Mapping analysis to predict EQ-5D-5 L utility values based on the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires in the Spanish population suffering from lower limb osteoarthritis.

BACKGROUND: The EQ-5D-5 L is a quality-of-life questionnaire based on individuals' preferences that is widely employed for cost-effectiveness analysis. Given the current demand for mapping algorithms to directly assign "utilities", this study aimed to generate different mapping models for predicting EQ-5D-5 L utility values based on scores of the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires provided by patients suffering from hip and knee osteoarthritis (OA), respectively, and to assess the predictive capability of these functions. METHODS: This was a prospective, observational study. Following the criteria of the American Rheumatism Association, 361 patients with hip OA and 397 with knee OA from three regions in Spain were included. Health-related quality of life (HRQoL) was assessed through the EQ-5D-5 L general questionnaire and the OHS and OKS specifically for lower limb OA. Based on the scores on the OHS and OKS questionnaires, EQ-5D-5 L utilities were estimated using 4 models: ordinary least squares (OLS), Tobit, generalized linear model (GLM), and beta regression (Breg). The models were validated on the same patients after 6 months: the mean absolute error (MAE) and mean squared error (MSE) with their 95% confidence intervals (CI), mean values of standard errors (SE), intraclass correlation coefficients (ICC), and Bland-Altman plots were obtained. RESULTS: The lowest MAEs were obtained using GLM and Breg models, with values of 0.1103 (0.0993-0.1214) and 0.1229 (0.1102-0.1335) for hip OA, and values of 0.1127 (0.1014-0.1239) and 0.1141 (0.1031-0.1251) for knee OA. MSE values were also lower using GLM and Breg. ICCs between predicted and observed values were around or over the 0.8 cut-off point. Bland-Altman plots showed an acceptable correlation, but precision was lower for subjects with worse HRQoL, which was also evident when comparing MAEs of the bottom and top halves of the utilities scale. Predictive equations for utilities based on OHS/OKS scores were proposed. CONCLUSIONS: The OHS and OKS scores allow for estimating EQ-5D-5 L utility indexes for patients with hip and knee OA, respectively, with adequate validity and precision. GLM and Breg produce the best predictions. The predictive power of proposed equations is more consistent for subjects in better health condition.

Asociación de diabetes respecto a variables sociodemográficas, hipertensión, hipercolesterolemia y enfermedad periodontal / Association diabetes between sociodemographic variables, hypertension, hypercholesterolemia and periodontal disease

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Conformations of the iduronate ring in short heparin fragments described by time-averaged distance restrained molecular dynamics.

The polyconformational behavior of L-iduronic acid (L-IdoA2S) in heparin derivatives has been previously analyzed in terms of intra-ring proton-proton vicinal coupling constants ((3)JHH) through mathematical fit of experimental and theoretical values (Ferro DR, Provasoli A, Ragazzi M, Casu B, Torri G, Bossennec V, Perly B, Sinay P, Petitou M, Choay J. 1990. Conformer Populations of L-Iduronic Acid Residues in Glycosaminoglycan Sequences. Carbohydr Res. 195:157-167; Muñoz-García JC, López-Prados J, Angulo J, Díaz-Contreras I, Reichardt N, de Paz JL, Martín-Lomas M, Nieto PM. 2012. Effect of the substituents of the neighboring ring in the conformational equilibrium of iduronate in heparin-like trisaccharides. Chemistry. 18:16319-16331.). However, this methodology is subjected to the experimental uncertainties of the J-coupling measurements, the force field deviations and the goodness of the least-squares fit. In the present work, we have used time-averaged distance restrained molecular dynamics (tar-MD) to largely reduce these errors, which enables accurate quantification of the population of conformers, or puckers, of the L-IdoA2S residue, in a set of eight heparin-like trisaccharides following the general sequence d-glucosamine (GlcN)-IdoA-GlcN, directly from the time evolution of the puckering coordinates θ and . Thus, by carrying out tar-MD simulations in explicit water, with the exclusive nuclear overhauser enhancement (NOE)-derived distance H2-H5 of the L-IdoA2S (2)SO conformer as the unique imposed constraint, we have been able to accurately and easily determine the different extents to which the iduronate ring populates the polar ((1)C4 chair) and equatorial ((2)SO skew-boat) areas of the puckering sphere depending on the sulfation pattern of the flanking GlcN residues, under low temperature conditions (278 K). The results indicate that 6-O-sulfation at the reducing-end GlcN residue facilitates the (1)C4 to (2)SO transitions of the iduronate ring by augmenting the flexibility of the C2-C3 torsion, driving the conformational equilibrium toward a majority of equatorial conformers.

Effect of the substituents of the neighboring ring in the conformational equilibrium of iduronate in heparin-like trisaccharides.

Based on the structure of the regular heparin, we have prepared a smart library of heparin-like trisaccharides by incorporating some sulfate groups in the sequence α-D-GlcNS- (1-4)-α-L-Ido2S-(1-4)-α-D-GlcN. According to the 3D structure of heparin, which features one helix turn every four residues, this fragment corresponds to the minimum binding motif. We have performed a complete NMR study and found that the trisaccharides have a similar 3D structure to regular heparin itself, but their spectral properties are such that allow to extract very detailed information about distances and coupling constants as they are isotropic molecules. The characteristic conformational equilibrium of the central iduronate ring has been analyzed combining NMR and molecular dynamics and the populations of the conformers of the central iduronate ring have been calculated. We have found that in those compounds lacking the sulfate group at position 6 of the reducing end glucosamine, the population of (2)S(0) of the central iduronate residue is sensitive to the temperature decreasing to 19% at 278 K. On the contrary, the trisaccharides with 6-O-sulfate in the reducing end glucosamine keep the level of population constant with temperature circa 40% of (2)S(0) similar to that observed at room temperature. Another structural feature that has been revealed through this analysis is the larger flexibility of the L-IdoAS- D-GlcN glycosidic linkage, compared with the D-GlcNS-L-IdoA. We propose that this is the point where the heparin chain is bended to form structures far from the regular helix known as kink that have been proposed to play an important role in the specificity of the heparin-protein interaction.

Factores asociados a disfunción craneomandibular en una población de un centro de salud / Factors associated with temporomandibular disorder in a health centre’s population

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