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- Herrick, Ariane L, et al.
(författare)
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Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:7, s. 1207-1218
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
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- Peytrignet, Sébastien, et al.
(författare)
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Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.
- 2018
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 57:2, s. 370-381
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001).The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.
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- Soler, Josep, et al.
(författare)
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Modelling of the LTDE-SD radionuclide diffusion experiment in crystalline rock at the Aspo Hard Rock Laboratory (Sweden)
- 2022
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Ingår i: Geologica Acta. - : Universitat Autònoma de Barcelona. - 1695-6133 .- 1696-5728. ; 20, s. 1-32
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Tidskriftsartikel (refereegranskat)abstract
- This study shows a comparison and analysis of results from a modelling exercise concerning a field experiment involving the transport and retention of different radionuclide tracers in crystalline rock. This exercise was performed within the Swedish Nuclear Fuel and Waste Management Company (SKB) Task Force on Modelling of Groundwater Flow and Transport of Solutes (Task Force GWFTS). Task 9B of the Task Force GWFTS was the second subtask within Task 9 and focused on the modelling of experimental results from the Long Term Sorption Diffusion Experiment in situ tracer test. The test had been performed at a depth of about 410m in the Aspo Hard Rock Laboratory. Synthetic groundwater containing a cocktail of radionuclide tracers was circulated for 198 days on the natural surface of a fracture and in a narrow slim hole drilled in unaltered rock matrix. Overcoring of the rock after the end of the test allowed for the measurement of tracer distribution profiles in the rock from the fracture surface (A cores) and also from the slim hole (D cores). The measured tracer activities in the rock samples showed long profiles (several cm) for non-or weakly-sorbing tracers (Cl-36, Na-22), but also for many of the more strongly-sorbing radionuclides. The understanding of this unexpected feature was one of the main motivations for this modelling exercise. However, re-evaluation and revision of the data during the course of Task 9B provided evidence that the anomalous long tails at low activities for strongly sorbing tracers were artefacts due to cross-contamination during rock sample preparation. A few data points remained for Cs-137, Ba-133, Ni-63 and Cd-109, but most measurements at long distances from the tracer source (>10mm) were now below the reported detection limits. Ten different modelling teams provided results for this exercise, using different concepts and codes. The tracers that were finally considered were Na-22, Cl-36, Co-57, Ni-63, Ba-133, Cs-137, Cd-109, Ra-226 and Np-237. Three main types of models were used: i) analytical solutions to the transport-retention equations, ii) continuum -porous-medium numerical models, and iii) microstructure-based models accounting for small-scale heterogeneity (i.e. mineral grains, porosities and/or microfracture distributions) and potential centimetre-scale fractures. The modelling by the different teams led to some important conclusions, concerning for instance the presence of a disturbed zone (a few mm in thickness) next to the fracture surface and to the wall of the slim hole and the role of micro-fractures and cm-scale fractures in the transport of weakly sorbing tracers. These conclusions could be reached after the re-evaluation and revision of the experimental data (tracer profiles in the rock) and the analysis of the different sets of model results provided by the different teams.
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