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1.
  • Deminger, Anna, 1973, et al. (författare)
  • Which measuring site in ankylosing spondylitis is best to detect bone loss and what predicts the decline : results from a 5-year prospective study
  • 2017
  • Ingår i: Arthritis Research & Therapy. - London, United,Kingdom : BioMed Central. - 1478-6362. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes.METHODS: In a longitudinal study, BMD in Swedish AS patients, 50 ± 13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes.RESULTS: Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, β = -0.15, p = 0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p < 0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (β = 3.15, p = 0.012).CONCLUSION: The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients.
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  • 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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  • Bengtsson, Karin, et al. (författare)
  • Cardiac conduction disturbances in patients with ankylosing spondylitis : results from a 5-year follow-up cohort study
  • 2019
  • Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 5:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To describe electrocardiographic (ECG) development in patients with ankylosing spondylitis (AS) and identify associations between baseline characteristics and cardiac conduction disturbances (CCD) at 5-year follow-up.Methods: In a longitudinal cohort study, 172 patients (54% men, mean age (SD) of 50 (13) years at baseline) with AS underwent ECG, physical examination, questionnaires and laboratory testing at baseline and at 5-year follow-up. Descriptive statistics and univariate and age- and sex-adjusted logistic regression analyses were used. CCD included both atrioventricular and intraventricular blocks.Results: Twenty-three of the 172 patients (13.4%) had a CCD at follow-up. Eight patients had developed a new CCD and eight had normalised their ECG. In the age- and sex-adjusted analyses, CCD at baseline (OR 24.8, 95% CI 7.3 to 84.5), male sex (OR 6.4, 95% CI 2.0 to 20.8), history of anterior uveitis (OR 4.4, 95% CI 1.3 to 14.5), higher ASDAS-CRP (OR 2.3, 95% CI 1.3 to 4.0), greater waist circumference (OR 1.3, 95% CI 1.1 to 1.6, per 5 cm), and medication with antiplatelets (OR 7.0, 95% CI 1.5 to 31.8) and beta-blockers (OR 3.4, 95% CI 1.0 to 11.5) were associated with a CCD at follow-up. Higher age and longer symptom duration were highly correlated and were both associated with a CCD at follow-up.Conclusions: The presence of CCD in AS is in part dynamic and associated with both AS and non-AS characteristics. Our results suggest that patients especially prone to present with CCDs are older men with a previous CCD, longer symptom duration, higher AS disease activity, a history of anterior uveitis and medication reflecting cardiovascular disease.
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  • 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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  • Bengtsson, Karin, 1980, et al. (författare)
  • Occurrence and relative risks for non-vertebral fractures in patients with ankylosing spondylitis compared with the general population: a register-based study from Sweden
  • 2023
  • Ingår i: Rmd Open. - : BMJ. - 2056-5933. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo estimate the incidence of non-vertebral fractures in ankylosing spondylitis (AS) compared with the general population.MethodsNationwide register-based cohort study including patients with AS (n=11 611, 65% men, mean age 48 years), and matched general population controls (n=58 050). Five prespecified fracture outcomes: (1) non-vertebral; (2) fracture of the proximal humerus, distal forearm or hip; (3) proximal humerus; (4) distal forearm and (5) hip) were identified through register linkages with follow-up 2007-2016. We used Poisson regression to calculate incidence rates (IRs), number of fractures per 1000 person-years at risk and IR ratios (IRRs), overall and by sex and age. IRRs were adjusted for history of any prior fracture.ResultsIRs (men/women) for non-vertebral fracture in AS were 11.9 (95% CI 11.0 to 12.9)/14.5 (95% CI 13.1 to 16.1) and in controls 10.0 (95% CI 9.7 to 10.4)/11.8 (95% CI 11.1 to 12.4), IRR (men/women) 1.2 (95% CI 1.1 to 1.3)/1.2 (95% CI 1.1 to 1.4). IRs (men/women) for fractures of the humerus, forearm or hip in AS were 4.0 (95% CI 3.5 to 4.6)/6.3 (95% CI 5.4 to 7.3) and in controls 2.7 (95% CI 2.5 to 2.9)/5.5 (95% CI 5.1 to 6.0), IRR (men/women) 1.5 (95% CI 1.3 to 1.7)/1.1 (95% CI 0.9 to 1.3). IRRs were statistically significantly elevated in men with AS versus controls for forearm fracture (1.4 (95% CI 1.1 to 1.7)) and hip fracture (1.8 (95% CI 1.4 to 2.3)), whereas not in women with AS where the IRRs were 1.1 (95% CI 0.9 to 1.4) and 1.0 (95% CI 0.6 to 1.4). For humerus fracture, IRRs were 1.4 (95% CI 0.99 to 1.9) in men with AS versus controls and 1.1 (95% CI 0.8 to 1.6) in women.ConclusionsBoth men and women with AS have a slightly higher risk of non-vertebral fractures than the general population. A statistically significantly higher risk of fractures of the proximal humerus, distal forearm or hip was found in men with AS in comparison to general population, where the relative risk was especially pronounced for hip fracture.
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  • 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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  • 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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  • Bilberg, Annelie, 1965, et al. (författare)
  • The impact of a structured weight-loss treatment on physical fitness in patients with psoriatic arthritis and obesity compared to matched controls: a prospective interventional study
  • 2022
  • Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 41, s. 2745-2754
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the effects of weight loss treatment on physical fitness in patients with psoriatic arthritis (PsA) and obesity compared to matched controls. Methods: In total, 46 patients with PsA (CASPAR) and BMI >= 33 kg/m(2) and 52 obese persons were included in this 12-month prospective open intervention study with a very low energy diet (640 kcal/day), followed by structured reintroduction of an energy-restricted diet and brief support for physical activity. The primary outcome was muscle strength assessed with hand-grip strength (Grippit) and leg muscle strength (timed stand test). Secondary outcomes were cardiorespiratory fitness, body composition, and physical functioning (SF-36PCS). Outcomes were assessed at baseline, 6 (M6), and 12 months (M12). Nonparametric statistics were used. Results: Median weight reduction at M6 was 18.9 kg in patients and 23.0 kg in controls, (p = 0.546). At M12, patients' median weight loss from baseline was 16.1 kg, corresponding with significant loss of total fat mass (- 30.1%), and lean mass (total - 7.0%, arm - 13.7%, and leg - 6.0%). Leg muscle strength improved in patients and controls at M6 (p < 0.001) and remained improved at M12 (p < 0.01), while hand-grip strength was unchanged in both groups. Cardiorespiratory fitness increased in controls at M6 (p = 0.018) and M12 (p = 0.028) but not in patients. Physical functioning improved in both groups at M6 (p < 0.001) and remained improved at M12 (p = 0.008) and (p < 0.01), respectively. Conclusion: The intervention resulted in positive effects on body weight and total body fat. Despite reduced lean body mass, the muscle strength did not deteriorate in patients with PsA and controls.
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  • Brink, Eva, 1952, et al. (författare)
  • Constructing grounded theory : A practical guide through qualitative analysis
  • 2006
  • Ingår i: International Journal of Qualitative Studies on Health and Well-being. - Järfälla : CoAction Publishing. - 1748-2623 .- 1748-2631. ; 1:3, s. 188-192
  • Recension (refereegranskat)abstract
    • BOOK REVIEW: Constructing grounded theory. A practical guide through qualitative analysis Kathy Charmaz, 2006, 208 pp. London: Sage. ISBN 2005928035
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  • Deminger, Anna, 1973, et al. (författare)
  • A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis
  • 2018
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Knowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex. Methods: Swedish patients with AS, age (mean +/- SD) 50 +/- 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples. Results: Of 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 +/- 2.8 vs. 1.2 +/- 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression >= 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women. Conclusion: This first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men.
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  • Deminger, Anna, 1973, et al. (författare)
  • Elevated serum level of hepatocyte growth factor predicts development of new syndesmophytes in men with ankylosing spondylitis
  • 2021
  • Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 60:4, s. 1804-1813
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To study baseline serum hepatocyte growth factor (s-HGF) as a predictor of spinal radiographic progression overall and by sex and to analyse factors correlated to changes in s-HGF in patients with AS. METHODS: At baseline and the 5-year follow-up, s-HGF was analysed with ELISA. Spinal radiographs were graded according to modified Stoke Ankylosing Spondylitis Spinal Score. Radiographic progression was defined as ≥2 modified Stoke Ankylosing Spondylitis Spinal Score units/5 years or development of ≥1 syndesmophyte. Logistic regression analyses were used. RESULTS: Of 204 baseline participants, 163 (80%) completed all examinations at the 5-year follow-up (54% men). Baseline s-HGF was significantly higher in men who developed ≥1 syndesmophyte compared with non-progressors, median (interquartile range) baseline s-HGF 1551 (1449-1898) vs 1436 (1200-1569) pg/ml, P = 0.003. The calculated optimal cut-off point for baseline s-HGF ≥1520 pg/ml showed a sensitivity of 70%, a specificity of 69% and univariate odds radio (95% CI) of 5.25 (1.69, 14.10) as predictor of development of ≥1 new syndesmophyte in men. Baseline s-HGF ≥1520 pg/ml remained significantly associated with development of ≥1 new syndesmophyte in men in an analysis adjusted for the baseline variables age, smoking, presence of syndesmophytes and CRP, odds radio 3.97 (1.36, 11.60). In women, no association with HGF and radiographic progression was found. Changes in s-HGF were positively correlated with changes in ESR and CRP. CONCLUSION: In this prospective cohort study elevated s-HGF was shown to be associated with development of new syndesmophytes in men with AS.
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  • Deminger, Anna, 1973, et al. (författare)
  • Factors associated with changes in volumetric bone mineral density and cortical area in men with ankylosing spondylitis : a 5-year prospective study using HRpQCT
  • 2022
  • Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 33:1, s. 205-216
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary: Patients with ankylosing spondylitis (AS) have impaired volumetric bone mineral density (vBMD) assessed with high-resolution peripheral computed tomography (HRpQCT). This first longitudinal HRpQCT study in AS shows that cortical and trabecular vBMD decreased at tibia and that signs of inflammation were associated with cortical bone loss at tibia and radius.Introduction: Patients with ankylosing spondylitis (AS) have reduced volumetric bone mineral density (vBMD) in the peripheral skeleton assessed with high-resolution peripheral quantitative computed tomography (HRpQCT). The aims were to investigate longitudinal changes in vBMD, cortical area, and microarchitecture and to assess factors associated with changes in vBMD and cortical area in men with AS.Methods: HRpQCT of radius and tibia was performed in 54 men with AS at baseline and after 5 years. Univariate and multivariable linear regression analyses were used.Results: At tibia, there were significant decreases exceeding least significant changes (LSC) in cortical and trabecular vBMD, mean (SD) percent change −1.0 (1.9) and −2.7 (5.0) respectively (p<0.001). In multivariable regression analyses, increase in disease activity measured by ASDAS_CRP from baseline to follow-up was associated with decreases in cortical vBMD (β −0.86, 95% CI −1.31 to −0.41) and cortical area (β −1.66, 95% CI −3.21 to −0.10) at tibia. At radius, no changes exceeded LSC. Nonetheless, increase in ASDAS_CRP was associated with decreases in cortical vBMD, and high time-averaged ESR was associated with decreases in cortical area. Treatment with TNF inhibitor ≥ 4 years during follow-up was associated with increases in cortical vBMD and cortical area at tibia, whereas exposure to bisphosphonates was associated with increases in cortical measurements at radius. No disease-related variables or treatments were associated with changes in trabecular vBMD.Conclusion: The findings in this first longitudinal HRpQCT study in patients with AS strengthen the importance of controlling disease activity to maintain bone density in the peripheral skeleton.
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  • Deminger, Anna, et al. (författare)
  • Hepatocyte growth factor is a predictor of development of new syndesmophytes in men with ankylosing spondylitis. A five year prospective study
  • 2019
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 78, s. 1240-1240
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Patients with ankylosing spondylitis (AS) have an increased risk of spinal new bone formation characterized by the development of syndesmophytes. Knowledge of predictors for development of syndesmophytes is limited. Hepatocyte growth factor (HGF) has regulatory effects on a variety of cells in many different organs. HGF signaling can affect both osteoclast and osteoblast lineages and has been shown to promote osteogenesis. Cross-sectional association between increased HGF and increased modified Stoke Ankylosing Spine Score (mSASSS) has previously been shown [1], whereas knowledge of HGF as a predictor for new bone formation is lacking.Objectives: To study serum HGF as a predictor for development of new syndesmophytes in patients with AS followed for five years.Methods: Serum levels of HGF was analyzed using ELISA in patients with AS (modified NY-criteria) and in healthy controls (HC) at baseline. Spinal lateral radiographs were obtained at baseline and at the 5-year follow-up and assessed for development of new syndesmophytes using mSASSS. Univariate and multivariable logistic regression analyses were used to assess predictors for development of ≥ 1 new syndesmophyte.Results: Serum HGF and radiographs at baseline and follow-up were available for 163 patients, 88 men and 75 women, baseline mean age 50±12 years. AS patients had higher serum HGF than HC (n=80), p=0.050. In the AS group, 36 patients (22%) developed ≥ 1 syndesmophyte, 27 men and 9 women. In the total AS group, neither did baseline serum HGF differ between those who developed ≥ 1 new syndesmophyte and those who did not progress, nor did it predict development of ≥ 1 new syndesmophyte in the univariate analysis, p=0.25. Interestingly, men who developed ≥1 new syndesmophyte had higher serum HGF than the non-progressors (1706±454 vs 1420±338 pg/mL, p=0.001) and increased serum HGF at baseline predicted development of ≥ 1 syndesmophyte (OR per 1 SD HGF 2.39, 95% CI 1.31 to 4.36) in the univariate analysis. Serum HGF did not predict new syndesmophytes in women, p=0.13. Multivariable analysis for men including age, smoking, baseline syndesmophyte and serum HGF showed high HGF (OR per 1SD 1.90, 95% CI 1.01 to 3.59) and ≥1 baseline syndesmophyte (OR 3.48, 95% CI 1.09 to 11.07) to independently predict development of ≥ 1 new syndesmophyte. If baseline CRP was included in the multivariable model, serum HGF and baseline syndesmophytes remained the significant predictors.Conclusion: High baseline serum HGF was shown to independently predict the development of at least one new syndesmophyte over five years in men with AS.
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21.
  • Exarchou, Sofia, et al. (författare)
  • Mortality in patients with psoriatic arthritis in Sweden: a nationwide, population-based cohort study
  • 2024
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - 0003-4967 .- 1468-2060. ; 83:4, s. 446-456
  • 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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22.
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23.
  • Exarchou, Sofia, et al. (författare)
  • The National Prevalence of Clinically Diagnosed Psoriatic Arthritis in Sweden in 2017
  • 2023
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 50:6, s. 781-788
  • 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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24.
  • Forsblad-d'Elia, Helena, et al. (författare)
  • Cardiac conduction system abnormalities in ankylosing spondylitis : a cross-sectional study.
  • 2013
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14, s. 237-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cardiac conduction disturbances are common in spondyloarthropathies such as ankylosing spondylitis (AS). Whether their occurrence can be linked to signs and symptoms of rheumatic disease activity is an unsettled issue addressed in this study.METHODS: In this cross-sectional study patients with AS according to modified New York criteria but without psoriasis, inflammatory bowel disease, dementia, pregnancy, other severe diseases such as malignancy and difficulties in answering questionnaires were invited; and 210 participated (120 men), mean age 49 years (SD 13; range: 16-77). Questionnaires, physical examination, ECG, and laboratory tests were performed at the same visit.RESULTS: Cardiac conduction disturbances were common and diagnosed in 10-33%, depending on if conservative or less conservative predefined criteria were applied. They consisted mostly of 1st degree atrio-ventricular block and prolonged QRS duration, but one patient had a pacemaker and 7 more had complete bundle branch blocks. Conduction abnormalities were associated mainly with age, male gender and body weight, and not with laboratory measures of inflammation or with Bath Ankylosing Spondylitis Disease Activity Index. Neither were they associated with the presence of HLA B27, which was found in 87% of all patients; the subtype B270502 dominated in all patients.CONCLUSIONS: Cardiac conduction abnormalities are common in AS, but not associated with markers of disease activity or specific B27 subtypes. Even relatively mild conduction system abnormalities might, however, indirectly affect morbidity and mortality.
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25.
  • Frodlund, Martina, et al. (författare)
  • The impact of immunomodulating treatment on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases compared to healthy controls. : A Swedish nationwide study (COVID19-REUMA)
  • 2023
  • Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 41:20, s. 3247-3257
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs).Methods: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or >= 4-fold increase in antibodies in individuals seropositive for both spike proteins.Results: Patients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, ritux-imab treatment and shorter time between last rituximab course and vaccination predicted impaired anti-body response. Antibody levels collected 21-40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2-12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001).Conclusions: Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccina-tion extends and also after an additional vaccine dose. Rituximab patients should be prioritized for (2023) booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.
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26.
  • Frodlund, Martina, et al. (författare)
  • The serological immunogenicity of the third and fourth doses of COVID-19 vaccine in patients with inflammatory rheumatic diseases on different biologic or targeted DMARDs : a Swedish nationwide study (COVID-19-REUMA)
  • 2024
  • Ingår i: Microbiology Spectrum. - : AMER SOC MICROBIOLOGY. - 2165-0497. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies investigating the immunogenicity of additional COVID-19 vaccine doses in immunosuppressed patients with inflammatory rheumatic diseases (IRD) are still limited. The objective was to explore the antibody response including response to omicron virus subvariants (sBA.1 and sBS.2) after third and fourth COVID-19 vaccine doses in Swedish IRD patients treated with immunomodulating drugs compared to controls. Antibody levels to spike wild-type antigens (full-length protein and S1) and the omicron variants sBA.1 and sBA.2 (full-length proteins) were measured. A positive response was defined as having antibody levels over cut-off or ≥fourfold increase in post-vaccination levels for both antigens. Patients with arthritis, vasculitis, and other autoimmune diseases (n = 414), and controls (n = 61) receiving biologic/targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) with or without conventional synthetic DMARDs participated. Of these, blood samples were available for 370 patients and 52 controls after three doses, and 65 patients and 15 controls after four doses. Treatment groups after three vaccine doses were rituximab (n = 133), abatacept (n = 22), IL6r inhibitors (n = 71), JAnus Kinase inhibitors (JAK-inhibitors) (n = 56), tumor necrosis factor inhibitor (TNF-inhibitors) (n = 61), IL12/23/17 inhibitors (n = 27), and controls (n = 52). The percentage of responders after three and four vaccine doses was lower in rituximab-treated patients (59% and 57%) compared to controls (100%) (P < 0.001). After three doses, the percentage of responders in all other groups was 100%, including response to omicron sBA.1 and sBA.2. In rituximab-treated patients, higher baseline immunoglobulin G (IgG) and longer time-period between rituximab and vaccination predicted better response. In this Swedish nationwide study including IRD patients three and four COVID-19 vaccine doses were immunogenic in patients treated with IL6r inhibitors, TNF-inhibitors, JAK-inhibitors, and IL12/23/17-inhibitors but not in rituximab. As >50% of rituximab patients responded to vaccines including omicron subvariants, these patients should be prioritized for additional vaccine doses.
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27.
  • Frodlund, Martina, et al. (författare)
  • The serological immunogenicity of the third and fourth doses of COVID-19 vaccine in patients with inflammatory rheumatic diseases on different biologic or targeted DMARDs: a Swedish nationwide study (COVID-19-REUMA)
  • 2024
  • Ingår i: Microbiology Spectrum. - : AMER SOC MICROBIOLOGY. - 2165-0497.
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies investigating the immunogenicity of additional COVID-19 vaccine doses in immunosuppressed patients with inflammatory rheumatic diseases (IRD) are still limited. The objective was to explore the antibody response including response to omicron virus subvariants (sBA.1 and sBS.2) after third and fourth COVID-19 vaccine doses in Swedish IRD patients treated with immunomodulating drugs compared to controls. Antibody levels to spike wild-type antigens (full-length protein and S1) and the omicron variants sBA.1 and sBA.2 (full-length proteins) were measured. A positive response was defined as having antibody levels over cut-off or >= fourfold increase in post-vaccination levels for both antigens. Patients with arthritis, vasculitis, and other autoimmune diseases (n = 414), and controls (n = 61) receiving biologic/targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) with or without conventional synthetic DMARDs participated. Of these, blood samples were available for 370 patients and 52 controls after three doses, and 65 patients and 15 controls after four doses. Treatment groups after three vaccine doses were rituximab (n = 133), abatacept (n = 22), IL6r inhibitors (n = 71), JAnus Kinase inhibitors (JAK-inhibitors) (n = 56), tumor necrosis factor inhibitor (TNF-inhibitors) (n = 61), IL12/23/17 inhibitors (n = 27), and controls (n = 52). The percentage of responders after three and four vaccine doses was lower in rituximab-treated patients (59% and 57%) compared to controls (100%) (P < 0.001). After three doses, the percentage of responders in all other groups was 100%, including response to omicron sBA.1 and sBA.2. In rituximab-treated patients, higher baseline immunoglobulin G (IgG) and longer time-period between rituximab and vaccination predicted better response. In this Swedish nationwide study including IRD patients three and four COVID-19 vaccine doses were immunogenic in patients treated with IL6r inhibitors, TNF-inhibitors, JAK-inhibitors, and IL12/23/17-inhibitors but not in rituximab. As >50% of rituximab patients responded to vaccines including omicron subvariants, these patients should be prioritized for additional vaccine doses. IMPORTANCE Results from this study provide further evidence that additional doses of COVID-19 vaccines are immunogenic and result in satisfactory antibody response in a majority of patients with inflammatory rheumatic diseases (IRD) receiving potent immunomodulating treatments such as biological or targeted disease-modifying anti-rheumatic drugs (DMARDs) given as monotherapy or combined with traditional DMARDs. We observed that rituximab treatment, both as monotherapy and combined with csDMARDs, impaired antibody response, and only roughly 50% of patients developed a satisfactory antibody response including response to omicron subvariants after the third vaccine. In addition, higher IgG levels at the last rituximab course before the third vaccine dose and a longer time after the last rituximab treatment increased the chance of a satisfactory antibody response. These results indicate that rituximab-treated patients should be prioritized for additional vaccine doses. CLINICAL TRIALS EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) with number 2021-000880-63.
  •  
28.
  • Frodlund, Martina, et al. (författare)
  • The serological immunogenicity of the third and fourth doses of COVID-19 vaccine in patients with inflammatory rheumatic diseases on different biologic or targeted DMARDs: a Swedish nationwide study (COVID-19-REUMA)
  • 2024
  • Ingår i: MICROBIOLOGY SPECTRUM. - : AMER SOC MICROBIOLOGY. - 2165-0497. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies investigating the immunogenicity of additional COVID-19 vaccine doses in immunosuppressed patients with inflammatory rheumatic diseases (IRD) are still limited. The objective was to explore the antibody response including response to omicron virus subvariants (sBA.1 and sBS.2) after third and fourth COVID-19 vaccine doses in Swedish IRD patients treated with immunomodulating drugs compared to controls. Antibody levels to spike wild-type antigens (full-length protein and S1) and the omicron variants sBA.1 and sBA.2 (full-length proteins) were measured. A positive response was defined as having antibody levels over cut-off or >= fourfold increase in post-vaccination levels for both antigens. Patients with arthritis, vasculitis, and other autoimmune diseases (n = 414), and controls (n = 61) receiving biologic/targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) with or without conventional synthetic DMARDs participated. Of these, blood samples were available for 370 patients and 52 controls after three doses, and 65 patients and 15 controls after four doses. Treatment groups after three vaccine doses were rituximab (n = 133), abatacept (n = 22), IL6r inhibitors (n = 71), JAnus Kinase inhibitors (JAK-inhibitors) (n = 56), tumor necrosis factor inhibitor (TNF-inhibitors) (n = 61), IL12/23/17 inhibitors (n = 27), and controls (n = 52). The percentage of responders after three and four vaccine doses was lower in rituximab-treated patients (59% and 57%) compared to controls (100%) (P < 0.001). After three doses, the percentage of responders in all other groups was 100%, including response to omicron sBA.1 and sBA.2. In rituximab-treated patients, higher baseline immunoglobulin G (IgG) and longer time-period between rituximab and vaccination predicted better response. In this Swedish nationwide study including IRD patients three and four COVID-19 vaccine doses were immunogenic in patients treated with IL6r inhibitors, TNF-inhibitors, JAK-inhibitors, and IL12/23/17-inhibitors but not in rituximab. As >50% of rituximab patients responded to vaccines including omicron subvariants, these patients should be prioritized for additional vaccine doses. IMPORTANCE Results from this study provide further evidence that additional doses of COVID-19 vaccines are immunogenic and result in satisfactory antibody response in a majority of patients with inflammatory rheumatic diseases (IRD) receiving potent immunomodulating treatments such as biological or targeted disease-modifying anti-rheumatic drugs (DMARDs) given as monotherapy or combined with traditional DMARDs. We observed that rituximab treatment, both as monotherapy and combined with csDMARDs, impaired antibody response, and only roughly 50% of patients developed a satisfactory antibody response including response to omicron subvariants after the third vaccine. In addition, higher IgG levels at the last rituximab course before the third vaccine dose and a longer time after the last rituximab treatment increased the chance of a satisfactory antibody response. These results indicate that rituximab-treated patients should be prioritized for additional vaccine doses. CLINICAL TRIALS EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) with number 2021-000880-63.
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29.
  • Grüner Sveälv, Bente, 1956, et al. (författare)
  • Prevalence of diastolic dysfunction in patients with ankylosing spondylitis: a cross-sectional study.
  • 2015
  • Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 44:2, s. 111-117
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To determine the prevalence of diastolic dysfunction (DD) in patients with ankylosing spondylitis (AS) by following recommended criteria from the American Society of Echocardiography (ASE) and using single variables reflecting DD. Method: A total of 187 patients with AS (105 men; mean age 51 ± 13 years; mean duration of disease 15 ± 11 years) fulfilled the inclusion criteria and underwent pulsed-wave and tissue Doppler imaging. Results: By following ASE recommended criteria, we observed that 12% of patients with AS had mild DD. We also compared single standard Doppler values with normal age-stratified reference values and showed a wide variation in the number of patients with AS outside the 95% confidence interval (CI) of normal values depending on the variable chosen (ranging from 1.1% to 30.5%). Conclusions: By following recommended criteria, our cross-sectional study shows that DD was infrequent and mild in patients with AS.
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30.
  • Hallström, Magnus, et al. (författare)
  • Physical function and sex differences in radiographic axial spondyloarthritis: a cross-sectional analysis on Bath Ankylosing Spondylitis Functional Index
  • 2023
  • Ingår i: Arthritis Research and Therapy. - : BioMed Central (BMC). - 1478-6354 .- 1478-6362. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Physical function is an important determinant of health-related quality of life in radiographic axial spondyloarthritis patients (r-axSpA). To improve the basis of effective healthcare efforts, we aimed to investigate which demographic and disease-related factors that influence Bath Ankylosing Spondylitis Functional Index (BASFI) in r-axSpA patients overall and stratified by sex. Furthermore, we sought to explore differences between sexes regarding separate BASFI questions and also to explore which factors that may contribute to these differences. Methods: This observational cross-sectional study included patients fulfilling the modified New York criteria for Ankylosing Spondylitis. Patients were assessed with 66/68 joint count and Bath Ankylosing Spondylitis Metrology Index (BASMI) measurements. Lateral X-rays were performed for Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP), and BASFI were registered. Multivariable linear regression analyses were used to investigate which factors that associate with BASFI. Results: A total of 353 r-axSpA patients were included, mean age 52.2 ± 12.7years, 62.3% males. No significant sex difference was seen in BASFI scores (2.7 ± 2.0 in males vs 2.9 ± 2.1 in females). Age, body mass index, ASDAS-CRP, BASMI or mSASSS, fatigue, and tenderness were found to associate independently with BASFI in different models (R 2 0.53–0.63). Investigation of separate BASFI questions revealed that the ability to look over shoulder was worse in males than females (mean 4.43 ± 3.37 vs 3.74 ± 3.06, p = 0.05) and most strongly correlated with mSASSS and BASMI among separate BASFI questions (r = 0.53, p < 0.001; r = 0.62, p < 0.001). The ability to climb stairs was worse in females than males (mean 2.49 ± 2.77 vs 1.54 ± 2.32, p < 0.001). Conclusions: No difference between male and female r-axSpA patients was seen in BASFI despite significant sex differences in BASMI, mSASSS, and CRP levels. Our results underline the impact of fatigue and tenderness on BASFI. The ability to climb stairs without a handrail was scored worse among females compared to males. Furthermore, the ability to look over the shoulder was worse in males than females and closely related to spinal mobility and structural spinal changes.
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31.
  • Huang, X. F., et al. (författare)
  • Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci
  • 2020
  • Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:6
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B 27 , implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS. METHODS. We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available alter SNP microarray genotyping, imputation, and quality-control filtering. RESULTS. We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 x 10(-8), odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 x 10(-7), OR = 1.22) and NOS2 (rs2274894, P = 8.22 x 10(-7), OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rsl0171979, P = 2.56 x 10(-6), OR = 1.20), KIFAP3 (rs508063, P = 5.64 x 10(-7), OR = 1.20), CLCN7 (rs67412457, P = 1.33 x 10(-6), OR = 1.25), ACAA2 (rs9947182, P = 9.70 x 10(-7), OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone. CONCLUSIONS. We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.
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32.
  • Izadi, Z., et al. (författare)
  • Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
  • 2021
  • Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. OBJECTIVE To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age >= 18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. EXPOSURES Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. MAIN OUTCOMES AND MEASURES The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. RESULTS A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. CONCLUSIONS AND RELEVANCE In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.
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33.
  • Kastbom, Alf, et al. (författare)
  • Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis
  • 2013
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 42:6, s. 465-468
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is important for interleukin-1beta (IL-1 beta) processing as part of an innate immune response. Caspase recruitment domain family, member 8 (CARD8) is an inhibitor of nuclear factor kappa B (NF-kappa B) and possibly also a part of the NLRP3 inflammasome. The objective of this study was to evaluate one single nucleotide polymorphism (SNP) in CARD8 and three SNPs in NLRP3 in ankylosing spondylitis (AS) susceptibility and disease phenotype. Method: We recruited 492 AS patients from Southern Sweden fulfilling the modified New York criteria for AS, and assessed phenotypic characteristics from medical records and questionnaires. Patients with psoriasis or clinically overt inflammatory bowel disease (IBD) were excluded, as were patients without human leucocyte antigen B27 (HLA-B27). Three NLRP3 SNPs (rs35829419, rs4353135, and rs10733113) and one SNP in CARD8 (rs2043211) were genotyped by commercially available TaqMan assays, and the results compared at genotype and allele levels to those of 793 population-based controls. In a subgroup of the patients (n = 169), faecal calprotectin was assessed as a marker of subclinical intestinal inflammation. Results: The minor allele (A) of CARD8-C10X (rs2043211) was associated with a decreased risk of AS in a dominant model [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54-0.94, p = 0.012] and at the allelic level (OR 0.81, 95% CI 0.68-0.97, p = 0.02), but was not associated with levels of faecal calprotectin. There was no association regarding NLRP3 SNPs and AS susceptibility, and none of the investigated SNPs were associated with iritis, anti-tumour necrosis factor (anti-TNF) therapy, or peripheral joint involvement. Conclusion: In a Swedish population, the minor allele of CARD8-C10X is associated with a decreased risk of AS, but not with levels of faecal calprotectin or disease phenotype.
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34.
  • Klingberg, Eva, et al. (författare)
  • A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin
  • 2019
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients with AS, ulcerative colitis (UC), and healthy controls (HC) and to determine relationships between fecal microbiota, fecal calprotectin, and disease-related variables in AS. Methods Fecal microbiota composition was assessed with GA-map (TM) Dysbiosis Test (Genetic Analysis, Oslo, Norway), which also reports the degree of deviation of the microbiota composition compared with a healthy control population, a Dysbiosis Index (DI) score 1-5. The AS patients were assessed with questionnaires, back mobility tests, fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results Totally, 150 patients with AS (55% men, median age 55.5 years, median BASDAI 3.2), 18 patients with UC (56% men, median age 30.5 years), and 17 HC (65% men, median age 22 years) were included. Principal component analysis showed highly separate clustering of fecal microbiota from the patients with AS, UC, and HC. Compared with HC, fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcus species, and Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae. Further, fecal microbiota composition differed between patients with normal (<= 50 mg/kg, n = 57) and increased (>= 200 mg/kg, n = 36) fecal calprotectin. Patients with increased fecal calprotectin had lower abundance of bacteria with anti-inflammatory properties such as Faecalibacterium prausnitzii and Clostridium and higher abundance of the genus Streptococcus. No association was found between the fecal microbiota composition and HLAB27 status, disease activity, function, or medication. Dysbiosis (defined as DI >= 3) was found in 87% of AS patients. Conclusions Patients with AS have a distinct fecal microbiota signature, which is linked to fecal calprotectin levels, a marker of intestinal inflammation, but not to other clinical parameters. These findings suggest a local interplay between intestinal microbiota and gut inflammation in AS.
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35.
  • Klingberg, Eva, et al. (författare)
  • A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis
  • 2017
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with ankylosing spondylitis (AS) are at increased risk of developing inflammatory bowel disease (IBD). We aimed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD. Methods: Fecal calprotectin was assessed at baseline (n = 204) and at 5-year follow-up (n = 164). The patients answered questionnaires and underwent clinical evaluations. At baseline and at 5-year follow-up, ileocolonoscopy was performed in patients with fecal calprotectin = 500 mg/kg and = 200 mg/kg, respectively. The medical records were checked for diagnoses of IBD during the follow-up period. Results: Fecal calprotectin > 50 mg/kg was found in two-thirds of the patients at both study visits. In 80% of the patients, fecal calprotectin changed by < 200 mg/kg between the two measuring points. Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin at 5-year follow-up. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with higher fecal calprotectin, and 3-week cessation of NSAIDs resulted in a drop of a median 116 mg/kg in fecal calprotectin. The use of tumor necrosis factor (TNF) blockers was associated with lower fecal calprotectin at both visits, but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up. The 5-year incidence of Crohn's disease (CD) was 1.5% and was predicted by high fecal calprotectin. Conclusions: Fecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits. CD developed in 1.5% of the patients with AS, and a high fecal calprotectin was the main predictor thereof. The results support a link between inflammation in the gut and the musculoskeletal system in AS. We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD
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36.
  • Klingberg, Eva, et al. (författare)
  • Aortic Regurgitation Is Common in Ankylosing Spondylitis : Time for Routine Echocardiography Evaluation?
  • 2015
  • Ingår i: American Journal of Medicine. - : Elsevier. - 0002-9343 .- 1555-7162. ; 128:11, s. 1244-50
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aim of this study was to assess the prevalence of aortic regurgitation and any relation to disease activity and specific human leukocyte antigen (HLA)-B27 subtypes in patients with ankylosing spondylitis.METHODS: Transthoracic echocardiography was performed in 187 patients (105 men), mean age (SD) 50 (13) years, and mean disease duration 24 (13) years, and was related to demographic, clinical, radiographic, electrocardiographic, and laboratory data.RESULTS: Aortic regurgitation was found in 34 patients (18%; 95% confidence interval [CI], 12%-24%): mild in 24, moderate in 9, and severe in one. The prevalence was significantly higher than expected from population data. Conduction system abnormalities were documented in 25 patients (13%; 95% CI, 8%-18%), and significantly more likely in the presence of aortic regurgitation (P = .005), which was related to increasing age and longstanding disease, and increased from ∼20% in the 50s to 55% in the 70s. It was also independently associated with disease duration, with higher modified Stoke Ankylosing Spondylitis Spine Score, and with a history of anterior uveitis. HLA-B27 was present in similar proportions in the presence vs absence of aortic regurgitation. For comparison, clinically significant coronary artery disease was present in 9 patients (5%; 95% CI, 2%-8%).CONCLUSION: Patients with ankylosing spondylitis frequently have cardiac abnormalities, but they more often consist of disease-related aortic regurgitation or conduction system abnormalities than manifestations of atherosclerotic heart disease. Because aortic regurgitation or conduction abnormalities might cause insidious symptoms not easily interpreted as of cardiac origin, we suggest that both electrocardiography and echocardiography evaluation should be part of the routine management of patients with ankylosing spondylitis.
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37.
  • Klingberg, Eva, et al. (författare)
  • Biomarkers of Bone Metabolism in Ankylosing Spondylitis in Relation to Osteoproliferation and Osteoporosis
  • 2014
  • Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 41:7, s. 1349-1356
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To identify biomarkers for bone metabolism in patients with ankylosing spondylitis (AS) and to determine the relationship between these biomarkers and disease activity, hack mobility, osteoproliferation, and bone mineral density (BMD). Methods. Scrum levels of Wingless protein (Wnt-3a), Dickkopf-1 (DKK-1), sclerostin, soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), and osteoproteeerin were assessed using ELISA. Ankylosing Spondylitis Disease Activity Score-C reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis patient global score, and C-reactive protein (CRP) were used as disease activity measures, and Bath Ankylosing Spondylitis Metrology Index (BASMI) as a measure of spinal mobility. Lateral spine radiographs were scored for chronic AS-related changes (mSASSS). BMD was measured with dual-enemy x-ray absorptiometry. Results. Two hundred four patients with AS (NY criteria; 57% men), with a mean age of 50 +/- 13 years and disease duration 15 +/- 11 years, and 80 age and sex-matched controls were included. The patients with AS had significantly higher serum levels of Wnt-3a (p < 0.001) and lower levels of sclerostin (p = 0.014) and sRANKL (p = 0.047) compared with the controls. High CRP was associated with low sclerostin (r(S) = 0.21, p = 0.003) and DKK-1 (r(S) = 0.14, p = 0.045). In multiple linear regression analyses, increasing BASMI and mSASSS were independently associated with older age, male sex, high CRP, and elevated serum levels of Wnt-3a. In addition, mSASSS remained associated with a high number of smoking pack-years after adjusting for age. Low BMD of femoral neck was associated with high mSASSS after adjusting for age. Conclusion. Serum levels of Wnt-3a are elevated in AS and associated with increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a biomarker for the osteoproliferative process.
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38.
  • Klingberg, Eva, et al. (författare)
  • Bone microarchitecture in ankylosing spondylitis and the association with bone mineral density, fractures, and syndesmophytes
  • 2013
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 15:6, s. 179-179
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that in healthy controls, to study vBMD in axial compared with peripheral bone, and to explore the relation between vertebral fractures, spinal osteoproliferation, and peripheral bone microarchitecture and density.METHODS: High-resolution peripheral quantitative computed tomography (HRpQCT) of ultradistal radius and tibia and QCT and dual-energy x-ray absorptiometry (DXA) of lumbar spine were performed in 69 male AS patients (NY criteria). Spinal radiographs were assessed for vertebral fractures and syndesmophyte formation (mSASSS). The HRpQCT measurements were compared with the measurements of healthy controls.RESULTS: The AS patients had lower cortical vBMD in radius (P = 0.004) and lower trabecular vBMD in tibia (P = 0.033), than did the controls. Strong correlations were found between trabecular vBMD in lumbar spine, radius (rS = 0.762; P < 0.001), and tibia (rS = 0.712; P < 0.001). When compared with age-matched AS controls, patients with vertebral fractures had lower lumbar cortical vBMD (-22%; P = 0.019), lower cortical cross-sectional area in radius (-28.3%; P = 0.001) and tibia (-24.0%; P = 0.013), and thinner cortical bone in radius (-28.3%; P = 0.001) and tibia (-26.9%; P = 0.016). mSASSS correlated negatively with trabecular vBMD in lumbar spine (rS = -0.620; P < 0.001), radius (rS = -0.400; p = 0.001) and tibia (rS = -0.475; p < 0.001) and also with trabecular thickness in radius (rS = -0.528; P < 0.001) and tibia (rS = -0.488; P < 0.001). Adjusted for age, syndesmophytes were significantly associated with decreasing trabecular vBMD, but increasing cortical vBMD in lumbar spine, but not with increasing cortical thickness or density in peripheral bone. Estimated lumbar vBMD by DXA correlated with trabecular vBMD measured by QCT (rS = 0.636; P < 0.001).CONCLUSIONS: Lumbar osteoporosis, syndesmophytes, and vertebral fractures were associated with both lower vBMD and deteriorated microarchitecture in peripheral bone. The results indicate that trabecular bone loss is general, whereas osteoproliferation is local in AS.
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39.
  • Klingberg, Eva, et al. (författare)
  • Calprotectin in ankylosing spondylitis - Frequently elevated in feces, but normal in serum
  • 2012
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 47, s. 435-444
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. To investigate indirectly the prevalence of intestinal inflammation in ankylosing spondylitis (AS) patients by assessing the levels of fecal calprotectin, to study levels of serum calprotectin in AS, and to correlate the concentrations of calprotectin in feces and serum with reported gastrointestinal symptoms, medication, and measures of disease activity. Methods. All patients fulfilling the Modified New York criteria of AS at the study centers were invited to participate. The patients answered questionnaires concerning medication, symptoms, and disease activity. Physical examination was performed, including back mobility tests. Samples of stools and blood were collected and analyzed for fecal and serum calprotectin. Results. Elevated levels of fecal calprotectin (>50 mg/kg) was found in 140 of 205 AS patients (68%). Levels of fecal calprotectin were associated with increasing age, disease duration, ESR, CRP, and serum calprotectin, but not with gastrointestinal symptoms. Fecal calprotectin was higher in patients using NSAIDs, salicylates, and proton pump inhibitors, but lower in patients using methotrexate and infliximab. Serum calprotectin levels were normal or low in 98% of AS patients and not different from the levels in healthy blood donors. Serum calprotectin levels were positively associated with ESR, CRP, WBC, and PLT. Conclusions. Two-thirds of AS patients had elevated levels of fecal calprotectin, without associated gastrointestinal symptoms. Serum calprotectin was mostly normal in AS, in contrast to various other inflammatory rheumatic diseases. We suggest that fecal calprotectin may be a marker for subclinical intestinal inflammation in AS and should be measured after stopping NSAIDs, but further endoscopic studies are needed. © Informa Healthcare.
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40.
  • Klingberg, Eva, et al. (författare)
  • Osteoporosis in ankylosing spondylitis - prevalence, risk factors and methods of assessment.
  • 2012
  • Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 14:3
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: INTRODUCTION: Osteoporosis can be a complication of ankylosing spondylitis (AS), but diagnosing spinal osteoporosis can be difficult since pathologic new bone formation interferes with the assessment of the bone mineral density (BMD). The aims of the current study were to investigate prevalence and risk factors for reduced BMD in a Swedish cohort of AS patients, and to examine how progressive ankylosis influences BMD with the use of dual-energy x-ray absorptiometry (DXA) of the lumbar spine in different projections. METHODS: Methods of assessment were questionnaires, back mobility tests, blood samples, lateral spine radiographs for syndesmophyte grading (mSASSS), DXA of the hip, radius and lumbar spine in anteroposterior (AP) and lateral projections with estimation of volumetric BMD (vBMD). RESULTS: AS patients (modified New York criteria), 87 women and 117 men, mean age 50 ± 13 years and disease duration 15 ± 11 years were included. According to World Health Organization (WHO) criteria 21% osteoporosis and 44% osteopenia was diagnosed in patients > = 50 years. Under age 50 BMD below expected range for age was found in 5%. Interestingly lateral lumbar DXA showed significantly lower BMD and revealed significantly more cases with osteoporosis as compared with AP DXA. Lumbar vBMD was not different between sexes, but women had significantly more lumbar osteoporosis measured with AP DXA (P < 0.001). Men had significantly higher mSASSS (P < 0.001). Low BMD was associated with high age, disease duration, mSASSS, Bath Ankylosing Spondylitis Metrology Index (BASMI), inflammatory parameters and low body mass index (BMI). Increasing mSASSS correlated significantly with decreasing lateral and volumetric lumbar BMD, while AP lumbar BMD showed tendency to increase. CONCLUSIONS: Osteoporosis and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting osteoporosis and are less affected by syndesmophyte formation.
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41.
  • Klingberg, Eva, et al. (författare)
  • Seasonal variations in serum 25-hydroxy vitamin D levels in a Swedish cohort
  • 2015
  • Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 49:3, s. 800-808
  • Tidskriftsartikel (refereegranskat)abstract
    • To study seasonal inter-individual and intra-individual variations in serum 25-hydroxy vitamin D (25(OH)D) and to explore parameters associated with 25(OH)D in a healthy Swedish adult population. 540 blood donors (60 % men; mean age 41 +/- A 13 years) and 75 thrombocyte donors (92 % men, aged 46 +/- A 11 years) were included. Serum was collected during 12 months and analyzed for 25(OH)D and parathyroid hormone (S-iPTH). The blood donors answered questionnaires concerning vitamin D supplements, smoking, physical activity, sunbed use and sun holidays. Repeated serum samples were collected from the thrombocyte donors to study the intra-individual variations in S-25(OH)D. S-25(OH)D varied greatly over the year correlating with the intensity of the UV-B irradiation (r (S) = 0.326; p < 0.001). During January-March, a S-25(OH)D level below the thresholds of 50 and 75 nmol/L was observed in 58 and 88 %, respectively, and during July-September in 11 and 50 % (p < 0.001). S-25(OH)D was negatively correlated with body mass index and S-iPTH, but was significantly higher in holiday makers in sunny destinations, sunbed users, non-smokers, and in the physically active. The intra-individual analyses showed a mean increase in S-25(OH)D by 8 nmol/L/month between April and August. Approximately 75 % had serum 25(OH)D values < 75 nmol/L during 75 % of the year and 50 % had serum 25(OH)D < 50 nmol/L during 50 % of the year. Serum 25(OH)D was strongly associated with parameters related to sun exposure, but only weakly with intake of vitamin D supplements.
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42.
  • Klingberg, Eva, et al. (författare)
  • The use of complementary and alternative medicine in outpatients with inflammatory rheumatic diseases in Sweden.
  • 2009
  • Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 38:6, s. 472-80
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To study the use of complementary and alternative medicine (CAM) drugs and methods in patients with inflammatory rheumatic diseases, at rheumatology clinics in western Sweden, and to investigate possible associations between CAM-using habits and other characteristics of the patients. METHODS: Randomly selected rheumatology outpatients were asked to complete questionnaires about CAM usage, diagnoses, medication, quality of life (using the 36-item Short Form Health Survey, SF-36), fatigue (using the 20-item Multiple Fatigue Inventory, MFI-20), the Health Assessment Questionnaire (HAQ), and visual analogue scales (VAS) for global health, pain, and fatigue. RESULT: A total of 200 patients were included, 137 women and 63 men, mean age 55+/-16 and 54+/-15 years, respectively. Ongoing CAM use was reported by 58 patients (29%): 45 (22.5%) were taking CAM drugs, 20 (10%) were using CAM methods. Altogether 130 patients (65%) had used CAM at some time of their lives; 103 patients (51%) had used CAM drugs ever and 90 patients (45%) had used CAM methods ever. Women used more CAM drugs compared with men. Younger patients used more CAM. CAM use was associated with parameters indicating poorer health, mental component score (MCS) and physical component score (PCS) of SF-36, and VAS for global health and fatigue. Ongoing CAM method was associated with less use of immunomodulatory drugs. CONCLUSION: CAM use is widespread among rheumatology patients in Sweden. A total of 65% of the patients had experience of CAM treatment. Female sex, younger age, and poor health were associated with CAM utilization.
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43.
  • Klingberg, Eva, et al. (författare)
  • The vitamin D status in ankylosing spondylitis in relation to intestinal inflammation, disease activity, and bone health: a cross-sectional study
  • 2016
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 27:6, s. 2027-2033
  • Tidskriftsartikel (refereegranskat)abstract
    • We assessed the vitamin D status in ankylosing spondylitis (AS) patients and healthy controls in the late winter when no vitamin D is produced by the sunlight. The vitamin D status was often poor, but not lower in AS and not associated with disease activity or signs of gut inflammation. The aims of the study were to investigate the vitamin D levels attained mainly by dietary intake in ankylosing spondylitis (AS) in comparison with healthy controls and in relation to gut inflammation, measured indirectly by fecal calprotectin, disease activity, osteoproliferation, bone mineral density (BMD), and vertebral fractures. Serum 25-hydroxy vitamin D (25(OH)D) was measured in 203 AS patients and 120 healthy controls at the end of "the vitamin D winter," when the out-door UVB irradiation is too low to allow synthesis of vitamin D-3 in the skin at the latitude of Gothenburg, Sweden. Fecal calprotectin was measured in stool samples. Disease activity was assessed with CRP, ESR, ASDAS(CRP,) BASDAI, BAS-G, BASFI, and BASMI. Lateral spine radiographs were scored for osteoproliferation and vertebral fractures using the mSASSS and Genant scores. BMD was measured in the lumbar spine and femoral neck. Vitamin D insufficiency (a serum 25(OH)D < 50 nmol/L) was found in approximately 50 % of the AS patients, but serum 25(OH)D was not different from healthy controls and not significantly correlated with fecal calprotectin, gastrointestinal symptoms, disease activity parameters, mSASSS, BMD, or vertebral fractures. The vitamin D status was often poor in the late winter in AS but not different from the healthy controls. No evidence for a connection between subclinical gut inflammation, malabsorption, and hypovitaminosis D was found. Serum 25(OH)D was not associated with disease activity, osteoproliferation, BMD, or vertebral fractures. We suggest that the lower vitamin D levels in AS, previously found by others, may be caused by reduced out-door UVB exposure.
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44.
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45.
  • Klingberg, Eva, et al. (författare)
  • Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study
  • 2019
  • Ingår i: Arthritis Res Ther. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundObesity is over-represented in patients with psoriatic arthritis (PsA) and associated with higher disease activity, poorer effect of treatment and increased cardiovascular morbidity. Studies on the effects of weight loss are however needed. This study aimed to prospectively study the effects of weight loss treatment with very low energy diet (VLED) on disease activity in patients with PsA (CASPAR criteria) and obesity (body mass index BMI 33kg/m(2)).MethodsVLED (640kcal/day) was taken during 12-16weeks, depending on pre-treatment BMI. Afterwards, an energy-restricted diet was gradually reintroduced. Weight loss treatment was given within a structured framework for support and medical follow-up.Treatment with conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs was held constant from 3months before, until 6months after baseline.Patients were assessed with BMI, 66/68 joints count, Leeds enthesitis index, psoriasis body surface area (BSA), questionnaires and CRP at baseline, 3 and 6months. Primary outcome was the percentage of patients reaching minimal disease activity (MDA) and secondary outcomes were reaching Psoriatic Arthritis Response Criteria (PsARC) and American College of Rheumatology (ACR) response criteria.ResultsTotally 41/46 patients completed the study, 63% women, median age 54years (IQR 48-62). At baseline increased BMI was associated with higher disease activity and poorer function.The median weight loss was 18.7kg (IQR 14.6-26.5) or 18.6% (IQR 14.7-26.3) of the baseline weight. A majority of the disease activity parameters improved significantly after weight loss, including 68/66 tender/swollen joints count, CRP, BSA, Leeds enthesitis index, HAQ and patient VAS for global health, pain and fatigue. A larger weight loss resulted in more improvement in a dose-response manner. The percentage of patients with MDA increased from 29 to 54%, (p=0.002). PsARC was reached by 46.3%. The ACR 20, 50 and 70 responses were 51.2%, 34.1% and 7.3% respectively.ConclusionsShort-term weight loss treatment with VLED was associated with significant positive effects on disease activity in joints, entheses and skin in patients with PsA and obesity. The study supports the hypothesis of obesity as a promotor of disease activity in PsA.Trial registrationClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016retrospectively registered
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46.
  • Klingberg, Eva, et al. (författare)
  • Weight loss is associated with sustained improvement of disease activity and cardiovascular risk factors in patients with psoriatic arthritis and obesity: a prospective intervention study with two years of follow-up
  • 2020
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obesity is overrepresented in patients with psoriatic arthritis (PsA) and associated with increased disease activity. We have previously shown in 41 patients with PsA (Caspar criteria) and obesity (body mass index; BMI >= 33 kg/m(2)) that weight loss treatment with Very Low Energy Liquid Diet (VLED), 640 kcal/day during 12-16 weeks, followed by a structured reintroduction of an energy restricted diet resulted in a median weight loss of 18.6% and concomitantly a significant improvement of the disease activity in joints, entheses and skin. The objectives of this follow-up were to study the effects of the weight loss treatment on disease activity in longer term (12 and 24 months) and to study the effects on cardiovascular risk factors. Methods: The patients were assessed with 66/68 joints count, Leeds enthesitis index (LEI), body surface area, blood pressure, BMI, questionnaires and fasting blood samples at the 12- and 24-month visits. Results: In total, 39 and 35 PsA patients attended the 12- and the 24-month visits, respectively. Median weight loss since baseline was 16.0% (IQR 10.5-22.4) and 7.4% (IQR 5.1-14.0) at the 12- and 24-months follow-up. The 66/68 swollen/tender joints score, LEI, CRP and HAQ score were still significantly reduced at the 12- and 24-month visits compared to baseline. The number of patients with Minimal Disease Activity increased from 28.2% (11/39) at baseline, to 38.5% (15/39;p = 0.008) and 45.7% (16/35;p = 0.016) at the 12- and 24-month visits. The weight loss was also associated with improved levels of serum lipids, glucose and urate and the antihypertensive treatment was reduced or stopped in five patients during the follow-up. Conclusions: Weight loss treatment, with VLED included in the program, was associated with long-term improvement of measures of disease activity, self-reported function and markers of the metabolic syndrome after 24-months follow-up.
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47.
  • Klingberg, Gunilla, 1960, et al. (författare)
  • Caries-related saliva properties in individuals with 22q11 deletion syndrome.
  • 2007
  • Ingår i: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. - : Elsevier BV. - 1528-395X .- 1079-2104 .- 2212-4411. ; 103:4, s. 497-504
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aims were to compare saliva secretion rate, buffer capacity, cariogenic bacteria, total protein, IgA, and electrolytes between patients with 22q11 deletion syndrome (22q11DS) and control subjects and to study correlations between saliva and serum levels of IgA and electrolytes in 22q11DS patients. STUDY DESIGN: Twenty-nine consecutive 22q11DS patients (mean age 12.6 years) and matched healthy control subjects were clinically examined, and stimulated saliva samples were collected. RESULTS: Patients with 22q11DS had impaired salivary secretion rate (P < .01) and buffer capacity (P < .05), higher numbers of cariogenic bacteria (P < .01), increased saliva protein concentrations (P < .001), and reduced output of electrolytes (P < .001-.05) compared with control subjects. A correlation between concentration in serum and saliva was found only for IgA (r = .622; P < .01). CONCLUSIONS: Different salivary components were affected in patients with 22q11DS, which may explain the increased caries risk seen in these patients.
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48.
  • 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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49.
  • 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.
  •  
50.
  • 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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