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Sökning: WFRF:(Holmen G) > (2005-2009)

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1.
  • Brodin, N., et al. (författare)
  • Coaching patients with early rheumatoid arthritis to healthy physical activity : A multicenter, randomized, controlled study
  • 2008
  • Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : Wiley. - 0004-3591 .- 1529-0131. ; 59:3, s. 325-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis. Methods. A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (=30 minutes, moderately intensive activity, most days of the week). Results. The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%, P > 0.05) and after (54% versus 44%, P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test, P = 0.000) (Grippit, P = 0.003), but not in any other variables assessed. Conclusion. A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change. © 2008, American College of Rheumatology.
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2.
  • Wassvik, Carola, 1975- (författare)
  • Computational Analysis of Aqueous Drug Solubility – Influence of the Solid State
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aqueous solubility is a key parameter influencing the bioavailability of drugs and drug candidates. In this thesis computational models for the prediction of aqueous drug solubility were explored. High quality experimental solubility data for drugs were generated using a standardised protocol and models were developed using multivariate data analysis tools and calculated molecular descriptors. In addition, structural features associated with either solid-state limited or solvation limited solubility of drugs were identified.Solvation, as represented by the octanol-water partition coefficient (logP), was found to be the dominant factor limiting the solubility of drugs, with solid-state properties being the second most important limiting factor.The relationship between the chemical structure of drugs and the strength of their crystal lattice was studied for a dataset displaying logP-independent solubility. Large, rigid and flat molecules with an extended ring-structure and a large number of conjugated π-bonds were found to be more likely to have their solubility limited by a strong crystal lattice than were small, spherically shaped molecules with flexible side-chains.Finally, the relationship between chemical structure and drug solvation was studied using computer simulated values of the free energy of hydration. Drugs exhibiting poor hydration were found to be large and flexible, to have low polarisability and few hydrogen bond acceptors and donors.The relationship between the structural features of drugs and their aqueous solubility discussed in this thesis provide new rules-of-thumb that could guide decision-making in early drug discovery.
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4.
  • Wassvik, Carola M, et al. (författare)
  • Molecular characteristics for solid-state limited solubility
  • 2008
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 51:10, s. 3035-3039
  • Tidskriftsartikel (refereegranskat)abstract
    • Solubility and solid-state characteristics were determined and multivariate data analysis was used to deduce structural features important for solid-state limited solubility of marketed drugs. Molecules with extended ring structures and large conjugated systems were less soluble, indicating that structural features related to rigidity and aromaticity result in solubility restricted by stable crystal structures. These descriptors successfully predicted the applied test set and can be useful for avoiding synthesis of compounds behaving like "brick dust".
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