SIBS Pittsburgh faculty have collaborated on several large observational studies and randomized trials that will be used as case studies in the summer program. These case studies include studies of heart and lung disease, diabetes, dental caries, and hepatitis-C, as well as population-based studies of African American families in Pittsburgh and a population-based survey of health risk factors in Allegheny County. Data from these studies will be used throughout the program.
- Bypass Angioplasty Revascularization Investigation (BARI)
BARI is a multi-center randomized clinical trial to compare the efficacy of coronary angioplasty and coronary artery bypass surgery for patients with multi-vessel coronary artery disease. Coronary angioplasty is a procedure done to open an artery in the heart that has been narrowed. This allows better blood flow through the artery and to heart muscle without the need for open-heart surgery. Coronary bypass surgery is a procedure to allow blood to flow to heart muscle despite blocked arteries. It uses a healthy blood vessel taken from another part of the body and connects it to the other arteries in the heart so that blood is bypassed around the diseased or blocked area.
The primary goal of BARI is to assess whether coronary angioplasty is any worse than coronary artery bypass surgery in terms of 5-year mortality. Although the primary result of the trial indicated no significant difference in overall 5-year mortality between these two procedures, in the subgroup of patients receiving medical treatment for diabetes, 5-year survival was significantly higher for those assigned to coronary artery bypass surgery compared to those receiving coronary angioplasty. In 1997, BARI was funded to extend patient follow-up to a minimum of 10 years to allow a comparison of the long-term outcome between these two initial treatment strategies. A subsequent randomized trial of these two procedures in patients with diabetes (BARI 2D) recently was completed.
- The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial
BARI 2D, an extension of BARI, is a multi-center randomized clinical trial designed to determine in patients with Type 2 diabetes and stable coronary artery disease (CAD): 1) the efficacy of initial elective coronary revascularization combined with aggressive medical therapy, compared to an initial strategy of aggressive medical therapy alone; and 2) the efficacy of a strategy of providing more insulin (endogenous or exogenous), versus a strategy of increasing sensitivity to insulin (reducing insulin resistance), in the management of hyperglycemia, with a target HbA1c level of < 7.0% for each strategy. Coronary revascularization is a method to alleviate the symptoms of ischemic heart disease and improve survival. HbA1c is a lab test that displays the average level of blood sugar (glucose) for the previous 3 months and HbA1c level of < 7.0% is a standard criteria for controlling diabetes.
The primary goal of the BARI 2D trial is to test the following two hypotheses: 1) Coronary Revascularization Hypothesis: a strategy of initial elective revascularization of choice (surgical or catheter-based) combined with aggressive medical therapy results in lower 5-year mortality compared to a strategy of aggressive medical therapy alone; 2) Method of Glycemic Control Hypothesis: with a target HbA1c level of <7.0%, a strategy of hyperglycemia management directed at insulin sensitization results in lower 5-year mortality compared to a strategy of insulin provision.
Ischemic heart disease occurs when the arteries that bring oxygen-rich blood to the heart are blocked. Although ischemic disease seems to be more common in men, more women than men die from this condition each year because the symptoms are not detected via the traditional diagnostic techniques that are based on men’s disease. Women tend to have different patterns of chest pain than men, and have chest pain without detectable obstructive arteries of the heart. The purpose of this study is to elucidate the mechanisms of heart disease in women.
- Women’s Ischemia Syndrome Evaluation (WISE) Extension
The goal of WISE is to identify approaches that would improve the diagnostic reliability of cardiovascular testing in evaluating ischemic heart disease in women. The study seeks to 1) assess the incremental long-term prognostic value of the novel testing developed in WISE, 2) develop sex-specific incremental outcome models to evaluate the prognostic value of female reproductive variables, and 3) assess the incremental cost effectiveness and resource efficiency of the innovative WISE testing techniques compared to traditional tests.
- Center for Oral Health Research in Appalachia (COHRA)
Dental caries (tooth decay) remain one of the most common chronic diseases, affecting both children and adults. Rates of caries in young children actually have been increasing in recent years, and the disparities between disadvantaged populations and other populations are enormous. The focus of COHRA is to identify factors that lead to the poor health, especially oral health, seen in many parts of Appalachia.
Genetic, environmental, and behavioral factors all make critical contributions to oral health, and essentially all of these factors cluster within families. Factors such as salivary flow, tooth anatomy, and host immunity are determined largely by genes. Health beliefs, attitudes, and behaviors are influenced strongly by the milieu of the family. Environmental factors and access to care typically are shared within the family/household unit. COHRA is a family-based study that incorporates extensive data on genetic, environmental, and behavioral factors. The goal is to understand which factors are most important in shaping oral health, and how those factors interact with each other. Once these factors are better understood, targeted interventions can be developed and tested in order to improve oral health and thereby reduce the disparities observed in Appalachia relative to other regions of the United States.
Pneumonia is an infection of the lung. Many different organisms my cause it, including bacteria, viruses, and fungi. The Pneumonia Patient Outcomes Research Team (PORT) was an observational study of care for more than 2000 pneumonia patients. The findings of this study led to subsequent randomized trials of different evidence-based guidelines for how to treat pneumonia patients and when to discharge them from the hospital.
- Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (VIRAHEP-C)
The main goal of Virahep-C is to understand the pattern and causes of non-response to pegylated interferon
plus ribavirin therapy in African American (AA) and Caucasian American (CA) patients with chronic hepatitis C genotype 1. Approximately equal numbers of AA and CA treatment-naïve hepatitis C patients were recruited in the study. All patients were treated for 24 weeks with weekly injections of peginterferon and daily doses of ribavirin. At 24 weeks, if a patient’s HCV RNA levels were below the level of detection (50 IU/ml) the same regimen was continued for another 24 weeks, otherwise the treatment was discontinued. All patients were followed for another 24 weeks after stopping therapy. The primary endpoint for the study is sustained virological response, defined as undetectable HCV RNA at the 24 week follow-up visit. The primary results from this study focused on assessing demographic and clinical characteristics attributable to the differential response rates between AAs and CAs. These results were published in Gastroenterology (2006 Aug;131(2):470-7).
Virahep-C included five studies that expand the goals of the study beyond the clinical endpoints:
- Viral Kinetics - Analyzes changes in viral titres in response to therapy
- Viral Genetics - Analyzes viral genomic sequences that may contribute to resistance to therapy
- Immunology - Analyzes cellular immune responses associated with viral resistance to therapy
- Interferon Signaling - Analyzes changes in lymphocyte gene expression associated with viral resistance to therapy by microarrays
- Human Genetics - Analyzes human genetic polymorphisms associated with viral resistance to therapy