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July 7, 2011

Research Notes

Colistin dosages established

An ongoing study led by Fernanda P. Silveira, associate director of education in the Department of Medicine’s Division of Infectious Diseases, has established preliminary dosing recommendations for a more than 50-year-old drug that has re-emerged as the best, and often only, treatment for some bacterial infections that are resistant to modern therapies. The study, conducted in conjunction with researchers from Monash University in Australia, appears in the July issue of the journal Antimicrobial Agents and Chemotherapy.

Researchers say preliminary results of the study are important because the drug, called colistin, was introduced in the 1950s before the inception of modern drug development protocols so there is little information available to determine the correct dose for patients.

Colistin is used for patients on renal replacement therapy or those who are critically ill.

Physicians increasingly have turned to colistin as the number of drug-resistant infections has risen. “These infections are associated with a high morbidity and mortality due to the lack of adequate antibiotics and also due to the fact that they normally occur in hospitalized patients, especially those who already are critically ill,” said Silvera.

Researchers determined dosages after testing the blood of 105 critically ill patients at various times prior to and after receiving colistin injections. The participants already were receiving colistin for either bacterial bloodstream infection or pneumonia.

The study was funded by the National Institutes of Health.

Cosmic data standards on the way

Pitt researchers have undertaken a four-year, $1.6 million project supported by the National Science Foundation to create a single online source that astronomers worldwide can use to organize and quickly share their latest celestial observations.

In the absence of an agreed-upon format, researchers currently create data sets with a wide variety of parameters and names for celestial bodies. In addition, smaller, potentially important projects that lack the communications heft of well-funded efforts can become lost in the din.

A publicly available tool called AstroShelf would allow researchers to add new measurements about astronomical objects, report their findings in real time and work with one another’s data, explained principal investigator Alexandros Labrinidis, a faculty member in computer science. Labrinidis leads the project with Pitt computer science professors Panos Chrysanthis and Liz Marai, as well as with Pitt physics and astronomy faculty members Jeffrey Newman, Michael Wood-Vasey and Arthur Kosowsky.

The Pitt team’s first step is to create a computational framework that will let astronomers link their observations to specific experiments, models or other observations. Labrinidis and Chrysanthis will lead the design of an annotation framework to create these links along with an automated workflow system that will streamline many of the tasks astronomers currently perform manually, such as coordinating followup observations. Marai will develop a visual interface allowing astronomers to work directly with images of the sky as they construct and test computational models of the universe. Together, the three of them will create software to interactively analyze experimental results, as well as to construct and test hypotheses.

AstroShelf also will allow images obtained using different types of light — such as infrared or X-rays — to be correlated with ease to reveal obscured details of distant galaxies and black holes.

AstroShelf  will  enable researchers to record and share preliminary results of their analyses, Labrinidis said. This capability would be particularly valuable for studying such transient events as supernovae, which are visible from Earth for only a short time and often require multi-institutional coordination to observe fully.

Past bias affects patient relations

African-American patients who have experienced racism or classism in health care settings have less positive doctor-patient communication during future visits with other health care providers, according to a study led by School of Medicine researchers. The study, which appears in the July issue of the journal Medical Care, also showed that past experiences with discrimination do not have the same impact on subsequent doctor-patient communication for white patients.

Leslie Hausmann, a faculty member in internal medicine and a research health scientist at the Veterans Affairs Pittsburgh Healthcare System Center for Health Equity Research and Promotion, said the study is important because it shows that the effects of discrimination on patient disengagement with the health care system can be seen at the level of doctor-patient interactions, and it offers an avenue toward intervention.

Hausmann surveyed 100 African-American and 253 white patients being treated for osteoarthritis at two Veterans Affairs clinics. Patients were surveyed about experiences with racism and classism in health care settings before their visit to the VA clinics. Their clinic appointments were then audiotaped and coded by the researchers for informational content and emotional tone. After going to the clinics, patients also evaluated the visits, including whether they felt informed during the visit, whether the provider was warm and respectful and whether it was easy to communicate with the provider.

The study found that 70 percent of African Americans perceived that they had experienced racism in a health care setting in the past, compared with just 26 percent of whites. Also, African-American patients who had experienced racism or classism in the past displayed less positive emotion during the visit and reported that they felt their health care providers were less warm and respectful and more difficult to communicate with. The information exchanged between patients and providers during visits was not affected by patients’ past experiences with discrimination. For white patients, neither the informational content nor emotional tone of visits was affected by past experiences of discrimination.

Past studies have shown that patients who feel discriminated against in health care settings tend to miss more appointments and are less likely to take medication as prescribed, among other things that can affect their health negatively.

“There may be a cycle where patients experience discrimination, the effects of which carry over and make future health care encounters less positive, which further reduces patient satisfaction, and so on. Over time, this cycle may lead to patients disengaging from the health care system altogether. It is important to find a way to break that cycle,” Hausmann said. “This study suggests that focusing on doctor-patient interactions may be useful in that regard. Educating providers about how their patients’ past experiences may affect how patients communicate, and training providers on how to maintain positive emotional tone while communicating with patients are good ways to start.”

Pitt collaborators were Michael J. Hannon and C. Kent Kwoh of medicine. The study was funded by the Veterans Health Administration.

Outpatient care OK for some PE patients

A multi-center study has found that outpatient care can be used safely and effectively in some low-risk patients with pulmonary embolism (PE). The findings, recently published online in The Lancet, support current practice guidelines that rarely are followed by physicians.

Pulmonary embolism is a blockage of the main artery of the lung or one of its branches. Most are due to pelvic and upper leg blood clots that grow in the vein before detaching and traveling to the lungs. The most common symptoms include unexplained shortness of breath or chest pain. On average, 650,000 PEs occur annually; it is the third-leading cause of hospital death.

Study senior author Donald M. Yealy, chair of the School of Medicine’s Department of Emergency Medicine, said, “Our findings support a shift in clinical management of PE for a substantial portion of low-risk patients, which may reduce hospitalizations and costs.”

Researchers looked at more than 300 patients at 19 emergency departments in Switzerland, Belgium, France and the United States who had been assigned randomly to inpatient or outpatient care between February 2007 and June 2010. These patients were judged to have a low risk of death, based on a validated clinical prognostic model. Of those screened, 30 percent met the eligibility criteria, suggesting that a shift in the clinical management of such patients may have a broad effect.

Patients assigned to outpatient treatment received standardized teaching from a nurse about self-injection with enoxaparin, an anticoagulant, and were to be discharged from the emergency department within 24 hours. Patients assigned to inpatient treatment were admitted to the hospital and received the same enoxaparin regimen. In both groups, the study protocol recommended early initiation of oral anticoagulation medications and continuation for a minimum of 90 days.

Outcomes for outpatient care showed that it was as safe and effective as inpatient care. For instance, researchers found that one of 171 outpatients developed recurrent venous thromboembolism, or blood clots forming within the veins, within 90 days compared with none of 168 inpatients. One patient in each group died within 90 days. Two of the outpatients and no inpatients had major bleeding within 14 days.

Patient satisfaction regarding care exceeded 90 percent for both groups, and both had essentially the same numbers of hospital readmissions, emergency department visits and outpatient visits to a doctor’s office within 90 days. But researchers found that cost savings from reductions in hospital stays might be partially offset by an increased frequency in home-nursing visits.

Pitt co-authors included Michael J. Fine of medicine and Roslyn A. Stone and Nathan A. Pugh of biostatistics.

The study was supported by grants from the National Heart, Lung and Blood Institute, the Swiss National Science Foundation and the Programme Hospitalier de Recherche Clinique 2007.

Developmental biology research published

The Department of Developmental Biology recently announced faculty research news.

Renal stem cells identified

A collaboration between Pitt researchers Neil Hukriede and Cuong Diep and a team at the University of Auckland for the first time has identified and characterized a renal stem cell in adult zebrafish kidneys.

The work was published recently in Nature.

Yang receives AHA funding

Faculty member Lei Yang has been awarded a four-year American Heart Association national scientist development grant. Yang’s work focuses on human stem cell research and the modeling of human cardiac disease.

Kidney research funded

Neil Hukriede has been awarded a $2.7 million, three-year NIH grant for the project, “Small Molecule-Mediated Augmentation of Kidney Regeneration.” The goal of this study is to characterize new chemical compounds that promote repair of acutely injured kidneys.

Diabetes research presented

Pitt researchers presented findings from several studies recently at the American Diabetes Association scientific sessions meeting in San Diego.

PCP training increases goal-setting

Most diabetes care is provided in primary care practices that are not structured for management of those with chronic diseases such as diabetes. Substantial evidence demonstrates the usefulness of collaborative goal setting with patients; however, physicians are not trained routinely to engage in this process.

Linda Siminerio, executive director of Pitt’s Diabetes Institute, and colleagues trained physicians in primary care to set self-management goals with their patients. In this study, practices documented monthly percentages of diabetes patients who had established a health-related goal with their physician. During the reported period, there was a dramatic increase in goal setting with patients, suggesting the process can serve as a model for patient-centered approaches in other regions to transform health care.

Better care through HTP

Hypoglycemia is a barrier to intensification of insulin therapy in the hospital. Use of standardized protocols is particularly important in military hospitals with frequent staff turnover related to deployments. To address this, Linda Siminerio and colleagues compared hypoglycemic events using nurse-directed hypoglycemic treatment protocol (HTP) versus no HTP at Wilford Hall Medical Center, Lackland Air Force Base, Texas.

Patients treated with HTP reached target blood glucose range in 52 minutes as opposed to 79 minutes for those treated with non-HTP. In addition, the mean length of stay for those treated with HTP was 8.02 hospital days versus 12.08 days for non-HTP treatment. The findings support use of HPT for improved patient care and safety in a military hospital setting.

Hp genotype, coronary artery disease linked

Haptoglobin (Hp) is a plasma protein that binds free hemoglobin, thereby inhibiting hemoglobin-induced oxidative damage. There are three major Hp genotypes in humans: Hp1-1, Hp 2-1 and Hp 2-2, and it has been shown that people with type 1 diabetes and either the Hp 2-1 or Hp 2-2 genotypes are more likely to have coronary artery disease than those with type 1 diabetes and the Hp 1-1 genotype.

Trevor J. Orchard, a faculty member in epidemiology, pediatrics and medicine, and colleagues examined whether hemoglobin relates to coronary artery disease and, if so, whether this association differs by Hp genotype.

Over 18 years of study, 15.1 percent of individuals with Hp 1-1, versus 31.5 percent of those with the Hp 2-1 or Hp 2-2 genotype developed coronary artery disease. Hemoglobin levels were similar between those with and without subsequent coronary artery disease. However, among those with the Hp 1-1 genotype, both hematocrit and hemoglobin were increased modestly in coronary artery disease cases. Conversely, both hematocrit and hemoglobin were decreased in coronary artery disease cases among those with the Hp 2-1 or the Hp 2-2 genotype.

In this cohort with childhood-onset type 1 diabetes, a strong interaction was observed between hemoglobin and the Hp genotype in terms of coronary artery disease incidence, which researchers say merits further exploration.

Choice aids weight loss

In two separate studies, Gretchen Piatt of medicine and colleagues assessed group lifestyle balance programs, which are interventions designed to educate those at high risk for developing diabetes on how to make healthy changes to their lifestyle, including information on physical activity and effective weight-loss techniques.

For the studies, 434 overweight individuals from rural communities in southwestern Pennsylvania were divided into one of four groups, including those that participated in a group lifestyle balance program face-to-face, by DVD or online. The fourth group made their own selection.

The first study assessed participants’ reported well-being and function. Researchers found that those in the self-selection group had the most improvement in physical and mental functioning when compared to the other groups. These results support giving patients an option for the type of intervention they would like to participate in, which may allow them to reach their goals more effectively.

In the second study, researchers compared the effectiveness of each intervention. They found that more than half the participants in all groups met the 5 percent weight-loss goal, and of those who met the goal, more than 80 percent had kept the weight off six months later. All participants in the self-selection group maintained their weight loss at six months. Additionally, participants in the self-selection group were 1.5 times less likely to have impaired fasting glucose when compared to other groups.

Diabetic life expectancy rising

The life expectancy of people diagnosed with type 1 diabetes dramatically increased during the course of a 30-year prospective study, according to researchers from the Graduate School of Public Health.

The life expectancy for participants diagnosed with type 1 diabetes 1965-80 was 68.8 years — a 15-year improvement compared to those diagnosed 1950-64. Meanwhile, the life expectancy of the general United States population increased less than one year during the same time period.

Trevor Orchard, the study’s lead author, said, “Type 1 diabetes mortality rates have decreased over time, but formal life expectancy estimates for those diagnosed with type 1 diabetes in the United States are lacking.”

The 30-year mortality of participants diagnosed with type 1 diabetes 1965-80 was 11.6 percent — a significant decline from the 35.6 percent 30-year mortality of those diagnosed 1950-64, according to the study.

Other Pitt authors included Rachel G. Miller, Aaron M. Secrest, Ravi K. Sharma and Thomas J. Songer.

The study was funded by the National Institutes of Health.

Orthopaedic research published

The Department of Orthopaedic Surgery announced that several faculty members’ research recently was published.

Concussion evaluation and prognosis

A study by faculty member Michael W. Collins and adjunct faculty member Mark R. Lovell took the first steps to show that concussion prognosis may be best predicted by evaluating symptom clusters and neurocognitive testing. It also cautioned against returning any athlete to play when symptomatic even if neurocognitive testing yields normal results.

Their article, “Sensitivity and Specificity of Subacute Computerized Neurocognitive Testing and Symptom Evaluation in Predicting Outcomes After Sports-Related Concussion,” appeared in the June issue of the American Journal of Sports Medicine.

Collins is chief of the sports medicine concussion program and director of the UPMC sports medicine concussion program.

Knee repairs examined

Christopher Harner’s article, “Changes in Tibiofemoral Contact Mechanics Following Radial Split and Vertical Tears of the Medial Meniscus,” appeared in the June 15 issue of The Journal of Bone & Joint Surgery. The study provided a scientific rationale for the treatment of radial and vertical tears of the medial meniscus.

Harner is Blue Cross of Western Pennsylvania Professor and medical director of the UPMC Center for Sports Medicine.

Neurological research funded

Neurological surgery faculty members Hiroko Yano and Robert M. Friedlander have received more than $395,000 in National Institutes of Health funding through March 2014 for their project, “Polycomb-Mediated Epigenetic Mechanisms in Neurodegenerative and Aging Brain.”

The researchers have been studying neuronal death in Huntington’s disease, one of several progressive and fatal neurodegenerative diseases.

Selective neuronal loss is driven by genetic and environmental factors exacerbated by advancing age.

Disruption in the expression of certain genes is central to many neurodegenerative diseases — Huntington’s disease among them — and to normal aging.

Their studies have demonstrated a central role for the serine/threonine kinase Rip2 in Huntington’s disease pathogenesis as well as in neuronal death from other causes. They found that Rip2 directly binds EED, a component of the major epigenetic regulator PRC2. This activity of EED suggests that Rip2 may affect Huntington’s disease and aging by altering an epigenetic pathway and causing cell death.


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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