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- Salomone, A., et al.
(författare)
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Direct observation of a lithiated oxirane: A synergistic study using spectroscopic, crystallographic, and theoretical methods on the structure and stereodynamics of lithiated ortho-trifluoromethyl styrene oxide
- 2014
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Ingår i: CHEMICAL SCIENCE. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 5:2, s. 528-538
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Tidskriftsartikel (refereegranskat)abstract
- α-Lithiated epoxides, long considered "fleeting" intermediates in the reactions of epoxides with strong bases, have nowadays proven to be key synthons for asymmetric synthesis. In this study, the solution and the solid state structure of an α-lithiated aryloxirane, namely α-lithiated ortho-trifluoromethyl styrene oxide (1-Li), were determined. Single crystal X-ray diffraction analysis of 1-Li performed at 100 K applying the X-TEMP-2 device revealed a self-assembled heterochiral dimeric structure with a rare central six-membered (O-Li-C)2 planar core, which is unprecedented in Li/oxygen carbenoids. Multinuclear magnetic resonance ( 1H, 13C, 19F, 7Li) studies suggested that 1-Li exists in THF solution as a mixture of two interconverting diastereomeric dimeric aggregates, each one featuring a single σ-contact between lithium and a carbon atom. Line shape analysis provided activation parameters for both the dynamic interconversion of the two dimers and the enantiomerisation of 1-Li, which proved to be mostly entropy controlled. The structural assignment in solution was supported by density functional theory computations through the investigation of conformers of monomeric and dimeric complexes of 1-Li featuring different degrees of specific solvation. A mechanism based on the equilibration of six-membered homo- and heterochiral dimers was proposed to explain the configurational instability exhibited by 1-Li in THF. © 2014 The Royal Society of Chemistry.
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| 3. |
- Doria, Andrea, et al.
(författare)
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Annual direct medical cost of active systemic lupus erythematosus in five European countries
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:1, s. 154-160
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To evaluate the annual direct medical cost of managing adult systemic lupus erythematosus (SLE) patients with active autoantibody positive disease in Europe. Methods A 2-year, retrospective, multicentre, observational study was conducted in five countries (France, Germany, Italy, Spain and the UK). Data included patients' characteristics, disease activity and severity, flare assessments and health resource use (eg, laboratory tests, medications, specialist visits and hospitalisations). Costs were assessed from the public payers' perspective. Cost predictors were estimated by multivariate regression models. Results Thirty-one centres enrolled 427 consecutive eligible patients stratified equally by disease severity. At baseline, mean (SD) age was 44.5 (13.8) years, 90.5% were women and mean (SD) SLE duration was 10.7 (8.0) years. The SELENA-SLEDAI (11.2 vs 5.3) and SLICC/ACR index (1.0 vs 0.7) scores were higher in severe patients. Over the study period, patients experienced on average 1.02 (0.71) flares/year. The mean annual direct medical cost was higher in severe compared to non-severe patients (Euro4748 vs Euro2650, p<0.001). Medication costs were Euro2518 in severe versus Euro1251 in non-severe patients (p<0.001). Medications represented 53% and 47% of the total cost for severe and non-severe patients, respectively, primarily due to immunosuppressants and biologics. Flares, especially severe flares, were identified as the major cost predictor, with each flare increasing the annual total cost by about Euro1002 (p<0.001). Conclusions The annual direct medical cost of SLE patients in Europe is related to disease severity and flares. Medical treatments were the main cost drivers. Severe flares and major organ involvement were identified as important cost predictors.
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