Statewide Availability of Buprenorphine/Naloxone in Acute Care Hospitals.

OBJECTIVES: Evaluate the availability of buprenorphine/naloxone for inpatients with opioid use disorder in a state's acute care hospitals. METHODS: An audit study of all acute care hospitals in New Mexico was performed. Hospitals were surveyed on the availability of buprenorphine/naloxone on their inpatient formularies and their ability to obtain buprenorphine/naloxone within 1 day should a patient need it. RESULTS: Of the surveyed hospitals, 45.5% did not have buprenorphine/naloxone on their inpatient formularies. Of the 26 counties in New Mexico with acute care hospitals, 10 did not have buprenorphine/naloxone available for inpatients. Three of these counties have drug overdose death rates equal to or higher than the state average. CONCLUSIONS: In 1 predominately rural state with an opioid overdose death rate higher than the national average, approximately half of acute care hospitals had buprenorphine/naloxone available to patients on their inpatient formulary. Efforts to increase buprenorphine/naloxone availability in hospitals are needed, particularly in rural areas where there may not be other locations to access treatment for opioid use disorder.

A computer-aided approach to identify novel Leishmania major protein disulfide isomerase inhibitors for treatment of leishmaniasis.

Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and transmitted by the bite of a sand fly. To date, most available drugs for treatment are toxic and beyond the economic means of those affected by the disease. Protein disulfide isomerase (PDI) is a chaperone protein that plays a major role in the folding of newly synthesized proteins, specifically assisting in disulfide bond formation, breakage, or rearrangement in all non-native proteins. In previous work, we demonstrated that Leishmania major PDI (LmPDI) has an essential role in pathogen virulence. Furthermore, inhibition of LmPDI further blocked parasite infection in macrophages. In this study, we utilized a computer-aided approach to design a series of LmPDI inhibitors. Fragment-based virtual screening allowed for the understanding of the inhibitors' modes of action on LmPDI active sites. The generated compounds obtained after multiple rounds of virtual screening were synthesized and significantly inhibited target LmPDI reductase activity and were shown to decrease in vitro parasite growth in human monocyte-derived macrophages. This novel cheminformatics and synthetic approach led to the identification of a new series of compounds that might be optimized into novel drugs, likely more specific and less toxic for the treatment of leishmaniasis.