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  • Abelson, Anna-Karin, et al. (författare)
  • STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk
  • 2009
  • Ingår i: Annals of the Rheumatic Diseases. - 0003-4967 .- 1468-2060. ; 68:11, s. 1746-1753
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE.
  • Agca, R., et al. (författare)
  • EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update
  • 2017
  • Ingår i: Ann Rheum Dis. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 76:1, s. 17-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.
  • Agmon-Levin, Nancy, et al. (författare)
  • International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies
  • 2014
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 73:1, s. 17-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.
  • Ahlstrand, Inger, et al. (författare)
  • Occupational balance and its relation to performance of valued life activities in persons with rheumatoid arthritis in working age
  • 2018
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 77:Suppl. 2, s. 186-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Experience of balance in everyday activities where work is an essential part is important to health and well-being, as has also been observed in previous studies in people with rheumatoid arthritis (RA). The Valued life activity scale (VLA-swe) is a questionnaire in which patient’s first report if the separate activities are valued or not to perform and secondly difficulties to perform these activities. Occupational Balance Questionnaire (OBQ) focuses on satisfaction with the amount and variation of occupations.Objectives The objectives were to 1) describe the relationship between performance of valued activities and experienced occupational balance, and to 2) identify aspects associated with low occupational balance in persons with RA.Methods 368 persons (age 18–65 years, 77% women) with RA responded to a questionnaire measuring occupational balance (OBQ) and performance of valued life activities (VLA-swe). Other aspects of interest were activity limitations measured by Health Assessment Questionnaire (HAQ), pain (measured by VAS), continuous stress (stressed continuously for more than a month during the last 12 months), children at home, education, and living situation. The relation between OBQ and performance in VLA across genders and Workers/Non-workers were analysed using non-parametric correlation analyses. To identify the impact of different aspects on the likelihood that participants would report lower occupational balance, OBQ was analysed using workers/nonworkers, stress, gender, age, pain and difficulties performing valued activities as independent variables in logistic regressions models. The study was approved by the Regional Ethics Committee (Dnr2011/452–31).Results The OBQ was significantly related to difficulties to perform valued activities reported by VLA (r=-0.41, p<0.001). Having more difficulties performing valued activities was the strongest predictor of lower occupation balance and increased the risk of reporting lower occupation balance with nearly five times (OR=4.54, p 0.001). Continuous stress increased the risk of having lower occupation balance more than three times (OR=3.27, p<0.0001) than those who not reported being stressed. The other variables show no significant impact on the likelihood that the participants would report lower occupational balance.Conclusions The results showed support for the relationship between occupation balance and performance of valued life activities and highlights to identify what’s important for the individual and to assume that in the rehabilitation. The results also show the importance of ability to manage stress, in order to enable for retaining ability to work and achieve high occupational balance.
  • Aili, Katarina, 1980-, et al. (författare)
  • Long term trajectories of chronic widespread pain : a 21-year prospective cohort latent class analysis
  • 2019
  • Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 78:Suppl 2, s. 239-239
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic widespread pain (CWP) is common (population prevalence of approximately 10%) and has a significant impact on the individual, healthcare, and society. Currently little is known about the actual course of CWP over time, in particular the pathways to the development and maintenance of CWP. One useful way to understand these pathways is to identify common clusters of people who share pain trajectories. Such information is clinically useful to identify factors that predict development, persistence, and resolution of CWP.Objectives: To identify different longitudinal pain trajectories over a period of 21 years.Methods: A 21-year longitudinal open-population cohort of n=1858 adults (aged 20-74) who completed surveys relating to their pain status in at least three of the five time points 1995, 1998, 2003, 2007, and 2016. Pain status (presence of persistent pain) was ascertained from a report of painful regions (0-18) on a pain mannequin and categorised into: NCP (No chronic pain), CRP (Chronic regional pain) and CWP (chronic widespread pain). Latent Class Growth Analysis (LCGA) was carried out based on these categories. Participants were assigned to a trajectory cluster where the posterior probability was the highest. Model fit was assessed by statistical indices and clinical interpretations of clusters.Results: LCGA identified five clusters describing different pathways of NCP, CRP and CWP over the 21 years. The cluster “Persistent NCP” was the most common pathway (n = 1052, 57%) representing those with no chronic pain over the whole time period. The “Persistent CRP or Migration from CRP to NCP” cluster included 411 individuals (22%) representing a group with stable or improving regional pain. In the groups who were shown to increase pain status, the “Migration from NCP to CRP or CWP” cluster included 92 individuals (5%), and there were 184 individuals (10%) in the cluster “Migration from CRP to CWP” representing a group with regional pain who developed CWP. The final cluster “Persistent CWP” included 119 individuals (6%) representing those with stable CWP throughout the time period. Figure 1 presents the mean number of pain sites over time by cluster.Conclusion: This study showed that whilst half of adults report no chronic pain over 21 years, a substantial proportion develop CWP or have persistent CWP over this time period. Whilst a common trajectory was movement from chronic regional pain to no chronic pain, a pattern of improving CWP was not seen suggesting this is an uncommon trajectory. This is the first study to show long-term trajectories for CWP, and further work is now required to understand factors that may identify individuals at risk of worsening pain status and factors that might promote improvement. These identified pathways of chronic pain over a lifespan improve the understanding of long-term development of chronic pain and chronic widespread pain. © Aili et al. 2019. No commercial re-use. See rights and permissions. Published by BMJ.
  • Aili, Katarina, 1980-, et al. (författare)
  • Passive coping strategies but not physical function are associated with worse mental health, in women with chronic widespread pain – a mixed method study
  • 2019
  • Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 78:Suppl 2, s. 2159-2159
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chronic widespread pain (CWP) is a common condition (approximately 10% prevalence), that affects women twice as often as men. There is a lack of knowledge in how different coping strategies relates to health status during CWP development in a general population.Objectives: To explore different ways of coping with CWP and to relate the different coping strategies to health-related factors, before and after developing CWP.Methods: A sequential explorative mixed methods study including 19 women 45-67 of age, who had reported CWP in a survey 2016, but not in 1995. Individual interviews were analysed with a phenomenographic approach, and resulted in four categories of coping strategies. These categories were further explored with regard to four dimensions of health status (physical function, bodily pain, vitality and mental health) as measured by SF-36 (0-100, a lower score indicates more disability) and sleep problems measured both in 1995, and 2016.Results: The qualitative analysis revealed four categories representing different coping strategies, where each woman was labelled by the most dominant category; the mastering woman, the persistent woman, the compliant woman and the conquered woman. The first two categories emerged as being active coping strategies, and the latter two as passive. Women with passive strategies reported significantly lower vitality (median 57.5 vs 75, p=0.007) and worse mental health (median 54 vs 93, p=0.021) in 1995, before they had developed CWP compared with those with active coping strategies. No differences were seen between the groups on physical function, bodily pain or sleep.In 2016, there were still a difference between the passive and active group regarding mental health (median 56 vs 80, p=0.022), but not for vitality (median 35 vs 40, p=0.707). No differences were seen between the groups on physical function or bodily pain. All eight women with passive strategies reported problems with sleep in 2016, as compared to 6 of the 11 women with active strategies (p=0.045).Conclusion: Women that reported CWP in 2016, but not in 1995, described both active and passive coping strategies. The qualitative findings were associated with differences in vitality and mental health already in 1995, before they had developed CWP. Further, those with passive coping strategies reported worse health with regard to mental health and sleep problems in 2016. Interestingly, the groups did not differ in bodily pain or physical function neither in 1995 nor in 2016, which implicates the importance for the clinician to take the typical coping strategy into consideration, when meeting these patients in clinical settings. © Aili, Bergman, Bremander, Haglund & Larsson 2019. No commercial re-use. See rights and permissions. Published by BMJ.
  • Aili, Katarina, et al. (författare)
  • Sleep problems and fatigue as a predictor for the onset of chronic widespread painover a 5- and 18-year perspective : a 20-year prospective study
  • 2018
  • Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 77, s. 87-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: If localised pain represent one end of a pain spectra, with overall better general health, chronic widespread pain (CWP) and fibromyalgia represent the other end of the spectra with worse general health and more comorbidities with other somatic diseases and mental illness. Sleep problems and fatigue are common among individuals reporting CWP and previous research indicate that sleep problems may be an important predictor for pain prognosis.Objectives: The aim of this population-based study was to investigate if sleep problems and fatigue predict the onset of CWP 5 and 18 years later.Methods: In order to get more stable baseline classifications of CWP, a wash-out period was used, including only individuals who had not reported CWP (according to ACR 1990 criteria for fibromyalgia) at baseline (−98) and three years prior baseline (−95). In all, data from 1249 individuals entered the analyses for the 5 year follow-up (−03) and 791 entered for the 18 year follow-up (−16). Four parameters related to sleep (difficulties initiating sleep, maintaining sleep, early morning awakening and non-restorative sleep), and one parameter related to fatigue (SF-36 vitality scale) were investigated as predictors for CWP. Binary logistic regression analysis were used for analyses.Results: All investigated parameters predicted the onset of CWP five years later (problems with initiating sleep (OR 1.91; 1.16–3.14), maintaining sleep (OR 1.85; 1.14–3.01), early awakening (OR 2.0; 1.37–3.75), non-restorative sleep (OR 2.27; 1.37–3.75) and fatigue (OR 3.70; 1.76–7.84)) in a model adjusted for age, gender, socio-economy and mental health. All parameters except problems with early awakening predicted the onset of CWP also 18 years later. In all, 785 individuals did not report any of the sleeping problems at baseline (fatigue not included), 268 reported one of the problems, 167 two, 128 three and 117 subjects reported to have all four sleep problems. Reporting all four sleep problems was significantly associated with CWP at follow-up at both time points when adjusting for age, gender, socio economy and mental health (OR 4.00; 2.03–7.91 and OR 3.95; 1.90–8.20); adjusting for age, gender, socio economy and number of pain regions (OR 2.94; 1.48–5.82 and OR 2.65; 1.24–5.64) and in a model adjusting for age, gender, socio economy and pain severity (OR 2.97;1.53–5.76; and OR 3.02;1.47–6.21) for the 5 year and 18 year follow-up respectively, compared to not reporting any of the sleep problems at baseline.Conclusions: Both sleeping problems and fatigue predicts the onset of CWP 5- and 18 years later. The results highlight the importance of the assessment of sleep quality in the clinic.
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