| 1. |
- Glintborg, B., et al.
(författare)
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Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries
- 2018
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:6, s. 465-474
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. Method: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. Results: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). Conclusion: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.
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| 2. |
- Nissen, M., et al.
(författare)
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The impact of a csDMARD in combination with a TNF inhibitor on drug retention and clinical remission in axial spondylarthritis
- 2022
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:12, s. 4741-4751
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis. Methods Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as >= 1 swollen joint at baseline (=TNFi start). Results Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis. Conclusion This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy.
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| 3. |
- Aas, W., et al.
(författare)
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Lessons learnt from the first EMEP intensive measurement periods
- 2012
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:17, s. 8073-8094
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Tidskriftsartikel (refereegranskat)abstract
- The first EMEP intensive measurement periods were held in June 2006 and January 2007. The measurements aimed to characterize the aerosol chemical compositions, including the gas/aerosol partitioning of inorganic compounds. The measurement program during these periods included daily or hourly measurements of the secondary inorganic components, with additional measurements of elemental- and organic carbon (EC and OC) and mineral dust in PM1, PM2.5 and PM10. These measurements have provided extended knowledge regarding the composition of particulate matter and the temporal and spatial variability of PM, as well as an extended database for the assessment of chemical transport models. This paper summarise the first experiences of making use of measurements from the first EMEP intensive measurement periods along with EMEP model results from the updated model version to characterise aerosol composition. We investigated how the PM chemical composition varies between the summer and the winter month and geographically. The observation and model data are in general agreement regarding the main features of PM10 and PM2.5 composition and the relative contribution of different components, though the EMEP model tends to give slightly lower estimates of PM10 and PM2.5 compared to measurements. The intensive measurement data has identified areas where improvements are needed. Hourly concurrent measurements of gaseous and particulate components for the first time facilitated testing of modelled diurnal variability of the gas/aerosol partitioning of nitrogen species. In general, the modelled diurnal cycles of nitrate and ammonium aerosols are in fair agreement with the measurements, but the diurnal variability of ammonia is not well captured. The largest differences between model and observations of aerosol mass are seen in Italy during winter, which to a large extent may be explained by an underestimation of residential wood burning sources. It should be noted that both primary and secondary OC has been included in the calculations for the first time, showing promising results. Mineral dust is important, especially in southern Europe, and the model seems to capture the dust episodes well. The lack of measurements of mineral dust hampers the possibility for model evaluation for this highly uncertain PM component. There are also lessons learnt regarding improved measurements for future intensive periods. There is a need for increased comparability between the measurements at different sites. For the nitrogen compounds it is clear that more measurements using artefact free methods based on continuous measurement methods and/or denuders are needed. For EC/OC, a reference methodology (both in field and laboratory) was lacking during these periods giving problems with comparability, though measurement protocols have recently been established and these should be followed by the Parties to the EMEP Protocol. For measurements with no defined protocols, it might be a good solution to use centralised laboratories to ensure comparability across the network. To cope with the introduction of these new measurements, new reporting guidelines have been developed to ensure that all proper information about the methodologies and data quality is given.
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| 4. |
- Fowler, D., et al.
(författare)
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Atmospheric composition change : Ecosystems-Atmosphere interactions
- 2009
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 43:33, s. 5193-5267
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Forskningsöversikt (refereegranskat)abstract
- Ecosystems and the atmosphere: This review describes the state of understanding the processes involved in the exchange of trace gases and aerosols between the earth's surface and the atmosphere. The gases covered include NO, NO2, HONO, HNO3, NH3, SO2, DMS, Biogenic VOC, O-3, CH4, N2O and particles in the size range 1 nm-10 mu m including organic and inorganic chemical species. The main focus of the review is on the exchange between terrestrial ecosystems, both managed and natural and the atmosphere, although some new developments in ocean-atmosphere exchange are included. The material presented is biased towards the last decade, but includes earlier work, where more recent developments are limited or absent. New methodologies and instrumentation have enabled, if not driven technical advances in measurement. These developments have advanced the process understanding and upscaling of fluxes, especially for particles, VOC and NH3. Examples of these applications include mass spectrometric methods, such as Aerosol Mass Spectrometry (AMS) adapted for field measurement of atmosphere-surface fluxes using micrometeorological methods for chemically resolved aerosols. Also briefly described are some advances in theory and techniques in micrometeorology. For some of the compounds there have been paradigm shifts in approach and application of both techniques and assessment. These include flux measurements over marine surfaces and urban areas using micrometeorological methods and the up-scaling of flux measurements using aircraft and satellite remote sensing. The application of a flux-based approach in assessment of O-3 effects on vegetation at regional scales is an important policy linked development secured through improved quantification of fluxes. The coupling of monitoring, modelling and intensive flux measurement at a continental scale within the NitroEurope network represents a quantum development in the application of research teams to address the underpinning science of reactive nitrogen in the cycling between ecosystems and the atmosphere in Europe. Some important developments of the science have been applied to assist in addressing policy questions, which have been the main driver of the research agenda, while other developments in understanding have not been applied to their wider field especially in chemistry-transport models through deficiencies in obtaining appropriate data to enable application or inertia within the modelling community. The paper identifies applications, gaps and research questions that have remained intractable at least since 2000 within the specialized sections of the paper, and where possible these have been focussed on research questions for the coming decade.
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| 5. |
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| 6. |
- Lindström, Ulf, et al.
(författare)
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Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 1410-1418
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Methods: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. Results: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. Conclusion: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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| 7. |
- Ramirez-Llodra, E., et al.
(författare)
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A snap shot of the short-term response of crustaceans to macrophyte detritus in the deep Oslofjord
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- A test deployment of a time-lapse camera lander in the deep Oslofjord (431 m) was used to obtain initial information on the response of benthic fauna to macroalgal debris. Three macroalgal species were used on the lander baited plate: Fucus serratus, Saccharina latissima and Laminaria hyperborea and observed during 41.5 hours. The deep-water shrimp Pandalus borealis were attracted to the macroalgae rapidly (3 min after the lander reached the seafloor), followed by amphipods. Shrimp abundances were significantly higher in areas covered by macroalgae compared to the adjacent seafloor and the number of shrimp visiting the macroalgae increased with time. Amphipods arrived 13 hours later and were observed mainly on decaying L. hyperborea. The abundance of amphipods on L. hyperborea increased rapidly, reaching a peak at 31 h after deployment. These initial observations suggest that debris from kelp forests and other macroalgal beds may play an important role in fuelling deep benthic communities in the outer Oslofjord and, potentially, enhance secondary production of commercial species such as P. borealis.
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| 8. |
- Simpson, David, 1961, et al.
(författare)
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The EMEP MSC-W chemical transport model - technical description
- 2012
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:16, s. 7825-7865
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Tidskriftsartikel (refereegranskat)abstract
- The Meteorological Synthesizing Centre-West (MSC-W) of the European Monitoring and Evaluation Programme (EMEP) has been performing model calculations in support of the Convention on Long Range Transboundary Air Pollution (CLRTAP) for more than 30 years. The EMEP MSC-W chemical transport model is still one of the key tools within European air pollution policy assessments. Traditionally, the model has covered all of Europe with a resolution of about 50 km x 50 km, and extending vertically from ground level to the tropopause (100 hPa). The model has changed extensively over the last ten years, however, with flexible processing of chemical schemes, meteorological inputs, and with nesting capability: the code is now applied on scales ranging from local (ca. 5 km grid size) to global (with 1 degree resolution). The model is used to simulate photo-oxidants and both inorganic and organic aerosols. In 2008 the EMEP model was released for the first time as public domain code, along with all required input data for model runs for one year. The second release of the EMEP MSC-W model became available in mid 2011, and a new release is targeted for summer 2012. This publication is in-tended to document this third release of the EMEP MSC-W model. The model formulations are given, along with details of input data-sets which are used, and a brief background on some of the choices made in the formulation is presented. The model code itself is available at www.emep.int, along with the data required to run for a full year over Europe.
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| 9. |
- Aas, Wenche, et al.
(författare)
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Trends in Air Pollution in Europe, 2000–2019
- 2024
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Ingår i: Aerosol and Air Quality Research. - 2071-1409 .- 1680-8584. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- This paper encompasses an assessment of air pollution trends in rural environments in Europe over the 2000–2019 period, benefiting from extensive long-term observational data from the EMEP monitoring network and EMEP MSC-W model computations. The trends in pollutant concentrations align with the decreasing emission patterns observed throughout Europe. Annual average concentrations of sulfur dioxide, particulate sulfate, and sulfur wet deposition have shown consistent declines of 3–4% annually since 2000. Similarly, oxidized nitrogen species have markedly decreased across Europe, with an annual reduction of 1.5–2% in nitrogen dioxide concentrations, total nitrate in the air, and oxidized nitrogen deposition. Notably, emission reductions and model predictions appear to slightly surpass the observed declines in sulfur and oxidized nitrogen, indicating a potential overestimation of reported emission reductions. Ammonia emissions have decreased less compared to other pollutants since 2000. Significant reductions in particulate ammonium have however, been achieved due to the impact of reductions in SOx and NOx emissions. For ground level ozone, both the observed and modelled peak levels in summer show declining trends, although the observed decline is smaller than modelled. There have been substantial annual reductions of 1.8% and 2.4% in the concentrations of PM10 and PM2.5, respectively. Elemental carbon has seen a reduction of approximately 4.5% per year since 2000. A similar reduction for organic carbon is only seen in winter when primary anthropogenic sources dominate. The observed improvements in European air quality emphasize the importance of comprehensive legislations to mitigate emissions.
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| 10. |
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| 11. |
- Christiansen, SN, et al.
(författare)
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SECULAR TRENDS IN BASELINE CHARACTERISTICS, TREATMENT RETENTION AND RESPONSE RATES IN 17453 BIONAIVE PSORIATIC ARTHRITIS PATIENTS INITIATING TNFI - RESULTS FROM THE EUROSPA COLLABORATION
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 131-132
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bionaïve psoriatic arthritis (PsA) patients treated in routine care is limited.Objectives:To investigate secular trends in baseline characteristics and retention, remission and response rates in PsA patients initiating a first TNFi.Methods:Prospectively collected data on bionaïve PsA patients starting TNFi in routine care from 15 European countries were pooled. According to year of TNFi initiation, three groups were defined a priori based on bDMARD availability: Group A (1999–2008), Group B (2009–2014) and Group C (2015–2018).Retention rates (Kaplan-Meier), crude and LUNDEX adjusted1 remission (Disease Activity Score (DAS28) <2.6, 28-joint Disease Activity index for PsA (DAPSA28) ≤4, Clinical Disease Activity Index (CDAI) ≤2.8) and ACR50 response rates were assessed at 6, 12 and 24 months. No statistical comparisons were made.Results:A total of 17453 PsA patients were included (4069, 7551 and 5833 in groups A, B and C).Patients in group A were older and had longer disease duration compared to B and C. Retention rates at 6, 12 and 24 months were highest in group A (88%/77%/64%) but differed little between B (83%/69%/55%) and C (84%/70%/56%).Baseline disease activity was higher in group A than in B and C (DAS28: 4.6/4.3/4.0, DAPSA28: 29.9/25.7/24.0, CDAI: 21.8/20.0/18.6), and this persisted at 6 and 12 months. Crude and LUNDEX adjusted remission rates at 6 and 12 months tended to be lowest in group A, although crude/LUNDEX adjusted ACR50 response rates at all time points were highest in group A. At 24 months, disease activity and remission rates were similar in the three groups (Table).Table 1.Secular trends in baseline characteristics, treatment retention, remission and response rates in European PsA patients initiating a 1st TNFiBaseline characteristicsGroup A(1999–2008)Group B(2009–2014)Group C(2015–2018)Age, median (IQR)62 (54–72)58 (49–67)54 (45–62)Male, %514847Years since diagnosis, median (IQR)5 (2–10)3 (1–9)3 (1–8)Smokers, %161717DAS28, median (IQR)4.6 (3.7–5.3)4.3 (3.4–5.1)4.0 (3.2–4.8)DAPSA28, median (IQR)29.9 (19.3–41.8)25.7 (17.2–38.1)24.0 (16.1–35.5)CDAI, median (IQR)21.8 (14.0–31.1)20.0 (13.0–29.0)18.6 (12.7–26.1)TNFi drug, % (Adalimumab / Etanercept / Infliximab / Certolizumab / Golimumab)27 / 43 / 30 / 0 / 036 / 31 / 14 / 5 / 1421 / 40 / 21 / 8 / 10Follow up6 months12 months24 monthsGr AGr BGr CGr AGr BGr CGr AGr BGr CRetention rates, % (95% CI)88 (87–89)83 (82–84)84 (83–85)79 (78–80)72 (71–73)72 (71–73)68 (67–69)60 (59–61)60 (59–62)DAS28, median (IQR)2.7 (1.9–3.6)2.4 (1.7–3.4)2.3 (1.7–3.2)2.5 (1.8–3.4)2.2 (1.6–3.1)2.1 (1.6–2.9)2.1 (1.6–3.1)2.0 (1.6–2.9)1.9 (1.5–2.6)DAPSA28, median (IQR)10.6 (4.8–20.0)9.5 (3.9–18.3)8.7 (3.6–15.9)9.1 (4.1–17.8)7.7 (3.1–15.4)7.6 (2.9–14.4)6.7 (2.7–13.7)6.6 (2.7–13.5)5.9 (2.4–11.8)CDAI, median (IQR)7.8 (3.0–15.2)8.0 (3.0–15.0)6.4 (2.6–12.2)6.4 (2.5–13.0)6.2 (2.5–12.1)5.8 (2.2–11.4)5.0 (2.0–11.0)5.5 (2.0–11.2)5.0 (2.0–9.0)DAS28 remission, %, c/L47 / 4255 / 4661 / 5153 / 4362 / 4566 / 4864 / 4268 / 3775 / 41DAPSA28 remission, %, c/L22 / 1926 / 2228 / 2325 / 2031 / 2232 / 2336 / 2334 / 1938 / 21CDAI remission, %, c/L23 / 2123 / 1926 / 2227 / 2127 / 2029 / 2134 / 2231 / 1735 / 19ACR50 response, %, c/L26 / 2322 / 1824 / 2027 / 2223 / 1721 / 1523 / 1518 / 1014 / 8Gr, Group; c/L, crude/LUNDEX.Conclusion:Over the past 20 years, patient age, disease duration and disease activity level at the start of the first TNFi in PsA patients have decreased. Furthermore, TNFi retention rates have decreased while remission rates have increased, especially remission rates within the first year of treatment. These findings may reflect a greater awareness of early diagnosis in PsA patients, a lowered threshold for initiating TNFi and the possibility for earlier switching in patients with inadequate treatment response.References:[1]Arthritis Rheum 2006; 54: 600-6.Acknowledgements:Novartis Pharma AG and IQVIA for supporting the EuroSpA Research Collaboration Network.Disclosure of Interests:Sara Nysom Christiansen Speakers bureau: BMS and GE, Grant/research support from: Novartis, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Simon Horskjær Rasmussen: None declared, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Grant/research support from: Novartis, Johan K Wallman Consultant of: Celgene, Eli Lilly, Novartis, Florenzo Iannone Speakers bureau: Abbvie, MSD, Novartis, Pfizer and BMS, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Michael J. Nissen Speakers bureau: Novartis, Eli Lilly, Celgene, and Pfizer, Consultant of: Novartis, Eli Lilly, Celgene, and Pfizer, Jakub Zavada: None declared, Maria Jose Santos Speakers bureau: AbbVie, Novartis, Pfizer, Manuel Pombo-Suarez: None declared, Kari Eklund: None declared, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, İsmail Sari: None declared, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Daniela Di Giuseppe: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen, AbbVie, Marco Sebastiani: None declared, Karen Minde Fagerli: None declared, Burkhard Moeller: None declared, Karel Pavelka Speakers bureau: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Consultant of: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Anabela Barcelos: None declared, Carlos Sánchez-Piedra: None declared, Heikki Relas: None declared, Ziga Rotar Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Thorvardur Love: None declared, Servet Akar: None declared, Ruxandra Ionescu Speakers bureau: Abbvie, Amgen, Boehringer-Ingelheim Eli-Lilly,Novartis, Pfizer, Sandoz, UCB, Gary Macfarlane Grant/research support from: GlaxoSmithKline, Marleen G.H. van de Sande: None declared, Merete L. Hetland Speakers bureau: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis., Mikkel Østergaard Speakers bureau: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth, Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth
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| 12. |
- Ciarelli, Giancarlo, et al.
(författare)
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Trends of inorganic and organic aerosols and precursor gases in Europe: Insights from the EURODELTA multi-model experiment over the 1990-2010 period
- 2019
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 12:12, s. 4923-4954
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of the EURODELTA-Trends (EDT) modeling experiment, several chemical transport models (CTMs) were applied for the 1990-2010 period to investigate air quality changes in Europe as well as the capability of the models to reproduce observed long-term air quality trends. Five CTMs have provided modeled air quality data for 21 continuous years in Europe using emission scenarios prepared by the International Institute for Applied Systems Analysis/Greenhouse Gas - Air Pollution Interactions and Synergies (IIASA/GAINS) and corresponding year-by-year meteorology derived from ERA-Interim global reanalysis. For this study, long-term observations of particle sulfate (SO2 4-), total nitrate (TNO3), total ammonium (TNHx) as well as sulfur dioxide (SO2) and nitrogen dioxide (NO2) for multiple sites in Europe were used to evaluate the model results. The trend analysis was performed for the full 21 years (referred to as PT) but also for two 11-year subperiods: 1990-2000 (referred to as P1) and 2000-2010 (referred to as P2). The experiment revealed that the models were able to reproduce the faster decline in observed SO2 concentrations during the first decade, i.e., 1990-2000, with a 64%-76% mean relative reduction in SO2 concentrations indicated by the EDT experiment (range of all the models) versus an 82% mean relative reduction in observed concentrations. During the second decade (P2), the models estimated a mean relative reduction in SO2 concentrations of about 34%-54%, which was also in line with that observed (47%). Comparisons of observed and modeled NO2 trends revealed a mean relative decrease of 25% and between 19% and 23% (range of all the models) during the P1 period, and 12% and between 22% and 26% (range of all the models) during the P2 period, respectively. Comparisons of observed and modeled trends in SO4 2- concentrations during the P1 period indicated that the models were able to reproduce the observed trends at most of the sites, with a 42%-54% mean relative reduction indicated by the EDT experiment (range of all models) versus a 57% mean relative reduction in observed concentrations and with good performance also during the P2 and PT periods, even though all the models overpredicted the number of statistically significant decreasing trends during the P2 period. Moreover, especially during the P1 period, both modeled and observational data indicated smaller reductions in SO42- concentrations compared with their gas-phase precursor (i.e., SO2), which could be mainly attributed to increased oxidant levels and pH-dependent cloud chemistry. An analysis of the trends in TNO3 concentrations indicated a 28%-39% and 29% mean relative reduction in TNO3 concentrations for the full period for model data (range of all the models) and observations, respectively. Further analysis of the trends in modeled HNO3 and particle nitrate (NO-3 ) concentrations revealed that the relative reduction in HNO3 was larger than that for NO-3 during the P1 period, which was mainly attributed to an increased availability of "free ammonia". By contrast, trends in modeled HNO3 and NO-3 concentrations were more comparable during the P2 period. Also, trends of TNHx concentrations were, in general, underpredicted by all models, with worse performance for the P1 period than for P2. Trends in modeled anthropogenic and biogenic secondary organic aerosol (ASOA and BSOA) concentrations together with the trends in available emissions of biogenic volatile organic compounds (BVOCs) were also investigated. A strong decrease in ASOA was indicated by all the models, following the reduction in anthropogenic non-methane VOC (NMVOC) precursors. Biogenic emission data provided by the modeling teams indicated a few areas with statistically significant increase in isoprene emissions and monoterpene emissions during the 1990-2010 period over Fennoscandia and eastern European regions (i.e., around 14 %-27 %), which was mainly attributed to the increase of surface temperature. However, the modeled BSOA concentrations did not linearly follow the increase in biogenic emissions. Finally, a comprehensive evaluation against positive matrix factorization (PMF) data, available during the second period (P2) at various European sites, revealed a systematic underestimation of the modeled SOA fractions of a factor of 3 to 11, on average, most likely because of missing SOA precursors and formation pathways, with reduced biases for the models that accounted for chemical aging of semi-volatile SOA components in the atmosphere.
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| 13. |
- Eskelund, Christian Winther, et al.
(författare)
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Detailed Long-Term Follow-Up of Patients Who Relapsed After the Nordic Mantle Cell Lymphoma Trials : MCL2 and MCL3
- 2021
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Ingår i: HemaSphere. - : Wolters Kluwer. - 2572-9241. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is an incurable disease with a highly variable clinical course. The prognosis after relapse is generally poor, and no standard of care exists. We investigated the postrelapse outcomes of 149 patients who were initially treated in the Nordic Lymphoma Group trials, MCL2 or MCL3, both representing intensive cytarabine-containing frontline regimens including autologous stem cell transplant. Patients with progression of disease before 24 months (POD24, n = 51, 34%) displayed a median overall survival of 6.6 months compared with 46 months for patients with later POD (n = 98, 66%; P < 0.001). MCL international prognostic index, cell proliferation marker, blastoid morphology, and TP53 mutations showed independent prognostic value irrespective of POD24, and in a combined, exploratory risk score, patients with 0, 1, 2-3, or 4-5 high-risk markers, respectively, displayed a 5-year overall survival of 62%, 39%, 31%, and 0%. By a comparison of median progression-free survival of the different salvage therapies in the relapse setting, bendamustine-rituximab was superior to all other combination chemotherapy regimens; however, it was also associated with longer responses to last line of therapy. Collectively, we confirm the prognostic impact of POD24 and highlight the relevance of other biomarkers, and we emphasize the importance of novel therapies for patients with high-risk features at first POD.
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| 14. |
- Ez-Zaitouni, Z., et al.
(författare)
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Imaging of the sacroiliac joints is important for diagnosing early axial spondyloarthritis but not all-decisive
- 2018
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 57:7, s. 1173-1179
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the contribution of the results of sacroiliac imaging to diagnosis and to the level of confidence in diagnosis in patients presenting with chronic back pain (CBP) and suspected of having axial spondyloarthritis (axSpA). Methods. Data from 513 patients from the SPondyloArthritisCaughtEarly cohort with CBP (>= 3 months, <= 2 years, onset <45 years) were analysed after full diagnostic work-up. Rheumatologists were asked not only to provide a diagnosis before and after the imaging results had been provided to them, but also to provide the level of confidence of this diagnosis on an 11-point numerical scale. Results. Before imaging, 317/513 patients were diagnosed with axSpA. Of these patients, 178/317 (56%) did not have signs of sacroiliitis on either MRI or radiography, which led to the rheumatologist refuting the initial diagnosis of axSpA in 81/178 (46%) patients. Of the 196/513 patients without axSpA before imaging, 35/196 (18%) had signs of sacroiliitis on imaging. Subsequently, 28/35 (80%) patients were diagnosed with axSpA. Overall, imaging was incongruent with the diagnosis before imaging in 213 patients. This led to a change in diagnosis in 109/213 (51%), which corresponds to 21% (109/513) of all patients in the cohort. In general, diagnostic confidence increased by having imaging results available (from 6.2 to 7.4, P<0.001). Conclusion: In patients with CBP suspected of having axSpA, sacroiliac imaging adds to the confidence in the final diagnosis. However, the number of changes in diagnosis suggests that imaging is important but not all-decisive in early axSpA diagnosis.
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| 15. |
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| 16. |
- Ez-Zaitouni, Z., et al.
(författare)
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The yield of a positive MRI of the spine as imaging criterion in the ASAS classification criteria for axial spondyloarthritis: results from the SPACE and DESIR cohorts
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:10, s. 1731-1736
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess the prevalence of spinal inflammation on MRI in patients with chronic back pain (CBP) of maximally 3 years duration and to evaluate the yield of adding a positive MRI-spine as imaging criterion to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). Methods Baseline imaging of the sacroiliac joints (X-SI), MRI of the sacroiliac joints (MRI-SI) and MRI-spine were scored by >= 2 experienced central readers per modality in the SPondyloArthritis Caught Early (SPACE) and DEvenir des Spondylarthropathies Indifferenciees Recentes (DESIR) cohorts. Inflammation suggestive of axSpA was assessed in the entire spine. A positive MRI-spine was defined by the presence of >= 5 inflammatory lesions. Alternative less strict definitions were also tested. Results In this study, 541 and 650 patients with CBP from the SPACE and DESIR cohorts were included. Sacroiliitis on X-SI and MRI-SI was found in 40/541 (7%) and 76/541 (14%) patients in SPACE, and in DESIR in 134/650 (21%) and 231/650 (36%) patients, respectively. In SPACE and DESIR, a positive MRI-spine was seen in 4/541 (1%) and 48/650 (7%) patients. Of the patients without sacroiliitis on imaging, 3/447 (1%) (SPACE) and 8/382 (2%) (DESIR) patients had a positive MRI-spine. Adding positive MRI-spine as imaging criterion led to new classification in only one patient in each cohort, as the other patients already fulfilled the clinical arm. Other definitions of a positive MRI-spine yielded similar results. Conclusion In two cohorts of patients with CBP with a maximum symptom duration of 3 years, a positive MRI-spine was rare in patients without sacroiliitis on MRI-SI and X-SI. Addition of MRI-spine as imaging criterion to the ASAS axSpA criteria had a low yield of newly classified patients and is therefore not recommended.
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| 17. |
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| 18. |
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| 19. |
- Hellamand, Pasoon, et al.
(författare)
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Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network
- 2024
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Ingår i: ARTHRITIS & RHEUMATOLOGY. - 2326-5191 .- 2326-5205. ; 76:4, s. 587-598
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. Methods: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. Results: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). Conclusion: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.
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| 20. |
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| 21. |
- Kolstad, Arne, et al.
(författare)
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Nordic MCL-3 study : 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 123:19, s. 2953-2959
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Tidskriftsartikel (refereegranskat)abstract
- The main objective of the MCL3 study was to improve outcome for patients not in CR before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. 160 consecutive, untreated stage II-IV MCL patients < 66 years received rituximab (R)- maxi-CHOP alternating with R-high-dose Ara-C (6 cycles total), followed by high-dose BEAM or BEAC and autologous stem cell transplantation 2005-2009. Zevalin (0.4 mCi/kg) was given to responders in only CRu/PR prior to high-dose therapy. The overall response rate (ORR) pre-transplant was 97%. After a median follow-up of 4.4 years the outcome did not differ from that of the historic control, the MCL2 trial with the same treatment except for Zevalin. Overall (OS), event free (EFS), and progression-free survival (PFS) at 4 years were 78, 62 and 71%, respectively. For patients in CRu/PR before transplant who received Zevalin duration of response was shorter than in the CR group. Inferior PFS, EFS- and OS were predicted by PET-positivity pre-transplant and detectable minimal residual disease (MRD) before and after transplant. In conclusion, a positive PET prior to transplant and MRD are strong predictors of outcome. Late intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant.
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| 22. |
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| 23. |
- Marchetto, Aldo, et al.
(författare)
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Good Agreement Between Modeled and Measured Sulfur and Nitrogen Deposition in Europe, in Spite of Marked Differences in Some Sites
- 2021
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Ingår i: Frontiers in Environmental Science. - : Frontiers Media SA. - 2296-665X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric nitrogen and sulfur deposition is an important effect of atmospheric pollution and may affect forest ecosystems positively, for example enhancing tree growth, or negatively, for example causing acidification, eutrophication, cation depletion in soil or nutritional imbalances in trees. To assess and design measures to reduce the negative impacts of deposition, a good estimate of the deposition amount is needed, either by direct measurement or by modeling. In order to evaluate the precision of both approaches and to identify possible improvements, we compared the deposition estimates obtained using an Eulerian model with the measurements performed by two large independent networks covering most of Europe. The results are in good agreement (bias <25%) for sulfate and nitrate open field deposition, while larger differences are more evident for ammonium deposition, likely due to the greater influence of local ammonia sources. Modeled sulfur total deposition compares well with throughfall deposition measured in forest plots, while the estimate of nitrogen deposition is affected by the tree canopy. The geographical distribution of pollutant deposition and of outlier sites where model and measurements show larger differences are discussed.
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| 24. |
- Pommier, Matthieu, 1984, et al.
(författare)
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Impact of regional climate change and future emission scenarios on surface O3 and PM2.5 over India
- 2018
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:1, s. 103-127
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Tidskriftsartikel (refereegranskat)abstract
- Eleven of the world's 20 most polluted cities are located in India and poor air quality is already a major public health issue. However, anthropogenic emissions are predicted to increase substantially in the short-term (2030) and medium-term (2050) futures in India, especially if no further policy efforts are made. In this study, the EMEP/MSC-W chemical transport model has been used to predict changes in surface ozone (O3) and fine particulate matter (PM 2.5 ) for India in a world of changing emissions and climate. The reference scenario (for present-day) is evaluated against surface-based measurements, mainly at urban stations. The evaluation has also been extended to other data sets which are publicly available on the web but without quality assurance. The evaluation shows high temporal correlation for O 3 (r = 0.9) and high spatial correlation for PM 2.5 (r = 0.5 and r = 0.8 depending on the data set) between the model results and observations. While the overall bias in PM 2.5 is small (lower than 6%), the model overestimates O 3 by 35%. The underestimation in NO x titration is probably the main reason for the O 3 overestimation in the model. However, the level of agreement can be considered satisfactory in this case of a regional model being evaluated against mainly urban measurements, and given the inevitable uncertainties in much of the input data. For the 2050s, the model predicts that climate change will have distinct effects in India in terms of O 3 pollution, with a region in the north characterized by a statistically significant increase by up to 4% (2 ppb) and one in the south by a decrease up to -3% (-1.4 ppb). This variation in O 3 is assumed to be partly related to changes in O 3 deposition velocity caused by changes in soil moisture and, over a few areas, partly also by changes in biogenic non-methane volatile organic compounds. Our calculations suggest that PM 2.5 will increase by up to 6.5% over the Indo-Gangetic Plain by the 2050s. The increase over India is driven by increases in dust, particulate organic matter (OM) and secondary inorganic aerosols (SIAs), which are mainly affected by the change in precipitation, biogenic emissions and wind speed. The large increase in anthropogenic emissions has a larger impact than climate change, causing O 3 and PM 2.5 levels to increase by 13 and 67% on average in the 2050s over the main part of India, respectively. By the 2030s, secondary inorganic aerosol is predicted to become the second largest contributor to PM 2.5 in India, and the largest in the 2050s, exceeding OM and dust.
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| 25. |
- Schaap, M., et al.
(författare)
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Performance of European chemistry transport models as function of horizontal resolution
- 2015
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1873-2844 .- 1352-2310. ; 112, s. 90-105
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Tidskriftsartikel (refereegranskat)abstract
- Air pollution causes adverse effects on human health as well as ecosystems and crop yield and also has an impact on climate change trough short-lived climate forcers. To design mitigation strategies for air pollution, 3D Chemistry Transport Models (CTMs) have been developed to support the decision process. Increases in model resolution may provide more accurate and detailed information, but will cubically increase computational costs and pose additional challenges concerning high resolution input data. The motivation for the present study was therefore to explore the impact of using finer horizontal grid resolution for policy support applications of the European Monitoring and Evaluation Programme (EMEP) model within the Long Range Transboundary Air Pollution (LRTAP) convention. The goal was to determine the "optimum resolution" at which additional computational efforts do not provide increased model performance using presently available input data. Five regional CTMs performed four runs for 2009 over Europe at different horizontal resolutions. The models' responses to an increase in resolution are broadly consistent for all models. The largest response was found for NO2 followed by PM10 and O-3. Model resolution does not impact model performance for rural background conditions. However, increasing model resolution improves the model performance at stations in and near large conglomerations. The statistical evaluation showed that the increased resolution better reproduces the spatial gradients in pollution regimes, but does not help to improve significantly the model performance for reproducing observed temporal variability. This study clearly shows that increasing model resolution is advantageous, and that leaving a resolution of 50 km in favour of a resolution between 10 and 20 km is practical and worthwhile. As about 70% of the model response to grid resolution is determined by the difference in the spatial emission distribution, improved emission allocation procedures at high spatial and temporal resolution are a crucial factor for further model resolution improvements. (C) 2015 Elsevier Ltd. All rights reserved.
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| 26. |
- Simpson, David, 1961, et al.
(författare)
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Comparison of modelled and monitored deposition fluxes of sulphur and nitrogen to ICP-forest sites in Europe
- 2006
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Ingår i: Biogeosciences. - 1726-4170 .- 1726-4189. ; 3:3, s. 337-355
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Tidskriftsartikel (refereegranskat)abstract
- The EMEP MSC-W Eulerian chemical transport model, and its predictions of deposition of acidifying and eutrophying pollutants over Europe, play a key role in the development of emission control strategies for Europe. It is important that this model is tested against observational data. Here we compare the results of the EMEP model with measured data from 160 sites of the European Union/ICP Forest (Level II) monitoring network, for the years 1997 and 2000. This comparison comprises: (a) Precipitation amount, (b) Total deposition of SO42- to coniferous and deciduous forests, (c) Wet deposition of SO42-, NO3- and NH4+ in open field sites, and (d) Concentrations of SO42-, NO3- and NH4+ in precipitation. Concerning precipitation, the EMEP model and ICP network showed very similar overall levels (within 4% for 1997 and 11% for 2000). The correlation was, however, poor (r2=0.15-0.23). This can be attributed largely to the influence of a few outliers, combined with a small range of rainfall amounts for most points. Correlations between modelled and observed deposition values in this study were rather high (r2 values between 0.4-0.8 for most components and years), with mean values across all sites being within 30%. The EMEP model tends to give somewhat lower values for SO42-, NO3- and NH4+ wet deposition to ICP, but differences in mean values were within 20% in 1997 and 30% in 2000. Modelled and observed concentrations of SO 42-, NO3- and NH4+ in precipitation are very similar on average (differences of 0-14%), with good correlation between modelled and observed data (r 2=0.50-0.78). Differences between the EMEP model and ICP measurements are thought to arise from a mixture of problems with both the observations and model. However, the overall conclusion is that the EMEP model performs rather well in reproducing patterns of S and N deposition to European forests.
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| 27. |
- Ørnbjerg, Lykke M., et al.
(författare)
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Patient-Reported Outcomes (PROs) and PRO Remission Rates in 12,262 Biologic-Naïve Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitors in Routine Care
- 2024
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 51:4, s. 378-389
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. Methods. Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire–Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. Results. For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)–adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. Conclusion. In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.
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