A Regional Analysis of Hepatitis C Virus Collaborative Care With Pharmacists in Indian Health Service Facilities.

BACKGROUND: American Indian/Alaska Natives (AI/ANs) are disproportionately affected by hepatitis C virus (HCV), with more than double the national rate of HCV-related mortality as well as the highest rates of acute HCV. The "cascade of care" for HCV consists of screening, confirmation, treatment, and sustained virologic clearance (SVR)/cure. At each stage of this process, patients can be lost to follow-up. Federal health care facilities in an administrative area of the Indian Health Service conducted a review to identify and address gaps in HCV treatment. Facilities generally treated HCV with a strong pharmacy component using a collaborative practice agreement and HCV telehealth services to external specialists. METHODS: All facilities had a pharmacist HCV program point of contact. Each pharmacist conducted a chart review of HCV patients and submitted aggregate results on HCV antibody status, HCV confirmation testing, stage of liver disease, initiation of treatment, and SVR/cure. Each facility also ranked current barriers to scaling up HCV treatment services from a defined list of options. RESULTS: Of 1789 HCV antibody positive patients, 77% (1381) had a confirmation test, of which 67% (929) were positive. Of these patients, 62% (576) had their liver fibrosis scored, and 58% (335) had initiated treatment. Of patients with an SVR/cure test, all (274/274) were negative. DISCUSSION: These data indicate that rural clinics can be successful providing HCV diagnosis and treatment. Pharmacists can play a key role in HCV clinical services. The outcomes of each step in the treatment process at the facility level can vary widely due to local factors. The barriers to HCV care that persist are nonclinical.

Kinetics of proton transfer from cationic carbon acids in water and aqueous DMSO. Effect of activating groups and solvent on intrinsic rate constants.

[reaction: see text] Acidity constants and rates of reversible deprotonation of acetonyltriphenylphosphonium ion (1H+), phenacyltriphenylphosphonium ion (2H+), N-methyl-4-phenacylpyridinium ion (3H+), and N-methyl-4-(phenylsulfonylmethyl)pyridinium ion (4H+) by amines in water, 50% DMSO-50% water (v/v), and 90% DMSO-10% water (v/v) have been determined. From the respective Brønsted plots, log k(o) values for the intrinsic rate constants of the various proton transfers were obtained. Solvent transfer activity coefficients of the carbon acids and their respective conjugate bases were also determined which helped in understanding how the pKa values and intrinsic rate constants depend on the solvent. Some of the main conclusions are as follows: (1) The pK(a) values of 1H+, 2H+, and 3H+ are significantly higher than that of 4H+ because of a stronger resonance stabilization of the corresponding conjugate bases 1, 2 and 3, respectively. (2) The electronic effects of the PPh3+ and the N-methyl-4-pyridylium group are similar but the mix between inductive and resonance effect is different. (3) All four acids become more acidic upon addition of DMSO to the solvent. In all cases, the main factor is the stronger solvation of H3O+ in DMSO; for 1H+, 2H+, and 3H+ but not 4H+ this factor is significantly attenuated by stronger solvation of the carbon acid in DMSO. (4) The intrinsic rate constants for proton transfer are relatively high for all four carbon acids and show little solvent dependence; this contrasts with nitroalkanes which have much lower intrinsic rate constants and show a strong solvent dependence. These results can be understood by a detailed analysis of the interplay between inductive, resonance, and solvation effects.

Kinetics of Proton Transfer from Benzoylnitromethane and 1,2-Diphenyl-2-nitroethanone to Various Bases. Resonance, Inductive, Solvation, Steric, and Transition State Hydrogen-Bonding Effects on Intrinsic Rate Constants.

The replacement of a hydrogen in nitromethane and in phenylnitromethane by the PhCO group has a strong acidifying effect, i.e., PhCOCH(2)NO(2), 5, is 5.8, 6.6, and 8.6 pK(a) units more acidic than CH(3)NO(2) in water, 50% DMSO-50% water (v/v), and 90% DMSO-10% water (v/v), respectively, and PhCOCH(Ph)NO(2), 6, is 2.0, 3.0, and 3.2 pK(a) units more acidic than PhCH(2)NO(2) in the same solvents. A major focus of this paper is an attempt to sort out the relative contributions of resonance, inductive/field, and solvation effects that lead to the increased acidities. To this end rate constants for the reversible deprotonation of 5 by secondary alicyclic amines in water, 50% DMSO-50% water (v/v), and 90% DMSO-10% water (v/v) and for the reversible deprotonation of 6 by secondary alicyclic amines, carboxylate ions, thiolate ions, and aryloxide ions in water, by secondary alicyclic and primary aliphatic amines in 50% DMSO, and by secondary alicyclic anions in 90% DMSO were determined. From Brønsted plots based on these data the intrinsic rate constants (k(o)) for the reactions of 5 and 6 with the various buffer families were obtained and compared with previously determined k(o) values for the deprotonation of CH(3)NO(2) and PhCH(2)NO(2), respectively. An analysis of the changes in k(o) induced by the introduction of the PhCO group, coupled with a comparison of solvent transfer activity coefficients for the transfer of the anions (5(-) and 6(-)) from water to 50% and 90% DMSO with those for CH(2)=NO(2)(-) and PhCH=NO(2)(-), respectively, indicates a substantial increase in the resonance stabilization of 5(-) relative to CH(2)=NO(2)(-) and a corresponding sharp drop in the solvational stabilization by hydrogen bonding from water; the effects on 6(-) are qualitatively similar but quantitatively much smaller. Our study also shows that the intrinsic rate constant for proton transfer from 6 to thiolate ions is higher than for proton transfer to aryl oxide ions and amines. This result indicates that, in contrast to most other proton-transfer reactions, hydrogen-bonding stabilization of the transition state for deprotonation of 6 is not an important factor.