| 1. |
- Batty, J. A., et al.
(författare)
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An Investigation of CYP2D6 Genotype and Response to Metoprolol CR/XL During Dose Titration in Patients With Heart Failure: A MERIT-HF Substudy
- 2014
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Ingår i: Clinical Pharmacology & Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 95:3, s. 321-330
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Tidskriftsartikel (refereegranskat)abstract
- To explore the pharmacogenetic effects of the cytochrome P450 (CYP) 2D6 genotype in patients with systolic heart failure treated using controlled/extended-release (CR/XL) metoprolol, this study assessed the CYP2D6 locus for the nonfunctional * 4 allele (1846G> A; rs3892097) in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF; n = 605). Participants were characterized as extensive, intermediate, or poor metabolizers (EMs, IMs, or PMs, respectively), based on the presence of the CYP2D6* 4 allele (EM: * 1* 1, 60.4%; IM: * 1* 4, 35.8%; and PM: * 4* 4, 3.8%). Plasma metoprolol concentrations were 2.1-/4.6-fold greater in the IM/PM groups as compared with the EM group (P < 0.0001). Metoprolol induced significantly lower heart rates and diastolic blood pressures during early titration, indicating a CYP2D6* 4 allele dose-response effect (P < 0.05). These effects were not observed at maximal dose, suggesting a saturable effect. Genotype did not adversely affect surrogate treatment efficacy. CYP2D6 genotype modulates metoprolol pharmacokinetics/pharmacodynamics during early titration; however, the MERIT-HF-defined titration schedule remains recommended for all patients, regardless of genotype.
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| 2. |
- Karlsson, R., et al.
(författare)
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Hydroxyl, water, ammonia, carbon monoxide and neutral carbon towards the Sgr A complex: VLA, Odin and SEST observations
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 554
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The Sagittarius A complex in the Galactic centre comprises an ensemble of molecular clouds of different species with a variety of geometrical and kinematic properties. This work aims to study molecular abundances, morphology, and kinematics by comparing hydroxyl, water, carbon monoxide, ammonia, and atomic carbon and some of their isotopologues, in the +50 km s-1 cloud, the circumnuclear disk (CND), the +20 km s-1 cloud, the expanding molecular ring and the line-of-sight spiral arm features, including the Local/Sgr arm, the −30 km s-1 arm, and the 3-kpc arm.Methods. We observed the +50 km s-1 cloud, the CND and the +20 km s-1 cloud, and other selected positions at the Galactic centre with the VLA, and the Odin satellite. The VLA was used to map the 1665 and 1667 MHz OH lambda doublet main lines of the (2Π3/2) state, and the Odin satellite was used to map the 557 GHz H2O (110 − 101) line as well as to observe the 548 GHz H218O (110-101) line, the 572 GHz NH3 (10 − 00) line, the 576 GHz CO J = 5 − 4 line and the 492 GHz C i (3P1–3P0) line. Furthermore, the SEST was used to map a region of the Sgr A complex in the 220 GHz C18O J = 2−1 line.Results. Strong OH absorption, H2O emission and absorption lines were seen at all observed positions, and the H218O line was detected in absorption towards the +50 km s-1 cloud, the CND, the +20 km s-1cloud, the expanding molecular ring, and the 3-kpc arm. Strong CO J = 5−4, C18O J = 2−1, and neutral carbon C i emissions were seen towards the +50 and +20 km s-1 clouds. NH3 was only detected in weak absorption originating in the line-of-sight spiral arm features. The abundances of OH and H2O in the +50 and +20 km s-1 clouds reflect the different physical environments in the clouds, where shocks and star formation prevail in the +50 km s-1 cloud and giving rise to a higher rate of H2O production there than in the +20 km s-1 cloud. In the CND, cloud collisions and shocks are frequent, and the CND is also subject to intense UV-radiation emanating from the supermassive black hole and the central star cluster. The CND is rich in H2O and OH, and these abundances are considerably higher than in the +50 and +20 km s-1 clouds. We compare our estimated abundances of OH, H2O, and NH3 with similar and differing results for some other sources available in the literature. As compared to the quiescent cloud values of a few × 10-9, or lower, the H2O abundance is markedly enhanced in the front sides of the Sgr A molecular cloud cores, (2−7) × 10-8, as observed in absorption, and highest in the CND. A similar abundance enhancement is seen in OH. The likely explanation is PDR chemistry including grain surface reactions, and perhaps also the influence of shocks. In the redward high-velocity line wings of the +50 and +20 km s-1 clouds and the CND, the H2O abundances are estimated to be (1−6) × 10-6 or higher, i.e., similar to the water abundances in outflows of the Orion KL and DR21 molecular clouds, which are said to be caused by the combined action of shock desorption from icy grain mantles and high-temperature, gas-phase shock chemistry.
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| 3. |
- Lorgelly, Paula K, et al.
(författare)
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An economic evaluation of rosuvastatin treatment in systolic heart failure: evidence from the CORONA trial.
- 2010
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 12:1, s. 66-74
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To estimate the cost-effectiveness of 10 mg rosuvastatin daily for older patients with systolic heart failure in the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) trial. METHODS AND RESULTS: This within trial analysis of CORONA used major cardiovascular (CV) events as the outcome measure. Resource use was valued and the costs of hospitalizations, procedures, and statin use compared. Cost-effectiveness was estimated as cost per major CV event avoided. There were significantly fewer major CV events in the rosuvastatin group compared with the placebo group (1.04 vs. 1.20 per patient; difference 0.164; 95% CI: 0.075-0.254, P < 0.001). The average cost of CV hospitalizations and procedures was significantly lower for those receiving rosuvastatin ( pound1531 vs. pound1769; difference pound238; 95% CI: pound73-403, P = 0.005); the additional cost of the statin resulted in significantly higher total costs for the rosuvastatin group ( pound1769 vs. pound2072; difference pound303; 95% CI: pound138-468, P < 0.001). Overall, rosuvastatin was found to cost pound1840 (95% CI: pound562-6028) per major CV event avoided. CONCLUSION: This economic analysis showed that a significant reduction in major CV events with rosuvastatin led to significantly reduced costs of CV hospitalizations and procedures. The reduction in associated costs for major CV events was found to offset partially (by 44%) the cost of rosuvastatin treatment in patients with systolic heart failure.
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