Interferon-γ inhibits interleukin-1β-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis

Introduction: The first few months after symptom onset represents a pathologically distinct phase in rheumatoid arthritis (RA). We used relevant experimental models to define the pathological role of interferon-γ (IFN-γ) during early inflammatory arthritis. Methods: We studied IFN-γ's capacity to modulate interleukin-1β (IL-1β) induced degenerative responses using RA fibroblast-like synoviocytes (FLS), a bovine articular cartilage explant (BACE)/RA-FLS co-culture model and an experimental inflammatory arthritis model (murine antigen-induced arthritis (AIA)). Results: IFN-γ modulated IL-1β driven matrix metalloproteinases (MMP) synthesis resulting in the down-regulation of MMP-1 and MMP-3 production in vitro. IFN-γ did not affect IL-1β induced tissue inhibitor of metalloproteinase-1 (TIMP-1) production by RA FLS but skewed the MMP/TIMP-1 balance sufficiently to attenuate glycosaminoglycan-depletion in our BACE model. IFN-γ reduced IL-1β expression in the arthritic joint and prevented cartilage degeneration on Day 3 of AIA. Conclusions: Early therapeutic intervention with IFN-γ may be critical to orchestrate tissue-protective responses during inflammatory arthritis

Enhancing authenticity, diagnosticity and equivalence (AD-Equiv) in multicentre OSCE exams in health professionals education: protocol for a complex intervention study

Introduction: Objective structured clinical exams (OSCEs) are a cornerstone of assessing the competence of trainee healthcare professionals, but have been criticised for (1) lacking authenticity, (2) variability in examiners’ judgements which can challenge assessment equivalence and (3) for limited diagnosticity of trainees’ focal strengths and weaknesses. In response, this study aims to investigate whether (1) sharing integrated-task OSCE stations across institutions can increase perceived authenticity, while (2) enhancing assessment equivalence by enabling comparison of the standard of examiners’ judgements between institutions using a novel methodology (video-based score comparison and adjustment (VESCA)) and (3) exploring the potential to develop more diagnostic signals from data on students’ performances. Methods and analysis: The study will use a complex intervention design, developing, implementing and sharing an integrated-task (research) OSCE across four UK medical schools. It will use VESCA to compare examiner scoring differences between groups of examiners and different sites, while studying how, why and for whom the shared OSCE and VESCA operate across participating schools. Quantitative analysis will use Many Facet Rasch Modelling to compare the influence of different examiners groups and sites on students’ scores, while the operation of the two interventions (shared integrated task OSCEs; VESCA) will be studied through the theory-driven method of Realist evaluation. Further exploratory analyses will examine diagnostic performance signals within data. Ethics and dissemination: The study will be extra to usual course requirements and all participation will be voluntary. We will uphold principles of informed consent, the right to withdraw, confidentiality with pseudonymity and strict data security. The study has received ethical approval from Keele University Research Ethics Committee. Findings will be academically published and will contribute to good practice guidance on (1) the use of VESCA and (2) sharing and use of integrated-task OSCE stations

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes