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- Kroes, JA, et al.
(författare)
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Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
- 2023
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking non-standardized, patient-level registry-data. Mepolizumab has shown clinical efficacy in RCTs and prospective real-world studies and could therefore serve as a proof of principle for this novel approach.AimTo harmonize data from 10 national severe asthma registries and characterize patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.MethodsIn this observational cohort study, registry data (5871 patients) were extracted for harmonization. Where harmonization was possible, patients who initiated mepolizumab between 1-1-2016 and 31-12-2021 were examined. Changes of a 12 (range 11–18) months period in frequent (≥2) exacerbations, maintenance OCS use and dose were analyzed in a privacy-preserving manner using meta-analysis of generalized estimating equation parameters. Periods before and during the COVID-19 pandemic were analyzed separately.ResultsIn 912 patients who fulfilled selection criteria mepolizumab significantly reduced frequent exacerbations (OR;95%CI: 0.18;0.13–0.25), maintenance OCS use (OR;95%CI: 0.75;0.61–0.92) and dose (mean; 95%CI: −3.93 mg·day−1; −5.24–2.62) in the Pre-Pandemic group, with similar trends in the Pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.ConclusionsBy harmonizing patient-level registry data and applying federated analysis, SHARP demonstrated the real-wold effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
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- Fasoli, A., et al.
(författare)
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Chapter 5 : Physics of energetic ions
- 2007
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 47:6, s. S264-S284
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Forskningsöversikt (refereegranskat)abstract
- This chapter reviews the progress accomplished since the redaction of the first ITER Physics Basis (1999 Nucl. Fusion 39 2137-664) in the field of energetic ion physics and its possible impact on burning plasma regimes. New schemes to create energetic ions simulating the fusion-produced alphas are introduced, accessing experimental conditions of direct relevance for burning plasmas, in terms of the Alfvenic Mach number and of the normalised pressure gradient of the energetic ions, though orbit characteristics and size cannot always match those of ITER. Based on the experimental and theoretical knowledge of the effects of the toroidal magnetic field ripple on direct fast ion losses, ferritic inserts in ITER are expected to provide a significant reduction of ripple alpha losses in reversed shear configurations. The nonlinear fast ion interaction with kink and tearing modes is qualitatively understood, but quantitative predictions are missing, particularly for the stabilisation of sawteeth by fast particles that can trigger neoclassical tearing modes. A large database on the linear stability properties of the modes interacting with energetic ions, such as the Alfven eigenmode has been constructed. Comparisons between theoretical predictions and experimental measurements of mode structures and drive/damping rates approach a satisfactory degree of consistency, though systematic measurements and theory comparisons of damping and drive of intermediate and high mode numbers, the most relevant for ITER, still need to be performed. The nonlinear behaviour of Alfven eigenmodes close to marginal stability is well characterized theoretically and experimentally, which gives the opportunity to extract some information on the particle phase space distribution from the measured instability spectral features. Much less data exists for strongly unstable scenarios, characterised by nonlinear dynamical processes leading to energetic ion redistribution and losses, and identified in nonlinear numerical simulations of Alfven eigenmodes and energetic particle modes. Comparisons with theoretical and numerical analyses are needed to assess the potential implications of these regimes on burning plasma scenarios, including in the presence of a large number of modes simultaneously driven unstable by the fast ions.
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