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Association of rubella and parvovirus B19 IgM positivity and suspected rheumatoid arthritis: a retrospective analysis from a large US national reference laboratory (2014-2023)

Por: Lee · M. K. · Alfego · D. · Naides · S. J.
Objective

Rubella and parvovirus B19 (B19V) infections can present with arthritis-like symptoms in adults instead of typical dermatological symptoms. We quantify associations between rubella and B19V, respectively, with arthritis-like complications using real-world diagnostic testing.

Design

Cross-sectional and retrospective cohort study.

Setting

Reference laboratories across the USA.

Participants

Participants with IgM tests for rubella (N=211 917) or B19V (N=644 473) performed at Labcorp from 2014 to 2023. Among these participants, participants with IgM tests for rubella (N=1867) or B19V (N=22 683) and longitudinal laboratory testing through Labcorp were followed for diagnostic tests for rheumatoid arthritis (RA) up to 1.5 years after the viral IgM tests.

Primary and secondary outcome measures

Primary outcomes were arthritis-like suspicions by providers and diagnostic testing for RA-associated biomarkers.

Results

Higher proportions of suspicions of arthritis (1.4%, p

Conclusions

Increased awareness of non-typical RA symptoms may facilitate differential diagnosis between rubella, B19V and RA. Recent B19V infections do not occur concurrently with RA; recent B19V infections should be considered in the differential diagnosis for RA when patients present with polyarticular joint symptoms.

Experiences of supervised high-intensity interval training--a motivator for exercise maintenance among patients with rheumatoid arthritis: a qualitative interview study

Por: Limbäck · G. · Bilberg · A.
Objective

High-intensity interval training (HIIT) has been shown to improve cardiovascular health and physical fitness in patients with rheumatoid arthritis (RA). However, patient perspectives on this type of exercise remain insufficiently explored. The aim of this study was to describe experiences of supervised HIIT among patients with RA and to elucidate how patients maintain exercise on their own after completing the supervised intervention.

Design

A qualitative study based on semistructured in-depth individual interviews analysed using qualitative content analysis.

Participants

Patients were recruited from a multicentre randomised controlled trial in Western Sweden. Twenty patients (16 women) with RA who had participated in the high-intensity exercise programme for 12 weeks were included in this qualitative interview study.

Setting

The supervised HIIT was conducted in a hospital setting.

Results

The results were divided into two domains, corresponding to the two broad open-ended questions. The first domain comprises four categories: (1) challenging and effective with HIIT, (2) belonging to a group facilitates exercise, (3) feeling confident when exercising and (4) stimulating to feel the effect of exercise on the body. The second domain comprises two themes: (1) taking responsibility for one’s health and (2) a feeling of resignation.

Conclusion

HITT was perceived as challenging yet manageable. Follow-up visits with a knowledgeable physiotherapist were requested, since exercise was perceived as a lifelong treatment and just as crucial as pharmacological treatment. Most patients described taking responsibility for their health and maintaining their exercise regime after the supervised intervention; however, some expressed a feeling of resignation and were unready for lifestyle changes. Nevertheless, having RA can be a motivator when exercise is viewed as an important part of medical treatment.

Fibroblast-Neuron interactions Driving persistent Pain in Rheumatoid Arthritis (FiND-Pain RA) - an observational study protocol

Por: Xenophontos · M. · Baldeweg · F. C. · Ross · R. · Rutter-Locher · Z. · Hill · S. · Ryan · S. · Ali Awadelkareem · M. · Law · S. T. · Bennett · D. L. · Buckley · C. D. · Humby · F. · Kirkham · B. W. · Denk · F. · Taams · L. S.
Introduction

Pain in patients with rheumatoid arthritis (RA) is an unmet clinical need. Targeting joint inflammation with disease-modifying antirheumatic drugs has not resulted in the anticipated reduction in pain for many patients. This can partly be explained by the concept of central sensitisation whereby spinal and supraspinal pathways have a lower threshold of activation, leading to increased perception of pain. Synovial stromal cells, such as fibroblasts, are also thought to play a role through peripheral sensitisation of nerves in the joint. Synovial fibroblasts are known to produce pro-algesic mediators such as interleukin 6 and nerve growth factor at the messenger RNA level. These pro-algesic mediators could activate sensory nerve fibres that send signals from the joint to the spinal cord, thereby driving persistent pain in RA. The purpose of this study is to evaluate which pro-algesic mediators are produced by lining versus sub-lining fibroblasts and whether the level of these mediators correlates with clinical measures of pain in patients with RA.

Methods and analysis

FiND-Pain RA is a multicentre observational study which will recruit 50 patients with seropositive RA who attend the rheumatology department of Guy’s and St Thomas’ Hospital, London, and the Nuffield Orthopaedic Centre, Oxford. Clinical examination, pain-focused patient-reported outcome measures, ultrasound examination and ultrasound-guided synovial biopsy of the knee will be performed. The levels of known and putative pro-algesic mediators will be measured in fibroblasts from the lining and sub-lining layer of the synovium. The location and spatial morphology of sensory nerve fibres and their proximity to lining and sub-lining fibroblasts will be characterised. The primary outcome will be to determine whether the knee pain scores of participants correlate with the level of leukaemia inhibitory factor, a novel putative pain-mediator expressed in sub-lining fibroblasts. The secondary outcomes will be to determine whether other pro-algesic mediators produced by lining or sub-lining fibroblasts correlate with clinical measures of pain and to assess the location and proximity of sensory nerve fibres to lining versus sub-lining fibroblasts.

Ethics and dissemination

The study is a sub-study of the PUMIA (Pain Phenotypes and their Underlying Mechanisms in Inflammatory Arthritis) study, which has been approved by the Bromley Research Ethics Committee (REC: 21/LO/0712). The findings of this study will be disseminated through open-access publications, as well as scientific and clinical conferences.

Sex differences in the efficacy, safety and persistence of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of phase III and long-term extension trials

Por: Strand · V. · Schulze-Koops · H. · Al-Emadi · S. · Kinch · C. D. · Gruben · D. · Germino · R. · Connell · C. A. · Mysler · E.
Objectives

Evaluate tofacitinib efficacy, safety and persistence by sex in rheumatoid arthritis (RA).

Design

Post hoc analyses using data from phase III placebo-controlled randomised controlled trials (ORAL Scan, ORAL Sync and ORAL Standard).

Setting

ORAL Scan, ORAL Sync and ORAL Standard were global, multicentre trials conducted across 111, 114 and 115 sites, respectively.

Participants

The trials enrolled adults with active RA and prior inadequate response to methotrexate (ORAL Scan/ORAL Standard) or ≥1 conventional synthetic or biologic disease-modifying antirheumatic drug (ORAL Sync). Post hoc analyses included 2265 patients (1870 female and 395 male).

Interventions

Patients received tofacitinib 5 mg or 10 mg two times a day, adalimumab or placebo.

Outcome measures

Efficacy outcomes to month 12 included American College of Rheumatology (ACR)20, 50 and 70 responses, Disease Activity Score in 28 joints (DAS28) (erythrocyte sedimentation rate (ESR))-defined low disease activity (LDA) and remission, DAS28 (C reactive protein (CRP)) ≤3.2 and

Results

At baseline, female patients had similar DAS28(CRP and ESR), slightly higher HAQ-DI and lower FACIT-F scores versus male patients (n=395). ORs for active treatments (tofacitinib and adalimumab) versus placebo were generally >1 for ACR20, 50 and 70 responses, DAS28(CRP) ≤3.2 and

Conclusions

In post hoc analyses, tofacitinib was efficacious across both sexes, with higher responses in males observed particularly for more stringent composite endpoints and patient-reported outcomes. Findings are generally consistent with studies of other advanced RA therapies. Safety and persistence were similar across sexes. Interpretation is limited by the small proportion of male patients (

Trial registration number

NCT00847613, NCT00856544, NCT00853385, NCT00661661 and NCT00413699.

PeRsonalIsed MEdicine in Rheumatoid Arthritis (PRIMERA) trial: a multicentre, open-label, randomised controlled trial comparing routine care with a tailor-made approach

Por: Dag · H. H. · Looijen · A. E. M. · Vonkeman · H. E. · Willemze · A. · Korswagen · L.-A. · Padmos · R. C. · van Gaalen · F. A. · Tchetverikov · I. · van der Kaap · J. H. · Veris-van Dieren · J. J. · Riyazi · N. · Spierings · J. · van der Helm-van Mil · A. H. M. · de Jong · P. H. P.
Introduction

Rheumatoid arthritis (RA) is a heterogeneous disease, which current treatment guidelines insufficiently accommodate, as they predominantly emphasise the suppression of disease activity. However, a step towards personalised medicine is preferred to further optimise treatment and requires homogeneous subgroups with similarities in pathophysiological mechanisms and treatment responses. Prior research has already demonstrated notable differences in the pathophysiology of patients with autoantibody-positive and autoantibody-negative RA, as well as differences in treatment responses, which may serve as a strong basis for personalised medicine. Additionally, there is evidence suggesting that an early treatment response is indicative of future courses. Based on these findings, we designed a personalised medicine trial in RA that compares the effectiveness and cost-effectiveness of a tailor-made approach with routine care.

Methods and analysis

The PeRsonalIsed Medicine in RA (PRIMERA) trial is a multicentre, open-label, randomised controlled trial that includes 300 adult patients with newly diagnosed, DMARD-naïve RA, according to 2010 American College of Rheumatology/EULAR criteria. Patients are randomised into either routine care or a tailor-made approach. Both management approaches use a treat-to-target strategy, aiming for low disease activity (LDA, Disease Activity Score using 44 joints (DAS) ≤2.4). In routine care, initial treatment consists of methotrexate along with a single intramuscular dose of glucocorticoids (GCs) and treatment can be intensified after 3, 7 and 10 months if LDA is not reached. Conversely, initial treatment in the tailor-made approach depends on the presence of autoantibodies, with patients with autoantibody-positive and autoantibody-negative RA starting with hydroxychloroquine or methotrexate together with a single intramuscular dose of GCs, respectively. Medication intensifications will be allowed at months 1, 3, 4, 7 and 10. Intensifications at months 1 and 4 depend on whether patients have an early sufficient response to GCs and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively. The tailor-made approach is superior to routine care if no more biological DMARDs (bDMARDs) or tsDMARDs are used after 10 months of treatment, while the mean DAS over time is lower. Our primary outcome is the proportional difference in bDMARD or tsDMARD usage after 10 months of treatment between routine care and the tailor-made approach. Secondary outcomes are DAS over time, time to achieve LDA, cost-effectiveness and patient-reported outcome measurements over time.

Ethics and dissemination

Ethical approval has been granted by Erasmus MC Medical Ethics Review Committee (MEC-2020-0825). The results will be disseminated through peer-review journals and medical congresses.

Trial registration number

ISRCTN16170070.

Efficacy and safety of microbiota-targeted therapeutics in autoimmune and inflammatory rheumatic diseases: protocol for a systematic review and meta-analysis of randomised controlled trials

Por: Kragsnaes · M. S. · Gilbert · B. T. P. · Sofiudottir · B. K. · Rooney · C. M. · Hansen · S. M.-B. · Mauro · D. · Mullish · B. H. · Bergot · A.-S. · Mankia · K. S. · Goel · N. · Bakland · G. · Johnsen · P. H. · Miguens Blanco · J. · Li · S. · Dumas · E. · Lage-Hansen · P. R. · Wagenaar
Introduction

An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.

Methods and analysis

This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.

Ethics and dissemination

No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.

PROSPERO registration number

CRD42025644244.

Mental health in patients with rheumatoid arthritis and axial spondyloarthritis: a cross-sectional, case-control tertiary centre study from Czechia

Por: Husakova · M. · Balajkova · V. · Pavelka · K. · Senolt · L. · Kucharikova · K. · Mohr · P. · Kotrs · J. · Olejarova · M.
Objectives

To evaluate the mental health burden in rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) using diagnostic and self-reported tools and to examine its associations with current disease activity, patient-reported outcomes and barriers to appropriate care.

Design

Single-centre, cross-sectional, case–control study.

Setting

Rheumatology centre of a tertiary care hospital, serving as a referral clinic with outpatient and inpatient care in Czech Republic.

Participants

233 patients with rheumatic diseases (113 RA, 120 axSpA) and 170 healthy controls (HC).

Outcome measures

Mental disorders (MD) were assessed through a structured psychiatric interview using the International Neuropsychiatric Interview (Mini International Neuropsychiatric Interview) administered by a trained professional and by self-reported questionnaires including the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Disease activity was evaluated with the Disease Activity Score-28 with C-reactive protein (DAS28-CRP) for RA and the Ankylosing Spondylitis Disease Activity Score with CRP (ASDAS-CRP) for axSpA, alongside patient-reported outcomes (PROs).

Results

At least one MD was present in 24.8% of RA, 31.7% of axSpA and 7.0% of HC (p

Conclusions

Mental disorders in RA and axSpA are closely associated with higher disease activity and unfavourable PROs, while access to and acceptance of psychiatric care remain markedly insufficient. Systematic integration of mental health assessment and management into rheumatology practice is strongly warranted.

Development of explainable machine learning models to predict side effects in patients with rheumatoid arthritis taking methotrexate treatment: a nationwide multicentre cohort study

Por: Jang · J. · Kim · W. J. · Park · S. W. · Moon · K. W. W.
Objectives

Methotrexate (MTX) effectively controls rheumatoid arthritis (RA) but often leads to side effects (SE) such as gastrointestinal (GI) issues, liver toxicity and bone marrow suppression. To develop clinically interpretable machine learning (ML) models that accurately predict MTX-related SE in patients with RA taking MTX. The aim was to enhance predictive accuracy and to identify patient-specific risk factors using explainable artificial intelligence (XAI), thereby enabling transparent clinical interpretation. We specifically sought to address the unmet need for individualised risk stratification using real-world, multicentre observational data.

Design

Retrospective case-control study.

Setting

Across 23 rheumatology clinics in South Korea, based on data from a nationwide multicentre cohort.

Participants

A total of 5077 patients with RA were initially enrolled from the Korean Observational Study Network for Arthritis. After excluding those with missing clinical, demographic or prescription data and those not receiving MTX, 2375 patients remained eligible. Among these, 1654 and 1218 patients were included in the overall SE and GI SE analysis groups, respectively, after 1:1 propensity score matching. All patients were aged ≥18 years and met the 1987 American College of Rheumatology classification criteria.

Primary and secondary outcome measures

The primary outcome was the presence of SE in patients with RA taking MTX, categorised into overall SE and GI SE, based on standardised patient questionnaires and clinical assessments. The secondary outcome was the identification of key predictors using SHapley Additive exPlanations (SHAP) to enhance the interpretability of ML predictions.

Results

Among six ML classifiers, extreme gradient boosting demonstrated the highest performance in predicting overall SE (area under the curve (AUC) 0.781, F1 score 0.672, area under the precision-recall curve (AUPRC) 0.757) and GI SE (AUC 0.701, F1 score 0.690, AUPRC 0.670). SHAP analysis identified key predictive features including age, physician visual analogue scale score, alanine aminotransferase, Health Assessment Questionnaire score, celecoxib use and drug adherence. Logistic regression confirmed statistical significance for multiple variables (eg, OR 4.63; 95% CI 1.41 to 20.90 for non-adherence >30 days; OR 1.45; 95% CI 1.14 to 1.85 for celecoxib use). DeLong’s test indicated that boosting models significantly outperformed support vector machine (p

Conclusions

Interpretable ML models using real-world clinical data can accurately predict SE in patients with RA taking MTX. These models may facilitate early identification of high-risk individuals and inform personalised treatment strategies. Integration into clinical decision support systems could improve MTX safety monitoring. Further prospective validation in external cohorts is warranted.

Current landscape of immune-mediated inflammatory rheumatic diseases in Brazils public and private systems: retrospective cohort study

Por: Monticielo · O. A. · Seguro · L. P. C. · de Ataide Mariz · H. · Daher Macedo · M. · Therumi Assao · V. · Lima · J. · Volpi e Silva · N. · Dos Reis-Neto · E. T.
Objective

This study aimed to describe the epidemiology, outcomes and costs of four immune-mediated inflammatory rheumatic diseases (IMIRDs)—systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS)—in Brazil’s public and private healthcare systems from 2018 to 2022.

Design

Retrospective observational study.

Setting

The study was conducted across hospital and outpatient levels of care in Brazil, based on nationwide data representing the public (Department of Informatics of the Unified Health System—DATASUS) and private (National Supplementary Health Agency—ANS) healthcare sectors.

Participants

The study analysed data from four distinct systems: 609 427 patients from the public Outpatient Information System (SIA), 32 119 patients from the public Hospital Information System (SIH), 19 083 deaths from the public Mortality Information System (SIM) and 11 846 hospitalisations from the private healthcare system (ANS).

Results

RA had the highest incidence, ranging from 19.9 to 24.9 per 100 000, while SLE remained stable (6.3–6.7 per 100 000). Prevalence increased for all diseases: RA rose from 95.7 to 136.8, SLE from 23.4 to 38.9, AS from 15.0 to 23.6 and PsA from 10.8 to 17.4 per 100 000. SLE had the highest hospitalisation (7.2%) and lethality rates (8.7%), along with the highest average outpatient cost (US$440.9 per patient). In the private system, RA and SLE accounted for the most hospitalisations (36.3% each). SLE had the highest proportion of emergency hospitalisations (70.5%), while PsA had the highest proportion of elective hospitalisations (61.8%).

Conclusions

RA had the highest prevalence and incidence rates among the studied IMIRDs, while SLE was associated with the highest lethality, outpatient costs and emergency hospitalisations. The rising prevalence of these diseases highlights their growing burden on Brazil’s healthcare systems.

Trial registration number

NCT06698900.

Running with rheumatoid arthritis: a qualitative study of Australian rheumatologists perceptions and recommendations

Por: Shearman · S. · Butler · J. · Hodges · A.
Objective

To explore how Australian rheumatologists perceive and recommend running for individuals with rheumatoid arthritis (RA), including their clinical experiences, observations and personal views.

Design

Qualitative exploratory study using semistructured interviews. Interviews were conducted via Microsoft Teams, transcribed verbatim and analysed thematically using NVivo software.

Setting

Australia; interviews were conducted remotely via Microsoft Teams with participants joining from either clinical or home environments.

Participants

13 practising Australian rheumatologists recruited through purposive and snowball sampling.

Results

Five themes were identified from thematic analysis: (1) perceived benefits of running, (2) risks and clinical cautions, (3) criteria required for discussing running, (4) barriers to running and (5) facilitators to running. Participants acknowledged various benefits of running for individuals with RA, such as improved mental health, lifestyle changes and support for joint health. Concerns included risks of running during active disease phases and overly rapid progression of training loads. Key criteria for recommending running included good disease control, the patient’s running history and personal goals. Barriers included patient concerns around joint harm, lack of guidelines and socioeconomic challenges. Facilitators included stable disease, symptom-guided pacing, gradual load increases, allied health referral and appropriate footwear.

Conclusion

Rheumatologists acknowledged both the potential benefits and risks of running for people with RA. Individualised recommendations based on disease status and patient preferences could enhance the integration of running into care plans. Further research is needed to develop specific guidelines and understand patient outcomes.

Cross-sectional survey investigating knowledge, attitudes and reasons for use of food supplements in rheumatological diseases: the IntegraRE study protocol

Por: Iacoponi · F. · Cardamone · E. · Pastorelli · A. · Rosetti · M. · Agrimi · U. · Silano · M. · Stacchini · P. · Laurenti · R. · Marotto · D. · Gargiulo · R. · Boniglia · C. · Di Giacomo · S.
Introduction

Rheumatological diseases represent a widespread heterogeneous group of disorders, united by chronic musculoskeletal inflammatory processes. Despite the increasing effectiveness of new therapies, the lack of adequate treatments for certain conditions and the occurrence of adverse drug reactions have led to the need for alternative strategies, including food supplements. These products are perceived by the patient as a valuable aid without adverse effects. However, adverse reactions to food supplements have been reported, although their incidence cannot be established due to the lack of consumption data. In this context, the IntegraRE project aims at collecting information on the use of food supplements in rheumatology, considering both physicians and patients.

Methods and analysis

A survey-based cross-sectional study has been designed into two consecutive phases: Phase 1 aims to investigate rheumatologists’ knowledge, attitudes and recommendations to patients regarding food supplements, while Phase 2 focuses on estimating patients’ intake of food supplements, including the specific products used, unit consumed and reasons for their consumption. Questionnaires will be collected from at least 287 rheumatologists and 2000 patients, geographically distributed in proportion to the Italian population. These will gather information on sociodemographic variables, lifestyle factors, knowledge, clinical practices and supplement consumption.

Ethics and dissemination

The study protocol has been approved by the Ethics Committee of the Italian National Institute of Health (approval no. AOO 0032395 on 24 July 2024). The results, which will be widely disseminated through conference presentations, peer-reviewed publications and dedicated project webpage, will provide an understanding of the use of food supplements in rheumatology and allow guidelines to be drawn up on their correct use in the clinical practice of rheumatological diseases. Overall, this survey will increase people’s awareness of the effects of food supplements and encourage their safe and conscious use.

Effectiveness of a home-based physical exercise intervention in patients with fragility fractures on functional independence and hospital readmissions: a protocol for a randomised controlled trial

Por: Segura-Ruiz · R. · Ruiz-Canete · M. · Munoz-Alonso · A. · Rivas-Cruces · C. · Serrano-Lazaro · P. · Armenteros-Ortiz · P. J. · Hidalgo-Lopezosa · P. · Lamberti · N. · Manfredini · F. · Lopez-Soto · P. J.
Introduction

Patients with fragility fractures are two times as likely to suffer future fractures as their peers who have not suffered a fracture. In addition, 40% of those who suffer fragility fractures do not recover their level of functioning in terms of activities of daily living after 1 year. The present study aims to verify the hypothesis that a semipersonalised home-based exercise intervention may improve patients’ independence and reduce the number of hospital admissions compared with usual care for a population that suffers fragility fractures.

Methods and analysis

This parallel-arm single-blinded randomised-controlled trial will take place at the University of Cordoba (Spain) between September 2022 and September 2024. Patients aged >50 years old who have undergone surgery for a fragility hip fracture and who were prefracture independent (Barthel index (BI)>60) will be invited to participate. Patients will be excluded if they present a different type of fracture, mild or greater cognitive impairment or contraindication to exercise training. Patients will then be randomised into exercise or usual care group. The former will receive a daily walking appointment (number of steps to be completed inside home, interspersed with sit-to-stand movements) with the total volume increasing weekly. The latter will receive the usual care. The outcomes, collected at baseline, at the end of training (3 months) and at follow-up (6 months) by blinded operators will include the BI and number of readmissions (primary outcomes) and quality of life, exercise capacity, strength, cognitive status, bone mineral density and laboratory biomarkers (secondary outcomes). Variables related to quality of life, cognitive status, laboratory markers and densitometry will also be analysed.

Ethics and dissemination

The research ethics committee of the province of Cordoba approved the project (number 326; date 28 July 2021). Patients who meet the eligibility criteria will receive a patient information document and the consent form and will be encouraged to ask any questions. The proposed research respects the fundamental principles of the Declaration of Helsinki, the Council of Europe Declaration on Human Rights and Biomedicine, the UNESCO Universal Declaration on the Human Genome and Human Rights, and the Oviedo Council on Human Rights and Biomedicine. The data obtained in this study will be confidential. They will be treated by the Organic Law 3/2018, of 5 December, on the Protection of Personal Data and Guarantee of Digital Rights, keeping it strictly confidential and not accessible to unauthorised third parties, and the Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on Data Protection (RGPD). Written informed consent will be obtained from all the participants. The study’s results will be published in peer-reviewed journals and presented at scientific congresses worldwide. The results will also be disseminated through patient advocacy group newsletters and social media platforms. Patient partners will help select the appropriate channels and develop plain-language summaries tailored to their communities’ needs.

Trial registration number

ClinicalTrials.gov ID: NCT04934358 (registration date: 14 June 2021).

Sonographic Assessment of the Optic Nerve Sheath in Giant Cell Arteritis (SONIC-GCA): protocol for a prospective, multicentre diagnostic test accuracy study

Por: Makhzoum · J.-P. · Mendel · A. · Touati · A. · Marcotte · G. · Barra · L. · Pagnoux · C.
Introduction

Giant cell arteritis (GCA) is a vision-threatening systemic vasculitis for which no universally accessible diagnostic tool exists. Optic nerve sheath diameter (ONSD), measurable via ultrasound, has emerged as a promising, non-invasive biomarker of cranial GCA. The Sonographic Assessment of the Optic Nerve Sheath in Giant Cell Arteritis (SONIC-GCA) aims to validate ONSD ultrasound as a diagnostic and monitoring tool in GCA.

Methods and analysis

SONIC-GCA is a prospective, multicentre study enrolling patients referred for the evaluation of suspected GCA. A total of 285 participants will undergo optic nerve sheath ultrasound and digital retinal funduscopy, followed by a standardised GCA assessment. All participants will be followed for a minimum of 6 months, at which time an external adjudication committee will confirm the diagnosis of GCA. Those diagnosed with GCA will be followed for 2 years, with repeated optic nerve sheath ultrasound and digital retinal funduscopy at months 3, 6, 12, 18, 24 and at relapse, if applicable.

The primary outcome is the diagnostic accuracy of ONSD to detect GCA, which will be evaluated using receiver operating characteristic curve analysis, with adjudicated GCA status serving as the reference standard. Secondary outcomes will address several complementary domains: its value for relapse monitoring will be assessed through time-dependent Cox proportional hazards models, examining whether baseline or longitudinal ONSD predicts relapse risk; intraobserver and interobserver reliability will be determined using intraclass correlation coefficients, providing quantitative estimates of measurement reproducibility; and its association with retinal findings will be evaluated by correlating ONSD measurements with ocular imaging and clinical retinal outcomes. Together, these analyses will comprehensively determine the diagnostic, prognostic and operational utility of ONSD in GCA.

Ethics and dissemination

The study has been peer-reviewed by the scientific committee and approved by the CIUSSS du Nord-de-l’Île-de-Montréal Research Ethics Board. Each participating site will obtain local ethics approval prior to enrolment. All participants will provide informed consent. Results will be disseminated through peer-reviewed publications, conference presentations and webinars.

Trial registration number

NCT05749094.

Work disability in systemic lupus erythematosus: a systematic review protocol of contributing factors and return-to-work facilitators

Por: Nowrouzi-Kia · B. · Lo · J. · Long · B.-Z. S. · Balakrishnar · K. · Sathananthan · A. · Choppella · M. · Touma · Z.
Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple body parts. With a fluctuating range of symptoms, SLE imposes significant challenges and limitations on individuals at work. The objective of this review is to synthesise the existing literature on work disability in patients with SLE and identify factors associated with work disability and facilitators of returning to work (RTW).

Methods and analysis

This systematic review is registered with PROSPERO (CRD420251011567). This protocol followed the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols) guidelines. The search will be conducted using Business Source Premier, CINAHL, Cochrane Library, Embase, MEDLINE, PsycINFO, Scopus and Web of Science from inception to March 2025. At least two independent reviewers will complete screening, data extraction and critical appraisal. Eligible studies will focus on individuals with SLE and examine the barriers and facilitators to RTW. Eligible studies will be peer-reviewed, published in English or available in English translations. Unpublished research, opinion pieces, conference papers, abstracts, book chapters, knowledge syntheses, commentaries and grey literature will be excluded.

Ethics and dissemination

This study does not require ethics approval. The results of the completed review will be published.

PROSPERO registration number

CRD420251011567.

Risk of cataract in patients with systemic lupus erythematosus: a retrospective cohort study in Taiwan

Por: Liu · D.-Y. · Chung · C. · Wang · Y.-T. · Lee · H.-M. · Cheng · T.-A. · Lin · C.-A. · Su · Y.-C. · Yao · P.-T. · Shen · T.-C. · Lin · H.-J. · Tsai · F.-J.
Objectives

To investigate whether systemic lupus erythematosus (SLE) increases the risk of cataract development and to evaluate the impact of corticosteroid use and dosage on this risk.

Design

Nationwide retrospective cohort study.

Setting

Using Taiwan’s National Health Insurance (NHI) database, which covers over 99.9% of the population.

Participants

The SLE cohort included 30 501 newly diagnosed adults from 2011 to 2020. For each patient with SLE, four individuals without SLE were selected from the NHI database using frequency matching by age (in 5 year intervals), gender and index year of diagnosis, resulting in a comparison cohort of 122 004 individuals.

Primary and secondary outcome measures

The primary outcome was incident cataract. Secondary outcomes included risk stratification by age, sex, comorbidities and corticosteroid dose.

Results

SLE patients had a higher incidence of cataracts than non-SLE individuals (adjusted HR (aHR) = 1.73, 95% CI 1.66 to 1.81). Stratified analyses showed elevated risks in women (aHR=1.74, 95% CI 1.66 to 1.83), men (aHR=1.68, 95% CI 1.52 to 1.86), and across age groups 20–49 years (aHR=2.32, 95% CI 2.11 to 2.56), 50–64 years (aHR=1.60, 95% CI 1.51 to 1.69), and ≥65 years (aHR=1.50, 95% CI 1.36 to 1.66). Analysis of corticosteroid exposure revealed that cumulative dose showed a trend towards increased risk at high exposure (adjusted OR (aOR) = 1.14, 95% CI 0.99 to 1.31), while average daily dose demonstrated a dose–response effect: 1–5 mg/day (aOR=1.31, 95% CI 1.13 to 1.52) and ≥5 mg/day (OR=2.48, 95% CI 2.16 to 2.86).

Conclusions

Adults with SLE have an increased risk of developing cataracts compared with matched controls, and higher average daily corticosteroid doses are associated with this risk. These findings highlight the need for careful monitoring of ocular complications in SLE patients.

Understanding internet-supported self-management for low back pain in primary care: a qualitative process evaluation of the SupportBack 2 randomised controlled trial

Por: Geraghty · A. W. A. · Hughes · S. · Roberts · L. · Hill · J. C. · Foster · N. E. · Hay · E. · Mansell · G. · White · M. · Davies · F. · Steele · M. · Little · P. · Yardley · L.
Objective

The SupportBack 2 randomised controlled trial (RCT) compared the clinical and cost-effectiveness of an internet intervention supporting self-management versus usual primary care in reducing low back pain (LBP)-related disability. In this study, we aimed to identify and understand key processes and potential mechanisms underlying the impact of the intervention.

Design

This was a nested qualitative process evaluation of the SupportBack 2 RCT (ISRCTN: 14736486 pre-results).

Setting

Primary care in the UK (England).

Participants

46 trial participants experiencing LBP without indicators of serious spinal pathologies (eg, fractures, infection) took part in telephone interviews at either 3 (n=15), 6 (n=14) or 12 months (n=17) post randomisation. Five physiotherapists who provided telephone support for the internet intervention also took part in telephone interviews.

Intervention

An internet intervention ‘SupportBack’ supporting self-management of LBP primarily through physical activity and exercise delivered in addition to usual care, with and without physiotherapist telephone support.

Analysis

Data were analysed thematically, applying a realist logic to develop context-mechanism-outcome configurations.

Results

Four explanatory themes were developed, with five context-mechanism-outcome configurations. Where benefit was reported, SupportBack appeared to work by facilitating a central associative process where participants linked increases in physical activity or exercise with improvements in LBP, then continued to use physical activity or exercise as key regulatory strategies. Participants who reported little or no benefit from the intervention appeared to experience several barriers to this associative process, including negative expectations, prohibitive beliefs about the cause of LBP or functional limitations preventing engagement. Physiotherapists appeared to provide accountability and validation for some; however, the remote telephone support that lacked physical assessment was viewed as limiting its potential value.

Conclusions

Digital interventions targeting physical activity and exercise to support LBP self-management may rely on mechanisms that are easily inhibited in complex, heterogeneous populations. Future research should focus on identifying and removing barriers that may limit the effectiveness of digital self-management support for LBP.

Using an outpatient physiotherapist-led behaviour change intervention to promote exercise adherence in people with vertebral fragility fracture: a longitudinal qualitative study

Por: Hannink · E. · Room · J. · Barker · K. L.
Objectives

To explore the longitudinal experience of taking part in a physiotherapy-led exercise adherence programme as part of the OsteoPorosis Tailored exercise adherence INtervention (OPTIN) trial.

Design

Longitudinal qualitative study using semi-structured interviews analysed with reflexive thematic analysis—an interpretive approach.

Setting

UK National Health Service.

Participants

12 participants with vertebral fragility fracture (VFF) within the exercise adherence intervention arm of the OPTIN trial (n=63 in each arm). Interviews were undertaken with each participant at three time points: (1) within the first 2 weeks of initial assessment, (2) at the end of the 16-week intervention and (3) a year post-baseline.

Results

We distilled five themes. (1) One size does not fit all: this focuses on the importance of a physiotherapist individualising the exercise programme and how participants adapt it into their lives. (2) My mind and body can be in conflict or work together: this spotlights the strong link between one’s emotional and mental state with their physical state, and how they can work to positively or negatively affect exercise adherence behaviour. (3) Expanding my circle of support: this revolves around the need for support systems beyond family and friends to the physiotherapist and other people with osteoporosis. (4) Transitioning from an exercise programme to a lifestyle change: this encompasses a longitudinal perspective of the exercise programme tapering, becoming intermittent or dropping off after a year, then being replaced by sustained lifestyle changes. (5) Moving from fear to empowerment: this explores the fear and loss of former identity after VFF diagnosis transforming into hope, confidence and empowerment through knowledge, advice and coping strategies.

Conclusions

Findings highlight the need to work with mind and body to empower lifestyle changes and the importance of educating, tailoring, empathising and allying with the participant—all critical areas clinicians can target when treating patients with VFFs.

Trail registration number

ISRCTN14465704.

Immediate versus gradual TocilizuMab discontinuAtion in GIant Cell Arteritis: protocol of the multicentre randomised open-label MAGICA trial

Por: Samson · M. · Fournel · I. · Bourredjem · A. · Cortier · M. · Galizzi · E. · Cransac · A. · Cladiere · C. · Fleck · C. · Brayer · M. · Carpentier · M. · Alberini · J.-L. · Devilliers · H. · Bonnotte · B.
Introduction

Giant cell arteritis (GCA) is a large-vessel vasculitis occurring in people aged over 50 years. Recent studies have shown that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, is remarkably effective in treating GCA and allows significant dose sparing of glucocorticoids. However, it makes it difficult to monitor disease activity. Furthermore, treatment is often prolonged over 1 year due to the fear of relapse after stopping TCZ and/or the absence of an optimal discontinuation scheme.

Methods and analysis

This study aims at comparing two discontinuation regimens in a population of GCA patients who have been treated with TCZ for 12–36 months and have discontinued glucocorticoids for at least 12 weeks. Patients will be randomised with a 1:1 ratio between two arms: immediate discontinuation (cessation) versus gradual discontinuation of TCZ (162 mg subcutaneously every 2 weeks for 12 weeks and then every 4 weeks for 12 additional weeks). Patients will be followed up for 78 weeks. The primary endpoint is relapse-free survival after 26 weeks of follow-up. A total of 120 patients will be randomised (60 in each group) for a period of 3 years.

Ethics and dissemination

The trial was approved by an independent ethics committee (CPP Sud Ouest et Outre Mer IV) and the French health authority (French National Agency for Medicines and Health Products Safety—ANSM) through the Clinical Trials Information System (CTIS) provided by the European Medicines Agency (EMA). The informed consent complies with the ICH GCP guideline and regulatory requirements. Eligible patients may only be included in the study after providing informed consent. Findings will be published in peer-reviewed journals and conference presentations.

Trial registration number

NCT06037460.

Combining virtual reality and hypnosis to alleviate chronic pain in elderly with hand arthritis: protocol for a randomised phase II clinical trial

Por: Fournier · V. · Simard · M.-F. · Yuen · S. Y. · Guine · J. · Rousseaux · F. · Lebeau · J. · Jerbi · K. · Richebe · P. · Landry · M. · Rainville · P. · Ogez · D.
Introduction

Chronic pain is a common health condition that significantly impacts the quality of life of those affected, affecting one in five people in Canada. The prevalence of this condition tends to increase with age, making it a major health issue given the ageing population. However, its management remains inadequate and requires significant mobilisation of healthcare professionals as well as the development of multiple therapeutic solutions. Among these, non-pharmacological interventions such as hypnosis and virtual reality have proven effective. Nevertheless, while the existing literature seems promising, it presents methodological limitations. Therefore, this study aims to assess the effectiveness of an intervention combining virtual reality and hypnosis in an ageing population suffering from a widespread chronic pain condition, that is, hand arthritis.

Methods and analysis

This study will be a single-centre randomised clinical trial. Participants will be randomly assigned to one of two conditions: one receiving an intervention combining virtual reality and hypnosis, and the other receiving only virtual reality. The effectiveness of the intervention on current perceived pain before and after the intervention (primary outcome) will be evaluated. Secondary outcomes will include anxiety and depressive symptoms, quality of life, relaxation and fatigue. Exploratory analyses will also be conducted to contribute to the emerging literature by examining physiological variables such as heart rate variability, respiratory rate and electrodermal activity during the intervention, and their relationship with primary and secondary outcomes.

Ethics and dissemination

The project was approved by the Research Ethical Committee of the Hospital Maisonneuve-Rosemont (Project no 2024-3539). Participants will be asked to provide written consent for their participation. Results from this study will be shared through peer-reviewed publications, as well as oral and poster presentations at scientific events. The protocol for this study was preregistered on Open Science Framework and raw anonymised data will be available on this platform (https://osf.io/vbh72/?view_only=1d17c5708f894faab6669d85e1fde75d).

Trial registration number

NCT06833905.

Temporal trends in the epidemiology of hip osteoarthritis in the USA, 1990-2019: a cross-sectional time-series study using GBD data

Por: Sayyed · A. · Dykhouse · G. L. · Manes · T. J. · Sabet · C. · Nemani · M. G. · Ngo · A. L. · Ibrahim · A. A. · Mckegg · P. C. · Patel · J. N.
Objectives

To evaluate temporal trends in the epidemiology of hip osteoarthritis (OA) in the USA from 1990 to 2019, with stratification by sex and geographic region.

Design

Cross-sectional time-series analysis using secondary data from the Global Burden of Disease (GBD) study.

Setting

US population-based analysis, stratified by the four US Census Bureau regions: Northeast, Midwest, South and West.

Participants

De-identified, aggregate population-level data representing all adults in the USA from 1990 to 2019, drawn from the GBD database.

Primary and secondary outcome measures

Age-standardised rates per 100 000 population for years lived with disability (YLDs), prevalence and incidence of hip OA. Outcomes were stratified by sex and region. Statistical significance was defined as p

Results

Between 1990 and 2019, hip OA in the USA increased by 23.91% in YLDs, 24.67% in prevalence and 25.22% in incidence. In 2019, the mean YLDs were 28.30 in women versus 25.48 in men; prevalence was 49.55 versus 41.08; and incidence was 919.29 versus 818.10 (all p

Conclusions

There has been a substantial rise in the burden of hip OA in the USA over the past three decades. Women and residents of the Northeastern USA are disproportionately affected. These findings underscore the need for targeted public health strategies that account for geographic and sex-based disparities in hip OA burden.

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