Sickle cell disease is characterized by episodes of excruciating pain and chronic organ damage leading to end-organ failure and premature death. In spite of significant improvement in our understanding of the pathophysiology, relatively few advances have been directly translated into treatments that help patients. The fact that the median survival has not improved in the 15 years since the introduction of hydroxyurea, a major treatment advance, suggests that access to expert care is yet another significant poor prognostic indicator for these patients. The overall goal of this program project is to explore avenues of research that are likely to result in new information that can be directly and quickly used in the management of patients with sickle cell disease. To accomplish this, we have assembled a consortium of five medical institutions, three referral groups and the major sickle cell community group all of whom have been working together for many years to care for over 70% of the sickle cell patients in Southern California. The Los Angeles Sickle Cell Consortium (LASCC), including the Sickle Cell Disease Foundation of California will collaborate on five projects that have a direct impact on patient care: 1) we proposed an inter-center project to determine the prevalence of iron overload and its physiologic consequences in adults., 2a) we will examine non-iron related cardiac dysfunction in chronically transfused patients and carry out a novel pilot treatment trial, 2b) we will carry out a randomized pilot study to determine if supplementation with L-glutamine improves exercise tolerance and decreases pain, 3) we will carry out health services research to determine why adult providers don't want to care for sickle patients, what services could be provided by LASCC to facilitate care by adult providers, whether a system we have devised to provide treatment assistance at the point of service is utilized and effective, and whether use of breakthrough technologies can modify care at pilot community emergency rooms or clinics. We will also determine if the treatment proposed in project 2b results in improvement in quality of life and cognitive function, 5) we will directly measure cerebral cortex oxygen delivery, cerebral blood flow, and capillary blood flow in chronically transfused patients and determine the HbS% /viscosity that optimizes these parameters. We will further determine if surrogate markers of sickling that can be measured by non-invasive, clinically applicable techniques are sensitive to changes in HbS% and, in collaboration with project 2b, are improved by supplementation with L-glutamine. This proposal leverages the unique expertise of the Los Angeles team and brings together the skills of investigators from the diverse areas of health services research, engineering, biophysics, cardiology, and nutritional sciences to address critical aspects of sickle cell disease management and delivery of care.
Showing the most recent 10 out of 26 publications
