AAV vector-meditated expression of HLA-G reduces injury-induced corneal vascularization, immune cell infiltration, and fibrosis.

Over 1.5 million individuals suffer from cornea vascularization due to genetic and/or environmental factors, compromising visual acuity and often resulting in blindness. Current treatments of corneal vascularization are limited in efficacy and elicit undesirable effects including, ironically, vision loss. To develop a safe and effective therapy for corneal vascularization, adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by human leukocyte antigen G (HLA-G), was investigated. Self-complementary AAV cassettes containing codon optimized HLA-G1 (transmembrane) or HLA-G5 (soluble) isoforms were validated in vitro. Then, following a corneal intrastromal injection, AAV vector transduction kinetics, using a chimeric AAV capsid, were determined in rabbits. One week following corneal trauma, a single intrastromal injection of scAAV8G9-optHLA-G1 + G5 prevented corneal vascularization, inhibited trauma-induced T-lymphocyte infiltration (some of which were CD8+), and dramatically reduced myofibroblast formation compared to control treated eyes. Biodistribution analyses suggested AAV vectors persisted only in the trauma-induced corneas; however, a neutralizing antibody response to the vector capsid was observed inconsistently. The collective data demonstrate the clinical potential of scAAV8G9-optHLA-G to safely and effectively treat corneal vascularization and inhibit fibrosis while alluding to broader roles in ocular surface immunity and allogenic organ transplantation.

Cost-benefit and cost-savings analyses of antiarrhythmic medication monitoring.

PURPOSE: The economic impact of pharmacist-managed antiarrhythmic drug therapy monitoring on an academic medical center's electrophysiology (EP) program was investigated. METHODS: Data were collected for the initial two years of patient visits (n = 816) to a pharmacist-run clinic for antiarrhythmic drug therapy monitoring. A retrospective cost analysis was conducted to assess the direct costs associated with three appointment models: (1) a clinic office visit only, (2) a clinic visit involving electrocardiography and basic laboratory tests, and (3) a clinic visit including pulmonary function testing and chest x-rays in addition to electrocardiography and laboratory testing. A subset of patient cases (n = 18) were included in a crossover analysis comparing pharmacist clinic care and usual care in an EP physician clinic. The primary endpoints were the cost benefits and cost savings associated with pharmacy-clinic care versus usual care. A secondary endpoint was improvement of overall EP program efficiency. RESULTS: The payer mix was 61.6% (n = 498) Medicare, 33.2% (n = 268) managed care, and 5.2% (n = 42) other. Positive contribution margins were demonstrated for all appointment models. The pharmacist-managed clinic also yielded cost savings by reducing overall patient care charges by 21% relative to usual care. By the second year, the pharmacy clinic improved EP program efficiency by scheduling an average of 24 patients per week, in effect freeing up one day per week of EP physician time to spend on other clinical activities. CONCLUSION: Pharmacist monitoring of antiarrhythmic drug therapy in an out-patient clinic provided cost benefits, cost savings, and improved overall EP program efficiency.