of other molecules. TLR-4 is known to react to lipopolysaccharide (LPS), a component found in the cell wall of bacteria. Reacting to LPS sets in motion a cascade of immune events that begins with the rapid maturation of dendritic cells.
Because of the liver’s position downstream from the intestines, dendritic cells there encounter large amounts of LPS as remnants of bacteria from the gut are carried by blood flowing through the liver’s portal vein. But unlike dendritic cells found elsewhere, such as in the spleen, dendritic cells that reside in the liver express less TLR-4, making them more apathetic toward LPS, researchers found in their studies of mice.
“With the liver constantly being exposed to LPS it must have a mechanism that prevents its immune cells from being activated all the time, and we believe the low expression of TLR-4 is in part responsible. The same thing is probably happening in the setting of transplantation,” explained de Creus, a research associate working in the laboratory of Angus Thomson, professor of surgery and immunology at the Starzl Institute and Pitt’s School of Medicine.
“In humans, perhaps it would be possible to manipulate dendritic cells of the donor organ so that they express little or no TLR-4. In this way, we might be able to induce complete immune tolerance of the liver,” de Creus added.
According to the researchers, their data are the first to show how TLRs are expressed by liver dendritic cells.
“This work has important implications for understanding the liver’s inherent tolerogenic potential,” Thomson said. “But we still don’t have enough information to understand why it is easier to get liver transplant patients off anti-rejection drugs compared to recipients of other organs.”
For her work, the American Transplant Congress recognized de Creus with a Young Investigator’s Award. Such an award is given to those under the age of 40 who submit a scientific abstract judged to be among the very best. The award provides the recipient with $1,000 to help defray the costs of attending the meeting.

Fewer drugs prescribed for lung transplant recipients

A lung transplant patient takes six pills a day, a regimen that is intended to safeguard the donor organ from immune system attack. But rejection plagues these patients more often and more vigorously than any other kind of organ recipient, so is it necessary that patients take that many pills?
Not according to the experience of surgeons at the University of Pittsburgh Medical Center (UPMC), where some lung transplant recipients are getting away with taking just one anti-rejection pill daily, and others just the one pill four or five times a week, with no ill effects.
Results of the novel clinical protocol were presented May 16 by Kenneth R. McCurry, assistant professor of surgery at Pitt’s School of Medicine, at the American Transplant Congress (ATC), the joint scientific meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.
With more than a year of follow-up in many patients, McCurry found that even those patients who have been able to reduce their medications to one pill a day benefit from the approach, which differs from the conventional twice-a-day triple-drug therapy, he said.
“Bombarding the immune system with several very potent drugs has done little to improve the outcomes for lung transplant recipients, who continue to have poor survival – about 75 percent at one year – compared to other organ recipients,” said McCurry, who also is director of lung and heart-lung transplantation at UPMC. “Moreover, the drugs have not done well to prevent chronic rejection, which affects about half of lung transplant patients by five years and usually results in organ failure and death. These bleak outcomes have motivated us to introduce an approach that we hope will enhance long-term survival, reduce the rates of complications associated with these drugs and improve quality of life.”
The approach is the only one of its kind involving lung transplant patients, in whom studies that seek to reduce anti-rejection drugs are rarely performed out of fear that the lungs, already the most vulnerable organ to rejection, would succumb to an irreversible immune system attack, placing patients at risk for death. Ironically, lung recipients have the greatest incidence of immunosuppression-related complications, such as infection and chronic kidney dysfunction, providing incentive to search for alternative immunosuppression approaches.
UPMC’s clinical protocol involves a one-time dose of a drug that depletes T cells – key immune system cells that are known to target the donor organ – that is given just before transplantation. Following transplantation, patients are treated with just one anti-rejection drug, tacrolimus, that is administered at reduced levels. Since many lung recipients are treated with prednisone for their underlying disease, the steroid is continued after transplant but at a negligible dose, 5 mg compared to 20 mg.
The rationale is to treat patients with as little immunosuppressive medication as possible following the transplant while preventing injury to the graft by the recipient’s immune system.
Since June 2002, more than 80 patients have been treated under the protocol. At ATC, McCurry reported results in many of these patients, including 31 who have been followed for more than a year after transplant, several for nearly two years.
“We are encouraged by these preliminary results. What remains to be seen is if our approach will have an impact on chronic rejection,” said McCurry.
“At this point, I think we can say that the standard multi-drug approach to immunosuppression may be excessive and leads to increased complications. Moreover, our promising early results suggest that altering the approach and reducing immunosuppression is not as risky as some would have guessed. The next step we should consider is a multi-center, randomized trial. Only with that kind of data might the transplant community embrace the notion that radical change is warranted,” he noted.
“Personally, I think our approach will presage significant improvements in outcomes for lung transplantation,” McCurry added.

Study will examine hormone treatment to prevent preterm births

Magee-Womens Hospital of the University of Pittsburgh Medical Center is enrolling women in their second trimester of pregnancy with twins or triplets in a clinical study to evaluate the efficacy of a hormone treatment to prevent preterm labor and delivery.
“Premature, low birthweight infants can face a host of medical complications with lifelong consequences,” said Steve N. Caritis, professor of obstetrics, gynecology and reproductive sciences at Pitt’s School of Medicine and principal investigator for the Magee study. “Women who are pregnant with twins or triplets have a higher risk of preterm birth than those women who are pregnant with a single baby.”
Babies born prior to 37 weeks gestation are described as preterm. Accounting for some 12 percent of all births in the United States, prematurity is the major cause of newborn illness and death, according to the American College of Obstetricians and Gynecologists.
The Magee study, called STTARS 17P for Study of Twins and Triplets; A Randomized Study, is designed to determine whether a hormone called 17 alphahydroxyprogesterone caproate (17P) will decrease the risk of preterm in women who are pregnant with twins or triplets.
Administration of this hormone has already been shown to be beneficial in preventing preterm birth in women with a prior history of premature birth, according to a National Institute of Child Health and Human Development-sponsored study reported in 2003 by the Maternal Fetal Medicine Units (MFMU) Network.
“Because early delivery has such health risks for babies, preventing preterm birth has become one of our primary goals,” said Caritis, who also is director of Magee’s Division of Maternal-Fetal Medicine and was an investigator on the 2003 MFMU study.
Since 1980, the number of twin births has risen by 74 percent in the United States, largely because of the introduction of assisted-reproductive technologies. In 2000, the most recent year for which United States birth data are available, the rate of twin births was the highest ever recorded at 29.3 per 1,000, or 2.9 percent. Preterm birth rates also are rising among twin gestations, with more than twice as many twin deliveries prior to 37 weeks’ gestation in 1996-97 than in 1981-82, according to the Centers for Disease Control and Prevention.
In all, 600 twin pregnancies and 150 triplet pregnancies will be studied. Women who are in their second trimester of pregnancy (less than 21 weeks’ gestation) with twins or triplets are eligible to enroll in the study, which involves monitoring whether weekly injections of 17P will decrease the risk of preterm birth. The study is randomized and double-blinded so that neither the study subjects nor the researchers will know who is getting injections of the hormone and who is getting injections of an inert substance, or placebo.
Women who take part should be prepared to provide medical history and to receive weekly injections and follow-up visits until 34 weeks’ gestation or delivery, whichever comes first.
The Pittsburgh site is part of a multi-center clinical trial of 17P in twin and triplet pregnancies that is taking place in 14 locations across the United States.
For more information on the study or to enroll, call study nurse Liz Daugherty at 412-641-4908, or study coordinator Peg Cotroneo at 412-641-4055.
The study is funded by a grant from the National Institute of Child Health and Human Development.

UCSUR report details quality of life for area women

More than 16 percent of Pittsburgh’s female population ages 18-64 are enrolled in an undergraduate education program, ranking Pittsburgh first among the 70 largest cities in the United States, according to a new Benchmarks Report by Pitt.
Funded by the Maurice Falk Fund, the study used 2000 census data to assess the social and economic status of women.
The report compares social and economic variables for women in the nation’s 70 largest cities, 50 largest counties, and 50 largest metropolitan statistical areas (MSAs). It shows that in the Pittsburgh area young women ages 25-34 are highly educated and have obtained bachelor’s degrees at higher rates than men.
The percentages of young women ages 25-34 with a bachelor’s degree in the city of Pittsburgh (42%), Allegheny County (41%), and the Pittsburgh MSA (35%) are among the highest in the nation, ranking 13th, 15th, and 21st, respectively. The percentages of young women with a high school degree in the city (93%), county (93%), and MSA (94%) are also among the highest in the nation, ranking third, first, and first, respectively.
The Pittsburgh area successfully retained educated young women ages 25-34 from 1990 to 2000, who now outnumber educated young men in the region. The number of young women residents with a bachelor’s degree increased by 9.5 percent in the city, 1.4 percent in the county, and 10.9 percent in the MSA.
“Our highly educated young workforce is a major advantage for regional economic development, and this workforce is increasing in size and improving in quality each year,” said report author Ralph Bangs, co-director of the Urban and Regional Research Program in Pitt’s University Center for Social and Urban Research (UCSUR).
The report also examined overall employment of Pittsburgh-area women of all ages and education levels. In 1999, 50.5 percent of women in the Pittsburgh MSA who worked any hours were employed full-time, ranking in the lowest third (35th) for metropolitan areas. However, the number of women working full-time in the Pittsburgh MSA increased by 42,000 (16.7%) from 1990 to 2000, whereas full-time employment of men in the region only increased in that time span by 25,000 (6.1%).
Overall, employed women in the Pittsburgh region are concentrated in such low-paying jobs as food preparation and serving and office and administrative support. Pittsburgh-area women are underrepresented in such nontraditional occupations as construction trades, firefighting and law enforcement, architecture and engineering, and production, as well as in such traditional occupations as state and local government and educational services.
The full report is available at

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