| 1. |
- Palmer, Nicholette D, et al.
(author)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Journal article (peer-reviewed)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 3. |
- Alimohammadi, Mohammad, et al.
(author)
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Scalp necrosis as a late sign of giant-cell arteritis
- 2013
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In: Case reports in immunology. - : Hindawi Limited. - 2090-6609 .- 2090-6617. ; 2013
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Journal article (peer-reviewed)abstract
- Retinal infarction and scalp necrosis are described as unusual but devastating complications of giant-cell arteritis. We report a patient with this rare complication and emphasize the importance of timely diagnosis and treatment of giant-cell arteritis.
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| 4. |
- Antovic, A., et al.
(author)
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Risks and treatment related aspects of COVID-19 infection in patients with ANCA-associated vasculitis
- 2023
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In: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 52:4, s. 418-423
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Journal article (peer-reviewed)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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| 5. |
- Bentham, James, et al.
(author)
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Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:12, s. 1457-1464
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry, constituting a new GWAS, a meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including ten new associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n = 16) of transcription factors among SLE susceptibility genes. This finding supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE.
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| 6. |
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| 7. |
- Bower, Hannah, et al.
(author)
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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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In: RMD open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:4
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Journal article (peer-reviewed)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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| 8. |
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| 9. |
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| 10. |
- Dahlqvist, Johanna, 1979-, et al.
(author)
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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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In: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Journal article (peer-reviewed)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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| 11. |
- Davies, Neil, et al.
(author)
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The founding charter of the Genomic Observatories Network
- 2014
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In: GigaScience. - 2047-217X. ; 3:2
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Journal article (peer-reviewed)abstract
- Abstract The co-authors of this paper hereby state their intention to work together to launch the Genomic Observatories Network (GOs Network) for which this document will serve as its Founding Charter. We define a Genomic Observatory as an ecosystem and/or site subject to long-term scientific research, including (but not limited to) the sustained study of genomic biodiversity from single-celled microbes to multicellular organisms.An international group of 64 scientists first published the call for a global network of Genomic Observatories in January 2012. The vision for such a network was expanded in a subsequent paper and developed over a series of meetings in Bremen (Germany), Shenzhen (China), Moorea (French Polynesia), Oxford (UK), Pacific Grove (California, USA), Washington (DC, USA), and London (UK). While this community-building process continues, here we express our mutual intent to establish the GOs Network formally, and to describe our shared vision for its future. The views expressed here are ours alone as individual scientists, and do not necessarily represent those of the institutions with which we are affiliated.
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| 12. |
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| 13. |
- Ekman, Diana, et al.
(author)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Journal article (peer-reviewed)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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| 14. |
- El-Jawahri, Areej, et al.
(author)
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Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation
- 2017
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In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 123:10, s. 1828-1838
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Journal article (peer-reviewed)abstract
- BACKGROUND: To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation.METHODS: We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n=3786) or allogeneic (n=7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT.RESULTS: The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P=0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P<0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR]=0.97; 95% CI, 0.95-0.99; P=0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P=0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P=0.002).CONCLUSION: Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a population that is at risk for post-transplant complications.
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| 15. |
- Hellbacher, Erik, et al.
(author)
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Malignant lymphoma in granulomatosis with polyangiitis : subtypes, clinical characteristics and prognosis
- 2019
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 58:11, s. 1655-1659
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Journal article (other academic/artistic)abstract
- Several autoimmune and inflammatory conditions, such as rheumatoid arthritis (RA) and primary Sjögrens’s syndrome (pSS), have repeatedly been linked to an increased risk of malignant lymphoma [1,2]. Certain inflammatory conditions are also associated with the development of specific lymphoma subtypes such as mucosa-associated lymphoid tissue (MALT) lymphoma in pSS and diffuse large B-cell lymphoma (DLBCL) in RA. The underlying mechanisms behind this association remain unclear. The highly increased risk of developing MALT lymphoma of the parotid gland in pSS indicates that local inflammatory processes can promote lymphoma development at the site of chronic inflammation [3]. In RA, an association between disease severity and risk of lymphoma has been shown.Granulomatosis with polyangiitis (GPA), formerly Wegener’s granulomatosis, is a systemic small vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) and characterized by granulomatous inflammation and necrotizing vasculitis of the airways and kidneys but possibly affecting any organ system. An increased risk of lymphoma in patients with GPA has been reported in several epidemiological studies [4,5]. However, very little is known about risk factors for lymphoma development in this group, possible relation to disease severity, treatment and lymphoma subtypes or the prognosis for the lymphomas. This is the first published study on GPA and lymphoma, giving detailed information on the GPA characteristics and possible risk factors for lymphoma and also lymphoma subtypes treatment and survival.
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| 16. |
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| 17. |
- Hertzell, Katarina Brodin, et al.
(author)
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Tick-borne encephalitis (TBE) vaccine to medically immunosuppressed patients with rheumatoid arthritis : A prospective, open-label, multi-centre study
- 2016
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In: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 34:5, s. 650-655
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Journal article (peer-reviewed)abstract
- BACKGROUND: Tick-borne Encephalitis (TBE) is endemic in south-eastern Sweden as well as in the Baltic regions, Central Europe and Russia. Ageing and immunosuppressed individuals are more prone to severe disease and neurological complications. We assessed the immunogenicity of TBE-vaccine in rheumatoid arthritis (RA) patients treated with tumor necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX).METHODS: TBE vaccine, FSME-Immune(®) or Encepur(®), was administered to non-immune RA patients as well as age and gender matched healthy controls. Individuals <60 years of age were given three doses at month 0, 1, 12. Individuals ≥60 years old were given an additional priming dose at month 3, i.e. a total of four doses. Tick-borne encephalitis neutralizing antibodies were assessed by a rapid fluorescent focus inhibition test.RESULTS: The study population consisted of 66 patients and 56 age and gender matched healthy controls. Median age was 58.5 years. The patients were either treated with TNFi (n=16), TNFi+MTX (n=36) or MTX (n=14). After the last TBE-vaccine dose, given one year after the first, 39% of the patients compared to 79% of the healthy controls had seroprotective levels (p=<0.05).CONCLUSIONS: Standard TBE-vaccine schedule does not confer enough immunogenicity in this group of immunosuppressed patients, who should be carefully informed about a higher risk for vaccination failure and risk of infection when exposed in high-endemic areas.
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| 18. |
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| 19. |
- Jacobs, Susan S., et al.
(author)
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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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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 202:10, s. 121-141
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Journal article (peer-reviewed)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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| 20. |
- Kaiser, Christina, et al.
(author)
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Injection-site reactions upon Kineret (anakinra) administration : experiences and explanations
- 2012
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In: Rheumatology International. - : Springer Science and Business Media LLC. - 0172-8172 .- 1437-160X. ; 32:2, s. 295-299
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Research review (peer-reviewed)abstract
- Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret is self-administered by daily subcutaneous injections in patients with active RA. The mechanism of action of anakinra is to competitively inhibit the local inflammatory effects of IL-1. Kineret is generally safe and well tolerated and the only major treatment-related side effects that appear are skin reactions at the injection site. Due to the relatively short half-life of anakinra, daily injection of the drug is required. This, in combination with the comparably high rates of injection-site reactions (ISRs) associated with the drug, can become a problem for the patient. The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause. The objective is also to present some clinical experiences of how the ISRs can be managed.
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| 21. |
- Knight, Ann, 1957-
(author)
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Clinical and Epidemiological Studies of Wegener´s Granulomatosis
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Wegener´s granulomatosis (WG) is an unusual, serious, systemic vasculitis with specific clinical findings. The studies in this thesis aim at broadening our understanding of the aetiology and outcome of WG.Patients with WG were identified in the In-patient Register 1975-2001. During this time the incidence increased three-fold, and neither ANCA-related increased awareness, nor diagnostic drift, seem to fully explain this trend, but it is still unclear if a true rise in incidence exists.Anti- neutrophil cytoplasmic antibodies (ANCA) have been presented as highly specific for vasculitis. In a series of consecutive cANCA/PR3-ANCA positive patients, we investigated the positive predictive value for ANCA, and the outcome of patients with a positive cANCA/PR3-ANCA but not vasculitis. These patients have a low future risk of developing vasculitis, possibly indicating that ANCA, in this setting, reflects neutrophil activating properties not specific to vasculitis.By linkage of the WG-cohort, and randomly selected population controls, to the Multi-generation register, we identified all first-degree relatives and spouses of patients and controls, totally encompassing some 2,000 patients and 70,000 relatives. Familial aggregation of WG was the exception, with absolute risks of < 1 per 1000.However, relative risks in first-grade relatives amounted to 1.56 (95% CI 0.35-6.90) such that a moderate familial aggregation cannot be excluded.In the WG-cohort, cancer occurrence and risk was compared to that of the general population. Patients with WG have an overall doubled risk of cancer, with particularly increased risks of bladder-cancer, haematopoietic cancers including lymphomas and squamous skin-cancer. In a case-control study nested within the WG-cohort, treatment with cyclophosphamide was compared among bladder-cancer patients and matched cancer-free controls. Absolute risk of bladder cancer as high as 10% some years after diagnosis were found, and this risk can partly be attributed to cyclophosphamide-treatment, with a dose-response relationship.
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| 22. |
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| 23. |
- Knight, Ann, et al.
(author)
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Increased Risk of Autoimmune Disease in Families with Wegener's Granulomatosis
- 2010
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 37:12, s. 2553-2558
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Journal article (peer-reviewed)abstract
- Objective. The etiology of Wegener's granulomatosis (WG) is unknown. Susceptibility genes for WG that also affect the risks of other autoimmune/inflammatory diseases have been identified, indicating the existence of shared interdisease genetic susceptibilities. To determine the effect, on a population level, of shared susceptibility on disease risk, we assessed the occurrence of autoimmune/inflammatory disease in first-degree relatives of patients with WG. Methods. In the Swedish Hospital Discharge Register we identified 2288 individuals discharged with the diagnosis of WG between 1970 and 2003. Through linkage to the Swedish Multi-generation Register we identified 787 parents, 1212 siblings, and 3650 children of these patients. From the Register of Total Population we identified 10 controls for each patient with WG, and 65,000 of their first-degree relatives. Through linkage to the nationwide Outpatients Register, we identified autoimmune/inflammatory disease among all relatives. Relative risks were estimated as hazard ratio (HR) using Cox regression. The study period was 2001-2006. Results. Biological first-degree relatives of patients with WG were at a moderately increased risk of any autoimmune/inflammatory disease (HR 1.32, 95% CI 1.18-1.49), including specific associations with, for example, multiple sclerosis (HR 1.92,95% CI 1.16-3.16), Sjogren's syndrome (HR 2.00,95% CI 1.07-3.73), and seropositive rheumatoid arthritis (HR 1.54,95% CI 1.09-2.19). Conclusion. Relatives of patients with WG are at increased risk of being diagnosed with other autoimmune/inflammatory diseases, indicating shared susceptibility between WG and other auto-immune/inflammatory disease.
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| 24. |
- Knight, Ann, et al.
(author)
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Increasing Incidence of Wegener´s granulomatosis in Sweden 1975-2001
- 2006
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In: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 33:10, s. 2060-2063
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Journal article (peer-reviewed)abstract
- Objective. Studies of Wegener's granulomatosis (WG) since the late 1980s indicate a probable increase in incidence of unknown cause and significance, possibly related to antineutrophil cytoplasmic antibody (ANCA) testing. To extend these observations and to include calendar periods before ANCA was introduced, we assessed time trends in the incidence of WG in Sweden in the period 1975-2001. Methods. In the population-based Swedish Inpatient Register, we identified 1938 individuals diagnosed with WG in the period 1975-2001, and calculated the annual age and sex adjusted incidences. Results. The incidence increased from 0.33 (95% CI 0.28-0.39) in the period 1975-85 to 0.77 (95% CI 0.69-0.85) in 1986-90, to 1.19 (95% CI 1.12-1.26) in 1991-2001, resulting in a mean incidence of 0.78 (95% CI 0.74-0.82). Conclusion. WG displays a strong temporal trend. While the increase coincides to some extent with the implementation of ANCA testing, suggestive of increased disease recognition, ANCA testing remains an incomplete explanation as increasing incidences were noted before as well as after their introduction.
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| 25. |
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| 26. |
- Knight, Ann, et al.
(author)
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Late-onset neutropenia after rituximab in ANCA-associated vasculitis
- 2016
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 45:5, s. 404-407
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Journal article (peer-reviewed)abstract
- Background: Rituximab (RTX) is being used increasingly in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV). Late-onset neutropenia (LON) and risks of infections have been observed following RTX therapy in rheumatological diseases including granulomatosis with polyangiitis (GPA) but data on microscopic polyangiitis (MPA) are lacking.Method: We studied the occurrence of LON in 59 AAV (47 GPA/12 MPA) patients treated with RTX. Patient charts were retrospectively reviewed for the occurrence of LON and clinical data were extracted and included in the analysis.Results: Seven of the total 59 patients (11.9%) developed LON after a median time of 86 days (range 56-168 days) since their latest RTX treatment. Of these seven LON patients, 5/47 (10.6%) had a diagnosis of GPA and 2/12 (16.7%) of MPA. Three of the patients developed LON after the first RTX treatment and four had received repeated courses. Five LON patients developed infectious symptoms. Six of the patients were hospitalized. Retreatment with RTX was given in three cases without further LON episodes.Conclusions: LON is a potentially severe side-effect of RTX occurring in both GPA and MPA and may develop after both single and repeated treatment courses. As infections are commonly seen, the condition requires an increased awareness. No predisposing factors for LON were identified.
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| 27. |
- Knight, Ann, et al.
(author)
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Leukemia and Myelodysplastic Syndrome in Granulomatosis with Polyangiitis : Subtypes, Clinical Characteristics, and Outcome
- 2015
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 42:4, s. 690-694
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Previous studies have shown that patients with granulomatosis with polyangiitis (GPA) have an increased risk of hematological malignancies, especially leukemia. Our aim was to assess clinical characteristics and treatment of patients with GPA complicated by hematological malignancies with focus on leukemia and to describe these malignancies in more detail.METHODS: From the Swedish population-based patient register, all individuals with a diagnosis of GPA from 1964-2012 were identified (n = 3224). Through linkage with the Swedish Cancer Register, we searched for all cases of leukemia [International Classification of Diseases (ICD) 7: 204-207 and corresponding codes ICD 8-10] registered after the first discharge listing GPA. The GPA diagnosis was evaluated using the European Medical Association classification algorithm. To confirm the hematological malignancy, all diagnostic bone marrow samples were reclassified. Clinical data of both the GPA and hematological malignancy were collected from medical files.RESULTS: Twenty-one cases were identified, all of myeloid origin, including 9 with myelodysplastic syndrome developing to acute myeloid leukemia (MDS-AML), 7 AML, 3 MDS, and 2 chronic myeloid leukemia. The median time from GPA diagnosis to hematological malignancy was 8 years (range 5-21). All patients had severe generalized GPA and had received high doses of cyclophosphamide (CYC; median cumulative dose 96.5 g). Cytopenia occurred in 76% of the patients prior to the hematological malignancy.CONCLUSION: The findings emphasize the longterm risk of leukemia and MDS in CYC-treated, severely ill patients with GPA. Cytopenia during the course of GPA may be a warning sign and warrants a liberal attitude toward bone marrow examination.
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| 28. |
- Knight, Ann, et al.
(author)
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Occupational risk factors for Wegener's granulomatosis : a case-control study
- 2010
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:4, s. 737-740
-
Journal article (peer-reviewed)abstract
- Background Wegener's granulomatosis is a systemic vasculitis of unknown aetiology. Previous studies have presented environmental exposures such as silica and farming as potential risk factors. Objective To investigate the potential risk for Wegener's granulomatosis associated with occupations involving contact with animals and various airway exposures, using a population-based approach. Methods In the Swedish Register of inpatient care 2288 cases with Wegener's granulomatosis were identified. Ten matched controls for every case were selected from the Swedish Population Register. By linking the cases and controls to the Swedish population censuses, information on employments before the diagnosis of Wegener's granulomatosis was collected. Relative risks were assessed as odds ratios using conditional logistic regression. Results Odds ratios for specific occupations ranged from 0.6 to 1.9, and centred symmetrically around 1. No statistically significant increased risk was noted for the investigated occupations.
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| 29. |
- Knight, Ann, et al.
(author)
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Risks and relative risks of Wegener's granulomatosis among close relatives of patients with the disease
- 2008
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:1, s. 302-7
-
Journal article (other academic/artistic)abstract
- OBJECTIVE: The etiology of Wegener's granulomatosis (WG) supposedly involves interplay between genetic susceptibility and environmental triggers. However, little is known about whether WG actually clusters in families. Information on the degree of familial aggregation in WG is of clinical relevance, because patients with WG often want to know whether their diagnosis puts their closest relatives at increased risk of the disease. The aim of this study was to investigate the risk of WG in relatives of patients with WG. METHODS: Using Swedish nationwide registers on morbidity, family structure, and vital status, we compared the occurrence of WG (register-based plus chart review) among 6,670 first-degree relatives and 428 spouses of 1,944 Swedish patients with WG with the occurrence among 68,994 first-degree relatives and 4,812 spouses of 19,655 control subjects from the general population. Relative risks were estimated using the Cox proportional hazards regression model. RESULTS: Two of the 6,670 first-degree relatives of patients with WG and 13 of the 68,994 first-degree relatives of their population controls had WG, resulting in a relative risk of 1.56 (95% confidence interval 0.35-6.90). None of the 428 spouses of patients had WG. CONCLUSION: In absolute terms, the occurrence of WG among close biologic and nonbiologic relatives of patients with WG is low. In terms of relative risk, our results provide strong evidence against a pronounced increase in familial risk such as that noted for systemic lupus erythematosus, irritable bowel disease, and multiple sclerosis but are compatible with familial aggregation of a magnitude similar to that for rheumatoid arthritis.
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| 30. |
- Knight, Ann, et al.
(author)
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Urinary bladder cancer in Wegener's granulomatosis : risks and relation to cyclophosphamide
- 2004
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 63:10, s. 1307-1311
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis.METHODS:In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated.RESULTS:The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis.CONCLUSION:The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.
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| 31. |
- Knight, Ann, et al.
(author)
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What is the significance in routine care of c-ANCA/PR3-ANCA in the abscence of systemic vasculitis? : A case series
- 2008
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In: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 26:3, s. S53-S56
-
Journal article (peer-reviewed)abstract
- Objective. ANCA has come to play an important role in diagnosing vasculitis. In selected populations c-ANCA/PR3-ANCA has a high specificity and sensitivity for vasculitis. In clinical practice, how individuals with c-ANCA/PR3-ANCA but without sufficient evidence of systemic vasculitis should be managed is unclear. We therefore retrospectively assessed the disease panorama and outcome in a consecutive series of individuals with c-ANCA/PR3-ANCA, and studied in detail those individuals who turned out not to fulfil criteria for vasculitic disease.Methods. The study population consisted of 74 consecutive patients who all had a positive test for C-ANCA and PR3-ANCA between 1992 and 2002 at the Immunology laboratory at Uppsala University Hospital, Sweden. The patients' medical files were reviewed and their diagnosis re-evaluated through June 2006.Results. 18 of the 74 ANCA-positive individuals did not present clinical evidence supportive of, or insufficient to support, a diagnosis of systemic vasculitis, but presented a range of other diseases. During a mean follow-up of 6.8 years, none of these 18 patients developed vasculitis.Conclusions. Individuals with a positive c-ANCA and PR3-ANCA but no vasculitis at the time of testing run an unknown but likely small risk of later developing vasculitis. In this group, a positive ANCA may represent background noise (borderline titres) or be a marker of inflammatory activity rather than of vasculitic disease (high titres).
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| 32. |
- Knight, Judith, et al.
(author)
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Understanding older people as occupational beings
- 2008
-
Conference paper (peer-reviewed)abstract
- There is limited research reporting older adults’ engagement in occupations. Until recently very little research has been undertaken ‘about the nature of occupation and its significance to humans. Research such as this project is beginning to provide the vehicle for addressing this by qualifying and quantifying the effect of occupation on various parts of older individuals’ lives. The overall aim of this study is to investigate the occupational engagement of older individuals’ and identify differences between UK and Swedish populations. The objectives are to explore motivating factors for participating in different occupations and patterns of occupations performed by older individuals as well as possible relationships between health, well-being and occupation in later life. Furthermore the objectives are to identity time spent on different occupations, the purpose of conducting these occupations and the breadth of roles. Finally the objectives are to draw comparisons between different categories of individuals, in particular cultural groups, retired people/still employed people and men/women. This study uses a mixed qualitative and quantitative methodology in the form of a structured interview and a time use diary. This research will contribute significantly to understanding the support services required to enable older adults to spend time performing meaningful occupations. In addition the findings will inform both remedial and preventive interventions promoting physical and psychological well being.
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| 33. |
- Lindberg, Hanna, et al.
(author)
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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
-
In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:6, s. 894-897
-
Journal article (peer-reviewed)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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| 34. |
- Lundtoft, Christian, et al.
(author)
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The HLA region in ANCA-associated vasculitis : characterisation of genetic associations in a Scandinavian patient population
- 2024
-
In: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 10:2, s. 1-10
-
Journal article (peer-reviewed)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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| 35. |
- Lyons, PA, et al.
(author)
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Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
- 2019
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5120-
-
Journal article (peer-reviewed)abstract
- Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
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| 36. |
- Molina, Berengere, et al.
(author)
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Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis : a European retrospective study
- 2023
-
In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 82:12, s. 1587-1593
-
Journal article (peer-reviewed)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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| 37. |
- Nordström, Dan, et al.
(author)
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Beneficial Effect of Interleukin 1 Inhibition with Anakinra in Adult-onset Still's Disease. An Open, Randomized, Multicenter Study
- 2012
-
In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:10, s. 2008-2011
-
Journal article (peer-reviewed)abstract
- Objective. To study the efficacy of anakinra versus disease-modifying antirheumatic drugs (DMARD) in refractory adult-onset Still's disease (AOSD). Methods. In a 24-week study, 22 patients with AOSD taking prednisolone >= 10 mg/day received anakinra (n = 12) or DMARD (n = 10). The primary endpoint was achievement of remission. Results. At 8 and 24 weeks, 7/12 and 6/12 receiving anakinra and 5/10 and 2/10 receiving DMARD achieved remission. Anakinra induced greater improvement in physical health measured by Medical Outcomes Study Short-Form 36 (SF-36; p < 0.011). During an open-label extension (OLE) of 28 weeks, 7/14 patients taking anakinra and 2/3 taking DMARD were in remission. Conclusion. Anakinra induced more beneficial responses than DMARD in patients with AOSD and was favored in the OLE phase. (ClinicalTrials.gov Protocol Registration NCT01033656).
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| 38. |
- Patterson, Nick, et al.
(author)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
-
In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
-
Journal article (peer-reviewed)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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| 39. |
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| 40. |
- Sattui, Sebastian E., et al.
(author)
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Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry : a retrospective cohort study
- 2021
-
In: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 3:12, s. E855-E864
-
Journal article (peer-reviewed)abstract
- Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged >= 18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61.0%) were women arid 469 (39.0%) were men, and their mean age was 63.8 years (SD 17.1). A total of 374 (31.1%) patients had polymyalgia rheumatica, 353 (29.4%) had ANCA-associated vasculitis, 183 (15.2%) had giant cell arteritis, 112 (9.3%) had Behcet's syndrome, and 180 (15.0%) had other vasculitis. Of 1020 (84. 9%) patients with outcome data, 512 (S0.2%) were not hospitalised, 114 (11.2%) were hospitalised and did not receive supplemental oxygen, 239 (23 - 4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15.2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1.44 [95% CI 1. 31-1- 571), were male compared with female (1.38 [1.05-1.801), had more comorbidities (per each additional comorbidity 1.39 [1- 23-1- 581), were taking 10 mg/day or more of prednisolone compared with none (2.14 [1.50-3.04J), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2.12 [1.49-3.021). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to info rm mitigation strategies for patients with these diseases.
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| 41. |
- Sejersen, Kristina, et al.
(author)
-
Serum calprotectin correlates stronger with inflammation and disease activity in ACPA positive than ACPA negative rheumatoid arthritis
- 2023
-
In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332.
-
Journal article (peer-reviewed)abstract
- ObjectivesThe aim of the present study was to evaluate the performance of serum and SF levels of the granulocyte protein calprotectin as an inflammatory biomarker in RA patients with knee synovitis.MethodsSeventy-six RA patients with ongoing knee synovitis were included. Data on DAS with 28 joints and their subcomponents and radiological destruction of the affected knee were collected. White blood cell count, CRP, ACPA against cyclic citrullinated peptide version 2 (anti-CCP2), IgM RF and calprotectin were analysed in parallel in circulation and in SF. Counts of polynuclear and mononuclear cells were measured in SF.ResultsSerum (S)-calprotectin correlated more strongly than SF-calprotectin with inflammatory markers and disease activity. Instead, SF-calprotectin showed a strong correlation to SF counts of white blood cells, and especially to polymorphonuclear cell counts (Spearman’s ρ = 0.72, P < 0.001). S-calprotectin showed markedly stronger correlation with inflammatory markers and disease activity in ACPA positive as compared with ACPA negative RA patients; a similar difference was observed for patients with and without IgM RF.ConclusionThe particularly strong association between circulating calprotectin and inflammation in ACPA positive RA is a new argument for a specific role for polymorphonuclear granulocytes/neutrophils in this RA subset. Measurement of calprotectin in SF does not convey any additional benefit compared with measurement in the circulation in RA patients with knee synovitis.
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| 42. |
- Sohrabian, Azita, et al.
(author)
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Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis
- 2018
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:9, s. 1345-1353
-
Journal article (peer-reviewed)abstract
- Introduction: Individual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.Methods: We have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.Results: The majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.Conclusions: Our data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.
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| 43. |
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| 44. |
- Sverdrup, Berit M, et al.
(author)
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Usage of skin care products and risk of rheumatoid arthritis : results from the Swedish EIRA study.
- 2012
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 14:1
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: The aim of this study was to investigate the association between exposure to cosmetics, often containing mineral oil, and the risk of developing rheumatoid arthritis (RA). The study was performed against the background that occupational exposure to mineral oil has recently been shown to be associated with an increased risk for RA in man, and that injection of or percutaneous exposure to mineral-oil-containing cosmetics can induce arthritis in certain rat strains.METHODS: A population-based case-control study of incident cases of RA was performed among the population aged 18 to 70 years in a defined area of Sweden during May 1996 to December 2003. A case was defined as an individual from the study base, who received for the first time a diagnosis of RA according to the 1987 American College of Rheumatology criteria. Controls were randomly selected from the study base with consideration taken for age, gender and residential area. Cases (n = 1,419) and controls (n = 1,674) answered an extensive questionnaire regarding environmental and lifestyle factors including habits of cosmetic usage. The relative risk of developing RA was calculated for subjects with different cosmetic usage compared with subjects with low or no usage. Analysis was also performed stratifying the cases for presence/absence of rheumatoid factor and antibodies to citrulline-containing peptides.RESULTS: The relative risks of developing RA associated with use of cosmetics were all close to one, both for women and men, for different exposure categories, and in relation to different subgroups of RA.CONCLUSION: This study does not support the hypothesis that ordinary usage of common cosmetics as body lotions, skin creams, and ointments, often containing mineral oil, increase the risk for RA in the population in general. We cannot exclude, however, that these cosmetics can contribute to arthritis in individuals carrying certain genotypes or simultaneously being exposed to other arthritis-inducing environmental agents.
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| 45. |
- Tran-Duy, A., et al.
(author)
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A Patient-Level Model to Estimate Lifetime Health Outcomes of Patients With Type 1 Diabetes
- 2020
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In: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:8, s. 1741-1749
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Journal article (peer-reviewed)abstract
- OBJECTIVE To develop a patient-level simulation model for predicting lifetime health outcomes of patients with type 1 diabetes and as a tool for economic evaluation of type 1 diabetes treatment based on data from a large, longitudinal cohort. RESEARCH DESIGN AND METHODS Data for model development were obtained from the Swedish National Diabetes Register. We derived parametric proportional hazards models predicting the absolute risk of diabetes complications and death based on a wide range of clinical variables and history of complications. We used linear regression models to predict risk factor progression. Internal validation was performed, estimates of life expectancies for different age-sex strata were computed, and the impact of key risk factors on life expectancy was assessed. RESULTS The study population consisted of 27,841 patients with type 1 diabetes with a mean duration of follow-up of 7 years. Internal validation showed good agreement between the predicted and observed cumulative incidence of death and 10 complications. Simulated life expectancy was similar to 13 years lower than that of the sex- and age-matched general population, and patients with type 1 diabetes could expect to live with one or more complications for similar to 40% of their remaining life. Sensitivity analysis showed the importance of preventing renal dysfunction, hypoglycemia, and hyperglycemia as well as lowering HbA(1c)in reducing the risk of complications and death. CONCLUSIONS Our model was able to simulate risk factor progression and event histories that closely match the observed outcomes and to project events occurring over patients' lifetimes. The model can serve as a tool to estimate the impact of changing clinical risk factors on health outcomes to inform economic evaluations of interventions in type 1 diabetes.
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| 46. |
- Tran-Duy, A., et al.
(author)
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Development of a life expectancy table for individuals with type 1 diabetes
- 2021
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 2228-2236
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Journal article (peer-reviewed)abstract
- Aims/hypothesis Tables reporting life expectancies by common risk factors are available for individuals with type 2 diabetes; however, there is currently no published equivalent for individuals with type 1 diabetes. We aimed to develop a life expectancy table using a recently published simulation model for individuals with type 1 diabetes. Methods The simulation model was developed using data from a real-world population of patients with type 1 diabetes selected from the Swedish National Diabetes Register. The following six important risk factors were included in the life table: sex; age; current smoking status; BMI; eGFR; and HbA(1c). For each of 1024 cells in the life expectancy table, a synthetic cohort containing 1000 individuals was created, with other risk factors assigned values representative of the real-world population. The simulations were executed for all synthetic cohorts and life expectancy for each cell was calculated as mean survival time of the individuals in the respective cohort. Results There was a substantial variation in life expectancy across patients with different risk factor levels. Life expectancy of 20-year-old men varied from 29.3 years to 50.6 years, constituting a gap of 21.3 years between those with worst and best risk factor levels. In 20-year-old women, this gap was 18.9 years (life expectancy range 35.0-53.9 years). The variation in life expectancy was a function of the combination of risk factor values, with HbA(1c) and eGFR consistently showing a negative and positive correlation, respectively, with life expectancy at any level combination of other risk factors. Individuals with the lowest level (20 kg/m(2)) and highest level of BMI (35 kg/m(2)) had a lower life expectancy compared with those with a BMI of 25 kg/m(2). Non-smokers and women had a higher life expectancy than smokers and men, respectively, with the difference in life expectancy ranging from 0.4 years to 2.7 years between non-smokers and smokers, and from 1.9 years to 5.9 years between women and men, depending on levels of other risk factors. Conclusions/interpretation The life expectancy table generated in this study shows a substantial variation in life expectancy across individuals with different modifiable risk factors. The table allows for rapid communications of risk in an easily understood format between healthcare professionals, health economists, researchers, policy makers and patients. Particularly, it supports clinicians in their discussion with patients about the benefits of improving risk factors.
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| 47. |
- Turesson, C., et al.
(author)
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Swedish Society of Rheumatology 2018 guidelines for investigation, treatment, and follow-up of giant cell arteritis
- 2019
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In: Scandinavian Journal of Rheumatology. - : TAYLOR & FRANCIS LTD. - 0300-9742 .- 1502-7732. ; 48:4, s. 259-265
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Research review (peer-reviewed)abstract
- Objective: To develop evidence-based guidelines for the management of giant cell arteritis (GCA) as a complement to guidelines in other areas of rheumatology, issued by the Swedish Society of Rheumatology.Methods: A working group selected key areas for recommendations, reviewed the available evidence, and wrote draft guidelines. These were discussed and revised according to standard procedures within the Swedish Society of Rheumatology, including a one-day meeting open to all members. For key recommendations, the quality of evidence was assessed according to GRADE. The final guidelines were approved by the Society board in March 2018.Results: The guidelines include recommendations on diagnostic procedures, pharmacological treatment, follow-up, and adjuvant treatment. Ultrasonography is complementary to temporal artery biopsy (TAB) in the diagnostic work-up. Other imaging techniques (magnetic resonance imaging and positron emission tomography/computed tomography) are important in evaluating large-vessel involvement. Glucocorticoids (oral, or intravenous in cases with ischaemic complications) remain the first line treatment for GCA. Addition of tocilizumab is recommended for patients with relapsing disease who meet five criteria, representing active disease that has been objectively verified by TAB or imaging. Tocilizumab may also be considered in patients with newly diagnosed GCA who are at major risk of severe glucocorticoid side effects. Based on current evidence, tocilizumab treatment for >1 year cannot be recommended.Conclusion: These guidelines are based on current evidence and consensus within Swedish rheumatology. Following major developments in diagnostics and treatment of GCA, such guidelines are important for clinical practice, and should be updated on a regular basis.
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| 48. |
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| 49. |
- Weitoft, Tomas, et al.
(author)
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Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies
- 2015
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In: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 54:10, s. 1923-1928
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF.METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3.RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients.CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.
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| 50. |
- Weitoft, Tomas, et al.
(author)
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Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis - a prospective cohort study
- 2014
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 16:3
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Journal article (peer-reviewed)abstract
- Introduction: Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA). Methods: In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for six months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analysed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor). Results: During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (P = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (P = 0.002). Conclusions: Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse.
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