Cost and cost‐effectiveness of a simplified treatment model with direct‐acting antivirals for chronic hepatitis C in Cambodia

Background & Aims In 2016, Médecins Sans Frontières established the first general population Hepatitis C virus (HCV) screening and treatment site in Cambodia, offering free direct‐acting antiviral (DAA) treatment. This study analysed the cost‐effectiveness of this intervention. Methods Costs, quality adjusted life years (QALYs) and cost‐effectiveness of the intervention were projected with a Markov model over a lifetime horizon, discounted at 3%/year. Patient‐level resource‐use and outcome data, treatment costs, costs of HCV‐related healthcare and EQ‐5D‐5L health states were collected from an observational cohort study evaluating the effectiveness of DAA treatment under full and simplified models of care compared to no treatment; other model parameters were derived from literature. Incremental cost‐effectiveness ratios (cost/QALY gained) were compared to an opportunity cost‐based willingness‐to‐pay threshold for Cambodia ($248/QALY). Results The total cost of testing and treatment per patient for the full model of care was$925(IQR $668‐1631), reducing to$376(IQR $344‐422) for the simplified model of care. EQ‐5D‐5L values varied by fibrosis stage: decompensated cirrhosis had the lowest value, values increased during and following treatment. The simplified model of care was cost saving compared to no treatment, while the full model of care, although cost‐effective compared to no treatment ($187/QALY), cost an additional $14 485/QALY compared to the simplified model, above the willingness‐to‐pay threshold for Cambodia. This result is robust to variation in parameters. Conclusions The simplified model of care was cost saving compared to no treatment, emphasizing the importance of simplifying pathways of care for improving access to HCV treatment in low‐resource settings

Nurses and medical assistants taking charge: task-shifting HIV care and HAART initiation in resource-constrained and rural Malawi

Mexico AIDS Conference 200

Application of tethered ruthenium catalysts to asymmetric hydrogenation of ketones, and the selective Hydrogenation of aldehydes

An improved method for the synthesis of tethered ruthenium(II) complexes of monosulfonylated diamines is described, together with their application to the hydrogenation of ketones and aldehydes. The complexes were applied directly, in their chloride form, to asymmetric ketone hydrogenation, to give products in excess of 99% ee in the best cases, using 30 bar of hydrogen at 60 °C, and to the selective reduction of aldehydes over other functional groups

Mechanistic and Kinetic Investigation on the Formation of Palladacyclopentadiene Complexes. A Novel Interpretation Involving a Bimolecular Self Reaction of a Monoalkyne Intermediate

The stoichiometric reaction between the complex [Pd(eta(2)-dmfu)(BiPy)] (dmfu = dimethylfumarate; BiPy = 2,2'-bipyridine) and the deactivated alkynes dmbd (dimethyl-2-butynedioate) and pna (methyl (4-nitrophenyl)propynoate), providing the respective palladacyclopentadienes, was investigated. The mechanism leading to the palladacyclopentadiene derivative involves a bimolecular self-rearrangement of the monoalkyne intermediate [Pd(eta(2)-alk)(BiPy)] (alk = dmbd, pna), followed by the customary attack of the free alkyne on the intermediate [Pd(eta(2)-alk)(BiPy)] itself and on the elusive and highly reactive "naked palladium" [Pd(BiPy)(0)] formed. The alkyne pna proved to be less effective in the displacement of dmfu than dmbd. The reaction under stoichiometric equimolar conditions of the latter with [Pd(eta(2)-dmfu)(BiPy)] allows the direct determination of the bimolecular self-reaction rate constant k(c) and consequently the assessment of all the rate constants involved in the overall mechanistic network

Ruthenium-Catalyzed Synthesis of Functional Conjugated Dienes via Addition of two Carbene Units to Alkynes

International audienceThe reaction of a variety of alkynes with N2CHSiMe3, in the presence of Cp*RuCl(cod) as the catalyst precursor, leads to the general formation of functional conjugated dienes. This selective formation results from the ruthenium-catalyzed creation of two carbon−carbon double bonds in a single step under mild conditions. Terminal alkynes produce 1,4-bistrimethylsilylbuta-1,3-dienes with Z stereoselectivity for the less hindered double bond whereas disubstituted alkynes favor E-configuration for the same double bond. Diynes react also as monoalkynes, and only one triple bond is transformed to give disilylated dienynes. The reaction can be applied to the in situ desilylation in methanol and formation of monosilylated dienes. The catalytic formation of 1,4-bisfunctional buta-1,3-dienes can also take place with N2CHCO2Et and N2CHPh. The reaction can be understood by addition of two carbene units to triple bonds. An initial [2 + 2] addition of the Ru═CHSiMe3 bond with the alkyne triple bond leads to an alkenyl ruthenium-carbene species capable of coordinating a second carbene unit to produce conjugated dienes

In vitro fermentation kinetics and end-products of cereal arabinoxylans and (1,3;1,4)-beta-glucans by porcine feces

Purified and semi-purified polysaccharides characteristic of cereals were fermented in vitro with a pig faecal inoculum, using the cumulative gas production technique, to examine the kinetics and end-products of fermentation after 48 h. It was shown that arabinoxylan and mixed linkage (1,3;1,4) β-glucan were rapidly fermented if soluble, while less soluble substrates (insoluble arabinoxylan, maize and wheat starch granules, and bacterial cellulose) were more slowly fermented. Relevant monosaccharides were fermented at very similar rates to soluble polymeric arabinoxylan and β-glucan, showing that depolymerisation was not a limiting step, in contrast to some previous studies. Bacterial cellulose is shown to be a useful model substrate for fermentation of plant cellulose which is difficult to obtain without harsh chemical treatments. Fermentation end-products were related to kinetics, with slow carbohydrate fermentation resulting in increased protein fermentation. Ratios of short-chain fatty acid products were similar for all arabinoxylan and β-glucan substrates. © 2010 Elsevier Ltd