| 1. |
- Bairkdar, Majd, et al.
(författare)
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Incidence and prevalence of systemic sclerosis globally : A comprehensive systematic review and meta-analysis
- 2021
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:7, s. 3121-3133
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Forskningsöversikt (refereegranskat)abstract
- Objectives: We aimed to conduct a systematic review and meta-analysis on the incidence and prevalence of SSc covering the entire literature. Methods: This study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement of 2009. We conducted a systematic search in MEDLINE, Web of Science and Embase to identify articles reporting incidence and/or prevalence of SSc. Two authors conducted the search, reviewed articles for inclusion and extracted relevant data. We used random-effects models to estimate the pooled prevalence and incidence of SSc and performed subgroup analyses by sex, case definition and region to investigate heterogeneity. We explored the association between calendar period and reported estimates using meta-regression. Results: Among 6983 unique records identified, we included 61 studies of prevalence and 39 studies of incidence in the systematic review. The overall pooled prevalence of SSc was 17.6 (95% CI 15.1, 20.5) per 100 000 and the overall pooled incidence rate of SSc was 1.4 (95% CI 1.1, 1.9) per 100 000 person-years. We observed significant regional variations in reported estimates; studies conducted in North America reported considerably higher estimates than other regions. The pooled incidence and prevalence in women were five times higher than in men. More recent studies reported higher estimates than older ones. Conclusion: In this comprehensive review of the incidence and prevalence of SSc across the world, there was large heterogeneity among estimates, which should be taken into consideration when interpreting the results.
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| 2. |
- Bairkdar, Majd, et al.
(författare)
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Survival in Swedish patients with systemic sclerosis : A nationwide population-based matched cohort study
- 2023
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 62:3, s. 1170-1178
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To conduct the first-ever nationwide, population-based cohort study investigating survival patterns of all patients with incident SSc in Sweden compared with matched individuals from the Swedish general population. Methods: We used the National Patient Register to identify patients with incident SSc diagnosed between 2004 and 2015 and the Total Population Register to identify comparators (1:5), matched on sex, birth year and residential area. We followed them until death, emigration or the end of 2016. Follow-up of the general population comparators started the same date as their matched patients were included. We estimated all-cause survival using the Kaplan-Meier method, crude mortality rates and hazard ratios (HRs) using flexible parametric models. Results: We identified 1139 incident patients with SSc and 5613 matched comparators. The median follow-up was 5.0 years in patients with SSc and 6.0 years for their comparators. During follow-up, 268 deaths occurred in patients with SSc and 554 in their comparators. The 5-year survival was 79.8% and the 10-year survival was 67.7% among patients with SSc vs 92.9% and 84.8%, respectively, for the comparators (P < 0.0001). The mortality rate in patients with SSc was 42.1 per 1000 person-years and 15.8 per 1000 person-years in their comparators, corresponding to an HR of 3.7 (95% CI 2.9, 4.7) at the end of the first year of follow-up and 2.0 (95% CI 1.4, 2.8) at the end of the follow-up period. Conclusion: Despite advances in understanding the disease and in diagnostic methods over the past decades, survival is still severely impacted in Swedish patients diagnosed with SSc between 2004 and 2015.
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| 3. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 4. |
- Berglund, Daniel, et al.
(författare)
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Measures of Additive Interactionand Effect Direction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Measures for additive interaction are defined using risk ratios. These ratios need to be modeled so that all combinations of the exposures are harmful, as the scale between protective and harmful factors differs. This remodeling is referred to as recoding. Previously, recoding has been thought of as random. In this paper, we will examine and discuss the impact of recoding in studies with small effect sizes, such as genome wide association studies, and the impact recoding has on significance testing.
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| 5. |
- Berglund, Daniel
(författare)
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Models for Additive and Sufficient Cause Interaction
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to develop and explore models in, and related to, the sufficient cause framework, and additive interaction. Additive interaction is closely connected with public health interventions and can be used to make inferences about the sufficient causes in order to find the mechanisms behind an outcome, for instance a disease.In paper A we extend the additive interaction, and interventions, to include continuous exposures. We show that there does not exist a model that does not lead to inconsistent conclusions about the interaction.The sufficient cause framework can also be expressed using Boolean functions, which is expanded upon in paper B. In this paper we define a new model based on the multifactor potential outcome model (MFPO) and independence of causal influence models (ICI).In paper C we discuss the modeling and estimation of additive interaction in relation to if the exposures are harmful or protective conditioned on some other exposure. If there is uncertainty about the effects direction there can be errors in the testing of the interaction effect.
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| 6. |
- Berglund, Daniel, et al.
(författare)
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On the Existence of Suitable Models for Additive Interaction with Continuous Exposures
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Additive interaction can be of importance for public health interventions and it is commonly defined using binary exposures. There has been expansions of the models to also include continuous exposures, which could lead to better and more precise estimations of the effect of interventions. In this paper we define the intervention for a continuous exposure as a monotonic function. Based on this function for the interventions we prove that there is no model for estimating additive interactions with continuous exposures for which it holds that; (i) both exposures have marginal effects and no additive interaction on the exposure level for both exposures, (ii) neither exposure has marginal effect and there is additive interaction between the exposures. We also show that a logistic regression model for continuous exposures will always produce additive interaction if both exposures have marginal effects.
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| 7. |
- Essner, Ann, Medicine Doktor, PhD, et al.
(författare)
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Physical activity and sport-specific training patterns in Swedish sporting and working trial dogs : A questionnaire survey
- 2022
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Ingår i: Frontiers in Veterinary Science. - : Frontiers Media S.A.. - 2297-1769. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore physical activity patterns, including conditioning exercise and sport-specific training, and management routines utilized by handlers of Swedish sporting and working dogs participating in agility, obedience, rally obedience and working trial disciplines.Procedures: Dog handlers provided information on competition-level dogs through an internet-based cross-sectional and descriptive survey on physical activity, sport-specific training and management. Results are reported overall and stratified by participation in specific disciplines.Results: We received 1615 replies to the questionnaire. After data cleaning, 1582 dogs (98%) remained for the analysis. Of these, 430 participated in agility, 790 in obedience, 596 in rally obedience, and 847 dogs had competed in a working trial, i.e., messenger, protection, search or tracking. Number of disciplines performed by each dog varied between one and five. Most common was participation in one (n = 767, 48%) or two (n = 541, 34%) disciplines. Out of the dogs competing in one discipline, 38% (n = 294) were considered to be specialized as they actively trained only that discipline for >= 10 months per year. The vast majority of the dogs (n = 1129, 71%) received more than 1 h of daily physical activity, e.g., walks, and only n = 51 (3%) were never exercised off-leash. Preferred self-selected gait was trot (n = 907, 57%) and gallop (n = 499, 32%). A fifth (n = 319, 20%) never played with other dogs. The majority (n = 1328, 84%) received more than 1 h of vigorous physical conditioning exercise per week. Almost three quarters (n = 1119, 71%) participated in physical conditioning exercise. Two thirds (n = 953, 60%) participated in at least 3 h of sport-specific training per week and only a very small portion (n = 35, 2%) trained their specific discipline less than once per week. Median total work load, i.e., all daily physical activity, vigorous physical conditioning exercise and sport-specific training, was 16.5 h per week.Conclusion and clinical relevance: We observe physical activity at moderate to high durations and moderate to vigorous intensities among Swedish sporting and working trial dogs. Most dogs received physical conditioning exercise, but not all dogs were warmed up before training and competition. Our study provides veterinary professionals and dog trainers with valuable insights on the physical exposures and management routines of sporting and working trial dogs.
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| 8. |
- Folkersen, Lasse, et al.
(författare)
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Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis : results from the COMBINE study.
- 2016
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Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1076-1551 .- 1528-3658. ; 22, s. 322-328
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients.METHODS: We collected 451 blood samples from 61 healthy individuals and 185 RA patients initiating treatment, before treatment initiation and at a 3 month follow-up time. All samples were subjected to high-throughput RNA sequencing, DNA genotyping, extensive proteomics and flow cytometry measurements, as well as comprehensive clinical phenotyping. Literature review identified 2 proteins, 52 single-nucleotide polymorphisms (SNPs) and 72 gene-expression biomarkers that had previously been proposed as predictors of TNF inhibitor response (∆DAS28-CRP).RESULTS: From these published TNFi biomarkers we found that 2 protein, 2 SNP and 8 mRNA biomarkers could be replicated in the 59 TNF initiating patients. Combining these replicated biomarkers into a single signature we found that we could explain 51% of the variation in ∆DAS28-CRP. This corresponds to a sensitivity of 0.73 and specificity of 0.78 for the prediction of three month ∆DAS28-CRP better than -1.2.CONCLUSIONS: The COMBINE biobank is currently the largest collection of multi-omics data from RA patients with high potential for discovery and replication. Taking advantage of this we surveyed the current state-of-the-art of drug-response stratification in RA, and identified a small set of previously published biomarkers available in peripheral blood which predicts clinical response to TNF blockade in this independent cohort.
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| 9. |
- Lourdudoss, Cecilia, et al.
(författare)
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Dietary Intake of Polyunsaturated Fatty Acids and Pain in Spite of Inflammatory Control Among Methotrexate-Treated Early Rheumatoid Arthritis Patients.
- 2018
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Ingår i: Arthritis care & research. - : Wiley. - 2151-464X .- 2151-4658. ; 70:2, s. 205-212
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate potential associations between dietary intake of polyunsaturated fatty acids (FAs) and pain patterns in early rheumatoid arthritis (RA) patients after 3 months of methotrexate (MTX) treatment.METHODS: We included 591 early RA patients with MTX monotherapy from a population-based prospective case-control study, the Epidemiological Investigation of Rheumatoid Arthritis. Dietary data on polyunsaturated FAs (food frequency questionnaires) were linked with data on unacceptable pain (visual analog scale [VAS] >40 mm), noninflammatory/refractory pain (VAS >40 mm and C-reactive protein [CRP] level <10 mg/liter), and inflammatory pain (VAS >40 mm and CRP level >10 mg/liter) after 3 months. Statistical analysis included logistic regression.RESULTS: After 3 months of MTX treatment, 125 patients (21.2%) had unacceptable pain, of which 92 patients had refractory pain, and 33 patients had inflammatory pain. Omega-3 FA intake was inversely associated with unacceptable pain and refractory pain (odds ratio [OR] 0.57 [95% confidence interval (95% CI) 0.35-0.95] and OR 0.47 [95% CI 0.26-0.84], respectively). The omega-6:omega-3 FA ratio, but not omega-6 FA alone, was directly associated with unacceptable pain and refractory pain (OR 1.70 [95% CI 1.03-2.82] and OR 2.33 [95% CI 1.28-4.24], respectively). Furthermore, polyunsaturated FAs were not associated with either inflammatory pain or CRP level and erythrocyte sedimentation rate at followup. Omega-3 FA supplementation was not associated with any pain patterns.CONCLUSION: Omega-3 FA was inversely associated with, and the omega-6:omega-3 FA ratio was directly associated with, unacceptable and refractory pain, but not with inflammatory pain or systemic inflammation. The inverse association between omega-3 FA and refractory pain may have a role in pain suppression in RA.
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| 10. |
- Manivel, Vivek Anand, et al.
(författare)
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Anticollagen type II antibodies are associated with an acute onset rheumatoid arthritis phenotype and prognosticate lower degree of inflammation during 5 years follow-up
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:9, s. 1529-1536
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAntifibrillar collagen type II (anti-CII) antibody-positive patients with rheumatoid arthritis (RA) have early but not late signs of increased inflammation and joint erosions. We wanted to replicate this in a large RA cohort, and to relate to human leukocyte antigen (HLA)-DRB1* alleles.MethodsAnti-CII and anti-cyclic citrullinated peptide (CCP)2 were measured at baseline in 773 patients with RA from the Swedish Epidemiological Investigation in Rheumatoid Arthritis (EIRA) study with clinical follow-up data from the Swedish Rheumatology Quality Register (SRQ) registry, and 1476 with HLA-DRB1* information. Comparisons were done concerning C reactive protein (CRP), erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), Disease Activity Score encompassing 28 joints based on ESR (DAS28), DAS28CRP, pain-Visual Analogue Scale (VAS), global-VAS and Health Assessment Questionnaire Score (HAQ) at eight occasions during 5 years, and association with HLA-DRB1* alleles.ResultsAnti-CII associated with elevated CRP, ESR, SJC, DAS28 and DAS28CRP at diagnosis and up to 6 months, whereas anti-CCP2 associated with SJC and DAS28 from 6 months to 5 years, but not earlier. The anti-CII-associated phenotype was strong, and predominated in anti-CII/anti-CCP2 double-positive patients. Anti-CII was associated with improvements in CRP, ESR, SJC, TJC and DAS28, whereas anti-CCP2 was associated with deteriorations in SJC and DAS28 over time. Anti-CII-positive patients achieved European League Against Rheumatism good or moderate response more often than negative patients. Anti-CII was positively associated with HLA-DRB1*01 and HLA-DRB1*03, with significant interaction, and double-positive individuals had >14 times higher mean anti-CII levels than HLA double negatives. Whereas smoking was associated with elevated anti-CCP2 levels, smokers had lower anti-CII levels.ConclusionsAnti-CII seropositive RA represents a distinct phenotype, in many respects representing the converse to the clinical, genetic and smoking associations described for anticitrullinated protein peptide autoantibodies. Although not diagnostically useful, early anti-CII determinations predict favourable inflammatory outcome in RA.
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