Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality

Cu-Promoted Sydnone Cycloadditions of Alkynes: Scope and Mechanism Studies

Cu salts have been found to promote the cycloaddition reaction of sydnones and terminal alkynes, providing significant reduction in reaction times. Specifically, the use of Cu(OTf)2 is found to provide 1,3-disubstituted pyrazoles, whereas simply switching the promoter system to Cu(OAc)2 allows the corresponding 1,4-isomers to be produced. The mechanism of the Cu-effect in each case has been investigated by experimental and theoretical studies, and they suggest that Cu(OTf)2 functions by Lewis acid activation of the sydnone, whereas Cu(OAc)2 promotes formation of reactive CuI acetylides

Asymmetric aza-Henry reaction under phase transfer catalysis: An experimental and theoretical study

An efficient catalytic asymmetric aza-Henry reaction under phase transfer conditions is presented. The method is based on the reaction of the respective nitroalkane with α-amido sulfones effected by CsOH·H2O base in toluene as solvent and in the presence of cinchone-derived ammonium catalysts. This direct aza-Henry reaction presents as interesting features its validity for both nonenolizable and enolizable aldehyde-derived azomethines and the tolerance of nitroalkanes, other than nitromethane, for the production of β-nitroamines. The synthetic value of the methodology described is demonstrated by providing (a) a direct route for the asymmetric synthesis of differently substituted 1,2-diamines and (b) a new asymmetric synthesis of γ-amino α,β-unsaturated esters through a catalytic, highly enantioselective formal addition of functionalized alkenyl groups to azomethines. Finally, a preferred TS that nicely fits the observed enantioselectivity has been identified. Most remarkable, an unusual hydrogen bond pattern for the catalyst-nitrocompound-imine complex is predicted, where the catalyst OH group interacts with the NO2 group of the nitrocompound

2- and 6-Purinylmagnesium Halides in Dichloromethane: Scope and New Insights into the Solvent Influence on the C 12Mg Bond

The generation of positionally stable purin-2- and 6-yl magnesium halides is complicated by the often very rapid isomerization to give the 8-yl Grignards. By conducting the reaction in dichloromethane (DCM), we demonstrated that the anion isomerization can be stopped and these stable purin-2- and 6-yl Grignards react directly with a broad scope of aldehydes in good yields. Furthermore, purine functionalization with ketones has been achieved for the first time in the presence of LaCl3 c5 2LiCl. Density functional theory calculations offer a possible explanation of the special role played by solvent in this chemistry and show that in DCM the C 12Mg bond has a less polar character, whereas in THF it is predominantly ionic and much more basic in nature