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1.
  • Alshaikh, Ahmed Baker, et al. (författare)
  • Decellularization and recellularization of the ovary for bioengineering applications; studies in the mouse.
  • 2020
  • Ingår i: Reproductive biology and endocrinology : RB&E. - : Springer Science and Business Media LLC. - 1477-7827. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Fertility preservation is particularly challenging in young women diagnosed with hematopoietic cancers, as transplantation of cryopreserved ovarian cortex in these women carries the risk for re-introducing cancer cells. Therefore, the construction of a bioengineered ovary that can accommodate isolated small follicles was proposed as an alternative to minimize the risk of malignancy transmission. Various options for viable bioengineered scaffolds have been reported in the literature. Previously, we reported three protocols for producing mouse ovarian scaffolds with the decellularization technique. The present study examined these scaffolds further, specifically with regards to their extracellular composition, biocompatibility and ability to support recellularization with mesenchymal stem cells.Three decellularization protocols based on 0.5% sodium dodecyl sulfate (Protocol 1; P1), or 2% sodium deoxycholate (P2), or a combination of the two detergents (P3) were applied to produce three types of scaffolds. The levels of collagen, elastin and sulfated glycosaminoglycans (sGAGs) were quantified in the remaining extracellular matrix. Detailed immunofluorescence and scanning electron microscopy imaging were conducted to assess the morphology and recellularization efficiency of the constructs after 14days in vitro utilizing red fluorescent protein-labelled mesenchymal stem cells.All protocols efficiently removed the DNA while the elastin content was not significantly reduced during the procedures. The SDS-protocol (P1) reduced the sGAG and the collagen content more than the SDC-protocol (P2). All scaffolds were biocompatible and recellularization was successful, particularly in several P2-derived scaffolds. The cells were extensively distributed throughout the constructs, with a denser distribution observed towards the ovarian cortex. The cell density was not significantly different (400 to 550 cells/mm2) between scaffold types. However, there was a tendency towards a higher cell density in the SDC-derived constructs. Scanning electron microscope images showed fibrous scaffolds with a dense repopulated surface structure.While there were differences in the key structural macromolecules between protocols, all scaffolds were biocompatible and showed effective recellularization. The results indicate that our SDC-protocol might be better than our SDS-protocol. However, additional studies are necessary to determine their suitability for attachment of small follicles and folliculogenesis.
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2.
  • Alshaikh, Ahmed Baker, et al. (författare)
  • Decellularization of the mouse ovary: comparison of different scaffold generation protocols for future ovarian bioengineering.
  • 2019
  • Ingår i: Journal of ovarian research. - : Springer Science and Business Media LLC. - 1757-2215. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to preserve fertility in young women with disseminated cancer, e.g. leukemia, an approach that has been suggested is to retransplant isolated small follicles within an ovarian matrix free from malignant cells and with no risk for contamination. The present study evaluates the first step to create a bioengineered ovarian construct that can act as growth-supporting tissue for isolated small follicles that are dependent on a stroma for normal follicular maturation. The present study used the intact mouse ovary to develop a mouse ovarian scaffold through various protocols of decellularization.Potential Immunogenic DNA and intracellular components were removed from whole mouse ovaries by agitation in a 0.5% sodium dodecyl sulfate solution (Protocol 1; P1), or in a 2% sodium deoxycholate solution (P2) or by a combination of the two (P3). The remaining decelluralized ovarian extracellular matrix structure was then assessed based on the DNA- and protein content, and was further evaluated histologically by haematoxylin and eosin-, Verhoeff's van gieson- (for elastin), Masson's trichrome- (for collagens) and Alcian blue (for glycosaminoglycans) staining. We also evaluated the decellularization efficiency using the mild detergent Triton-X100 (1%).Sodium dodecyl sulfate efficiently removed DNA and intracellular components from the ovarian tissue but also significantly reduced the integrity of the remaining ovarian extracellular matrix. Sodium deoxycholate, a considerably milder detergent compared to sodium dodecyl sulfate, preserved the ovarian extracellular matrix better, evident by a more distinct staining for glycosaminoglycan, collagen and elastic fibres. Triton-X100 was found ineffective as a decellularization reagent for mouse ovaries in our settings.The sodium dodecyl sulfate generated ovarian scaffolds contained minute amounts of DNA that may be an advantage to evade a detrimental immune response following engraftment. The sodium deoxycholate generated ovarian scaffolds had higher donor DNA content, yet, retained the extracellular composition better and may therefore have improved recellularization and other downstream bioengineering applications. These two novel types of mouse ovarian scaffolds serve as promising scaffold-candidates for future ovarian bioengineering experiments.
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3.
  • Andersson, Sofia E M, 1979, et al. (författare)
  • Activation of Fms-like tyrosine kinase 3 signaling enhances survivin expression in a mouse model of rheumatoid arthritis.
  • 2012
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Survivin is known as an inhibitor of apoptosis and a positive regulator of cell division. We have recently identified survivin as a predictor of joint destruction in patients with rheumatoid arthritis (RA). Flt3 ligand (Flt3L) is expressed in the inflamed joints and has adjuvant properties in arthritis. Studies on 90 RA patients (median age 60.5 years [range, 24-87], disease duration 10.5 years [range, 0-35]) show a strong positive association between the levels of survivin and Flt3L in blood. Here, we present experimental evidence connecting survivin and Flt3L signaling. Treatment of BALB/c mice with Flt3L led to an increase of survivin in the bone marrow and in splenic dendritic cells. Flt3L changed the profile of survivin splice variants, increasing transcription of the short survivin40 in the bone marrow. Treatment with an Flt3 inhibitor reduced total survivin expression in bone marrow and in the dendritic cell population in spleen. Inhibition of survivin transcription in mice, by shRNA lentiviral constructs, reduced the gene expression of Flt3L. We conclude that expression of survivin is a downstream event of Flt3 signaling, which serves as an essential mechanism supporting survival of leukocytes during their differentiation, and maturation of dendritic cells, in RA.
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5.
  • Bengtsson, Karin, 1980, et al. (författare)
  • Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study
  • 2017
  • Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
  • 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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7.
  • Bengtsson, Karin, 1980, et al. (författare)
  • Comparisons between comorbid conditions and health care consumption in rheumatoid arthritis patients with or without biological disease-modifying antirheumatic drugs : a register-based study
  • 2016
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Symptoms and prognosis of patients with rheumatoid arthritis (RA) have improved with more intensive therapy, including the biological disease-modifying anti-rheumatic drugs (bDMARDs). Real life data concerning how comorbidities are distributed among patients treated or not treated with bDMARDs are scarce. Our objective was to investigate differences in comorbidity and health care consumption in RA patients, with and without bDMARDs.METHODS: This cross-sectional study was performed in the Southwestern part of Sweden. Patients, aged ≥ 18 years and diagnosed with RA in secondary health care during 2009-2010, were identified in the regional health care database. Aggregated data of comorbidity and health care consumption were retrieved between 2006 and 2010. RA patients treated with bDMARDs on 31st December 2010 were identified in the Swedish Rheumatology Quality Register (SRQ), which includes the biologics register Anti-Rheumatic Therapy in Sweden (ARTIS). Descriptive, comparative, univariate and multiple logistic regression analyses were used to identify factors associated with bDMARDs.RESULTS: Seven thousand seven hundred and twelve (7712) RA patients were identified (age 64.8 ± 14.9 years, women 74.3%), of whom 1137 (14.7%) were treated with bDMARDs. Overall, the most common comorbidities were infections (69.2%), hypertension (41.1%), chronic respiratory disease (15.3%), ischemic heart disease (14.0%) and malignancy (13.7%). Patients without bDMARDs were older and had more comorbidity. In the multiple logistic regression analysis, older age, cerebrovascular and chronic respiratory disease, heart failure, depression and malignancy were all associated with no present bDMARDs. Infections were associated with bDMARDs. Patients treated with bDMARDs consumed more secondary outpatient care but less visits in primary health care compared to patients without bDMARDs.CONCLUSIONS: Patients treated with bDMARDs versus no bDMARDs were younger and had significantly lower period prevalence for most common comorbidities, with the exception of infections. Differences in comorbidities between RA patients with or without bDMARDs should be taken into consideration when evaluating effectiveness and safety of bDMARDs in ordinary care.
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9.
  • Bengtsson, Karin, 1980, et al. (författare)
  • Incidence of extra-articular manifestations in ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis : Results from a national register-based cohort study
  • 2021
  • Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:6, s. 2725-2734
  • 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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11.
  • Bengtsson, Karin, 1980, et al. (författare)
  • Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population : A register-based study from Sweden
  • 2018
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 541-548
  • 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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12.
  • Bergsten, Ulrika, et al. (författare)
  • Gender differences in illness perceptions and disease management in patients with gout, results from a questionnaire study in Western Sweden.
  • 2023
  • Ingår i: BMC musculoskeletal disorders. - 1471-2474. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims were to examine gender differences in patients with gout with regard to a) self-reported gout severity, b) illness perceptions (IP), c) impact on daily activities and Quality of Life (QoL), d) advice from healthcare professionals, e) having changed dietary- or alcohol habits.Adult patients with gout identified in primary and secondary care in Sweden between 2015 and 2017 (n=1589) were sent a questionnaire about demographics, gout disease severity, IP (using the Brief Illness Perception Questionnaire, (B-IPQ)) and disease management. T-tests, Chi square tests, ANalysis Of VAriance (ANOVA) and linear regression models were used for gender comparisons.Eight hundred sixty-eight patients responded to the questionnaire. Women, n=177 (20%), experienced more severe gout symptoms (p=0.011), albeit similar frequencies of flares compared to men. Women experienced modest but significantly worse IP with regard to consequences, identity, concerns and emotional response (p<0.05) as well as daily activities such as sleeping (p<0.001) and walking (p=0.042) and QoL (p=0.004). Despite this and a higher frequency of obesity in women (38 vs 21%, P<0.001) and alcohol consumption in men (p<0.001), obese women had received significantly less advice regarding weight reduction (47 vs 65%, p=0.041) compared to obese men. On the other hand, women reported having acted on dietary advice to a larger degree.Despite only modestly worse gout severity and perception, women appear to have been given less information regarding self-management than men. These gender differences should be given attention and addressed in clinical care.
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13.
  • Bjersing, Jan, 1966, et al. (författare)
  • Changes in pain and insulin-like growth factor 1 in fibromyalgia during exercise: the involvement of cerebrospinal inflammatory factors and neuropeptides
  • 2012
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354. ; 14:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Introduction: Fibromyalgia (FM) is characterized by chronic pain. Impaired growth hormone responses and reduced serum insulin-like growth factor 1 (IGF-1) are common in FM. The aim was to examine changes in serum IGF-1, cerebrospinal fluid (CSF), neuropeptides, and cytokines during aerobic exercise in FM patients. Methods: In total, 49 patients (median age, 52 years) with FM were included in the study. They were randomized to either the moderate- to high-intensity Nordic Walking (NW) program (n = 26) or the supervised low-intensity walking (LIW) program (n = 23). Patients participated in blood tests before and after 15 weeks of aerobic exercise. Changes in serum levels of free IGF-1, pain rating on a 0- to 100-mm scale, pain threshold, and 6-minute walk test (6MWT) were examined. CSF, neuropeptides, matrix metalloproteinase 3 (MMP-3), and inflammatory cytokines were determined. Nonparametric tests were used for group comparisons and correlation analyses. Results: Serum free IGF-1 levels did not change during 15 weeks of exercise between the two groups, although the 6MWT significantly improved in the NW group (p = 0.033) when compared with LIW. Pain did not significantly change in any of the groups, but tended to decrease (p = 0.052) over time in the total group. A tendency toward a correlation was noted between baseline IGF-1 and a decrease of pain in response to exercise (r = 0.278; p = 0.059). When adjusted for age, this tendency disappeared. The change in serum free IGF-1 correlated positively with an alteration in CSF substance P (SP) levels (rs = 0.495; p = 0.072), neuropeptide Y (NPY) (rs = 0.802; p = 0.001), and pain threshold (rs = 0.276; p = 0.058). Differing CSF SP levels correlated positively to a change in pain threshold (rs = 0.600; p = 0.023), whereas the shift in CSF MMP-3 inversely correlated with an altered pain threshold (rs = -0.569; p = 0.034). Conclusions: The baseline level of serum free IGF-1 did not change during high or low intensity of aerobic exercise. Changes in IGF-1 correlated positively with a variation in CSF SP, NPY, and pain threshold. These data indicate a beneficial role of IGF-1 during exercise in FM. Trial registration: ClinicalTrials.govNCT00643006.
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14.
  • Bokarewa, Maria, 1963, et al. (författare)
  • Smoking is associated with reduced leptin and neuropeptide Y levels and higher pain experience in patients with fibromyalgia.
  • 2014
  • Ingår i: Mediators of inflammation. - : Hindawi Limited. - 1466-1861 .- 0962-9351. ; 2014
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking deregulates neuroendocrine responses to pain supporting production of neuropeptide Y (NpY) by direct stimulation of nicotinic receptors or by inhibiting adipokine leptin. Present study addressed the effect of cigarette smoking on adipokines and pain parameters, in 62 women with fibromyalgia (FM) pain syndrome with unknown etiology. Pain was characterized by a visual analogue scale, tender point (TP) counts, pressure pain threshold, and neuroendocrine markers NpY and substance P (sP). Levels of IGF-1, leptin, resistin, visfatin, and adiponectin were measured in blood and cerebrospinal fluid. Current smokers (n = 18) had lower levels of leptin compared to ex-smokers (n = 25, P = 0.002), while the expected NpY increase was absent in FM patients. In smokers, this was transcribed in higher VAS-pain (P = 0.04) and TP count (P = 0.03), lower pain threshold (P = 0.01), since NpY levels were directly related to the pain threshold (rho = 0.414) and inversely related to TP counts (rho = -0.375). This study shows that patients with FM have no increase of NpY levels in response to smoking despite the low levels of leptin. Deregulation of the balance between leptin and neuropeptide Y may be one of the essential mechanisms of chronic pain in FM.
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15.
  • Bursill, D., et al. (författare)
  • Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout
  • 2019
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 78:11, s. 1592-1600
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. Methods A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. Results The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). Conclusion Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.
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16.
  • Bursill, D., et al. (författare)
  • Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout
  • 2019
  • Ingår i: Arthritis Care & Research. - : Wiley. - 2151-464X. ; 71:3, s. 427-434
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. Methods Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. Results There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (>= 80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. Conclusion Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.
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17.
  • Dehlin, Mats, 1968, et al. (författare)
  • Association between perinatal factors and future risk for gout-a nested case-control study
  • 2022
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Increased level of urate is the strongest risk factor for gout development but since only a minority of hyperuricemics are affected by gout, other pathogenic factors must be considered. Low birth weight is associated with future morbidities causing hyperuricemia, such as diabetes and renal disease. The purpose of this study was to investigate if, and to what extent, maternal and perinatal factors, including birth weight, are associated with future risk of being diagnosed with gout. Methods A population-based retrospective nested case-control registry study based on regional and national health care registers in Sweden. All incident cases of gout born in 1973 and onward who had received >= 1 diagnosis of gout from 2000 through 2019 in the region of western Sweden were included. Up to 5 non-gout controls were matched to each case by age, sex, and county at the year of first gout diagnosis. A range of maternal, gestational, and perinatal factors were analyzed for their potential association to future gout development. This included the health of the mother, gestational length, birth weight, number of siblings, and congenital malformations. Results Maternal diabetes, any congenital malformation, and being small for gestational age were factors that significantly increased the risk for future gout development, odds ratio (95% CI) 3.1 (1.3 to 7.4) (p=0.01), 1.33 (1.04 to 1.7) (p=0.02), and 1.75 (1.3 to 2.3) (p<.0001), respectively. Conclusions In this study, maternal diabetes and being small for gestational age increased the risk for future gout development in young adults. As of today, these conditions are becoming more prevalent and may contribute to the ongoing gout epidemic. These results require both confirmation and further delineation of underlying mechanisms.
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18.
  • Dehlin, Mats, 1968, et al. (författare)
  • Cerebrospinal Flt3 ligand correlates to tau protein levels in primary Sjögren's syndrome.
  • 2013
  • Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 42:5, s. 394-399
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting the exocrine glands and internal organs including the central nervous system (CNS). The fms-related tyrosine kinase 3 ligand (Flt3L) is a maturation factor essential for brain homeostasis. Blood levels of Flt3L are increased in inflammatory diseases including the inflamed salivary glands in pSS. The present study evaluated the role of Flt3L in the CNS of patients with pSS and in two non-autoimmune conditions, fibromyalgia (FM) and Alzheimer's disease (AD). Method: Levels of Flt3L were measured in cerebrospinal fluid (CSF) and serum of patients with pSS (n = 15), FM (n = 29), and AD (n = 39) and related to CNS symptoms and to markers of inflammation and degeneration. Results: Levels of CSF Flt3L in pSS and AD were significantly lower than in FM (p = 0.005 and p = 0.0003, respectively). Flt3L in pSS correlated to tau proteins [total tau (T-tau), r = 0.679; phosphorylated tau (P-tau), r = 0.646] and to a marker for microglia activation, monocyte chemoattractant protein 1 (MCP-1). Similar correlations were present in FM and AD patients. One-third of pSS patients had low levels of CSF Flt3L. This group had decreased levels of amyloid precursor protein metabolites (Aβ40 and Aβ42) in CSF, which was not seen in FM patients. Conclusions: This study shows a strong correlation between CSF Flt3L and tau proteins in pSS patients suggesting ongoing degradation/remodelling in the CNS. In pSS patients, low levels of Flt3L were linked to changes in amyloid turnover and may represent processes similar to those in AD.
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19.
  • Dehlin, Mats, 1968, et al. (författare)
  • Consequences of Gout and Hyperuricemia : Gikt och hyperurikemi starkt associerade med folksjukdomar
  • 2020
  • Ingår i: Läkartidningen. - 1652-7518. ; 117
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyperuricemia (HU) and gout are strongly associated with CVD, associations that are most likely due to shared etiologies rather than causality. HU is for example causally related to the metabolic syndrome and in particular to obesity. Gout and HU can both be caused by and lead to decreased kidney function. On the other hand, there are observational data suggesting that HU may protect against neurodegenerative diseases such as Alzheimer and Parkinson's disease. Ongoing RCTs with urate and urate lowering therapy (ULT) will help to resolve some of these controversies. Nevertheless, gout is a "curable disease" by ULT, a treatment which in adequate doses may also have positive effect on several associated co-morbidities.
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20.
  • Dehlin, Mats, 1968 (författare)
  • Differentiation factor Fms-like tyrosine kinase 3 ligand is a modulator of cell responses in autoimmune diseases
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Fms-like tyrosine kinase 3 (Flt3) is a receptor on common stem cell progenitors and has a crucial role in hematopoesis, regulating cell proliferation and differentiation in man and mice. The growth factor Flt3 is activated by its soluble ligand, Flt3-L, leading to differentiation of multipotent stem cells and lymphoid progenitors. Flt3-L functions as a differentiation factor for dendritic cells (DC) in the periphery. These properties of the Flt3/Flt3-L system lead us to further investigate the role of the growth factor Flt3-L in rheumatic disease. In paper I, Flt3-L was found to be strongly expressed at the site of inflammation in human RA, the joint. Levels of Flt3-L were significantly higher in the synovial fluid compared to serum in RA patients and levels of Flt3-L in RA synovial fluid were significantly higher compared to synovial fluid from non-inflammatory joint diseases. Furthermore, intra-articular administration of a B-cell line overexpressing Flt3-L resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and caused arthritis in a minority of cases. Thus, Flt3-L is expressed at the site of inflammation in human RA and facilitates tissue destructive properites in the joint cavity. In paper II, mice with antigen-induced arthritis, mBSA-arthritis, were treated with the Flt3-inhibitor sunitinib. Treatment was started together with mBSA immunization or together with the induction of arthritis. Abrogation of Flt3 signalling reduced the intensity of synovitis and the frequency of bone destruction. Inhibition of Flt3 reduced also the number of differentiated (mature) dendritic cells concomitant with reduction of antibody production and bone metabolism. In addition to this, we investigated the ability of mouse bone marrow cells to migrate towards Flt3-L in a migration assay. Flt3-L was found to be a potent chemoattractant facilitating mobilization of Flt3+ cells from the bone marrow. Thus, the processes of antigen presentation, influx of leukocytes into synovial tissue and bone remodelling are mediated by Flt3 signalling in antigen-induced arthritis. In paper III, Flt3-L in CSF correlated to levels of Tau and pTau of patients with Sjögrens syndrome, fibromyalgia and Alzheimers disease, implying involvement of Flt3L in brain homeostasis. Furthermore, CSF Flt3-L in pSS correlated to a marker for microglia activation, MCP-1. Levels of Flt3-L in CSF were significantly decreased in pSS, and AD, compared to FM. Low levels of Flt3-L were associated to low levels of amyloid degradation peptides in pSS and AD patients. Thus, in CNS of patients with pSS Flt3-L is strongly correlated to neuroaxonal plasticity and microglia activation and reduced levels of CSF-Flt3-L in pSS are linked to changes in tau and amyloid turnover resembling processes ongoing in AD patients. Taken together, these results indicate that Flt3-L is involved in the inflammatory and tissue remodelling processes in joints and neuroaxonal structures of the brain. Flt3/Flt3-L signalling is an essential regulator of antigen-induced processes in autoimmune diseases.
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21.
  • Dehlin, Mats, et al. (författare)
  • Dr. Dehlin, et al reply.
  • 2019
  • Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 46:11
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • It was with great interest that we read the letter from Watson and colleagues1 describing their investigation of how a primary care diagnosis of gout compares to a primary care diagnostic rule for gout and the 1977 American Rheumatism Association (ARA) classification criteria of acute arthritis of primary gout. They present positive predictive values (PPV) of 74% for the diagnostic rule and 80% for the ARA criteria.
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22.
  • Dehlin, Mats, 1968, et al. (författare)
  • Factors associated with initiation and persistence of urate-lowering therapy
  • 2017
  • Ingår i: Arthritis Resarch and Therapy. - 1478-6354. ; 19
  • 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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23.
  • Dehlin, Mats, 1968, et al. (författare)
  • Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors
  • 2020
  • Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4790 .- 1759-4804. ; 16, s. 380-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Gout is a chronic crystal deposition disorder in which sustained hyperuricaemia leads to formation and deposition of monosodium urate crystals in the joints. The prevalence and incidence of gout are increasing globally, which may be related to changes in the prevalence of gout risk factors (such as obesity) and comorbidities. Gout is the most common inflammatory arthritis and occurs when hyperuricaemia, sustained elevation of serum urate levels resulting in supersaturation of body tissues with urate, leads to the formation and deposition of monosodium urate crystals in and around the joints. Recent reports of the prevalence and incidence of gout vary widely according to the population studied and methods employed but range from a prevalence of <1% to 6.8% and an incidence of 0.58-2.89 per 1,000 person-years. Gout is more prevalent in men than in women, with increasing age, and in some ethnic groups. Despite rising prevalence and incidence, suboptimal management of gout continues in many countries. Typically, only a third to half of patients with gout receive urate-lowering therapy, which is a definitive, curative treatment, and fewer than a half of patients adhere to treatment. Many gout risk factors exist, including obesity, dietary factors and comorbid conditions. As well as a firmly established increased risk of cardiovascular disease and chronic kidney disease in those with gout, novel associations of gout with other comorbidities have been reported, including erectile dysfunction, atrial fibrillation, obstructive sleep apnoea, osteoporosis and venous thromboembolism. Discrete patterns of comorbidity clustering in individuals with gout have been described. Increasing prevalence and incidence of obesity and comorbidities are likely to contribute substantially to the rising burden of gout.
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24.
  • Dehlin, Mats, 1968, et al. (författare)
  • Impact of psoriasis disease activity and other risk factors on serum urate levels in patients with psoriasis and psoriatic arthritis-a post-hoc analysis of pooled data from three phase 3 trials with secukinumab
  • 2021
  • Ingår i: Rheumatology Advances in Practice. - : Oxford University Press (OUP). - 2514-1775. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. Our aims were to determine if the Psoriasis Area Severity Index (PASI) score and serum urate (SU) levels were associated at baseline and whether the change in PASI score during 12 weeks of treatment resulted in a significant change in SU, adjusted for relevant confounders. Methods. Data from patients with psoriasis/PsA (n = 1042/204) in three phase 3 randomized control trials treated with secukinumab (dose 300 mg, n = 628) or placebo (n = 414) were pooled. At baseline, values for SU, PASI and the following covariates were assessed: age, sex, BMI, estimated glomerular filtration rate, and medication with diuretics. To assess the changes in PASI (DPASI) and SU (Durate), the differences (week 12 minus baseline) in patients receiving the active drug were used. Multivariable linear regression, adjusting for covariates, was used to assess the association between PASI and SU at baseline with all patients pooled and to assess the association between Durate and DPASI over 12 weeks of treatment with secukinumab. Results. The degree of skin involvement of psoriasis showed a statistically significant, albeit modest, association with SU (R-2 = 0.014, P < 0.0001 univariately), whereas known risk factors for hyperuricaemia had a much larger impact cross-sectionally at baseline (R-2 = 0.33, P < 0.0001). Furthermore, a substantial improvement in PASI score resulted in only a modest decrease of SU over 12 weeks of treatment with secukinumab (R-2 = 0.014, P < 0.0001 univariately). Conclusions. There is a statistically significant, albeit modest, association with both extent and change in PASI score and SU in patients with psoriasis, compatible with a potential pathophysiological relationship between urate and psoriasis.
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25.
  • Dehlin, Mats, 1968, et al. (författare)
  • Incidence and prevalence of gout in Western Sweden
  • 2016
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of the present study was to describe prevalence and trends in the incidence of gout and patterns of urate-lowering treatment (ULT) in the Western Swedish Health Care Region (WSHCR) from 2002 to 2012. Methods: We used regional and national healthcare registers to estimate the prevalence and incidence of gout in 2012, and trends in incidence for each calendar year from 2005 to 2012. We also investigated the pattern of ULT for gout using the Swedish Prescribed Drug Register. Results: In 2012, in the population aged 20 years and above, the prevalence of gout was 1.8 % (95 % confidence interval (CI) 1.77 to 1.82) and the incidence was 190 cases (95 % CI 180 to 200) per 100,000 person-years. Applying more strict definitions for a gout case rendered a prevalence of 1.36 % (95 % CI 1.34 to 1.38) and 0.5 (95 % CI 0.49 to 0.51) per 100,000 person-years, respectively. The incidence of gout increased steadily and significantly from 2005 to 2012, with an almost 50 % increase in the total population. There was no significant difference in the prevalence of gout in rural compared to urban areas. ULT was dispensed to only 42 % of patients with gout in 2012 who had ever been diagnosed with gout during the preceding 10-year period. Conclusions: Gout is the most common arthritic disease in WSHCR, Sweden, and has increased substantially over the last decade, with only a minority of prevalent cases in 2012 receiving ULT.
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26.
  • Dehlin, Mats, 1968, et al. (författare)
  • Incident Gout: Risk of Death and Cause-Specific Mortality in Western Sweden: A Prospective, Controlled Inception Cohort Study
  • 2022
  • Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundExcess mortality in gout has been attributed to cardiovascular diseases (CVD). Considering the decline in CVD mortality in the general population, we wanted to evaluate overall mortality in gout and cause-specific contributions to mortality beyond CVD and temporal trends. MethodsAll incident cases of gout between 2006 and 2015 in western Sweden and 5 population controls per case matched for age, sex, and county were identified. Comorbidities were identified for 5 years preceding the index date. Follow-up ended at death, migration, or end of study on December 2017. Effect of gout on death risk was calculated using COX regression on the whole population and stratified by sex, adjusted for demographics, and comorbidities. Death incidence rates were compared between the two time periods, 2006-2010 and 2011-2015. ResultsWe identified 22,055 cases of incident gout and 98,946 controls, median age (Q1, Q3) 69-68 (57, 79/56, 78) years and 67.6-66.5% males. Except for dementia, all comorbidities were significantly more common at baseline among gout cases. Overall, the risk for death in incident gout was neither increased overall nor in men, but women had a 10% elevated risk. In adjusted models for cause-specific mortality, death from CVD, renal disease, and digestive system diseases were significantly increased in the total gout population while death from dementia, cancer, and lung diseases were significantly decreased. There were no significant differences in overall incident death rate ratios between cases and controls in the two time periods examined. ConclusionsAn increased risk for CVD, renal disease, and diseases of the digestive system in patients with gout highlights the importance of addressing CVD risk factors in gout management. Gout was associated with reduced mortality from dementia, which may have implications on urate lowering therapy and possible effects on dementia risk.
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27.
  • Dehlin, Mats, 1968, et al. (författare)
  • Inhibition of fms-like tyrosine kinase 3 alleviates experimental arthritis by reducing formation of dendritic cells and antigen presentation.
  • 2011
  • Ingår i: Journal of leukocyte biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 90:4, s. 811-7
  • Tidskriftsartikel (refereegranskat)abstract
    • TKs are intracellular signaling molecules essential for cell homeostasis. Inhibition of TKs is used in treatment of malignancies and diabetes mellitus. The present study evaluated the role of Flt3 in antigen-induced arthritis. Mice were immunized with mBSA, and arthritis was induced by an i.a. injection of mBSA. Treatment with the Flt3 inhibitor sunitinib was started together with mBSA immunization or together with the induction of arthritis. The mBSA-injected joints were evaluated morphologically for signs of synovitis and bone/cartilage destruction. Markers of bone metabolism and antibody responses were measured by ELISA. Maturation of DCs in the bone marrow and spleen was evaluated by flow cytometry. Sunitinib treatment reduced the intensity of synovitis and the incidence of bone destruction. The reduction in bone destruction was seen when the treatment was started at the time of immunization or at the time of arthritis induction. The antiarthritic effect was achieved by inhibition of DCs, reduction of antibody production, and bone metabolism. Inhibition of Flt3 is a potent antiarthritic mechanism reducing antigen presentation, synovial inflammation, and bone resorption. Down-regulation of TKs may be a useful tool in the treatment of human RA.
  •  
28.
  • Dehlin, Mats, 1968, et al. (författare)
  • Intra-articular fms-like tyrosine kinase 3 ligand expression is a driving force in induction and progression of arthritis.
  • 2008
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: One of the hallmarks of rheumatoid arthritis (RA) is hyperplasia and inflammation of the synovial tissue being characterized by in situ occurrence of highly differentiated leukocytes. Fms-like tyrosine kinase 3 (Flt3) has a crucial role in hematopoiesis, regulation of cell proliferation, differentiation and apoptosis. Typically, Flt3 is expressed on early myeloid and lymphoid progenitors and is activated by its soluble ligand (Flt3-L). The highly differentiated cellular pattern in the synovium of the RA patients made us hypothesize that Flt3-L, with its ability to induce proliferation and differentiation, could be of importance in induction and/or progression of arthritis. METHODOLOGY/PRINCIPAL FINDINGS: To investigate occurrence of Flt3-L in RA we have measured its levels in matched serum and synovial fluid samples from 130 patients and 107 controls. To analyse the pro-inflammatory role of Flt3-L, we continuously overexpressed this protein locally in healthy mouse joints using homologous B-cell line transfected with Flt3-L gene. Additionally, recombinant Flt3-L was instillated intra-articularly in combination with peptidoglycans, a Toll Like Receptor 2-ligand with stong arthritogenic properties. Our results show significantly higher levels of Flt3-L in the synovial fluid as compared to serum levels in RA subjects (p = 0.0001). In addition, RA synovial fluid levels of Flt-3-L were significantly higher than these obtained from synovial fluids originating from non-inflammatory joint diseases (p = 0.022). Intra-articular administration of B-cell line transfected with Flt3-L gene resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and only in a minority of cases caused synovial proliferation! Flt3-ligand potentiated peptidoglycan induced arthritis as compared to mice injected with peptidoglycan alone (p<0.05). CONCLUSIONS/SIGNIFICANCE: Our findings indicate that Flt3-L is strongly expressed at the site of inflammation in human RA. It exerts both pro-inflammatory and tissue destructive properties once in the joint cavity. Owing to these properties, treatment attempts to neutralize this molecule should be considered in RA.
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29.
  • Dehlin, Mats, 1968, et al. (författare)
  • Lifestyle factors and comorbidities in gout patients compared to the general population in Western Sweden: results from a questionnaire study.
  • 2022
  • Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 51:5, s. 390-393
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to identify lifestyle factors associated with gout in patients with prevalent gout compared to the general population.Adult patients with gout identified in primary and secondary care in Western Sweden between 2015 and 2017 were sent a questionnaire asking about demographics, lifestyle, and comorbidities. Five age- and gender-matched controls were identified in a random sample of 52348 individuals aged 16-84years who participated in the National Public Health survey in Sweden, year 2015. Logistic regression models were used to compare cases and controls with regard to lifestyle factors and comorbidities.Of the 1589 invited gout patients, 868 (55%) responded. After matching for age and gender, 728 were included in the analysis (82.4% male; mean±sd age 69.3±10.5 years for men and 71.8±9.9 years for women with gout). Male and female gout patients were significantly more likely to be overweight or obese (men 79% vs 66%; women 78.5% vs 65.3%), to have binge-drinking behaviour (men 29.9% vs 11%; women 13.7% vs 2.9%), and to be ex-smokers, compared to controls. Moreover, male gout patients reported lower levels of physical activity, while diabetes and hypertension were more common in both genders with gout than in controls.In this questionnaire study, gout patients reported significantly more obesity and binge-drinking behaviour and less physical activity than controls. This suggests that there are great unmet needs for the management of lifestyle factors, particularly regarding overweight/obesity and binge drinking, in patients with gout.
  •  
30.
  •  
31.
  • Dehlin, Mats, 1968, et al. (författare)
  • Sex and country differences in gout: cross-country comparison between Sweden and the UK.
  • 2023
  • Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 52:6, s. 673-682
  • Tidskriftsartikel (refereegranskat)abstract
    • Compare characteristics, sex differences, and management of gout in Sweden and the UK.The results from two separate primary care gout surveys from Sweden and the UK were compared. Participants aged ≥18 years with gout were sent a questionnaire asking about lifestyle, gout characteristics, uratelowering therapy (ULT), comorbidities, disability, and disease impact. For sex comparison, participants were pooled across countries.In total, 784 (80% male) participants from Sweden and 500 (87% male) from the UK were included. Swedish patients were significantly older at gout onset, mean (SD) age 72 (12) versus 63 (13) years, (p<0.0001), with more comorbidities, and more frequent use of ULT (48% vs 35%, p=0.0005, age-adjusted). Use of alcohol and diuretics was significantly more common among UK patients, who also reported a higher number of gout flares, mean (SD) 2.2 (1.7) versus 1.6 (3.6), (p=0.003) age-adjusted. Females with gout were older at gout onset, mean (SD) age 67 (13) versus 56 (15), (p<0.0001), more often obese, and reported higher use of diuretics. Furthermore, females reported greater impact of gout, more pain and physical limitations, whereas no sex differences were seen in ULT or flares.In the UK, gout was more frequently associated with modifiable risk factors. People with gout in Sweden were more commonly taking ULT and had lower frequency of gout flares and impact of gout. Females with gout more commonly took diuretics, had higher body mass index, and reported greater physical disability, which should be considered when managing gout in women.
  •  
32.
  • Dehlin, Mats, 1968, et al. (författare)
  • The Validity of Gout Diagnosis in Primary Care: Results from a Patient Survey.
  • 2019
  • Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 46:11, s. 1531-1534
  • Tidskriftsartikel (refereegranskat)abstract
    • Validate primary care diagnosis of gout by the Mexico and the Netherlands classification criteria.Questionnaires on gout characteristics were sent to all individuals aged ≥ 18 with ≥ 1 International Classification of Diseases, 10th ed. diagnosis of gout at 12 primary care centers.Positive predictive values for gout diagnosis ranged from 71% for the Netherlands criteria to 80% for the Mexico criteria. Maximum inflammation within 24 h was the most common reported symptom (86%).The vast majority of gout cases in primary care fulfill classification criteria and are valid for research purposes.
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33.
  • Dehlin, Mats, 1968, et al. (författare)
  • Trends in Gout Hospitalization in Sweden.
  • 2018
  • Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 45:1, s. 145-146
  • Tidskriftsartikel (refereegranskat)
  •  
34.
  • Dehlin, Mats, 1968, et al. (författare)
  • Validity of gout diagnosis in Swedish primary and secondary care - a validation study
  • 2015
  • Ingår i: Bmc Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 16:149
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The diagnostic golden standard for gout is to detect monosodium urate (MSU) crystals in synovial fluid. While some gout classification criteria include this variable, most gout diagnoses are based on clinical features. This discrepancy between clinical practice and classification criteria can hinder gout epidemiological studies. Here, the objective was to validate gout diagnoses (International Classification of Diseases (ICD)-10 gout codes) in primary and secondary care relative to five classification criteria (Rome, New York, ARA, Mexico, and Netherlands). The frequency with which MSU crystal identification was used to establish gout diagnosis was also determined. Methods: In total, 394 patients with >= 1 ICD-10 gout diagnosis between 2009 and 2013 were identified from the medical records of two primary care centers (n = 262) and one secondary care center (n = 132) in Gothenburg, Sweden. Medical records were assessed for all classification criteria. Results: Primary care patients met criteria cutoffs more frequently when >= 2 gout diagnoses were made. Even then, few primary care patients met the Rome and New York cutoffs (19 % and 8 %, respectively). The ARA, Mexico, and Netherlands cutoffs were met more frequently by primary care patients with >= 2 gout diagnoses (54 %, 81 %, and 80 %, respectively). Mexico and Netherlands cutoffs were met more frequently by the rheumatology department patients (80 % and 71 %, respectively), even when patients with only 1 gout diagnosis were included. Analysis of MSU crystals served to establish gout diagnoses in only 27 % of rheumatology department and 2 % of primary care cases. Conclusions: If a patient was deemed to have gout at >= 2 primary care center or >= 1 rheumatology-center visits according to an ICD-10 gout code, the positive predictive value of this variable in relation with the Mexico and Netherlands classification criteria was >= 80 % for both primary care and rheumatology care settings in Sweden. MSU crystal identification was rarely used to establish gout diagnosis.
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35.
  • Drivelegka, Panagiota, et al. (författare)
  • Association between serum level of urate and subclinical atherosclerosis: results from the SCAPIS Pilot
  • 2020
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Hyperuricemia is closely associated with cardiovascular disease (CVD). However, it has not been definitively established whether this association is independent of traditional cardiovascular risk factors (CVRFs) and whether it is gender-dependent. The aim of this study was to investigate in a population-based cohort (age range, 50-64 years) stratified by sex the association between the serum urate (SU) concentration and subclinical atherosclerosis, as reflected in the coronary artery calcification (CAC) score, common carotid intima-media thickness (CIMT), and carotid plaque score. Methods The study involved participants in the Swedish CArdioPulmonary bioImage Study (SCAPIS) Pilot cohort (N = 1040; 48.8% males). This pilot cohort is part of the large population-based SCAPIS with 30,000 participants in the age range of 50-64 years, aimed at improving risk prediction for CVD. Subjects with a self-reported previous history of CVD (N = 68) or gout (N = 3) were excluded. The CAC score was assessed with the Agatston method using computed tomography. CIMT and carotid plaques were quantified by ultrasound. The associations between the SU quartiles and different levels of CAC, CIMT, and carotid plaques were assessed by multivariable logistic regression. Results Age, BMI, education level, smoking, physical activity, hs-CRP, hypertension, and dyslipidemia showed no differences between males and females, while CAC (score > 0) and diabetes were both twice as common in men than in women (58% vs 26% and 8% vs 4%, respectively). Higher SU quartiles were in both sexes associated with BMI, hs-CRP, and the prevalence of hypertension, and in women, they were also associated with the prevalence of dyslipidemia. The three upper quartiles of SU (>308 mu mol/L) were linked to higher CAC scores in men, when adjusting for CVRFs, but not in women. CIMT and carotid plaques showed no correlation to SU in either sex. Conclusions Higher levels of SU are associated with the presence of CAC in men but not in women, whereas SU is not associated with CIMT or carotid plaques in either men or women. This implies that the biological effects of SU differ in men and women or that SU has varying effects on different vascular beds or during the different stages of the atherosclerotic process.
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36.
  • Drivelegka, Panagiota, et al. (författare)
  • Comorbidity in gout at the time of first diagnosis: sex differences that may have implications for dosing of urate lowering therapy
  • 2018
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:108
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study is to examine the occurrence of comorbidities at the time of first diagnosis of gout compared with matched population controls, overall and by sex, as well as to examine the crude and age-standardized prevalence of these comorbidities in men and women with gout at first diagnosis. Methods: A population-based study used data from Swedish national and regional registers, including 14,113 gout patients aged >= 20 years, with a first recorded diagnosis of gout between 1 January 2006 and 31 December 2012, and 65,782 population controls, matched by age, sex and county. Prevalence ratios (95% confidence intervals) comparing gout cases and controls were calculated, overall and by sex. Crude and age-standardized prevalence (95% confidence interval) of all comorbidities in gout patients were calculated, to show differences between sexes, taking also the higher age at diagnosis in women into account. Results: All examined comorbidities were 1.2-2.5-fold more common in gout patients at diagnosis than in population controls in both sexes. Women with gout were on average 6 years older than men at first gout diagnosis and most comorbidities, including obesity and diuretic use, were or tended to be more frequent in women than in men. When standardizing for age, women had a higher prevalence of thromboembolism (6.6% vs 5.2%) and chronic obstructive pulmonary disease (3.1% vs 2.4%). Men, on the other hand, had a higher prevalence of coronary heart disease (9.4% vs 6.4%), atrial fibrillation (9.0% vs 6.0%), congestive heart failure (7.7% vs 6.6%) and stroke (4.1% vs 3.3%). Conclusions: The occurrence of most comorbidities was significantly increased at first diagnosis of gout in both sexes. Women were older at diagnosis and had higher occurrence of most comorbidities, including obesity and diuretic use, factors that increase serum urate, and this needs to be taken into account when starting and optimizing urate lowering therapy. These sex differences were attenuated when standardizing for age and the occurrence of cardiovascular diseases was actually higher in men. BOTT RD, 1988, JOURNAL OF CLINICAL EPIDEMIOLOGY, V41, P237
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37.
  • Drivelegka, Panagiota, et al. (författare)
  • Incident gout and risk of first-time acute coronary syndrome: a prospective, population-based, cohort study in Sweden
  • 2023
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 75:6, s. 1292-1299
  • 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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38.
  • Esposito, Daniela, et al. (författare)
  • Pituitary dysfunction in granulomatosis with polyangiitis
  • 2017
  • Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 20:5, s. 594-601
  • Tidskriftsartikel (refereegranskat)abstract
    • Granulomatosis with polyangiitis (GPA) is a multisystem disease, characterized by necrotizing small-vessel vasculitis, which mainly affects the respiratory tract and the kidneys. Pituitary involvement in GPA is rare, present in about 1% of all cases of GPA. To date, only case reports or small case series have been published. Herein we report clinical features, imaging findings, treatment and outcomes in three patients with GPA-related pituitary dysfunction (PD). A retrospective analysis of three cases of GPA-related PD was conducted, followed by systematic review of the English medical literature using PubMed. The three cases include three women aged between 32 and 37 years. PD was the presenting feature in one and two developed PD in the course of the disease. All patients had a pituitary lesion on MRI. Conventional treatment with high doses of glucocorticoids and cyclophosphamide led to resolution or improvement of the MRI abnormalities, whereas it was not effective in restoring PD. A systematic review identified 51 additional patients, showing that GPA can lead to partial or global PD, either at onset or, during the course of the disease. Secondary hypogonadism is the predominant manifestation, followed by diabetes insipidus (DI). Sellar mass with central cystic lesion is the most frequent radiological finding. GPA should be carefully considered in patients with a sellar mass and unusual clinical presentation with DI and systemic disease. Although conventional induction-remission treatment improves systemic symptoms and radiological pituitary abnormalities, hormonal deficiencies persist in most of the patients. Therefore, follow-up should include both imaging and pituitary function assessment.
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39.
  • Fatima, Tahzeeb, et al. (författare)
  • Association between serum urate and CSF markers of Alzheimer's disease pathology in a population-based sample of 70-year-olds
  • 2021
  • Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The relationship between urate and biomarkers for Alzheimer's disease (AD) pathophysiology has not been investigated. Methods: We examined whether serum concentration of urate was associated with cerebrospinal fluid biomarkers, amyloid beta (A beta)(42), A beta(40), phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), and A beta(42)/A beta(40) ratio, in cognitively unimpaired 70-year-old individuals from Gothenburg, Sweden. We also evaluated whether possible associations were modulated by the apolipoprotein E (APOE) epsilon 4 allele. Results: Serum urate was positively associated with A beta(42) in males (beta = 0.55 pg/mL, P = .04). There was a positive urate-APOE epsilon 4 interaction (1.24 pg/mL, P-interaction = .02) in relation to A beta(42) association. The positive urate and A beta(42) association strengthened in male APOE epsilon 4 carriers (beta = 1.28 pg/mL, P = .01). Discussion: The positive association between urate and A beta(42) in cognitively healthy men may suggest a protective effect of urate against deposition of amyloid protein in the brain parenchyma, and in the longer term, maybe against AD dementia.
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40.
  • Fatima, Tahzeeb, et al. (författare)
  • The absolute risk of gout by clusters of gout-associated comorbidities and lifestyle factors-30 years follow-up of the Malmo Preventive Project
  • 2020
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Gout is predicted by a number of comorbidities and lifestyle factors. We aimed to identify discrete phenotype clusters of these factors in a Swedish population-based health survey. In these clusters, we calculated and compared the incidence and relative risk of gout. Methods Cluster analyses were performed to group variables with close proximity and to obtain homogenous clusters of individuals (n = 22,057) in the Malmo Preventive Project (MPP) cohort. Variables clustered included obesity, kidney dysfunction, diabetes mellitus (DM), hypertension, cardiovascular disease (CVD), dyslipidemia, pulmonary dysfunction (PD), smoking, and the use of diuretics. Incidence rates and hazard ratios (HRs) for gout, adjusted for age and sex, were computed for each cluster. Results Five clusters (C1-C5) were identified. Cluster C1 (n = 16,063) was characterized by few comorbidities. All participants in C2 (n = 750) had kidney dysfunction (100%), and none had CVD. In C3 (n = 528), 100% had CVD and most participants were smokers (74%). C4 (n = 3673) had the greatest fractions of obesity (34%) and dyslipidemia (74%). In C5 (n = 1043), proportions with DM (51%), hypertension (54%), and diuretics (52%) were highest. C1 was by far the most common in the population (73%), followed by C4 (17%). These two pathways included 86% of incident gout cases. The four smaller clusters (C2-C5) had higher incidence rates and a 2- to 3-fold increased risk for incident gout. Conclusions Five distinct clusters based on gout-related comorbidities and lifestyle factors were identified. Most incident gout cases occurred in the cluster of few comorbidities, and the four comorbidity pathways had overall a modest influence on the incidence of gout.
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41.
  • Frisell, Thomas, et al. (författare)
  • Comparative effectiveness of abatacept, rituximab, tocilizumab and TNFi biologics in RA : Results from the nationwide Swedish register
  • 2019
  • Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 58:8, s. 1367-1377
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Current guidelines rank abatacept, rituximab, tocilizumab and TNF-inhibitors (TNFi) as having equal effectiveness for the treatment of RA, at least as second line therapies. These recommendations are mainly based on meta-analysis of randomized controlled trials, with few direct drug-drug comparisons. Our objective was to compare the real-world absolute and relative effectiveness among RA patients starting any of the available biologic DMARDs (bDMARDs). Methods: We used the Swedish Rheumatology Register to identify patients with RA initiating TNFi, rituximab, abatacept or tocilizumab in 2010-2016 as first bDMARD (n = 9333), or after switch from TNFi as first bDMARD (n = 3941). National Swedish registers provided additional covariates and censoring events. Effectiveness was assessed 3 and 12 months after treatment start, as the proportion remaining on therapy and with EULAR Good Response, HAQ improvement >0.2, zero swollen/tender joints and CDAI remission. Adjusted differences were estimated with multivariable linear regression. Results: Patients starting non-TNFi (vs TNFi) as first bDMARD had a higher proportion remaining on drug and reaching most response outcomes as first bDMARD (1-year EULAR Good Response/HAQ improvement: TNFi 24.9/25.4%, rituximab 28.6/37.2%, abatacept 31.9/33.7%, tocilizumab 50.9/43.1%). After switch from a first TNFi, rituximab and tocilizumab, but not abatacept, were associated with significantly better response measures than TNFi (1-year EULAR Good Response/HAQ improvement: TNFi 11.6/16.1%, rituximab 24.8/33.2%, abatacept 13.1/17.5%, tocilizumab 34.1/29.4%). Differences remained significant after adjusting for potential confounders. Conclusion: Treatment outcomes among RA patients treated in Swedish clinical practice are in line with a superior effectiveness of non-TNFi bDMARDs, in particular tocilizumab and rituximab, compared with TNFi.
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42.
  • Landgren, Anton J., 1989, et al. (författare)
  • Cardiovascular risk factors are highly overrepresented in Swedish patients with psoriatic arthritis compared with the general population.
  • 2020
  • Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 49:3, s. 195-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: We aimed to determine the prevalence of cardiovascular risk factors in patients with psoriatic arthritis (PsA) followed at a large Swedish Rheumatology Clinic, and to compare differences in cardiovascular risk factors between men and women with PsA and with the general population. Method: A questionnaire was sent to patients with PsA registered at the Rheumatology Clinic at Sahlgrenska University Hospital, Gothenburg (n=982). Comparisons with the general population were made using data from the Swedish National Public Health Survey. Descriptive statistics are presented. Body mass index (BMI) was calculated using self-reported height and weight. Results: Overall, 692 (70.6%) of the patients with PsA responded. The mean±sd age was 55.6±11.4years and 52% were women. Obesity (BMI ≥30 kg/m2) was more prevalent (p<0.001) in patients with PsA (28.6%) than in matched subjects from the general population (16.3%). Hypertension was also more prevalent (p<0.001) in PsA (40.3%) than in matched subjects from the general population (24.1%), as was diabetes, with a prevalence of 10.5% in the PsA population compared with 6.2% in matched subjects (p<0.001). Conclusion: We found obesity to be highly overrepresented in patients with PsA compared with matched subjects from the general population. This difference was particularly seen in women with PsA. Hypertension and ever smoking were also more prevalent in women with PsA compared with matched subjects from the general population.
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43.
  • Landgren, Anton J., 1989, et al. (författare)
  • Cardiovascular risk factors in gout, psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis: a cross-sectional survey of patients in Western Sweden.
  • 2021
  • Ingår i: RMD open. - : BMJ. - 2056-5933. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to compare traditional (trad) cardiovascular risk factors (CVRFs) among patients with gout, psoriatic arthritis (PsA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS) stratified by sex.A survey was sent to patients with gout (n=1589), PsA (n=1200), RA (n=1246) and AS (n=1095). Patients were retrieved from Sahlgrenska University Hospital, the hospitals of Uddevalla and Skövde, and 12 primary care centres in Western Sweden. The prevalence of self-reported trad-CVRFs was compared between diagnoses by age standardisation with the 2018 population of Sweden as the standard population.In total, 2896 (56.5%) of 5130 patients responded. Hypertension was the most frequently found comorbidity, reported by 65% of patients with gout, 41% with PsA, 43% with RA and 29% with AS. After age standardisation, women and men with gout had significantly more obesity (body mass index ≥30kg/m2), hypertension, diabetes, hyperlipidaemia and multiple trad-CVRFs, compared with those with PsA, RA and AS. Obesity was significantly more common in PsA than in RA. In women, obesity, hypertension and multiple trad-CVRFs were more frequently reported in PsA than in RA and AS, whereas similar prevalence of CVRFs and coexistence of multiple trad-CVRFs were found in men with PsA, RA and AS.Women and men with gout had the highest prevalence of trad-CVRFs. Differences in occurrence of CVRFs by sex were found in patients with PsA, RA and AS. In women, patients with PsA had higher occurrence of trad-CVRFs than those with RA and AS, whereas in men the distribution of CVRFs was similar in PsA, RA and AS.
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44.
  • Landgren, Anton J., 1989, et al. (författare)
  • Health-related quality of life by gout severity in women and men with gout in primary care: results from a questionnaire study in Western Sweden.
  • 2023
  • Ingår i: Scandinavian journal of rheumatology. - 1502-7732. ; 52:6, s. 683-8
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to compare health-related quality of life (HRQoL) by gout severity, overall and by sex.A questionnaire was sent to patients with gout (n=1444) identified at 12 primary care centres in Western Sweden. The questionnaire asked about comorbidities, gout-specific aspects, and HRQoL, using the RAND 36-Item Health Survey. Responders were divided into 'mild', 'moderate', or 'severe' gout based on the number of self-reported flares (0, 1-2, ≥3) during the past 12months.Out of 1444 gout patients, 784 (54.3%) responded to the questionnaire. Among the respondents, 673 [560 (83.2%) men and 113 (16.8%) women] provided answers regarding the number of gout flares in the past year. Of these, 322 (47.8%), 218 (32.4%), and 133 (19.8%) were classified as having mild, moderate, and severe gout, respectively. Allopurinol use was more frequent in those with mild disease. In more severe gout, HRQoL was reduced compared to less severe gout [severe vs mild gout, mean values for physical component summary (PCS) score 39.5 vs 43.6, p =0.002, and mental component summary (MCS) score 46.6 vs 51.1, p <0.001]. When excluding those with a flare in the past month, the HRQoL was still worse in severe gout (vs mild), although differences were attenuated and not statistically significant for the PCS and for women.Gout severity, defined as the number of flares during the past year, was associated with significant reductions in HRQoL.
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45.
  • Landgren, Anton J., 1989, et al. (författare)
  • Health-related quality of life in gout, psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis, results from a cross-sectional survey in Western Sweden.
  • 2023
  • Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 52:5, s. 506-518
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammatory joint diseases (IJDs) substantially affect health-related quality of life (HRQoL). We aimed to compare HRQoL between patients with gout, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS): (i) overall; (ii) stratified by sex; and (iii) between women and men with the same IJD diagnosis.A survey including the RAND36-Item Health Survey for assessing HRQoL was sent to patients with a diagnosis of gout, PsA, RA, or AS, registered at a rheumatology clinic or primary care centre during 2015-2017. HRQoL was compared across IJDs. Because of age differences between diagnoses, age-matched analyses were performed.In total, 2896/5130 (56.5%) individuals responded to the questionnaire. Of these, 868 had gout, 699 PsA, 742 RA, and 587 AS. Physical component summary (PCS) scores were more affected than mental component summary (MCS) scores for all diagnoses (PCS range: 39.7-41.2; MCS range: 43.7-48.9). Patients with gout reported better PCS scores than patients with PsA, RA, and AS, who reported similar scores in age-matched analysis. MCS scores were close to normative values for the general population and similar across IJDs. When comparing women and men with respective IJDs, women reported worse PCS (range, all IJDs: 34.5-37.4 vs 37.5-42.5) and MCS (PsA: 44.0 vs 46.8; RA: 46.1 vs 48.7) scores.We found that patients with gout reported better PCS scores than patients with other IJDs, for whom the results were similar. Women reported overall worse PCS and MCS scores than men.
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46.
  • Landgren, Anton J., 1989, et al. (författare)
  • Incidence of and risk factors for nephrolithiasis in patients with gout and the general population, a cohort study
  • 2017
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nephrolithiasis (NL) is known to be associated with gout, although there are few comparative studies on risk and risk factors for NL in gout compared to population cohorts. In this cohort study we investigated: (1) overall incidence of NL in gout (cases) and general population controls; (2) risk and risk factors (common comorbidities and medications) for first-time NL in cases and controls separately. Methods: Cases (n = 29,968) and age-matched and sex-matched controls (n = 138,678) were identified from the regional healthcare database in western Sweden (VEGA). The analyzed risk factors (comorbidities and current medication use) for first-time NL, and socioeconomic factors were retrieved from VEGA and other national Swedish registers. For cases, follow up began on 1 January 2006 or on the first diagnosis of gout if this occurred later, and for controls on their index patient's first diagnosis of gout. Follow up ended on death, emigration or 31 December 2012. Incidence rates (IR) per 1000 person-years and hazard ratios (HR) were calculated. The incidence calculations were performed for cases (regardless of prior NL) and their controls. HRs with first occurrence of NL as outcome were calculated only in those without previous NL. Results: In cases there were 678 NL events (IR: 6.16 events per 1000 person-years (95% CI: 5.70-6.64) and in controls 2125 NL events (IR 3.85 events per 1000 person-years (95% CI: 3.69-4.02), resulting in an age-sex-adjusted incidence rate ratio of 1.60 (95% CI: 1.47-1.74). Point estimates for predictive factors were similar in cases and controls, except for a significant interaction for losartan which increased the risk of NL only in controls (HR = 1.49 (95% CI: 1.03-2.14). Loop diuretics significantly decreased the risk of NL by 30-34% in both cases and controls. Further significant predictors of NL in gout cases were male sex, diabetes and obesity and in controls male sex and kidney disease. Conclusions: The risk (age and sex adjusted) of NL was increased by 60% in cases compared to controls. None of the commonly used medications increased the risk of NL in gout patients.
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47.
  •  
48.
  • Landgren, Anton J., 1989, et al. (författare)
  • Serum IL-23 significantly decreased in obese patients with psoriatic arthritis six months after a structured weight loss intervention.
  • 2023
  • Ingår i: Arthritis research & therapy. - 1478-6362. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with psoriatic arthritis (PsA) are frequently obese. We have previously shown decreased disease activity in patients with PsA with a body mass index (BMI)≥33kg/m2 following weight loss treatment with Very Low Energy Diet (VLED), resulting in a median weight loss of 18.6% at six months (M6) after baseline (BL). In this study we assessed the effects of VLED on cytokines and adipokines at M6 in the same patients with PsA and controls (matched on sex, age and weight).VLED (640kcal/day) during 12 or 16weeks, depending on BL BMI<40 or≥40kg/m2, was taken and followed by an energy-restricted diet. Cytokines and adipokines were measured with Magnetic Luminex Assays at BL and M6.Serum interleukin (IL)-23, (median (interquartile range) 0.40 (0.17-0.54) ng/mL vs. 0.18 (0.10-0.30) ng/mL, p<0.001) and leptin (26.28 (14.35-48.73) ng/mL vs. 9.25 (4.40-16.24) ng/mL, p<0.001) was significantly decreased in patients with PsA. Serum total (tot)-adiponectin and high molecular weight (HMW) adiponectin increased significantly. Similar findings were found in controls. Also, in patients with PsA, ∆BMI was positively correlated with ∆IL-23 (rS=0.671, p<0.001). In addition, significant positive correlations were found between ΔBMI and ΔDisease Activity Score (DAS28CRP), ΔCRP, Δtumor necrosis factor (TNF)-α, ΔIL-13, ∆IL-17 and Δleptin, and negative correlations between ΔBMI and Δtot-adiponectin.Weight loss was associated with decreased levels of leptin and cytokines, in particular IL-23. These findings may partly explain the anti-inflammatory effect of weight reduction in PsA.ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016, retrospectively registered.
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49.
  • Landgren, Anton J., 1989, et al. (författare)
  • Sex differences in cytokines and adipokines in obese patients with PsA and controls undergoing a weight loss intervention.
  • 2024
  • Ingår i: RMD open. - 2056-5933. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In this post hoc analysis of a previously published study, we compared cytokines and adipokine levels in women and men with psoriatic arthritis (PsA) at baseline (BL) and 6 months (M6) following a weight loss intervention.Patients with PsA (n=41) between 25 and 75 years of age, with body mass index (BMI)≥33 kg/m2 were included in a weight loss intervention with a very low energy diet (VLED) for 12 or 16 weeks depending on BL BMI<40 or ≥40 kg/m2. As controls (n=39), obese individuals, already planned for VLED treatment were recruited and matched for sex, age and weight to the patients with PsA. Cytokines and adipokines were measured at BL and M6.At BL, serum levels of interleukin (IL)-23, leptin and high molecular weight-adiponectin were higher in women with PsA compared with men, whereas serum levels of interferon (IFN)-γ, IL-12/IL-23 p40 and IL-13 were significantly lower in women. Serum IL-23 was significantly reduced at M6 compared with BL in women but not in men with PsA. In women with PsA, the reduction in IL-23 at M6, ∆IL-23, were positively correlated with ∆Disease Activity Score 28 C reactive protein (CRP) (Spearman's correlation (rS)=0.486, p=0.016), ∆CRP (rS=0.468, p=0.021), ∆leptin (rS=0.683, p<0.001) and negatively correlated with ∆total-adiponectin (rS=-0.433, p=0.035). Also in women, ∆Disease Activity in Psoriatic Arthritis was positively correlated with ∆tumour necrosis factor-α (rS=0.417, p=0.034), ∆IL-1β (rS=0.550, p=0.034), ∆IFN-γ (rS=0.414, p=0.035) and ∆leptin (rS=0.410, p=0.038). None of these correlations were significant in men with PsA.Women and men with PsA differed with regard to serum levels of cytokines and adipokines before and after weight loss.
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50.
  • Lindström, Ulf, et al. (författare)
  • Childhood hospitalisation with infections and later development of ankylosing spondylitis: a national case-control study
  • 2016
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The role of environmental exposures in the pathogenesis of ankylosing spondylitis (AS) remains unclear. In particular, two types of exposures have been suspected to play a role: mechanical stress and infections. The objective of this case-control study was to determine if childhood infections are associated with later development of AS. Methods: The cases with AS were identified through the Swedish national outpatient specialised-care register, based on having been given at least one AS diagnosis in the register between 2001 and 2010. Five controls per case were identified in the Swedish population register, matched at the time-point of the index case's first spondyloarthritis diagnosis on sex, birth year, and county. All cases/controls matched prior to the age of 17 years were excluded, as well as all cases/controls given a diagnosis of reactive arthritis or juvenile arthritis at any time point, or any other diagnosis of a rheumatic disease, psoriasis, iridocyclitis, or inflammatory bowel disease before the time-point of matching. All events of hospitalisation with an infection before the age of 17 years were retrieved from the register, and categorised according to the focus of the infection. Odds ratios (ORs) and confidence intervals (CIs) were determined through conditional logistic regression analyses. Results: Of the 2453 cases with AS and 10,257 controls, 17.4 % of the cases and 16.3 % of the controls had been hospitalised with an infection before the age of 17 years (OR 1.08, 95 % CI 0.96-1.22). Appendicitis (1.5 % cases; 2.5 % controls; OR 0.59, 95 % CI 0.41-0.83), respiratory tract infections (cases 11.2 %; controls 9.2 %; OR 1.24, 95 % CI 1.07-1.44) and, in particular, tonsillitis (cases 3.7 %; controls 2.8 %; OR 1.31, 95 % CI 1.03-1.67) were associated with AS. There were no associations between AS and any other type of infection, and the point estimates were similar in several sensitivity analyses. Conclusions: Childhood appendicitis was associated with a decreased risk, whereas respiratory tract infections were associated with an increased risk for later development of AS. These findings support a possible relationship between childhood infections and later development of AS, although the study is limited to infections resulting in inpatient care.
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