Rheumatoid Arthritis Surveillance in Ontario: Monitoring the Burden, Quality of Care and Patient Outcomes through Linkage of Administrative Health Data

Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. Using the Ontario administrative health data housed at the Institute for Clinical Evaluative Sciences, researchers have quantified the population-level burden and epidemiology of RA, mapped its geographic distribution in relation to rheumatologist supply, studied trends in access to rheumatology care and treatment and evaluated patient outcomes. The findings highlight the excess morbidity and mortality associated with the growing burden of RA in the face of a strained rheumatology supply, and raise urgent questions about how best to meet the needs of Ontarians with RA

Which Oats to Grow

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Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR

We show how dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy can be used to characterize polymorphs and solvates of organic solids. We applied DNP to three polymorphs and one hydrated form of the asthma drug molecule theophylline. For some forms of theophylline, sample grinding and impregnation with the radical-containing solution, which are necessary to prepare the samples for DNP, were found to induce polymorphic transitions or desolvation between some forms. We present protocols for sample preparation for solid-state magic-angle spinning (MAS) DNP experiments that avoid the polymorphic phase transitions in theophylline. These protocols include cryogrinding, grinding under inert atmosphere, and the appropriate choice of the impregnating liquid. By applying these procedures, we subsequently demonstrate that two-dimensional correlation experiments, such as H-1-C-13 and H-1-N-15 HETCOR or C-13-C-13 INADEQUATE, can be obtained at natural isotopic abundance in reasonable times, thus enabling more advanced structural characterization of polymorphs

Rapid Structure Determination of Molecular Solids Using Chemical Shifts Directed by Unambiguous Prior Constraints

NMR-based crystallography approaches involving the combination of crystal structure prediction methods, ab initio calculated chemical shifts and solid-state NMR experiments are powerful methods for crystal structure determination of microcrystalline powders. However, currently structural information obtained from solid-state NMR is usually included only after a set of candidate crystal structures has already been independently generated, starting from a set of single-molecule conformations. Here, we show with the case of ampicillin that this can lead to failure of structure determination. We propose a crystal structure determination method that includes experimental constraints during conformer selection. In order to overcome the problem that experimental measurements on the crystalline samples are not obviously translatable to restrict the single-molecule conformational space, we propose constraints based on the analysis of absent cross-peaks in solid-state NMR correlation experiments. We show that these absences provide unambiguous structural constraints on both the crystal structure and the gas-phase conformations, and therefore can be used for unambiguous selection. The approach is parametrized on the crystal structure determination of flutamide, flufenamic acid, and cocaine, where we reduce the computational cost by around 50%. Most importantly, the method is then shown to correctly determine the crystal structure of ampicillin, which would have failed using current methods because it adopts a high-energy conformer in its crystal structure. The average positional RMSE on the NMR powder structure is = 0.176 Å, which corresponds to an average equivalent displacement parameter Ueq = 0.0103 Å2

Na+ mobility in sodium strontium silicate fast ion conductors

We present the first direct evidence of Na-ion mobility in sodium strontium silicate fast ion conductors, based on variable temperature 23Na solid state NMR spectroscopy and spin-lattice relaxation measurements