| 1. |
- Jacobsson, Josefin, et al.
(författare)
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Genetic variants near the MGAT1 gene are associated with body weight, BMI and fatty acid metabolism among adults and children
- 2012
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 36:1, s. 119-129
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-β-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men. Design: Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children. Results: Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95% confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95% CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95% CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95% CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95%CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95% CI:0.093-0.373, P=0.001) and 0.147 (95% CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038). Conclusion: Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity.
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| 2. |
- Abrahamsson, Carl-Olof, et al.
(författare)
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Xylosylated naphthoic acid-amino acid conjugates for investigation of glycosaminoglycan priming.
- 2008
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 1873-426X .- 0008-6215. ; 343:9, s. 1473-1477
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Tidskriftsartikel (refereegranskat)abstract
- Three different series of xylosylated naphthoic acid-amino acid conjugates containing one or two amino acid residues were synthesized for the investigation of glycosaminoglycan priming and potential use as anti-tumor drugs. All xylosylated naphthoic acid-conjugates inhibited the growth of normal lung fibroblasts to some extent, whereas the growth of tumor derived T24 carcinoma cells was not affected. There was no correlation between amino acid conjugation, retention time and the antiproliferative activity. Only one compound initiated the priming of glycosaminoglycans. Modification of the naphthalene ring with one or two amino acid residues did not have any effect on proteoglycan biosynthesis or glycosaminoglycan priming in T24 carcinoma cells.
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| 3. |
- Aili, Ulrika, et al.
(författare)
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Antiproliferative effects of peracetylated naphthoxylosides.
- 2009
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X. ; 19, s. 1763-1766
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Tidskriftsartikel (refereegranskat)abstract
- The antiproliferative activity, and the capability of priming of glycosaminoglycan chains, of two series of peracetylated mono- and bis-xylosylated dihydroxynaphthalenes have been investigated for normal HFL-1 cells, as well as transformed T24 cells, and compared to the unprotected analogs. Our data show increased antiproliferative activity upon peracetylation, but a loss of selectivity towards T24 cells.
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| 4. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Annan publikation (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 5. |
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| 6. |
- Andersson, Håkan S., 1967-, et al.
(författare)
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Alpha-nemertides - a novel family of nemertean peptide neurotoxins
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We recently discovered a novel family of neuroactive peptides in nemerteans, which we have named alpha-nemertides (1). One of these peptides, nemertide alpha-1, has been the subject of detailed studies with regard to structure and effects. The peptide exhibits exceptional potency against a number of arthropod species. Moreover, in vitro experiments suggest that alpha-1 acts primarily on voltage-gated sodium channels, and that this action is selective for arthropods by two orders of magnitude over vertebrate species. Using transcriptomic and proteomic approaches, we have identified 10 alpha-nemertides, but this number is likely to increase. These peptides alongside with a series of mutants are currently under evaluation by our group, with the goal to improve our understanding of structure-function relationships. In addition, we are considering potential practical uses of alpha-nemertides. In this talk, I will describe the current status of this research project.1. E. Jacobsson et al., Peptide ion channel toxins from the bootlace worm, the longest animal on Earth. Scientific reports 8, 4596 (2018).
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| 7. |
- Andersson, Håkan S., 1967-, et al.
(författare)
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Discovery of novel ion-channel active peptide toxins in a North Sea Ribbon Worm
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Ribbon worms (nemerteans) are marine predators, which capture their prey using a proboscis containing a mixture of toxins which brings on rapid paralysis [1]. In addition, their epidermis contains thick mucus of similar toxic constitution. One very potent toxin reported in ribbon worm mucus is tetrodotoxin (TTX). However, despite significant efforts, Strand et al. [2] were unable to detect any TTX, neither in the mucus of the ribbon worm Lineus longissimus, nor from Vibrio alginolyticus cultures isolated from and cultivated in the mucus. These observations challenged the notion of general presence of TTX in ribbon worm mucus, and prompted us to look for other toxins [3]. Using LC-MS analysis of mucus extracts, we identified three peptides present in significant amounts. The peptides were sequenced using a combination of MS/MS analysis and transcriptomics, and whereas one of them strongly resembles the only peptide toxin previously characterized from ribbon worms, Neurotoxin B-IV [4], the other two were found to represent a previously unknown class of peptide toxins. The most abundant of these was synthesized, and its 3D structure determined. Preliminary toxicity tests on shore crab (C. maenas) indicated toxicity (through paralysis) on par with that of TTX. Further analyses have indicated that its toxic effects are due to binding to voltage sensitive sodium channels. With L. longissimus as our primary target, we are now mapping the presence of peptide toxins in ribbon worms, with the objectives to establish routes for synthesis, and to characterize the biological activities and structures of these peptides. The number of peptides of this novel class is increasing, and synthesis and characterization is well underway. The striking potencies of these peptides make them potentially amenable as novel insecticidal or anthelmintic leads, pharmacological tools or in biotechnology applications. References1. Strand M, Sundberg P. Nationalnyckeln till Sveriges flora och fauna [DO-DP]. Stjärnmaskar-Slemmaskar: Sipuncula-Nemertea: Artdatabanken, SLU; 2010.2. Strand M, Hedstrom M, Seth H, McEvoy EG, Jacobsson E, Goransson U, Andersson HS, Sundberg P. The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus-Just a False Positive? Marine Drugs. 2016;14(4).3. Strand M, Andersson HS. Slemmaskens hemlighet. Forskning & Framsteg. 2016;(2):26-33.4. Blumenthal KM, Kem WR. Structure and action of heteronemertine polypeptide toxins. Primary structure of Cerebratulus lacteus toxin B-IV. The Journal of Biological Chemistry. 1976;251(19):6025-9.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Andersson, Håkan S., 1967-, et al.
(författare)
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The toxicity of ribbon worms: alpha-nemertides or tetrodotoxin, or both?
- 2016
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Ingår i: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 82:Supplement 1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The marine ribbon worms (nemerteans) are predators which capture their prey by everting a proboscis carrying a mixture of toxins which brings on rapid paralysis [1]. Moreover, ribbon worms have a thick layer of epidermal mucus of similar constitution. Tetrodotoxin (TTX) has been identified as one of these toxins [2]. The extreme toxicity of TTX (lethal by ingestion of 0.5-2 mg) is due to its ability to block voltage-gated sodium channels. Although several bacterial species (among these Vibrio sp.) have been linked to its synthesis, the biogenic origin and biosynthesis is unclear. One hypothesis is that TTX production occurs in a symbiotic relationship with its host, in this case the ribbon worm [3]. We have made significant effort to identify TTX in a setup for production through the cultivation of Vibrio alginolyticus in nutrient broth infused with mucus from the ribbon worm Lineus longissimus. Toxicity was demonstrated by fraction injections into shore crabs, but no TTX was found, and it could be shown conclusively that toxicity was unrelated to TTX and the Vibrio culture itself, and rather a constituent of the ribbon worm mucus [4]. The following studies led us to the discovery of a new class of peptides, the alpha-nemertides, in the mucus of the ribbon worms, which could be directly linked to the toxic effects. A literature review of the available evidence for TTX in ribbon worms show that the evidence in most cases are indirect, although notable exceptions exist. This points to the necessity to further investigate the presence and roles of TTX and alpha-nemertides in ribbon worms.
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| 12. |
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| 13. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study
- 2017
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP). Methods: This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001-2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively. Results: Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31-1.82)), PsA (1.76 (1.59-1.95)) and uSpA (1.36 (1.05-1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37-0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06-1.48)) and PsA (1.34 (1.22-1.48)), and nonsignificantly increased in uSpA (1.16 (0.91-1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP. Conclusions: Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.
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| 14. |
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| 15. |
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| 16. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Incidence of extra-articular manifestations in ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis : Results from a national register-based cohort study
- 2021
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:6, s. 2725-2734
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate the incidence and strength of association of extra-articular manifestations [EAMs, here: anterior uveitis (AU), IBD and psoriasis] in patients with AS, undifferentiated SpA (uSpA) and PsA, compared with controls. Methods: Three mutually exclusive cohorts of patients aged 18-69 years with AS (n = 8517), uSpA (n = 10 245) and PsA (n = 22 667) were identified in the Swedish National Patient Register 2001-2015. Age-, sex- and geography-matched controls were identified from the Swedish Population Register. Follow-up began 1 January 2006, or six months after the first SpA diagnosis, whichever occurred later, and ended at the first date of the EAM under study, death, emigration, 70 years of age, and 31 December 2016. Incidence rates (IRs) and incidence rate ratios were calculated for each EAM, and stratified by sex and age. Results: Incidence rate ratios for incident AU, IBD and psoriasis were significantly increased in AS (20.2, 6.2, 2.5), uSpA (13.6, 5.7, 3.8) and PsA (2.5, 2.3, n.a) vs controls. Men with AS and uSpA had significantly higher IRs per 1000 person-years at risk for incident AU than women with AS (IR 15.8 vs 11.2) and uSpA (IR 10.1 vs 6.0), whereas no such sex difference was demonstrated in PsA or for the other EAMs. Conclusions: AU, followed by IBD and psoriasis, is the EAM most strongly associated with AS and uSpA. Among the SpA subtypes, AS and uSpA display a largely similar pattern of EAMs, whereas PsA has a considerably weaker association with AU and IBD.
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| 17. |
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| 18. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population : A register-based study from Sweden
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 541-548
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To describe the incidence of atrioventricular (AV) block II-III, atrial fibrillation (AF), pacemaker implantation (PM) and aortic regurgitation in patients with ankylosing spondylitis (AS), undifferentiated spondyloarthritis (uSpA) and psoriatic arthritis (PsA) compared with the general population (GP) and with each other. Methods A prospective nationwide study with cohorts of patients with AS (n=6448), PsA (n=16 063) and uSpA (n=5190) and a GP (n=2 66 435) cohort, identified in 2001-2009 in the Swedish National Patient and Population registers. Follow-up began on 1 January 2006 and ended at event, death, emigration or 31 December 2012. Age-standardised and sex-standardised incidence rates and hazard ratios (HRs) were calculated. Results The highest incidence rates were noted for AF (5.5-7.4 events per 1000 person-years), followed by PM (1.0-2.0 events per 1000 person-years). HRs for AV block, AF, PM and aortic regurgitation were significantly increased in AS (HRs 2.3, 1.3, 2.1 and 1.9), uSpA (HRs 2.9, 1.3, 1.9 and 2.0) and PsA (HRs 1.5, 1.5, 1.6 and 1.8) compared with the GP cohort. The highest HRs were seen for AV block in male uSpA (HR 4.2) and AS (HR 2.5) compared with GP. Compared with PsA, significantly increased HRs were noted for PM (HR 1.5) in AS and for AV block (HR 1.8) in uSpA. Conclusions Patients with SpA are at increased risk of aortic regurgitation, cardiac rhythm disturbances and, as a probable consequence, also PM. Particularly for AF, the most common arrhythmia, increased caution is warranted, whereas AV block should be looked for especially in men with AS or uSpA.
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| 19. |
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| 20. |
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| 21. |
- Bergström, Ulf, et al.
(författare)
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Cardiovascular morbidity and mortality remain similar in two cohorts of patients with long-standing rheumatoid arthritis seen in 1978 and 1995 in Malmo, Sweden.
- 2009
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 48, s. 1600-1605
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Patients with RA have an increased risk of cardiovascular disease. Management of RA has changed substantially over time. Our aim was to evaluate changes in cardiovascular morbidity and mortality over the period of 1978-2002. Methods. Two cohorts of consecutive patients with RA seen at outpatient clinics in Malmö, Sweden, were started in 1978 (n = 148) and 1995 (n = 161) and compared with the corresponding background population. Patients were followed for 8 years, and fatal and non-fatal cardiovascular first events were identified using two national registers, hospital discharge and cause of death. Standardized morbidity ratio (SMoR) and standardized mortality ratio (SMR), adjusted for age and sex were calculated. Results. Sex distribution, age at disease onset and disease duration were similar in both groups. The 1995 cohort was more extensively treated with DMARDs and had less disease activity and disability. Total cardiovascular morbidity was increased in the 1978 cohort (SMoR 158; 95% CI 111, 225) as well as in the 1995 cohort (SMoR 168; 95% CI 118, 232). This was mainly due to an increased risk of coronary artery disease. Overall mortality was elevated in the 1978 cohort but not in the 1995 cohort. There was no change in cardiovascular excess mortality (SMR 175; 95% CI 100, 284; and 172; 100, 276 for the two cohorts, respectively). Conclusions. There were similar elevations in the incidence of cardiovascular comorbidity in RA patients, identified two decades apart compared with the general population, in spite of more extensive treatment and reduced disease severity in the more recent cohort.
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| 22. |
- Bergström, Ulf, et al.
(författare)
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Effects of adalimumab treatment on endothelial cell activation markers in the skeletal muscle of patients with rheumatoid arthritis.
- 2014
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X .- 0392-856X. ; 32:6, s. 883-890
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Tidskriftsartikel (refereegranskat)abstract
- Patients with rheumatoid arthritis (RA), particularly those with severe disease, have increased risk of cardiovascular disease (CVD). Previous studies suggest that endothelial cell activation may contribute to this co-morbidity, and that treatment with tumour necrosis factor (TNF) inhibitors could reduce the risk of CVD in these patients. The aim of this study was to investigate endothelial cell activation markers in muscle tissue of patients after adalimumab treatment.
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| 23. |
- Bergström, Ulf, et al.
(författare)
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Effects of Treatment with Adalimumab on Blood Lipid Levels and Atherosclerosis in Patients with Rheumatoid Arthritis
- 2018
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Ingår i: Current Therapeutic Research - Clinical and Experimental. - : Elsevier BV. - 0011-393X. ; 89, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment with tumor necrosis factor inhibitors for rheumatoid arthritis has been associated with a decreased risk of cardiovascular disease in observational studies. There are conflicting data on the influence of tumor necrosis factor inhibitors on lipid levels. Objectives: To evaluate the effect of treatment with adalimumab on blood lipid levels, lipoproteins, and atherosclerosis of the carotid artery. Methods: Fourteen patients with active rheumatoid arthritis (11 women and 3 men; mean age 63.7 years; median disease duration 9.0 years; and 78% rheumatoid factor positive) were treated with adalimumab 40 mg subcutaneously every 2 weeks and followed for 3 months. The patients had not been treated with adalimumab previously and had not received other tumor necrosis factor inhibitors within the past 3 months or moderate/high dose corticosteroids within the past 2 weeks. The intima-media thickness of the common carotid artery was assessed using B mode ultrasonography. Triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol levels were analyzed in fresh fasting blood samples, whereas apolipoprotein B and apolipoprotein A1 (apoA1) levels were determined in thawed plasma samples using standard turbidimetric immunoassays. Results: Total cholesterol (mean = 5.36 vs 5.96 mmol/L; P = 0.005), LDL cholesterol (mean = 3.33 vs 3.77 mmol/L; P =.005), HDL cholesterol (mean = 1.43 vs 1.55 mmol/L; P = 0.048), apolipoprotein B (mean = 1.04 vs 1.13 g/L; P =.012), and apoA1 (mean = 1.42 vs 1.58 g/L; P = 0.005) all increased, but there were no major changes in the LDL to HDL cholesterol ratio (median = 2.56 vs 2.35; P = 0.27) or the apolipoprotein B to apoA1 ratio (mean = 0.76 vs 0.74; P = 0.46). There was no change in triglyceride levels (P = 0.55). Disease activity decreased significantly from baseline to the 3-month evaluation (disease activity score based on 28 joints mean = 5.6 vs 4.1; P = 0.007). An increase in apoA1 correlated with decreases in the patient global assessment of disease severity (r = 0.79; P = 0.001) and C-reactive protein level (r = 0.74; P = 0.003). Changes in the apoliprotein B to apoA1 ratio correlated with changes in erythrocyte sedimentation rate (r = 0.54; P = 0.046). There was no major change in the common carotid artery intima-media thickness (mean = 0.78 vs 0.80 mm; P = 0.48). Conclusions: Although these results suggest that control of inflammation could have a beneficial effect on the lipid profile through an increase in HDL cholesterol levels, the observed protective effect on cardiovascular disease events by tumor necrosis factor blockers is likely to be explained by other mechanisms than changes in lipid levels or short-term effects on atherosclerosis of the carotid artery. © 2018 The Authors
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| 24. |
- Bergström, Ulf, et al.
(författare)
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Lower disease activity and disability in Swedish patients with rheumatoid arthritis in 1995 compared with 1978
- 1999
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Ingår i: Scandinavian Journal of Rheumatology. - 1502-7732. ; 28, s. 160-165
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate differences in disease activity, disability, and medical treatment in consecutive patients with rheumatoid arthritis seen at the outpatient clinics in Malmö, in 1978 (n=148) and 1995 (n=164). The groups were similar with regard to age, gender, disease duration, and the proportion having had hip or knee replacement surgery. The patients in 1995 had lower values for CRP (p<0.001), Ritchie Articular Index (mean values: 5.5 vs. 9.9, p<0.001), and Steinbrocker functional class index (mean values: 1.96 vs. 2.16, p<0.001) than the 1978 group. The 1995 patient group was also more extensively treated with DMARD:s (68 vs. 51%, p<0.01) and glucocorticosteroids (23 vs. 12%, p<0.02) and had historically been treated with almost twice as many DMARD:s (2.7 vs. 1.5, p<0.001). Similar findings regarding disease activity and disability were made when restricting the analysis to subgroups of patients that were seropositive or had a shorter disease duration (<5 yrs). The lower disease severity in the 1995 group may be secondary to a more active medical treatment, although other possibilities such as differences in selection and secular changes in disease severity unrelated to medication cannot be excluded.
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| 25. |
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| 26. |
- Bergström, Ulf, et al.
(författare)
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Pulmonary dysfunction, smoking, socioeconomic status and the risk of developing rheumatoid arthritis.
- 2011
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 2005-2013
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Environmental risk factors are of potential interest for both prevention and treatment of RA. The purpose of this study was to examine the effect of pulmonary function, smoking and socio-economic status on the future risk of RA. Methods. Between 1974 and 1992, 22 444 men and 10 902 women were included in the Malmö Preventive Medicine Program (MPMP). Pulmonary function was assessed by a standard screening spirometry. Chronic obstructive pulmonary disease (COPD) and restrictive pulmonary dysfunction were defined based on pulmonary function tests. Individuals who developed RA were identified by linking the MPMP database to national and local RA registers. The patients were classified according to the 1987 ACR criteria for RA. Four matched controls for every case were selected. Results. We identified 290 cases of incident RA (151 men/139 women; mean age at diagnosis 60 years). The median time from inclusion to diagnosis was 12 years. Forced vital capacity and forced expiratory volume within 1 s values were similar in cases and controls, overall and also in separate analysis of those screened ≤8 years before diagnosis. There was no association between COPD or restrictive pulmonary dysfunction and subsequent development of RA. Current smoking was a strong predictor for RA [odds ratio (OR) 1.79; 95% CI 1.32, 2.42]. Blue-collar workers had an increased risk of RA (OR 1.54; 95% CI 1.12, 2.10), independent of smoking. Conclusion. Pulmonary dysfunction did not predict RA, but smoking and low socio-economic status were independent risk factors for RA. Other effects of smoking may be important for RA susceptibility
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| 27. |
- Bergström, Ulf, et al.
(författare)
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Smoking, low formal level of education, alcohol consumption, and the risk of rheumatoid arthritis.
- 2013
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 42:2, s. 123-130
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Suggested predictors of rheumatoid arthritis (RA) include environmental exposure, such as smoking. Our purpose was to investigate potential predictors of RA in a nested case-control study based on a prospective cohort. Method: Between 1991 and 1996, 30 447 persons were included in the Malmö Diet and Cancer Study (MDCS). Individuals who developed RA after inclusion up to 31 December 2004 were identified by linking the database to different registers. Four controls were selected for every case. Data on lifestyle factors were collected in the MDCS. Results: We identified 172 incident cases of RA [36 men/136 women, mean age at diagnosis 63 years, 69% rheumatoid factor (RF) positive, median time from inclusion to diagnosis 5 (range 1-13) years]. In bivariate analyses, baseline smoking [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.31-3.12] and a low level of formal education (i.e. ≤ 8 years; OR 2.42, 95% CI 1.18-4.93 vs. University degree) predicted subsequent development of RA. Infrequent baseline alcohol consumption was a predictor of RA (OR 3.47, 95% CI 1.91-6.30) compared to recent use (within the past month), and individuals with moderate baseline alcohol consumption (3.5-15.2 g/day vs. < 3.5 g/day) tended to have a reduced risk of RA (OR 0.48, 95% CI 0.22-1.05) in multivariate analyses, adjusted for smoking and level of education. Conclusions: Smoking and a low level of formal education were found to be independent predictors of RA. Moderate alcohol consumption may also be associated with a reduced risk.
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| 28. |
- Caruso, Vanni, et al.
(författare)
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mRNA GPR162 changes are associated with decreased food intake in rat, and its human genetic variants with impairments in glucose homeostasis in two Swedish cohorts
- 2016
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Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 581:2, s. 139-145
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Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized. Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding. In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis.
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| 29. |
- Dahlberg, Anders, et al.
(författare)
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Svampar – Fungi
- 2010
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Ingår i: Rödlistade arter i Sverige 2010 – The 2010 Red List of Swedish Species. - 9789188506351 ; , s. 231-246
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 30. |
- Dehlin, Mats, 1968, et al.
(författare)
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Factors associated with initiation and persistence of urate-lowering therapy
- 2017
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Ingår i: Arthritis Resarch and Therapy. - 1478-6354. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gout is the most common inflammatory arthritic disease and is caused by crystal deposition secondary to persistent hyperuricemia. Etiological treatment with urate-lowering therapy (ULT) has been available since the 1950s but previous studies have demonstrated suboptimal degree of treatment. In recent years we have seen recommendations for ULT earlier in the course of the disease, but there are few contemporary reports reflecting the current situation. Therefore we set out to investigate proportion receiving and persisting with ULT after gout diagnosis and predictors thereof. Method: A population-based cohort study using regional and national population-based registers. Cohort of patients (n = 7709) from western Sweden with incident gout aged 18 years and above from 2011 to 2013. An incident case of gout was defined as having been given a diagnosis of gout (ICD-10 M10, M14.0-14.1) not preceded by a gout diagnosis or a dispensation of ULT during the previous 5 years. Main outcome measures were cumulative incidence and predictors for start of, and persistence with, ULT in gout. Results: Within the first year after first gout diagnosis, 32% received ULT. Male sex, presence of diabetes or cardiovascular comorbidity, reduced kidney function but not diagnosed "end-stage kidney failure"increased the likelihood of receiving ULT. Of those starting ULT a majority (75%) did not persist with ULT treatment within the first 2 years. Age < 50 years, lack of comorbidities, and "normal kidney function"or "end-stage kidney failure"were associated with non-persistence with ULT. Conclusions: Only a minority of patients received ULT and a majority of these did not persist with treatment over the next 2 years. However, the older patients with renal impairment and comorbidities, possibly suffering from a more severe gout disease, were more likely to receive and persist with treatment. There is thus still room for considerable improvement with regards to management of ULT in gout.
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| 31. |
- Di Giuseppe, D., et al.
(författare)
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The occurrence of multiple treatment switches in axial spondyloarthritis. Results from five Nordic rheumatology registries
- 2022
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:9, s. 3647-3656
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline). Methods Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009-2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with >= 3, >= 4 or >= 5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with >= 3 b/tsDMARDs stratified by calendar-period (2009-2011, 2012-2013, 2014-2015, 2016-2018). In the subgroup of patients starting a first b/tsDMARD 2009-2015, baseline characteristics associated with multi-switching (within 3 years' follow-up) were explored using multiple logistic regression analyses. Results Among 8398 patients included, 6056 patients (63% male, median age 42 years) started a first b/tsDMARD in 2009-2015, whereof proportions treated with >= 3, >= 4 or >= 5 b/tsDMARDs within 3 years' follow-up were 8%, 3% and 1%, respectively. Calendar-period did not affect the cumulative incidence of multi-switching. Baseline characteristics associated with multi-switching (>= 3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities and having psoriasis but not uveitis. Conclusion In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extra-articular manifestations illustrating the ongoing challenge of treating this patient group.
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| 32. |
- Drivelegka, Panagiota, et al.
(författare)
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Incident gout and risk of first-time acute coronary syndrome: a prospective, population-based, cohort study in Sweden
- 2023
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 75:6, s. 1292-1299
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the risk of first-time acute coronary syndrome (ACS) in a large cohort of primary and secondary care patients with incident gout, compared to the general population. Methods: Using register data for the period 2007 ̶ 2017, we conducted a prospective, population-based cohort with 20,146 patients with incident gout (mean age, 65.6 years; 67.4% males) and 83,517 matched population controls, without prior history of coronary heart disease. We calculated incidence rates (IR) and hazard ratios (HR) adjusted for baseline comorbidities and dispensed prescriptions. In a sensitivity analysis, we included gout cases and controls with no previously diagnosed comorbidity (6,075 cases and 44,091 controls). Results: The IR of first-time ACS was significantly increased in the gout cohort, compared to controls (9.1 vs 6.3/1,000 person-years). Unadjusted cox regression showed that gout patients had higher risk of first-time ACS compared to controls (HR, 1.44; 95%CI, 1.33-1.56), with higher HR in women (HR, 1.64; 95%CI, 1.41 ̶ 1.90) than in men (HR, 1.36; 95%CI, 1.24 ̶ 1.50). In multivariable analysis the risk diminished but remained significant (HR, 1.15; 95%CI, 1.06-1.25). The risk was similar in the sensitivity analysis (HR, 1.20; 95%CI, 1.01-1.44), and still higher in women (HR, 1.34; 95%CI, 0.86-2.08), than in men (HR, 1.18; 95%CI, 0.97-1.44). Conclusion: Patients with incident gout have a 44% increased risk of first-time ACS, higher in women than in men. This risk is largely explained by the underlying comorbidities, but there is still a modestly increased risk that may be due to gout-related factors.
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| 33. |
- Ellervik, Ulf, et al.
(författare)
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2-Bromoethyl glycosides for synthesis of glycoconjugates on solid support
- 2005
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 61:9, s. 2421-2429
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Tidskriftsartikel (refereegranskat)abstract
- 2-Bromoethyl glycosides can easily and in high yields be transformed into sulfones by treatment with a suitable thiol followed by oxidation with mCPBA. The observation that the so formed sulfones were cleaved by treatment with NaOMe/MeOH was used to design a new safety catch linker for synthesis of glycoconjugates on solid support. (C) 2005 Elsevier Ltd. All rights reserved.
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| 34. |
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| 35. |
- Exarchou, Sofia, et al.
(författare)
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Lifestyle Factors and Disease Activity Over Time in Early Axial Spondyloarthritis: The SPondyloArthritis Caught Early (SPACE) Cohort
- 2022
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 49:4, s. 365-372
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Our aim was to study the importance of baseline BMI, smoking, and alcohol consumption (AC) for disease activity (DA) over 1 year in early axial spondyloarthritis (axSpA), stratified by sex. Methods. In the SPondyloArthritis Caught Early cohort ( patients with chronic back pain onset at age < 45 yrs, with pain for >= 3 months and >= 2 yrs), the Ankylosing Spondylitis Disease Activity Score (ASDAS) was recorded at inclusion, 3, and 12 months. All patients included in the analysis had axSpA based on a high physician's level of confidence at baseline. Differences in ASDAS over 1 year by BMI (normal < 25 kg/m(2), overweight 25-29.9 kg/m(2), and obese >= 30 kg/m(2)), smoking history (never/previous/current), and AC (none, 0.1-2 units/week, 3-5 units/week, and >= 6 units/week) at baseline were estimated using mixed linear regression models. Results. There were 344 subjects (mean age of 30.3 yrs; 49.4% men). In women, obesity was associated with 0.60 (95% CI 0.28-0.91) higher ASDAS compared to normal BMI. In both sexes, AC tended to be associated with lower DA over 1 year, with a significant association only in women with the highest AC (mean difference of -0.55, 95% CI -1.05 to -0.04). Smoking was associated with higher ASDAS over 1 year compared to never smoking in both sexes, although the difference reached statistical significance only in female former smokers. Results were similar in multivariable analysis, adjusted for all lifestyle factors and other confounders. Conclusion. In early axSpA, BMI and smoking are associated with higher DA over 1 year, and AC with lower DA. The magnitude of the modest associations may differ between men and women.
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| 36. |
- Exarchou, Sofia, et al.
(författare)
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Mortality in ankylosing spondylitis: results from a nationwide population-based study
- 2016
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:8, s. 1466-1472
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Information on mortality in ankylosing spondylitis (AS) is scarce. Our study therefore aimed to assess: (1) mortality in AS versus the general population, and (2) predictors of death in the AS population. Methods Nationwide cohorts of patients with AS diagnosed at rheumatology or internal medicine outpatient clinics (n=8600) and age-matched, sex-matched and county-matched general population comparators (n=40 460) were identified from the National Patient Register and the census register, respectively. The follow-up period began on 1 January 2006 or at the first date of registered diagnosis thereafter and extended until death, emigration or 31 December 2012, whichever occurred first. Socioeconomic variables, AS-related clinical manifestations, joint surgery, comorbidities and medication were identified from other national registers. Cox regression models were used to determine mortality and predictors for death in the AS cohort. Results There were 496 deaths in the AS cohort and 1533 deaths in the control cohort resulting in an age-adjusted and sex-adjusted HR of 1.60 (95% CI 1.44 to 1.77), with increased mortality for men (age-adjusted HR=1.53, 95% CI 1.36 to 1.72) and women (ageadjusted HR=1.83, 95% CI 1.50 to 2.22). Within the AS cohort, statistically significant predictors for death were a lower level of education, general comorbidities (diabetes, infections, cardiovascular, pulmonary and malignant diseases) and previous hip replacement surgery. Conclusions Mortality was increased for male and female patients with AS. Predictors of death within the AS cohort included socioeconomic status, general comorbidities and hip replacement surgery.
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| 37. |
- Exarchou, Sofia, et al.
(författare)
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Mortality in patients with psoriatic arthritis in Sweden: a nationwide, population-based cohort study
- 2024
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - 0003-4967 .- 1468-2060. ; 83:4, s. 446-456
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo compare all-cause mortality and causes of death between patients with psoriatic arthritis (PsA) and the general population in Sweden.MethodsAdults with at least one main PsA diagnosis (International Classification of Diseases-10: L40.5/M07.0-M07.3) from outpatient rheumatology/internal medicine departments 2001-2017 were identified from the National Patient Register. Each case was matched to five population comparator-subjects on sex/county/age at the case's first arthritis diagnosis. Follow-up ran from 1 January 2007, or from first PsA diagnosis thereafter, until death, emigration or 31 December 2018. Mortality was assessed overall, and stratified by sex and duration since diagnosis (diagnosis before/after 1 January 2007), using matched Cox proportional hazard regression (excluding/including adjustments for comorbidity) or Breslow test, as appropriate. Incidence rate ratios (IRR) of death, overall and stratified by sex/duration since diagnosis/age, as well as causes of death in PsA cases and comparator-subjects were also described.ResultsAll-cause mortality was elevated in PsA (HR: 1.11 (95% CI: 1.07 to 1.16); IRR: 1.18 (95% CI: 1.13 to 1.22)), mainly driven by increased risks in women (HR: 1.23 (95% CI: 1.16 to 1.30)) and cases with longer time since diagnosis (HR: 1.18 (95% CI: 1.12 to 1.25)). IRR of death were significantly increased for all ages except below 40 years, with the numerically highest point-estimates for ages 40-59 years. When adjusted for comorbidity, however, the elevated mortality risk in PsA disappeared. Causes of death were similar among PsA cases/comparator-subjects, with cardiovascular disease and malignancy as the leading causes.ConclusionsMortality risk in PsA in Sweden was about 10% higher than in the general population, driven by excess comorbidity and with increased risks mainly in women and patients with longer disease duration.
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| 38. |
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| 39. |
- Exarchou, Sofia, et al.
(författare)
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The National Prevalence of Clinically Diagnosed Psoriatic Arthritis in Sweden in 2017
- 2023
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 50:6, s. 781-788
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Psoriatic arthritis (PsA) prevalence estimates vary across studies; studies based on national data are few. We aimed to estimate the prevalence of clinically diagnosed PsA in Sweden in 2017, overall and stratified by sex, age, education, and geography, and to quantify disease-modifying antirheumatic drug (DMARD) use among those in contact with specialized rheumatology care between 2015 and 2017.Methods. Individuals who were 18 to 79 years of age, alive and residing in Sweden on December 31, 2017, and had a prior PsA diagnosis were identified from the National Patient Register (NPR) and/or the Swedish Rheumatology Quality Register (SRQ). PsA prevalence was estimated according to a base case (BC) defini-tion (ie, & GE; 1 main PsA International Classification of Diseases code from rheumatology or internal medicine departments in the NPR or a PsA diagnosis in the SRQ), according to 4 sensitivity analysis definitions, and for those seen in specialized rheumatology care between 2015 and 2017. In the latter group, DMARD use during 2017 was also assessed. Data for stratifications were retrieved from national registers.Results. The crude national prevalence of PsA for adults, aged 18 to 79 years, was estimated at 0.39%, according to the BC definition; 0.34% after accounting for diagnostic misclassification; and 0.32% to 0.50% across all sensitivity analyses. The prevalence was lower in males and in those with a higher level of education. The prevalence for those seen in specialized rheumatology care between 2015 and 2017 was estimated at 0.24%. During 2017, 32% of patients in this population received biologic or targeted synthetic DMARDs, and 41% received conventional synthetic DMARDs only.Conclusion. The prevalence of clinically diagnosed PsA in adults, aged 18 to 79 years, in Sweden in 2017 was around 0.35%. Among PsA cases in recent contact with specialized rheumatology care, almost three-fourths received DMARD therapy in 2017.
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| 40. |
- Exarchou, Sofia, et al.
(författare)
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The prevalence of clinically diagnosed ankylosing spondylitis and its clinical manifestations: a nationwide register study
- 2015
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Prevalence estimates of ankylosing spondylitis vary considerably, and there are few nationwide estimates. The present study aimed to describe the national prevalence of clinically diagnosed ankylosing spondylitis in Sweden, stratified according to age, sex, geographical, and socio-economic factors, and according to subgroups with ankylosing spondylitis-related clinical manifestations and pharmacological treatment. Methods: All individuals diagnosed with ankylosing spondylitis according to the World Health Organization International Classification of Disease codes, between 1967 and 2009, were identified from the National Patient Register. Data regarding disease manifestations, patient demographics, level of education, pharmacological treatment, and geographical region were retrieved from the National Patient Register and other national registers. Results: A total of 11,030 cases with an ankylosing spondylitis diagnosis (alive, living in Sweden, and 16 to 64 years old in December 2009) were identified in the National Patient Register, giving a point prevalence of 0.18% in 2009. The prevalence was higher in northern Sweden, and lower in those with a higher level of education. Men had a higher prevalence of ankylosing spondylitis (0.23% versus 0.14%, P < 0.001), a higher frequency of anterior uveitis (25.5% versus 20.0%, P < 0.001) and were more likely to receive tumor necrosis factor inhibitors than women (15.6% versus 11.8% in 2009, P < 0.001). Women were more likely than men to have peripheral arthritis (21.7% versus 15.3%, P < 0.001), psoriasis (8.0% versus 6.9%, P = 0.03), and treatment with oral corticosteroids (14.0% versus 10.4% in 2009, P < 0.001). Conclusion: This nationwide, register-based study demonstrated a prevalence of clinically diagnosed ankylosing spondylitis of 0.18%. It revealed phenotypical and treatment differences between the sexes, as well as geographical and socio-economic differences in disease prevalence.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Gebremichael, Teklay, 1985-
(författare)
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Lightweight Cryptographic Group Key Management Protocols for the Internet of Things
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Internet of Things (IoT) is increasingly becoming an integral component of many applications in consumer, industrial and other areas. Notions such as smart industry, smart transport, and smart world are, in large part, enabled by IoT. At its core, the IoT is underpinned by a group of devices, such as sensors and actuators, working collaboratively to provide a required service. One of the important requirements most IoT applications are expected to satisfy is ensuring the security and privacy of users. Security is an umbrella term that encompasses notions such as confidentiality, integrity and privacy, that are typically achieved using cryptographic encryption techniques.A special form of communication common in many IoT applications is group communication, where there are two or more recipients of a given message. In or-der to encrypt a message broadcast to a group, it is required that the participating parties agree on a group key a priori. Establishing and managing a group key in IoT environments, where devices are resources-constrained and groups are dynamic, is a non-trivial problem. The problem presents unique challenges with regard to con-structing protocols from lightweight and secure primitives commensurate with the resource-constrained nature of devices and maintaining security as devices dynamically leave or join a group.This thesis presents lightweight group key management protocols proposed to address the aforementioned problem, in a widely adopted model of a generic IoT network consisting of a gateway with reasonable computational power and a set of resource-constrained nodes. The aim of the group key management protocols is to enable the gateway and the set of resource-constrained devices to establish and manage a group key, which is then used to encrypt group messages. The main problems the protocols attempt to solve are establishing a group key among participating IoT devices in a secure and computationally feasible manner; enabling additionor removal of a device to the group in a security preserving manner; and enabling generation of a group session key in an efficient manner without re-running the protocol from scratch. The main challenge in designing such protocols is ensuring that the computations that a given IoT device performs as part of participating in the protocol are computationally feasible during initial group establishment, group keyupdate, and adding or removing a node from the group.The work presented in this thesis shows that the challenge can be overcome by designing protocols from lightweight cryptographic primitives. Specifically, protocols that exploit the lightweight nature of crypto-systems based on elliptic curves and the perfect secrecy of the One Time Pad (OTP) are presented. The protocols are designed in such a way that a resource-constrained member node performs a constant number of computationally easy computations during all stages of the group key management process.To demonstrate that the protocols are practically feasible, implementation resultof one of the protocols is also presented, showing that the protocol outperforms similar state-of-the-art protocols with regard to energy consumption, execution time, memory usage and number of messages generated.
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| 45. |
- Glintborg, B., et al.
(författare)
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Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries
- 2018
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:6, s. 465-474
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. Method: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. Results: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). Conclusion: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.
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| 46. |
- Glintborg, B., et al.
(författare)
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Is the risk of infection higher during treatment with secukinumab than with TNF inhibitors? An observational study from the Nordic countries
- 2023
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 62:2, s. 647-658
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The positioning of secukinumab in the treatment of axial SpA (axSpA) and PsA is debated, partly due to a limited understanding of the comparative safety of the available treatments. We aimed to assess the risk of the key safety outcome infections during treatment with secukinumab and TNF inhibitors (TNFi). Methods Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IRs) with 95% CIs per 100 patient-years were calculated. Adjusted hazard ratios were estimated through Cox regression, with secukinumab as the reference. Several sensitivity analyses were performed to investigate confounding by indication. Results Among 7708 patients with SpA and 5760 patients with PsA, we identified 16 229 treatment courses of TNFi (53% bionaive) and 1948 with secukinumab (11% bionaive). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9-6.3), compared with 1.7% (IR 2.3; 1.7-3.0) during 3201 courses with adalimumab, with the IRs for other TNFi lying in between these values. The adjusted HR for adalimumab, compared with secukinumab, was 0.58 (0.39-0.85). In sensitivity analyses, the difference from secukinumab was somewhat attenuated and in some analyses no longer statistically significant. Conclusion When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication.
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| 47. |
- Glintborg, B., et al.
(författare)
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One-Year Treatment Outcomes of Secukinumab Versus Tumor Necrosis Factor Inhibitors in Spondyloarthritis: Results From Five Nordic Biologic Registries Including More Than 10,000 Treatment Courses
- 2022
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Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X .- 2151-4658. ; 74:5, s. 748-758
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) using adalimumab as the main comparator. Methods This was an observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis, nonradiographic axial SpA, or undifferentiated SpA) starting secukinumab or a TNFi during 2015-2018 were identified from 5 Nordic clinical rheumatology registries. Data on comorbidities and extraarticular manifestations (psoriasis, uveitis, and inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios [HRadj] for treatment discontinuation) and 6-month response rates (Ankylosing Spondylitis Disease Activity Score [ASDAS] score <2.1, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] <40 mm, crude/LUNDEX-adjusted, adjusted logistic regression analyses with odds ratios [ORs]) stratified by line of biologic treatment (first, second, and third plus). Results In total, 10,853 treatment courses (842 secukinumab and 10,011 TNFi, of which 1,977 were adalimumab) were included. The proportions of patients treated with secukinumab during the first, second, and third-plus lines of treatment were 1%, 6%, and 22%, respectively). Extraarticular manifestations varied across treatments, while other baseline characteristics were largely similar. Secukinumab had a 1-year retention comparable to adalimumab as a first or second line of treatment but poorer as a third-plus line of therapy (secukinumab 56% [95% confidence interval (95% CI) 51-61%] versus adalimumab 70% [95% CI 64-75%]; HRadj 1.43 [95% CI 1.12-1.81]). Across treatment lines, secukinumab had poorer estimates for 6-month response rates than adalimumab, statistically significantly only for the third-plus line (adjusted analyses: ASDAS score <2.1 OR 0.56 [95% CI 0.35-0.90]; BASDAI <40 mm OR 0.62 [95% CI 0.41-0.95]). Treatment outcomes varied across the 5 TNFi. Conclusion Secukinumab was mainly used in biologics-experienced patients with SpA. Secukinumab and adalimumab performed similarly in patients who had failed a first biologic, although with increasing prior biologic exposure, adalimumab was superior.
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| 48. |
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| 49. |
- Gustafsson, Agnetha, et al.
(författare)
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Evaluation of various attenuation corrections in lung SPECT in healthy subjects
- 2003
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Ingår i: Nuclear Medicine Communications. - : Ovid Technologies (Wolters Kluwer Health). - 0143-3636 .- 1473-5628. ; 24:10, s. 1087-1095
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Tidskriftsartikel (refereegranskat)abstract
- The effect of increasingly more sophisticated attenuation correction methods on image homogeneity has been studied in seven healthy subjects. The subjects underwent computed tomography (CT), single photon emission computed tomography (SPECT) and transmission computed tomography (TCT) of the thorax region in the supine position. Density maps were obtained from the CT and TCT studies. Attenuation corrections were performed using five different methods: (1) uniform correction using only the body contour; (2) TCT based corrections using the average lung density; (3) TCT based corrections using the pixel density; (4) CT based corrections using average lung density; and (5) CT based corrections using the pixel density. The isolated attenuation effects were assessed on quotient images generated by the division of images obtained using various attenuation correction methods divided by the non-uniform attenuation correction based on CT pixel density (reference method). The homogeneity was calculated as the coefficient of variation of the quotient images (CVatt), showing the isolated attenuation effects. Values of CVatt were on average 12.8% without attenuation correction, 10.7% with the uniform correction, 8.1% using TCT map using the average lung density value and 4.8% using CT and average lung density corrections. There are considerable inhomogeneities in lung SPECT slices due to the attenuation effect. After attenuation correction the remaining inhomogeneity is considerable and cannot be explained by statistical noise and camera non-uniformity alone. ((C) 2003 Lippincott Williams Wilkins).
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| 50. |
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