Csaba P. Kovesdy, MD
Title of Project
The influence of race on medication adherence and health outcomes in veterans with diabetes
Health outcomes for patients with diabetes remain suboptimal in the United States, and factors like medication nonadherence, quality of care, distance to providers, and racial disparities contribute to this issue throughout the country. However, it is not well understood whether particular disparities, such as race, exert a strong influence on outcomes when other confounders are controlled for. Using the Veterans Affairs (VA) suite of databases, the extent of oral diabetes medication nonadherence throughout the country will be assessed and it will be determined whether racial disparities in outcomes exist among adults with diabetes who are adherent to prescribed therapies. This study will involve the building of a unique dataset among VA patients with diabetes on oral pharmacotherapy. Once compiled, the resulting group of patients will be assessed for initial and ongoing adherence to prescribed therapies, both statistically and geographically, overall and by race. Subsequently, those patients adherent to their therapy will be analyzed for differences in short- and long-term health outcomes according to patient race when controlling for standard demographic and socioeconomic covariates. By isolating particular, known contributors to outcomes, such an analysis will provide data that may signal the presence of reduced treatment effects potentially due to underlying biological influencers.
John Devincenzo, MD
Stephania Cormier, PhD
Title of Project
Mucosal dendritic cells in the infant fail to mature in response to early viral infections resulting in reduced IgA
Acute respiratory tract infections are a significant cause of respiratory morbidity and mortality in infants and children worldwide. The incidence of clinical pneumonia in children aged less than 5 years in developing countries is close to 151.8 million new cases annually, 13.1 million (8.7%) of which are severe enough to require hospitalization. Respiratory syncytial virus (RSV) is the leading viral respiratory pathogen in infants. Mortality rates from RSV in infants are 9 times higher than influenza in this age group. Development of an effective vaccine has been significantly hampered by our lack of understanding of the host immune system at time of initial infection – infancy. The mucosal immune system is an integrated network of tissues, cells and effector molecules that protects the host from infections and environmental insults at mucous membrane surfaces. Mucosal surfaces are immunologically unique, as they act both as a barrier and as the primary interface between the host and the physical environment from which the pathogen arrives. There is currently great interest in developing mucosal vaccines against a variety of microbial pathogens, but little is known about the mucosal immune response capabilities at young ages. We propose to study a key aspect of the mucosal immune response (IgA production), its control and capabilities during infancy in response to the major pathogen of infancy (RSV). We hypothesize that Type 1 interferon production by plasmacytoid dendritic cells (pDC) upon viral infection induces activation of B cells to produce IgA in a T cell independent manner in neonatal/infant RSV. The Aims of the project are to determine that 1) Age of the pDC at time of initial infection with RSV dictates B cell antibody isotype response, 2) Production of type 1 interferons (IFNs) drives B cells to produce IgA, and 3) B cells are activated in a T cell independent manner in neonatal/infant RSV.