Atrial Fibrillation Patients on Warfarin and Their Transition to Direct Oral Anticoagulants.

BACKGROUND: The standard of care for stroke prevention in nonvalvular atrial fibrillation (AF) is the use of direct oral anticoagulants (DOACs). However, many patients established on warfarin therapy have not been considered for a transition to a DOAC. OBJECTIVES: Assess the AF patient population of Brigham and Women's Hospital (BWH) Anticoagulation Management Service (AMS) currently being treated with warfarin, transition eligible patients to a DOAC, and identify barriers to the transitional process. METHODS: Patient characteristics were analyzed to describe the overall AF population and a systematic process was used to determine clinical candidacy for a transition from warfarin to a DOAC. After being deemed eligible by both the referring physician and the AMS pharmacist, each patient was contacted and offered the opportunity for DOAC transition. Endpoints included number of successful transitions and commonly encountered barriers. RESULTS: Out of the 1407 total AF patients on warfarin managed by BWH AMS, there were 787 patients identified as candidates for DOAC transition and a successful transition was completed for 250 (31.8%) of them. Barriers to transition included patient preference for warfarin (n = 247, 31.4%), referring physician preference for warfarin (n = 112, 14.2%), cost (n = 88, 11.2%), AMS pharmacist preference for warfarin (n = 70, 8.9%), and previous DOAC intolerance (n = 20, 2.5%). CONCLUSIONS: Every institution or provider network that manages AF patients on warfarin should assess their population on a regular basis to identify candidates for DOAC therapy. Our initiative outlines a process for identifying and transitioning DOAC-eligible AF patients established on warfarin therapy and describes the most commonly encountered barriers to DOAC therapy.

Interaction with lipid II induces conformational changes in bovicin HC5 structure.

Bovicin HC5 is a lantibiotic produced by Streptococcus bovis HC5 that targets the cell wall precursor lipid II. An understanding of the modes of action against target bacteria can help broadening the clinical applicability of lantibiotics in human and veterinary medicine. In this study, the interaction of bovicin HC5 with lipid II was examined using tryptophan fluorescence and circular dichroism spectroscopy with model membrane systems that do or do not allow pore formation by bovicin HC5. In the presence of lipid II, a blue-shift of 12 nm could be observed for the fluorescence emission maximum of the tryptophan residue for all of the membrane systems tested. This change in fluorescence emission was paralleled by a decrease in accessibility toward acrylamide and phospholipids carrying a spin-label at the acyl chain; the tryptophan residue of bovicin HC5 was located near the twelfth position of the membrane phospholipid acyl chains. Moreover, the binding of lipid II by bovicin HC5 induced remarkable conformational changes in the bovicin HC5 structure. The interaction of bovicin HC5 with lipid II was highly stable even at pH 2.0. These results indicate that bovicin HC5 interacts directly with lipid II and that the topology of this interaction changes under different conditions, which is relevant for the biological activity of the peptide. To our knowledge, bovicin HC5 is the only bacteriocin described thus far that is able to interact with its target in extreme pH values, and this fact might be related to its unique structure and stability.