| 1. |
- Izadi, Z., et al.
(författare)
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Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
- 2021
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
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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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| 2. |
- Oskarsdottir, Solveig, 1953, et al.
(författare)
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Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome
- 2023
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- This review aimed to update the clinical practice guidelines for managing children and adolescents with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society, the international scientific organization studying chromosome 22q11.2 differences and related conditions, recruited expert clinicians worldwide to revise the original 2011 pediatric clinical practice guidelines in a stepwise process: (1) a systematic literature search (1992-2021), (2) study selection and data extraction by clinical experts from 9 different countries, covering 24 subspecialties, and (3) creation of a draft consensus document based on the literature and expert opinion, which was further shaped by survey results from family support organizations regarding perceived needs. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text reviews, including 1545 meeting criteria for potential relevance to clinical care of children and adolescents. Informed by the available literature, recommendations were formulated. Given evidence base limitations, multidisciplinary recommendations represent consensus statements of good practice for this evolving field. These recommendations provide contemporary guidance for evaluation, surveillance, and management of the many 22q11.2DSassociated physical, cognitive, behavioral, and psychiatric morbidities while addressing important genetic counseling and psychosocial issues.& COPY; 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
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| 3. |
- Judd, N., et al.
(författare)
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Cognitive and brain development is independently influenced by socioeconomic status and polygenic scores for educational attainment
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:22, s. 12411-12418
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors and socioeconomic status (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural associations independently. Here we used a polygenic score for educational attainment (EduYears-PGS), as well as SES, in a longitudinal study of 551 adolescents to tease apart genetic and environmental associations with brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent associations with brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional association with surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This study demonstrates a regional association of EduYears-PGS and the independent prediction of SES with cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence.
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| 4. |
- Huang, X. F., et al.
(författare)
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Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci
- 2020
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:6
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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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| 5. |
- Boot, E., et al.
(författare)
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Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome
- 2023
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- This review aimed to update the clinical practice guidelines for managing adults with 22q11.2 deletion syndrome (22q11.2DS). The 22q11.2 Society recruited expert clinicians worldwide to revise the original clinical practice guidelines for adults in a stepwise process according to best practices: (1) a systematic literature search (1992-2021), (2) study selection and synthesis by clinical experts from 8 countries, covering 24 subspecialties, and (3) formulation of consensus recommendations based on the literature and further shaped by patient advocate survey results. Of 2441 22q11.2DS-relevant publications initially identified, 2344 received full-text review, with 2318 meeting inclusion criteria (clinical care relevance to 22q11.2DS) including 894 with potential relevance to adults. The evidence base remains limited. Thus multidisciplinary recommendations represent statements of current best practice for this evolving field, informed by the available literature. These recommendations provide guidance for the recognition, evaluation, surveillance, and management of the many emerging and chronic 22q11.2DS-associated multisystem morbidities relevant to adults. The recommendations also address key genetic counseling and psychosocial considerations for the increasing numbers of adults with this complex condition.& COPY; 2023 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 6. |
- Exarchou, S., et al.
(författare)
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MORTALITY IN PATIENTS WITH PSORIATIC ARTHRITIS IN SWEDEN
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80, s. 130-131
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In contrast to the increased mortality reported in other inflammatory diseases such as rheumatoid arthritis and psoriasis, prior mortality studies in psoriatic arthritis (PsA) have shown inconsistent results.Objectives:To compare all-cause mortality between PsA patients in Sweden and matched general population controls, and to describe cause of death distributions in the two groups.Methods:All individuals in Sweden with ≥1 main diagnosis of PsA (ICD-10: L40.5/M07.0-M07.3) from outpatient visits to rheumatology or internal medicine clinics at age ≥18 years (y) 2001-2017 were identified from the Swedish National Patient Register. Each case was matched to 5 general population controls based on sex, county and age in the year of the first registered arthritis diagnosis for the case. Cases and controls were followed from 1 Jan, 2007, or from first PsA diagnosis thereafter for index cases, until first occurrence of death (data from the Swedish Cause of Death Register), emigration or 31 Dec, 2018. Mortality was assessed overall, as well as stratified by sex (45% males) and disease duration (PsA diagnosis prior to 2007 [38% of cases] vs. 2007-2017), using matched Cox proportional hazard regression, or – in case the Cox assumption regarding proportionality did not hold – matched Breslow test. To account for potential PsA misclassification (in a previous validation study, 86% of 400 cases fulfilled PsA classification criteria), a sensitivity analysis was performed by randomly replacing 20% of cases with one of their own controls. Moreover, incidence rate ratios (IRR) of death were calculated overall and stratified by sex, disease duration and age. Finally, causes of death (from the Cause of Death Register) were described for PsA cases and controls.Results:Over the 12y follow-up, 3 121 deaths occurred among 33 036 PsA cases (268 402 person-years at risk) and 12 884 deaths among 161 144 controls (1 302 250 person-years), resulting in an increased mortality among the PsA cases (HR 1.11 [95%CI 1.07-1.16], p<0.001, Figure and Table; sensitivity analysis HR 1.09 [1.05-1.14]). The increased mortality was seen mainly among female PsA cases and among cases with longer disease duration (Figure; Table). IRR:s of death were significantly increased for all ages except <40y, with the numerically highest point-estimates for ages 40-49y and 50-59y (Table). Cause of death frequencies among the PsA cases/controls: cardiovascular disease 29/27%; diabetes mellitus 2.1/2.5%; chronic kidney disease 0.4/0.3%; infection 5.7/4.5%; chronic pulmonary disease 5.1/4.1%; malignancy 29/34%; suicide 2.3/2.0%; other 27/26%.Table 1.Mortality rates and incidence rate ratiosPsA casesPopulation controlsNumber of deathsPerson-yearsat riskMortality rate*Number of deathsPerson-yearsat riskMortality rate*Incidence rate ratio (95%CI)Overall3 121268 40211.612 8841 302 2509.91.18 (1.13-1.22)Males1 459120 51712.16 468580 28511.11.09 (1.03-1.15)Females1 662147 88611.26 416721 9668.91.27 (1.20-1.34)Longer disease duration1 943139 37913.97 459670 17411.11.25 (1.19-1.32)Shorter disease duration1 178129 0239.15 425632 0778.61.06 (1.00-1.13)Age intervals (years)<401833 5680.598163 2780.60.89 (0.54-1.48)40-499050 5521.8322246 9551.31.37 (1.08-1.73)50-5928065 8204.31 131321 7303.51.21 (1.06-1.38)60-6972370 22410.33 132341 5879.21.12 (1.04-1.22)70-7996037 23225.84 160178 90923.31.11 (1.03-1.19)≥801 05011 00795.44 04149 79181.21.18 (1.10-1.26)* Per 1000 person-years.Conclusion:In this nationwide 12y assessment, the mortality risk among PsA patients in Sweden was increased by around 10% as compared to the general population, mainly driven by increased risks among females and patients with longer disease duration. Cause of death distributions were numerically similar between PsA cases and controls.References:Disclosure of Interests:Sofia Exarchou Consultant of: AbbVie, Novartis, Daniela Di Giuseppe: None declared, Gerd-Marie Alenius: None declared, Eva Klingberg Speakers bureau: Eli Lilly, Consultant of: Novartis, Grant/research support from: Roche, Valgerdur Sigurdardottir Consultant of: Novartis, Sanofi, Sara Wedrén: None declared, Ulf Lindström: None declared, Carl Turesson Speakers bureau: AbbVie, BMS, Pfizer, Roche, Consultant of: Roche, Grant/research support from: BMS, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Johan Askling Grant/research support from: For ARTIS: AbbVie, BMS, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB. This study was supported by AbbVie, Amgen, Eli Lilly, Novartis and Pfizer. The sponsors were allowed to comment on the study protocol and were provided with a report of the results, but had no influence on the study design or decision to submit the abstract., Johan K Wallman Consultant of: Celgene, Eli Lilly, Novartis
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| 7. |
- Kiruja, J., et al.
(författare)
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Maternal near-miss and death incidences – Frequencies, causes and the referral chain in Somaliland : A pilot study using the WHO near-miss approach
- 2017
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 12, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- Background Somaliland is a self-declared country with a population of 3.5 million. Most of its population reside in rural areas. The objective of this pilot near-miss study was to monitor the frequency and causes of maternal near-miss and deaths and the referral chain for women to access Skilled Birth Attendants (SBA). Method: A facility-based study of all maternal near-miss and mortality cases over 5 months using the WHO near-miss tool in a main referral hospital. Reasons for bypassing the Antenatal Care facility (ANC) and late arrival to the referral hospital were investigated through verbal autopsy. Results: One hundred and thirty-eight (138) women with severe maternal complications were identified: 120 maternal near-miss, 18 maternal deaths. There were more near-miss cases on arrival (74.2%) compared with events that developed inside the hospital (25.8%). Likewise, there were more maternal deaths (77.8%) on arrival than was the case during hospitalization (22.2%). The most common mode of referral among maternal near-miss events was family referrals (66.7%). Of 18 maternal deaths, 15 were family referrals. Reasons for bypassing ANC were as follows: lack of confidence in the service provided; lack of financial resources; and lack of time to visit ANC. Reasons for late arrival to the referral hospital were as follows: lack of knowledge and transportation; and poor communication. Conclusion and clinical implication: To increase the utilization of ANC might indirectly lower the number of near-miss and death events. Collaboration between ANC staff and referral hospital staff and a more comprehensive near-miss project are proposed. © 2017 Elsevier B.V.
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| 8. |
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| 9. |
- Schumann, G, et al.
(författare)
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Stratified medicine for mental disorders
- 2014
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Ingår i: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - : Elsevier BV. - 1873-7862. ; 24:1, s. 5-50
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Wallman, J. K., et al.
(författare)
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High degree of classification criteria fulfillment among patients with clinical psoriatic arthritis diagnoses in Sweden
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, s. 1725-1726
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The clinical diagnosis of psoriatic arthritis (PsA) may be challenging. In Sweden, the vast majority of PsA cases are diagnosed within rheumatology or internal medicine (IM). Knowledge of the correspondence between clinical ICD diagnoses and classification criteria fulfillment is crucial to interpret studies identifying cases based on ICD codes.Objectives:To assess the degree to which patients with clinical PsA diagnoses in Sweden fulfill established PsA classification criteria.Methods:Four hundred patients with ≥1 outpatient physician visit to one of five rheumatology or IM departments (3 university/2 county departments, spread across Sweden) 2013-2015 with a main ICD-10 diagnosis of PsA (L40.5/M07.0-M07.3), were randomly selected from the Swedish National Patient Register (80 cases/site). Based on a structured medical record review, positive predictive values (PPV) of a clinical PsA diagnosis (i.e. ≥1 visit with a PsA ICD-10 code) for fulfillment of the following classification criteria were assessed: CASPAR,[1] Moll & Wright,[2] Vasey & Espinoza,[3] and Modified ESSG criteria for PsA,[4] respectively (as well as for any of these); ASAS criteria for peripheral or axial spondyloarthritis (SpA) [5]; and the 1987 ACR criteria for rheumatoid arthritis (RA).[6] Subanalyses regarding CASPAR fulfillment were also performed restricted to patients with available rheumatoid factor and peripheral X-ray status (central CASPAR items; n=227), and among patients with ≥2 ICD codes for PsA, of which ≥1 from a rheumatology/IM department (n=353).Results:Out of 400 clinically diagnosed PsA patients, 343 (86%) fulfilled any of the 4 PsA classification criteria, with a PPV for CASPAR fulfillment of 69% (rising to 73-82% in the subanalyses;Figure 1). Substantial overlap was seen regarding fulfillment of the 4 PsA criteria (Figure 2A). Moreover, 86% fulfilled the ASAS peripheral or axial SpA criteria, while the 1987 ACR definition of RA was met by 27% – in both cases with the great majority also classifiable as PsA (Figure 2B). Most patients not fulfilling any PsA criteria had either no verified arthritis or polyarticular disease (Table). Overall, only 6.5% of the clinical PsA diagnoses were judged as clearly wrong by the rheumatologists performing the medical record assessments.Conclusion:The validity of clinical ICD-10 diagnoses for PsA in the Swedish National Patient Register is good, with a PPV of 86% for the fulfillment of established PsA classification criteria.References:[1]Arthritis Rheum2006;54:2665-73[2]Semin Arthritis Rheum 1973;3:55-78[3]In: Calin A, editor. Spondyloarthropathies. Orlando: Grune & Stratton; 1984:151-85[4]Ann Rheum Dis2005;64(Suppl II):ii3–ii8[5]Ann Rheum Dis2011;70:25-31[6]Arthritis Rheum1988;31:315-24Patient characteristics (n=400), stratified by classification criteria fulfillmentFulfilling anyPsA criterian=343Not fulfilling anyPsA criterian=57Male sex, %4644Age, yrs; mean (SD)59 (14)62 (15)Symptom duration, yrs; mean (SD)18 (12)16 (13)Psoriasis, %8947Nail psoriasis, %3811Arthritis, %9358 Monoarthritis, %*7.90 Oligoarthritis, %*4522 Polyarthritis, %*4778DIP-joint arthritis, %287.0Dactylitis, %281.8Enthesitis, %4219Inflammatory back pain, %275.3RF positive, %5.814ACPA positive, %4.43.5Arthritic X-ray changes in hands/feet, %3321* % of patients with arthritis of known distribution. Missing data: 0-4%, except forRF (33%), ACPA (37%) and X-ray changes (20%).Acknowledgments:This work was supported by Celgene, Novartis, Pfizer, Reumatikerförbundet and Psoriasisförbundet.Disclosure of Interests:Johan K Wallman Consultant of: AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma, Gerd-Marie Alenius: None declared, Eva Klingberg Grant/research support from: Roche, Consultant of: Novartis, Speakers bureau: Eli Lilly, Valgerdur Sigurdardottir Consultant of: Novartis, Sara Wedrén: None declared, Sofia Exarchou: None declared, Ulf Lindström: None declared, Daniela Di Giuseppe: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer
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