going beyond BASDAI

This work was supported by a Research Grant from the InvestigatorInitiated Studies program of Merck Sharp & Dohme (Grant No. 56078). The sponsor did not interfere with the study question, analysis or interpretation of results. AS is supported by a doctoral grant from Fundação para a Ciência e Tecnologia (Foundation for Science and Technology) (SFRH/BD/108246/2015).OBJECTIVES: To compare definitions of high disease activity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in selecting patients for treatment with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: Patients from Rheumatic Diseases Portuguese Register (Reuma.pt) with a clinical diagnosis of axial spondyloarthritis (axSpA) were included. Four subgroups (cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of high disease activity) were compared regarding baseline characteristics and response to bDMARDs at 3 and 6 months estimated in multivariable regression models. RESULTS: Of the 594 patients included, the majority (82%) had both BASDAI≥4 and ASDAS ≥2.1. The frequency of ASDAS ≥2.1, if BASDAI<4 was much larger than the opposite (ie, ASDAS <2.1, if BASDAI≥4): 62% vs 0.8%. Compared to patients fulfilling both definitions, those with ASDAS ≥2.1 only were more likely to be male (77% vs 51%), human leucocyte antigen B27 positive (79% vs 65%) and have a higher C reactive protein (2.9 (SD 3.5) vs 2.1 (2.9)). Among bDMARD-treated patients (n=359), responses across subgroups were globally overlapping, except for the most 'stringent' outcomes. Patients captured only by ASDAS responded better compared to patients fulfilling both definitions (eg, ASDAS inactive disease at 3 months: 61% vs 25% and at 6 months: 42% vs 25%). CONCLUSION: The ASDAS definition of high disease activity is more inclusive than the BASDAI definition in selecting patients with axSpA for bDMARD treatment. The additionally 'captured' patients respond better and have higher likelihood of predictors thereof. These results support using ASDAS≥2.1 as a criterion for treatment decisions.publishersversionpublishe

Solemnidad festiva con que en la insigne, leal, noble y coronada ciudad de Valencia se celebrò la feliz nueva de la canonizacion de su milagroso arçobispo Santo Tomas de Villanueva

Los sermones son de: Melcior Fuster, Josep Vicent del Olmo, Josep Sanchís, Antoni Bonaventura Guerau, Domingo Sarrio, Marcelo Marona, Cristóbal Abella y Jerónimo de CórdobaMúltiples errores en la pagSign.: *8, *-***4, A-Yy4, A-Nn4ReclamosPort. grabada calcogr. atribuida a Gregorio Heredia (v. Ferran Salvador), grabado calcogr., algunos de ellos firmados por Juan Felipe (Páez. Repertorio 1, 723/6) y otros atribuidos a G. Heredia (Ferran Salvador) y Nicolás Viñerta (Palau), capitales orn. y viñeta a final de cap. xilográfica, frisos tipográficos

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent <i>N</i>‑Benzylphenethylamine 5‑HT_2A Serotonin Receptor Agonist Ligands

Based on the structure of the superpotent 5-HT_2A agonist 2-(4-bromo-2,5-dimethoxyphenyl)-<i>N</i>-[(2-methoxyphenyl)­methyl]­ethanamine, which consists of a ring-substituted phenethylamine skeleton modified with an <i>N</i>-benzyl group, we designed and synthesized a small library of constrained analogues to identify the optimal arrangement of the pharmacophoric elements of the ligand. Structures consisted of diversely substituted tetrahydroisoquinolines, piperidines, and one benzazepine. Based on the structure of (<i>S</i>,<i>S</i>)-<b>9b</b>, which showed the highest affinity of the series, we propose an optimal binding conformation. (<i>S</i>,<i>S</i>)-<b>9b</b> also displayed 124-fold selectivity for the 5-HT_2A over the 5-HT_2C receptor, making it the most selective 5-HT_2A receptor agonist ligand currently known

Extensive Rigid Analogue Design Maps the Binding Conformation of Potent <i>N</i>‑Benzylphenethylamine 5‑HT_2A Serotonin Receptor Agonist Ligands

Based on the structure of the superpotent 5-HT_2A agonist 2-(4-bromo-2,5-dimethoxyphenyl)-<i>N</i>-[(2-methoxyphenyl)­methyl]­ethanamine, which consists of a ring-substituted phenethylamine skeleton modified with an <i>N</i>-benzyl group, we designed and synthesized a small library of constrained analogues to identify the optimal arrangement of the pharmacophoric elements of the ligand. Structures consisted of diversely substituted tetrahydroisoquinolines, piperidines, and one benzazepine. Based on the structure of (<i>S</i>,<i>S</i>)-<b>9b</b>, which showed the highest affinity of the series, we propose an optimal binding conformation. (<i>S</i>,<i>S</i>)-<b>9b</b> also displayed 124-fold selectivity for the 5-HT_2A over the 5-HT_2C receptor, making it the most selective 5-HT_2A receptor agonist ligand currently known