| 1. |
- Antovic, A., et al.
(författare)
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Risks and treatment related aspects of COVID-19 infection in patients with ANCA-associated vasculitis
- 2023
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 52:4, s. 418-423
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Tidskriftsartikel (refereegranskat)abstract
- Objective Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) require immunosuppressive therapy for disease control and relapse prevention and may be at risk for severe coronavirus disease 2019 (COVID-19). The study objective was to analyse risk factors and outcomes of COVID-19 in well-characterized AAV patients. Method Data were retrieved from March 2020 to May 2021 from medical records of AAV cohorts in Stockholm and Uppsala, Sweden. COVID-19 was confirmed by positive PCR test or by ELISA. Severe COVID-19 was defined as need for non-invasive ventilation, intensive care unit care, and/or death. Age, gender, ANCA antibody type, ongoing immunosuppressive medication, and estimated glomerular filtration rate were recorded. Results The cohort comprised 310 AAV patients, of whom 29 (9%) were diagnosed with COVID-19. Four deaths were attributed to COVID-19. Fifteen patients (52%) were on prednisolone in the COVID-19 group and 130 (46%) in the non-COVID group, with significantly higher doses in COVID-19 patients (p < 0.01). Ongoing induction therapy was more prevalent in the COVID-19 group (p < 0.01). Severe COVID-19 was diagnosed in 9/29 (31%). Significant risk factors for severe COVID-19 were impaired kidney function (p = 0.01) and more intense immunosuppressive therapy (p = 0.02), with a trend for age (p = 0.07). Maintenance therapy with rituximab was not associated with severe COVID-19. Conclusions Our findings highlight risks and suggest that more attention should be given to optimal AAV treatment in a pandemic situation. They also emphasize the need for continued shielding, mitigation strategies, and effective vaccination of AAV patients.
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| 2. |
- Bower, Hannah, et al.
(författare)
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Are JAKis more effective among elderly patients with RA, smokers and those with higher cardiovascular risk? A comparative effectiveness study of b/tsDMARDs in Sweden.
- 2023
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Ingår i: RMD open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether the relative effectiveness of janus kinase inhibitors (JAKis) versus tumour necrosis factor inhibitors (TNFi) or other biological disease-modifying antirheumatic drugs in rheumatoid arthritis differ by the presence or absence of risk factors for cardiovascular (CV) disease, age, sex and smoking.Through Swedish registers, we identified 13493 individuals with 3166 JAKi, 5575 non-TNFi and 11 286 TNFi treatment initiations 2016-2022. All lines of therapy were included, with the majority in second line or higher. Treatment response was defined as the proportion reaching European Alliance of Associations for Rheumatology (EULAR) good response and Clinical Disease Activity Index (CDAI) remission, respectively, within 6 months. Crude percentage point differences in these proportions (JAKis, and non-TNFis, vs TNFis) overall and by risk factors were observed, and adjusted for confounders using linear regression models. Predicted probabilities of response and remission were estimated from adjusted Poisson models, and presented across CV risk and age.Overall, adjusted percentage point differences indicated higher response (+5.0%, 95% CI 2.2% to 7.9%) and remission (+5.8%, 95% CI 3.2% to 8.5%) with JAKis versus TNFis. The adjusted percentage point differences for response in those above 65, at elevated CV risk, and smokers were +5.9% (95% CI 2.7% to 9.0%), +8.3% (95% CI 5.3% to 11.4%) and +6.0% (95% CI 3.3% to 8.7%), respectively. The corresponding estimates for remission were +8.0% (95% CI 5.3% to 10.8%), +5.6% (95% CI 3.0% to 8.2%) and +7.6% (95% CI 5.5% to 9.7%).As used in clinical practice, response and remission at 6 months with JAKis are higher than with TNFi. Among patients with risk factors of concern, effectiveness is similar or numerically further increased. For individualised benefit-to-risk ratios to guide treatment choice, safety and effectiveness in specific patient segments should be considered.
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| 3. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 4. |
- Ekman, Diana, et al.
(författare)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 5. |
- Jacobs, Susan S., et al.
(författare)
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Home oxygen therapy for adults with chronic lung disease an official american thoracic society clinical practice guideline
- 2020
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 202:10, s. 121-141
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquidoxygen use in patients who are mobile outside the home and require .3 L/min of continuous-flow oxygen during exertion (very-lowquality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (bestpractice statement). Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.
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| 6. |
- Jacquet, Jennifer, et al.
(författare)
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Support US OCTOPUS Act to keep octopuses wild.
- 2024
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Ingår i: Science (New York, N.Y.). - 1095-9203. ; 385:6710, s. 721-722
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Tidskriftsartikel (refereegranskat)abstract
- Commercial octopus farming is incapable of meeting welfare requirements, unsustainable, and unnecessary for sustenance. Although no commercial octopus farms currently exist, a Spanish seafood company plans to build one in the Canary Islands for Octopus vulgaris. In March, the US state of Washington banned octopus farming. Similar legislation has been introduced in California and Hawai‘i . Now, the federal government is proposing action. The US Congress should pass the OCTOPUS Act, a federal law that would prohibit commercial octopus aquaculture in the United States and the import of commercially farmed octopus or octopus products.
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| 7. |
- Lindberg, Hanna, et al.
(författare)
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Are Farming and Animal Exposure Risk Factors for the Development of Granulomatosis with Polyangiitis? Environmental Risk Factors Revisited : A Case-control Study
- 2021
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:6, s. 894-897
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the possible association between animal exposure and risk for granulomatosis with polyangiitis (GPA).Methods. Patients with GPA at the Department of Rheumatology, Uppsala University Hospital, between January 1, 2011, and December 31, 2018, were consecutively included. All patients filled in a questionnaire on possible environmental exposures: occupation, hobbies, and animal contact. As controls we included 128 patients with rheumatoid arthritis (RA) and 248 population controls collected from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, matched for age, sex, and geographical area of residence. The controls filled out a questionnaire on current and past contact with farming and animals, at the time of the RA patient’s diagnosis.Results. A total of 62 patients with GPA, 128 patients with RA, and 248 population controls were included in the study. GPA was significantly associated with horse exposure, with a 2- to 3-fold increased risk compared with RA (OR 3.08, 95% CI 1.34–7.08) and population controls (OR 2.61, 95% CI 1.29–5.29). Borderline increased risks were found for any animal contact, but no association was found when analyzing contact with cats/dogs only. A significant association was found between GPA and farming compared to the population controls (OR 7.60, 95% CI 3.21–17.93).Conclusion. This study has identified for the first time, to our knowledge, a significant association between exposure to specific animals, namely horses, and the development of GPA. The results also support previous studies reporting an association between farming and GPA, underscoring the possibility of exogenous factors as initiators in the development of GPA.
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| 8. |
- Lundtoft, Christian, et al.
(författare)
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The HLA region in ANCA-associated vasculitis : characterisation of genetic associations in a Scandinavian patient population
- 2024
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Ingår i: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 10:2, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV.METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively.RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.
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| 9. |
- Molina, Berengere, et al.
(författare)
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Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis : a European retrospective study
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 82:12, s. 1587-1593
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Tidskriftsartikel (refereegranskat)abstract
- Background Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA.Patients and methods We conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm3.Results Fifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268–4501) occurring at 13 weeks (IQR 4–36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab.Conclusion These results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.
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| 10. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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