| 1. |
- Torsteinsdottir, Ingunn, et al.
(author)
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Production and elimination of hyaluronan in rheumatoid arthritis patients : estimation with a loading test
- 1999
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In: Seminars in Arthritis & Rheumatism. - 0049-0172 .- 1532-866X. ; 28:4, s. 268-279
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the benefit of determining the maximal elimination rate (Vmax) and the endogenous production of hyaluronan (HYA) in relation to the basal HYA concentration (c0) in rheumatoid arthritis (RA) patients; and to evaluate the compatibility of a new model for HYA kinetics, taking renal elimination into separate account in the overall clearance of HYA from the blood. METHODS: The calculations of production and elimination of HYA were based on the HYA loading test, which was performed in 21 patients with RA and 15 healthy controls. A blood sample was drawn before the loading test, followed by an intravenous (i.v.) injection of HYA as a single bolus dose of 7.5 mg. Blood samples were taken regularly during the next 60 minutes. A theoretical model with computational analysis of the data collected was used for calculating HYA production and elimination. RESULTS: Patients with RA had significantly higher c0 than healthy controls, although in 10 of 21 patients c0 was within the normal range. The RA patients also had higher Vmax than healthy controls, but the difference was not significant. The calculated production of HYA was increased in RA patients (P = .001) and correlated with c0 (P < .0001). The new model for HYA kinetics, in which the renal elimination was taken separately into account, proved to be more compatible than the previous model. CONCLUSION: The HYA loading test can help determine whether the increased serum level of HYA in RA patients is due to a high production or reduced elimination of HYA or both.
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| 2. |
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| 3. |
- Christiansen, Sara Nysom, et al.
(author)
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Patient-reported outcomes in axial spondyloarthritis and psoriatic arthritis patients treated with secukinumab for 24 months in daily clinical practice
- 2024
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In: Seminars in Arthritis and Rheumatism. - 0049-0172 .- 1532-866X. ; 65
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Journal article (peer-reviewed)abstract
- Objectives: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. Patients and methods: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0–10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. Results: We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84–1.02]). Conclusion: In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Erlandsson, Malin, 1972, et al.
(author)
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Survivin improves the early recognition of rheumatoid arthritis among patients with arthralgia : A population-based study within two university cities of Sweden
- 2018
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In: Seminars in Arthritis & Rheumatism. - : Saunders Elsevier. - 0049-0172 .- 1532-866X. ; 47:6, s. 778-785
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Research review (peer-reviewed)abstract
- Objectives: The aim of this study was to validate the use of survivin for preclinical recognition of rheumatoid arthritis (RA) among patients with unexplained arthralgia.Methods: Serum levels of survivin and the arthritis-specific autoantibodies RF and ACPA were measured in total of 5046 patients with musculoskeletal complains during 12 consecutive months in Gothenburg and in Umea. Among them, 303 arthralgia patients were identified and prospectively followed.Results: After 48 months, 12.2% of the arthralgia patients developed RA. Most of RA cases had high serum survivin, which increased the relative risk for RA (RR = 5.90,p = 3 x 10(-7)). Combination of survivin with autoantibodies was present in only 4.6% of the arthralgia patients and increased further the risk of RA and shortened time to RA development. Presence of any single autoantibody in the survivin-negative patients was associated with a minor risk for RA and had RA-free survival similar to the reference group.Conclusion: This study shows that measurement of survivin in serum improves estimation of RA risk and prospectively predicts RA development in patients with arthralgia. Survivin may indicate a phase preceding autoantibody production.
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| 8. |
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| 9. |
- Geijer, Mats, 1957, et al.
(author)
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Health-related quality of life in early psoriatic arthritis compared with early rheumatoid arthritis and a general population
- 2021
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 51:1, s. 246-252
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Journal article (peer-reviewed)abstract
- Objective: Both psoriatic arthritis (PsA) and rheumatoid arthritis (RA) have a significant impact on quality of life, but few reports have compared the two diseases. The current study assessed health-related quality of life (HRQoL) in PsA at diagnosis and after five years compared with early rheumatoid arthritis (RA) and a matched general population. Methods: Patients with early PsA and early RA included in two Swedish registries with HRQoL data measured by the Medical Outcomes Study Short Form 36 (SF-36) at baseline and at five years follow-up were included. Differences in SF-36 scores compared with the general population were calculated for each patient. Physical function, disease activity, the delay before diagnosis, pain, and general wellbeing were used as explanatory variables. Statistical tests included t-tests and univariate and multivariate linear regression. Results: PsA (n = 166) and RA (n = 133) patients of both sexes had significantly reduced HRQoL at disease onset. After five years, PsA patients still had impairments in several domains of SF-36, whereas RA patients had an almost normalized HRQoL. The time from symptom onset to diagnosis, disease activity, and disability independently contributed to the reduced improvement in PsA. Conclusion: Both early PsA and RA are characterized by severely reduced HRQoL. Despite more severe disease at inclusion, normalization of HRQoL is seen in patients with RA but not PsA. This may be due to delay in the diagnosis of PsA or more powerful interventions in RA. Earlier detection, lifestyle intervention, and more aggressive management strategies may be needed for PsA. (C) 2020 Elsevier Inc. All rights reserved.
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| 10. |
- Holm, Paetur M., et al.
(author)
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Effects of neuromuscular control and strengthening exercises on MRI-measured thigh tissue composition and muscle properties in people with knee osteoarthritis - an exploratory secondary analysis from a randomized controlled trial
- 2024
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In: SEMINARS IN ARTHRITIS AND RHEUMATISM. - 0049-0172 .- 1532-866X. ; 65
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Journal article (peer-reviewed)abstract
- Objective: To investigate the effects of adding strength training to neuromuscular control exercises on thigh tissue composition and muscle properties in people with radiographic -symptomatic knee osteoarthritis (KOA). Methods: In this exploratory secondary analysis of a randomized controlled trial, using a complete -case approach, participants performed 12 weeks of twice -weekly neuromuscular control exercise and patient education (NEMEX, n = 34) or NEMEX plus quadriceps strength training (NEMEX+ST, n = 29). Outcomes were MRImeasured inter- and intramuscular adipose tissue (InterMAT, IntraMAT), quadriceps muscle cross-sectional area (CSA), knee -extensor strength, specific strength (strength/lean CSA) and 30 s chair -stands. Betweengroup effects were compared using a mixed model analysis of variance. Results: At 12 weeks, responses to NEMEX+ST overlapped with NEMEX for all outcomes. Both groups reduced InterMAT (NEMEX+ST=25 %, NEMEX=21 %); between -group difference: 0.8cm2 (95 % CI: -0.1, 1.7). NEMEX+ST decreased IntraMAT (2 %) and NEMEX increased IntraMAT (4 %); between -group difference 0.1 %-points (-0.3, 0.5). Both groups increased quadriceps CSA and lean CSA (CSA minus IntraMAT), improved knee -extensor strength and specific strength, and improved chair -stand performance with a trend towards greater effects in NEMEX+ST. Conclusion: Adding strength training to 12 weeks of neuromuscular control exercises provided largely similar effects to neuromuscular control exercises alone in decreasing InterMAT and IntraMAT, in improving kneeextensor strength, CSA and in improving performance -based function in KOA persons, with a trend towards greater effects with additional strength training. Notably, both groups substantially reduced InterMAT and improved specific strength (an index of muscle quality). Our hypothesis -generating work warrants exploration of the roles played by InterMAT and IntraMAT in exercise effects in KOA.
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| 11. |
- Isgren, Anniella, et al.
(author)
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High Survivin Levels Predict Poor Clinical Response to Infliximab Treatment in Patients with Rheumatoid Arthritis
- 2012
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 41:5, s. 652-657
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Research review (peer-reviewed)abstract
- Objective: To evaluate if the measurement of survivin in the blood of patients with rheumatoid arthritis (RA) undergoing infliximab treatment has predictive value for treatment response. Methods: The study included 87 consecutive RA patients (age 24-89 years, disease duration 18-526 months) treated with regular infusions of influximab. Survivin levels were measured by enzyme-linked immunosorbent assay and evaluated in relation to the total dose of infliximab, disease activity (DAS28), response to infliximab treatment (change in DAS28 > 1.2), and radiographic damage (vdH-Sharp score). Results: Thirty-seven percent of patients were survivin-positive (survivin > 0.9 ng/mL) and showed severe radiographic damage at the start of infliximab treatment compared with survivin-negative (P = 0.027). Patients with high survivin levels were unlikely to respond to infliximab treatment (OR 4.02 [1.22-14.61], P = 0.022) and achieve remission (OR 4.32[1.01-30.11], P = 0.048) compared with patients with low survivin levels. Conclusions: High survivin levels are associated with severe radiographic damage at the start of treatment and a poor response to infliximab. Survivin measurement should be considered an additional tool for aiding the selection and follow-up of antirheumatic treatment. (C) 2012 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:652-657
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| 12. |
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| 13. |
- Jönsen, Andreas, et al.
(author)
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Direct and indirect costs for systemic lupus erythematosus in Sweden. A nationwide health economic study based on five defined cohorts
- 2016
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In: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 45:6, s. 684-690
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Research review (peer-reviewed)abstract
- Objectives: The main objectives of this study were to calculate total costs of illness and cost -driving disease features among patients with systemic lupus erythematosus (SLE) in Sweden. Methods: Five cohorts of well-defined SLE patients, located in different parts of the country were merged. Incident and prevalent cases from 2003 through 2010 were included. The American College of Rheumatology (ACR) classification criteria was used. From the local cohorts, data on demographics, disease activity (SLEDAI 2K), and organ damage (SDI) were collected. Costs for inpatient care, specialist outpatient care and drugs were retrieved from national registries at the National Board of Health and Welfare. Indirect costs were calculated based on sickness leave and disability pensions from the Swedish Social Insurance Agency. Results: In total, 1029 SLE patients, 88% females, were included, and approximately 75% were below 65 years at the end of follow-up, and thus in working age. The mean number of annual specialist physician visits varied from six to seven; mean annual inpatient days were 3.1-3.6, and mean annual sick leave was 123-148 days, all per patient. The total annual cost was 208,555 SEK ($33,369 = 22,941(sic)), of which direct cost was 63,672kr ($10,188 = 7004(sic)) and the indirect cost was 144,883 SEK ($23,181 = 15,937(sic)), all per patient. The costs for patients with short disease duration were higher. Higher disease activity as measured by a SLEDAI 2K score > 3 was associated with approximately 50% increase in both indirect and direct costs. Damage in the neuropsychiatric and musculoskeletal domains were also linked to higher direct and indirect costs, while organ damage in the renal and ocular systems increased direct costs. Conclusion: Based on this study and an estimate of slightly more than 6000 SLE patients in Sweden, the total annual cost for SLE in the country is estimated at $188 million (= 129.5 million (sic)). Both direct (30%) and indirect costs (70%) are substantial. Medication accounts for less than 10% of the total cost. The tax paid national systems for health care and social security in Sweden ensure equal access to health care, sick leave reimbursements, and disability pensions nationwide. Our extrapolated annual costs for SLE in Sweden are therefore the best supported estimations thus far, and they clearly underline the importance of improved management, especially to reduce the indirect costs. (C) 2016 Elsevier Inc. All rights reserved.
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| 14. |
- Kundakci, Burak, et al.
(author)
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International, multidisciplinary Delphi consensus recommendations on non-pharmacological interventions for fibromyalgia
- 2022
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In: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 57
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Journal article (peer-reviewed)abstract
- Objectives: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia.Methods: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving <30% votes were rejected and those obtaining 30-70% votes were recirculated for up to two additional rounds.Results: Seventeen experts participated (Europe (n = 10), North America (n = 6), and Israel (n = 1)) in the Delphi exercise and completed all three rounds. Aerobic exercise, education, sleep hygiene and cognitive behavioural therapy were recommended as core treatments for all symptoms. Mind-body exercises were recommended as core interventions for pain, fatigue and sleep problems. Mindfulness was voted core treatment for depression, and adjunctive treatment for other symptoms. Other interventions, namely music, relaxation, hot bath, and local heat were voted as adjunctive treatments, varying between symptoms.Conclusions: This study provided evidence-based expert consensus recommendations on non-pharmacological treatments for fibromyalgia that may be used to individualise treatments in clinical practice targeting the diverse symptoms associated with fibromyalgia.
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| 15. |
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| 17. |
- Lodin, Karin, et al.
(author)
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Patient global assessment and inflammatory markers in patients with idiopathic inflammatory myopathies : A longitudinal study
- 2024
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In: Seminars in Arthritis & Rheumatism. - : Elsevier. - 0049-0172 .- 1532-866X. ; 65
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Journal article (peer-reviewed)abstract
- AimTo explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM).MethodsPGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function.ResultsPGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity.ConclusionIncreased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials.
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| 18. |
- Lourido, Lucia, et al.
(author)
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Association of serum anti-centromere protein F antibodies with clinical response to infliximab in patients with rheumatoid arthritis : A prospective study
- 2020
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In: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 50:5, s. 1101-1108
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Journal article (peer-reviewed)abstract
- Background: One-third of rheumatoid arthritis (RA) patients demonstrate no clinical improvement after receiving tumor necrosis factor inhibitors (TNFi). The presence of serum autoantibodies is a hallmark in RA and may provide information on future response to treatment. The aim of this prospective study was to search for novel serum autoantibodies useful to predict clinical response to TNFi. Methods: The autoantibody repertoire was profiled on RA patients treated with TNFi as a first line of biologic therapy (N= 185), who were recruited in three independent cohorts. The presence and levels of autoantibodies in serum at baseline were analysed in association with the clinical response after 24 weeks follow-up. A multiplex bead array built using antigens selected from an initial untargeted screening was employed to identify the autoantibodies on a discovery cohort (N= 50) and to verify and validate the results on verification (N= 61) and validation (N= 74) cohorts. Non-parametric tests, meta-analysis and Receiver Operating Curves (ROC) were performed in order to assess the clinical relevance of the observed findings. Results: Novel autoantibodies were associated with the clinical response to TNFi, showing different reactivity profiles among the different TNFi. The baseline levels of IgG antibodies against Centromere protein F (CENPF), a protein related to cell proliferation, were significantly (p <0.05) increased in responders (N=111) to infliximab (IFX) compared to non-responders (N= 44). The addition of anti-CENPF antibodies to demographic and clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate responders, showing an area under the curve (AUC) of 0.756 (95% CI [0.639-0.874], p = 0.001). A further meta-analysis demonstrated the significant association of anti-CENPF levels with the patient's subsequent response to IFX, showing a standardized mean difference (SMD) of-0.65 (95% CI [-1.02;-0.27], p = 0.018). Conclusions: Our study reveals for the first time the potential of circulating anti-CENPF antibodies to predict the clinical response to IFX before starting the treatment. This finding could be potentially useful to guide therapeutic decisions and may lead to further studies focusing on the role of CENPF on RA pathology. (C) 2020 Elsevier Inc. All rights reserved.
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| 19. |
- Nielsen, Wils, et al.
(author)
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OMERACT 2023 Systemic Lupus Erythematosus Special Interest Group : Winnowing and Binning Preliminary Candidate Domains for the Core Outcome Set
- 2024
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In: Seminars in Arthritis & Rheumatism. - : Elsevier. - 0049-0172 .- 1532-866X. ; 65
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review.OBJECTIVE: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS.METHODS: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators.RESULTS: The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies.CONCLUSION: A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.
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| 20. |
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| 21. |
- Parperis, Konstantinos, et al.
(author)
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Insights into suicidal behavior among psoriatic arthritis patients : a systematic review and a genetic linkage disequilibrium analysis
- 2023
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In: Seminars in Arthritis & Rheumatism. - : Elsevier. - 0049-0172 .- 1532-866X. ; 62
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Research review (peer-reviewed)abstract
- Objectives: To systematically assess the magnitude of suicidal behavior among PsA patients and identify associated risk factors. Also identify common genes or coinherited single nucleotide polymorphisms (SNPs) implicated in suicidal behavior and PsA.Methods: Based on the PRISMA guidelines, we conducted a systematic literature review of the online databases PubMed/Medline, Web of Science, and EMBASE from inception to May 2022. Full-text original articles that describe suicidal behavior in PsA patients were eligible. All registered genome-wide association study (GWAS) data in the GWAS catalog database for PsA and psychiatric traits, such as suicidal behavior, and depression, were downloaded for further analysis.Results: A total of 48 articles were identified, and 6 were relevant to the study question. Among the 122,160 PsA patients, 700 had suicidal behavior (0,57%). The range of age in one study was between 30 and 49 years, and 64% of PsA patients with suicidal behavior were female. Among 13,899 PsA patients 74 had suicidal ideation (0.53%) and 125 suicide attempts occurred (0.9%). In two studies, among 17,383 patients, 13 complete suicides occurred (0.07%). A genetic haplotype on chromosomal region 6p21.1, spanning from 29,597,596 to 32,251,264 Mb, contains predisposing SNPs for PsA and depression. 6p21.1–6p21.3 is the chromosomal region containing the HLA genes of classes I, II and III.Conclusion: Suicide behavior in PsA patients was associated with depression and other psychiatric comorbidities. Further evidence supports a genetic origin, at least partly. Awareness of these findings can help clinicians to recognize suicide behavior and prevent suicide attempts.
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| 22. |
- Parperis, Konstantinos, et al.
(author)
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Suicidal behavior in patients with systematic lupus erythematosus : systematic literature review and genetic linkage disequilibrium analysis
- 2022
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In: Seminars in Arthritis & Rheumatism. - : Saunders Elsevier. - 0049-0172 .- 1532-866X. ; 54
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Research review (peer-reviewed)abstract
- Background: Previous studies suggested that patients with Systematic Lupus Erythematosus (SLE) have a higher risk of suicidal behavior, including suicidal ideation, attempt and complete suicide. Systematic data describing the SLE patients’ clinical characteristics and risk factors of suicidal behavior are lacking.Objectives: To determine the magnitude of suicidal behavior among SLE patients and to examine predictors associated with suicidal behavior. An additional aim was to identify common genes or coinherited single nucleotide polymorphisms (SNP) implicated in suicidal behavior and SLE.Methods: We conducted a systematic literature review based on PRISMA guidelines using the online databases PubMed/Medline, EMBASE and Web of Science, from inception to August 2021. Full-text original articles that examined the relationship between SLE patients with suicidal behavior were eligible for our review. Two reviewers independently reviewed articles to assess eligibility using the Newcastle-Ottawa Scale and the Joanna Briggs Institute criteria. Systematic reviews, metanalysis, narrative review, case reports, case series, including less than 10 patients, and conference abstracts, were excluded. All registered genome-wide association study (GWAS) data in the GWAS catalog database for SLE and psychiatric traits (suicidal behavior, depression, anxiety, psychosis) were downloaded for further analysis. Special in silico tools were used to examine if any genetic polymorphisms (SNPs) that predispose for SLE or psychiatric traits can be inherited together as a single haplotype. This could be posing a risk factor for a coexisting psychiatric condition in SLE patients.Results: Of the 64 articles identified, 22 were relevant to the study question; cross-sectional (n = 8) and prospective cohorts (n = 6) were the most frequently retrieved studies. Among the 27,106 SLE patients with SLE, 802 had suicidal behavior (2.9%), and of those, 87.9% were female. Suicide attempt occurred in 573/802 (71.4%) and complete suicide in 18/802 (3%). Major depressive disorder was the most frequently reported coexisting psychiatric condition associated with suicidal behavior, followed by psychosis and social phobia. In addition, several clinical manifestations were linked to suicidal behavior, particularly neuropsychiatric lupus, serositis, mucocutaneous, and renal involvement. Further, high scores in disease activity and damage indices were associated with suicidal behavior. A haplotype in chromosomal region 6p21.33 was found to contain a combination of risk alleles predisposing for SLE and depression, the most common psychiatric disorder associated with suicidal behavior.Conclusion: Suicide behavior in SLE patients was associated with depression, neuropsychiatric lupus, active disease and damage. Further evidence supports a genetic origin of psychiatric symptoms in SLE patients. Awareness of these findings can guide clinicians to recognize suicide behavior promptly and prevent suicide attempts.
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| 23. |
- Pullerits, Rille, 1969, et al.
(author)
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High mobility group box protein 1-A prognostic marker for structural joint damage in 10-year follow-up of patients with juvenile idiopathic arthritis.
- 2017
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In: Seminars in arthritis and rheumatism. - : Elsevier BV. - 1532-866X .- 0049-0172. ; 46:4, s. 444-450
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Journal article (peer-reviewed)abstract
- High mobility group box protein 1 (HMGB1) is an important pro-inflammatory mediator in adult rheumatoid arthritis. The diagnostic utility of HMGB1 in Juvenile Idiopathic Arthritis (JIA) is still unclear. The aim was to examine whether serum HMGB1 levels are associated with inflammation, radiological disease progression, and long-term prognosis in JIA.We included 131 children with JIA from a population-based prevalence study; 38 of them were prospectively followed up for 10 years. Clinical and laboratory disease characteristics at study entry and after 10 years as well as radiological progression over 10 years were recorded. HMGB1 levels were analyzed by an ELISA.The HMGB1 levels were similar in children with different JIA subgroups and in children with established (53%) or newly diagnosed (47%) disease. HMGB1 levels did not differ between groups at entry into the study or at 10 years, by sex, or by the presence or absence of RF or ANA antibodies. HMGB1 levels at the study entry correlated with HMGB1 levels at 10 years and with blood neutrophil count. Most importantly, children with destructive arthritis at 10 years had a tendency toward higher HMGB1 levels at study entry (median 1.2 vs 0.6ng/ml, ns) and displayed 4-fold higher circulating HMGB1 levels (median 3.4 vs 0.8ng/ml, p = 0.0014) than children without radiological destructions.Our results suggest that HMGB1 is a marker of inflammatory activity in children with JIA. Higher serum HMGB1 levels are related to more destructive JIA and could be used as a negative prognostic marker at the disease start.Clinicaltrials.gov NCT01905319. Registered July 16, 2013.
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| 29. |
- Westerlind, Helga, et al.
(author)
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Incidence and prevalence of systemic sclerosis in Sweden, 2004–2015, a register-based study
- 2022
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 53
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Journal article (peer-reviewed)abstract
- Objectives: we aim to present an in-depth report of the incidence and prevalence of systemic sclerosis (SSc) in Sweden in a nation-wide register-based study covering the entire Swedish population Methods: each individual residing in Sweden is given a unique personal identity number. We linked the National Patient Register and the Total Population Register to identify 1) patients with prevalent SSc on 2015–12–31 and 2) patients with incident SSc during the time period 2004–2015 based on ICD-10 codes. We estimated prevalence and incidence overall and stratified on age, sex, and county. Results: we identified 1774 prevalent cases, median age was 65 years (IQR 19.2) and 84% were women. The point prevalence estimate was 22.7 per 100,000 (95%CI 13.3–32.0). 1139 individuals were newly diagnosed with SSc during 2004–2015 with a median age of 60 years (IQR 20.6) and 80% were women. The mean standardized incidence was 11.9 per 1,000,000 person-years (95%CI 5.1–18.7). The annual incidence remained stable over the study period. Women had five times higher incidence and prevalence than men. The highest prevalence stratified by age strata was observed in the group aged 70–79. Conclusion: SSc incidence and prevalence in Sweden are comparable to estimates from southern Europe, as opposed to the previous assumption of lower occurrence in northern Europe. We further observe that SSc incidence has been rather constant throughout recent years in Sweden with no obvious increase.
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| 31. |
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| 32. |
- Yavuz, Sule, et al.
(author)
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Lymphopenia as a risk factor for neurologic involvement and organ damage accrual in patients with systemic lupus erythematosus : A multi-center observational study
- 2020
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In: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 50:6, s. 1387-1393
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Detailed analysis of hematological manifestations (HM) in systemic lupus erythematosus (SLE) are limited and their clinical impact on disease remain obscure. Here, we aimed to decipher factors associated with different hematological abnormalities in SLE patients and to assess their impact on disease related outcomes.METHODS: A dataset (GIPT) originating from SLE patients of six European tertiary centers was assessed. Six-monthly visits of each patient for at least 2 years were registered. The association between hematologic manifestations (HM; per ACR-1997criteria) and clinical/serologic variables, as well as the impact of HM on disease related outcomes (damage, infection and hemorrhage) were explored. Scores on the Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI2K), the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) and events for any infection and hemorrhage were recorded. Results were compared with a cross-sectional, well-characterized SLE dataset from Sweden. Descriptive statistics, the generalized estimating equations (GEE), general linear models (GLM), Cox regression models were applied.RESULTS: We monitored 1425 longitudinal visits in 286 SLE patients with HM (GIPT dataset: 88% female, 95% Caucasian, 68% dsDNA positive). Thrombocytopenia (regression coefficient [95% confidence interval] 1.86[1.1-3.13]) and neurologic involvement (ACR-8) (2.1[1.10-3.89]) were associated with lymphopenia (<1000/mm3); the latter was an independent predictor of organ damage accrual (1.68[1.2-2.62]). These associations were confirmed in an independent dataset of 1348 SLE patients (86% female, 93% Caucasian, 61% dsDNA positive) in Sweden.Severe lymphopenia (<500/mm3) and severe thrombocytopenia (<20 K/mm3) were associated with increased risk for infection (hazard ratio [95% confidence interval] 2.56[1.23-5.31]) and hemorrhage (4.38[2.10-11.1]), respectively, independent of the effect of other predictors.CONCLUSION: Lymphopenia in SLE is independently associated with neurologic involvement and organ damage accrual, and thus, may be considered as a marker of severe/progressive disease.
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| 33. |
- Yuan, Shuai, et al.
(author)
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Interleukins and rheumatoid arthritis : bi-directional Mendelian randomization investigation
- 2022
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In: Seminars in Arthritis & Rheumatism. - : Elsevier. - 0049-0172 .- 1532-866X. ; 53
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Journal article (peer-reviewed)abstract
- Objectives: To assess the causality of the associations between interleukins (ILs) and rheumatoid arthritis (RA) using Mendelian randomization (MR) design. Methods: Genetic instruments and summary-level data for ten ILs were obtained from three genome-wide association meta-analyses. Corresponding data on RA were obtained from a meta-analysis of 22 genome-wide association studies (14,361 cases and 43,923 controls) and the FinnGen consortium (6236 cases, 4596 seropositive cases, 1937 seronegative cases, and 172,834 controls). Forward and reverse MR analyses were performed. Results: The odds ratios (ORs) of RA were 2.08 (95% confidence interval (CI), 1.56-2.77; p<0.001), 2.14 (95% CI, 1.85-2.49; p<0.001), and 0.95 (95% CI, 0.92-0.97; p<0.001) for one standard deviation increase in genetically predicted IL-1 beta, IL-6 and IL-6 receptor antagonist (IL-6ra) levels, respectively. There were suggestive associations of genetically predicted IL-1 receptor antagonist (IL-1ra) (OR, 0.85, 95% CI, 0.76, 0.96; p=0.010) and IL-18 (OR, 1.07, 95% CI, 1.00, 1.15; p=0.043) levels with RA risk. Subtype-specific associations were observed for seropositive RA (IL-1 beta, IL-1ra, and IL-6) and seronegative RA (IL-2 receptor alpha subunit, IL-8, and IL-18). Reverse MR analysis found a suggestive association between genetic liability to RA and IL-6 receptor antagonist (change 0.015; 95% CI, 0.003-0.028; p=0.015). Conclusions: This MR study suggests that long-term IL-1 and IL-6 inhibition may reduce the risk of RA, particularly seropositive RA. Upregulations of ILs involved in IL-6 signaling pathways appears to be downstream effects of RA, which supports the blocking IL-6 treatment for RA.
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| 34. |
- Ørnbjerg, L. M., et al.
(author)
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Predictors of ASDAS-CRP inactive disease in axial spondyloarthritis during treatment with TNF-inhibitors: Data from the EuroSpA collaboration
- 2022
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 56
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Journal article (peer-reviewed)abstract
- Objectives: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. Methods: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. Results: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97–0.98), men vs. women: 1.88 (1.60–2.22), current vs. non-smoking: 0.76 (0.63–0.91), HLA-B27 positive vs. negative: 1.51 (1.20–1.91), TNF start year 2015–2018 vs. 2009–2014: 1.24 (1.06–1.45), CRP>10 vs. ≤10 mg/l: 1.49 (1.25–1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58–1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99–1.00) and 0.99 (0.99–1.99), respectively Conclusion: Common baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.
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| 35. |
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| 36. |
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| 37. |
- Bäcklund, Rebecka Teresia, et al.
(author)
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Diet and the risk of rheumatoid arthritis- a systematic literature review
- 2023
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 58
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Research review (peer-reviewed)abstract
- ObjectivesDiet has received attention as a factor possibly contributing to the development of Rheumatoid arthritis (RA). Several dietary exposures have been examined in various populations using different diet assessment methods. The aim of this study was to systematically assess the literature on the relation between dietary patterns, different food and food groups, macronutrients, non-alcoholic beverages and the risk of developing RA.MethodsA systematic literature search was performed to identify relevant articles on diet and the risk of developing RA. The selection of articles and overall quality assessment of all included studies were performed independently by two examiners. Overall study quality was evaluated using the Newcastle-Ottawa Scales. We excluded all articles where the temporal relation between dietary data collection and time of RA diagnosis was not presented. Main findings were summarized for cohort-based studies and case-control studies separately.ResultsA total of 984 articles were screened. Nineteen relevant cohort-based studies, and eight case-control studies, were included in our review. Two articles were excluded due to lacking data on the relation between RA diagnosis and time of dietary data collection and one due to incorrect outcome. Identified studies suggested protective effects of fish, vegetables and Mediterranean-style diets, although study results and methods were heterogenous. An issue in some case-control studies was that unvalidated diet assessment methods were used. A vast majority of the cohort-based studies used validated diet assessment methods, although the definitions of exposures studied varied.ConclusionThere is lack of consistent evidence on the role of diet in the development of RA, partly due to differences in study quality and methodology Limited evidence suggests that some healthy eating habits may reduce the risk of RA. More high-quality studies in the area are needed for a deeper understanding of the effect of diet, and to enable strategies to prevent RA.
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| 38. |
- Castellví, I., et al.
(author)
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Safety and effectiveness of abatacept in systemic sclerosis: The EUSTAR experience
- 2020
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 50:6, s. 1489-1493
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Journal article (peer-reviewed)abstract
- Objective: To analyze the safety and effectiveness of abatacept (ABA) given in routine care to patients with systemic sclerosis (SSc). Methods: Retrospective multicenter observational study that enrolled patients with SSc treated with ABA. We collected epidemiological data and clinical outcomes. First, we analyzed the frequency of adverse effects. Secondly, we compared the evolution of different organ manifestations during ABA treatment. We collected data from 6 months before start of therapy to the last follow-up the following parameters: modified Rodnan Skin Score (mRSS), joints, lung and gastrointestinal involvement, concomitant medications, and laboratory tests. Results: Data on twenty-seven patients with SSc were collected (93% females; 67% limited SSc). Rheumatoid arthritis was the most frequent concomitant autoimmune disease. ILD was present in 15 patients. Anti-Scl 70 antibodies were present in 13 patients and rheumatoid factor and ACPA antibodies were present in eight and seven patients respectively. The main indication to use abatacept was joint involvement (59%) followed by myositis (26%). A total of 16 adverse effects were reported in 28 months of abatacept treatment including five that required hospitalization. Most of them occurred in the first 3 months after starting abatacept. After 12 months, the number of tender and swollen joints decreased compared to baseline (p<0.03 and p<0.02 respectively). Moreover, a beneficial effect of abatacept on HAQ-DI at 3 and 6 months (p<0.05) and on morning stiffness at 6 and 12 months (p<0.03) was observed. We also observed a decrease in the modified Rodnan skin score (p<0.05). No changes in lung or gastrointestinal involvement were found. Conclusions: ABA demonstrated a good safety profile and seems to have some effectiveness on joint involvement and related disability in SSc patients treated in routine care. © 2020 Elsevier Inc.
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| 39. |
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| 40. |
- Damgaard, Astrid Jensen, et al.
(author)
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Self-management support needs of patients with inflammatory arthritis and the content of self-management interventions : a scoping review
- 2023
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In: Seminars in Arthritis and Rheumatism. - 0049-0172. ; 60
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Research review (peer-reviewed)abstract
- Background: Self-management skills can empower a person to manage the physical, psychological, and social impact of a health condition. However, the components of self-management interventions differ widely between studies and interventions. By performing a scoping review, we aimed to describe patients’ self-management needs and how health professionals (HPs) can provide effective self-management support to patients with inflammatory arthritis (IA). Objectives: 1) to identify the evidence for self-management support needs of patients with IA, and 2) to identify the content (theory/theoretical approach, mode of delivery, duration and frequency) of self-management interventions that target patients with IA. Methods: In May 2021, we performed a systematic literature search (from 2000 onward) in five databases (CINAHL (Ebsco), Cochrane Library, Embase (Ovid), Medline (Ovid) and PsycINFO (Ovid)) regarding self-management in patients with IA. Results: Out of 11,748 records identified, we included 31 articles describing patients’ support needs and 33 articles describing the content of self-management interventions. Patients’ support needs were sorted into six topics: 1) disease impact and the pharmacological treatment, 2) care continuity and relations with HPs, 3) the importance of non-pharmacological treatment, 4) the need for support from family and friends, 5) support needs related to work issues, and 6) contextual preferences for self-management support. The theory/theoretical approach, mode of delivery, duration and frequency varied widely and were often unclearly or insufficiently described. In addition, the self-management concept was scarcely – or not – defined in the included articles. The identified topics for support needs were compared with the described content in the included articles. Only a few self-management interventions focused on patients’ need for support in relation to work, and to family and friends. Conclusion: HPs provided self-management support to patients with IA in various ways, but there were gaps between the patients’ support needs and the identified interventions. In developing self-management interventions, the self-management concept needs to be defined and a clear theory is required to support the development of the intervention. Future studies should seek to investigate various modes of delivery, frequency and duration, to develop effective interventions that meet patients’ support needs.
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| 41. |
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| 42. |
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| 43. |
- Flouri, Irini, et al.
(author)
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Comparative effectiveness and survival of infliximab, adalimumab, and etanercept for rheumatoid arthritis patients in the Hellenic Registry of Biologics: Low rates of remission and 5-year drug survival
- 2014
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 43:4, s. 447-457
-
Research review (peer-reviewed)abstract
- Objective: To compare effectiveness, drug survival, and safety between infliximab, adalimumab, and etanercept, in a nationwide cohort of rheumatoid arthritis (RA) patients. Methods: This study is a prospective cohort study of 1208 active RA patients. Effectiveness, drug survival, and serious adverse events during entire follow-up (median 2.9 years) were monitored. Results: EULAR and CDAI responses were comparable between the three agents (EULAR good/moderate responses at 12 months ranged 76-79%). At 12 months, 15-23% achieved remission. For adalimumab and etanercept, adjusted hazard rate (HR) for EULAR/ACR remission (reference: infliximab) was 2.7 and 2.1 (95% confidence interval was 1.7-4.1 and 1.3-3.4, respectively); males (HR 1.6; 1.1-2.4), use of glucocorticoids (HR 2.0; 13-3.0), and swollen joint count > 7 (HR 0.36; 0.24-0.55) were independent predictors. Five-year drug survival was 31%, 43%, and 49% for infliximab, adalimumab, and etanercept, respectively (p = 0.010). Infliximab was associated with significantly more withdrawals due to adverse events. Disease activity, CRP, and use of glucocorticoids predicted efficacy-related drug survival; age, use of methotrexate, and prior DMARDs failures predicted safety-related survival. Risk for serious infections was lower with adalimumab (odds ratio [OR] 0.62; 0.38-1.00) or etanercept (OR 0.39; 0.21-0.72) than infliximab, independent of the effects of age (OR 1.65; 1.37-2.00 per 10 years), tender joint count > 10 (OR 1.86; 1.21-2.86), and glucocorticoids >35 mg/week (OR 1.83; 1.12-2.99). Conclusions: Response rates were comparable among anti-TNF agents. Overall, 5-year drug survival was below 50%, with infliximab demonstrating increased safety-related discontinuations. Remission rates are low in clinical practice. Strategies to increase effectiveness and long-term survival of anti-TNF agents in RA are needed. (C) 2014 Elsevier Inc. All rights reserved.
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| 44. |
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| 45. |
- Jarraya, Mohamed, et al.
(author)
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Meniscus morphology : Does tear type matter? A narrative review with focus on relevance for osteoarthritis research
- 2017
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 46:5, s. 552-561
-
Journal article (peer-reviewed)abstract
- Objective: To give a narrative overview of meniscal tears with a radiologic emphasis on the morphologic type, technical considerations, and on the relevance of the type of meniscal tear in the context of osteoarthritis (OA) research. Design: Total 20 years of the PubMed database were searched for epidemiological, radiological, arthroscopic and biomechanical reports, and review articles focusing on meniscal tears in middle-aged and older individuals, in the setting of OA. Case reports, publications on meniscal tears in young active individuals, and publications not in English were excluded. Results: Meniscal intra-substance signal abnormalities are associated with an increased risk of a degenerative meniscal tear in the same segment. Posterior radial tears of the medial meniscus appear to be a highly relevant event in OA of the knee, with associated cartilage loss and meniscal extrusion. Radial tears are more commonly missed on MRI than other types, and should be carefully looked for on coronal and axial images. While medial meniscus posterior root tears are of "radial" morphology, there is growing interest in looking at them as a separate entity, mainly because they require a different therapeutic approach. Conclusion: There is a lack of data on the relevance of different morphologic types of meniscal tears to the natural history of knee OA, both cross-sectionally and-especially-longitudinally. Further epidemiologic studies should focus on specific meniscal tears based on their morphology to better understand their relevance in the genesis and progression of knee OA.
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| 46. |
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| 47. |
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| 48. |
- Luyten, F. P., et al.
(author)
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Toward classification criteria for early osteoarthritis of the knee
- 2018
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 47:4, s. 457-463
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Journal article (peer-reviewed)abstract
- Objective: To propose draft classification criteria for early stage osteoarthritis (OA) of the knee for use in a primary care setting. Methods: A group of basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists in a workshop setting discussed potential classification criteria for early osteoarthritis of the knee. The workshop was divided into sessions around relevant topics with short state of the art presentations followed by breakout sessions, consensus discussions, and consolidation into a consensus document. Results: Three classes of criteria were agreed: (1) Pain, symptoms/signs, self-reported function, and quality of life using tools such as KOOS: scoring ≤85% in at least 2 out of these 4 categories; (2) Clinical examination: at least 1 present out of joint line tenderness or crepitus; (3) Knee radiographs: Kellgren & Lawrence (KL) grade of 0 or 1. MRI is at present not recommended as an aid to identify or define early OA in routine clinical practice or primary care, in light of the absence of validated consensus criteria and the high population prevalence of structural joint changes detected by this method. Biomarkers may have future utility in early OA classification, but no individual or set of biomarkers is yet robust enough. Conclusion: Based on our consensus proposal, draft classification criteria for early OA of the knee for use in clinical studies should include patient reported outcomes such as pain and function, together with clinical signs and KL grade 0-1 on radiographs.
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| 49. |
- Mahmoudian, Armaghan, et al.
(author)
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Towards classification criteria for early-stage knee osteoarthritis : A population-based study to enrich for progressors
- 2021
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 51:1, s. 285-291
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Journal article (peer-reviewed)abstract
- Objective: To facilitate a greater likelihood of favorable response to new disease-modifying therapies, recruitment of patients at an earlier stage of their disease into clinical trials may be an attractive strategy. Hence, there is a need to develop widely accepted classification criteria for early-stage knee osteoarthritis (OA). We have proposed a set of classification criteria for early-stage knee OA (2018 classification criteria) now being further refined. Here, we test the draft criteria for enrichment for clinical and structural progression. Design: Performance of the 2018 classification criteria for early stage knee OA was tested using data from the Osteoarthritis Initiative (OAI). The OAI comprises data of 4796 men and women aged 45–79 years with or at risk for knee OA at baseline. Based on the 2018 classification criteria, a knee with Kellgren & Lawrence (K&L) grade of 0-I, two out of four Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales equal or less than 85, and presence of at least one of joint line tenderness or crepitus, was considered as early-stage knee OA. Knees with K&L grade 0-I that did not fulfill the 2018 criteria, were considered as controls. Logistic regression analysis was used to evaluate the predictive performance of the criteria set for structural as well as clinical progression. We further explored the discriminatory capability of criteria by including the average KOOS4 score, and relevant clinical examination findings such as the presence of effusion and/or Heberden's nodes. Results: We identified 1315 (27%) knees from OAI fulfilling the 2018 early-stage knee OA classification criteria. The female to male ratio was higher in the early knee OA group compared to controls. The early-stage knee OA group were on average slightly younger and had higher body mass index vs controls (mean [SD] age: 59.2 [8.9] years vs. 60.2 [9.1] and mean [SD] BMI 28.3 [7.0] vs. 26.8 [6.0]). By applying the 2018 criteria, there was a substantial enrichment compared to controls at 48 and 96 months for both structural (OR=1.1–1.4, and AUC=0.72–0.74) and clinical progressors (OR=2.1–2.5, 95% and AUC=0.66). Expanding the clinical examination findings by including joint effusion and/or Heberden's nodes improved the enrichment for both structural and clinical progressors (OR=4.2, 95% confidence interval=3.2–5.5 and OR=3.3, 95% confidence interval=2.8–3.5, respectively). Replacing scoring of the 4 separate KOOS domains by a KOOS4 score performed comparably. Conclusions: The proposed 2018 early-stage knee OA classification criteria showed encouraging performance characteristics with regard to an enrichment for structural and clinical progression using longitudinal OAI data. Our results indicate that the addition of clinical findings improves the performance of previous criteria to define early-stage disease and risk for progression.
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| 50. |
- Nguyen, Audrey D., et al.
(author)
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Gastrointestinal tract involvement in systemic sclerosis : The roles of diet and the microbiome
- 2023
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In: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 60
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Journal article (peer-reviewed)abstract
- Background: Alterations in gastrointestinal (GI) microbial composition have been reported in patients with systemic sclerosis (SSc). However, it is unclear to what degree these alterations and/or dietary changes contribute to the SSc-GI phenotype. Objectives: Our study aimed to 1) evaluate the relationship between GI microbial composition and SSc-GI symptoms, and 2) compare GI symptoms and GI microbial composition between SSc patients adhering to a low versus non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet. Methods: Adult SSc patients were consecutively recruited to provide stool specimens for bacterial 16S rRNA gene sequencing. Patients completed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0) and the Diet History Questionnaire (DHQ) II and were classified as adhering to a low or non-low FODMAP diet. GI microbial differences were assessed using three metrics of alpha diversity (species richness, evenness, and phylogenetic diversity), as well as beta diversity (overall microbial composition). Differential abundance analysis was performed to identify specific genera associated with SSc-GI phenotype and low versus non-low FODMAP diet. Results: Of the 66 total SSc patients included, the majority were women (n = 56) with a mean disease duration of 9.6 years. Thirty-five participants completed the DHQ II. Increased severity of GI symptoms (total GIT 2.0 score) was associated with decreased species diversity and differences in GI microbial composition. Specifically, pathobiont genera (e.g., Klebsiella and Enterococcus) were significantly more abundant in patients with increased GI symptom severity. When comparing low (N = 19) versus non-low (N = 16) FODMAP groups, there were no significant differences in GI symptom severity or in alpha and beta diversity. Compared with the low FODMAP group, the non-low FODMAP group had greater abundance of the pathobiont Enterococcus. Conclusion: SSc patients reporting more severe GI symptoms exhibited GI microbial dysbiosis characterized by less species diversity and alterations in microbial composition. A low FODMAP diet was not associated with significant alterations in GI microbial composition or reduced SSc-GI symptoms; however, randomized controlled trials are needed to evaluate the impact of specific diets on GI symptoms in SSc.
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