Inflammatory disease microbiomes share a functional pathogenicity predicted by C-reactive protein.

We examine disease-specific and cross-disease functions of the human gut microbiome by colonizing germ-free mice, at risk for inflammatory arthritis, colitis, or neuroinflammation, with over 100 human fecal microbiomes from subjects with rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, ulcerative colitis, Crohn's disease, or colorectal cancer. We find common inflammatory phenotypes driven by microbiomes from individuals with intestinal inflammation or inflammatory arthritis, as well as distinct functions specific to microbiomes from multiple sclerosis patients. Inflammatory disease in mice colonized with human microbiomes correlated with systemic inflammation, measured by C-reactive protein, in the human donors.

Ethnicity-specific patterns of epigenetic age acceleration in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an age-related chronic inflammatory disease which may include accelerated biological ageing processes in its pathogenesis. To determine if increased biological age is associated with risk of RA and/or is present once disease is established. We used DNA methylation to compare biological age (epigenetic age) of immune cells in adults at risk of RA and those with confirmed RA, including twins discordant for RA.

Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra-Articular Space.

Intra-articular glucocorticoid injections are effective in controlling inflammation and pain in arthritides but restricted by short duration of action and risk of joint degeneration. Controlled drug release using biocompatible hydrogels offers a unique solution, but limitations of in situ gelation restrict their application. Gellan sheared hydrogels (GSHs) retain the advantages of hydrogels, however their unique microstructures lend themselves to intra-articular application - capable of shear thinning under force but restructuring at rest to enhance residence.

Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these "at-risk" stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA.

Prodromal symptoms of rheumatoid arthritis in a primary care database: variation by ethnicity and socioeconomic status.

Objectives: To assess whether prodromal symptoms of RA, as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status.

Methods: A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between 1 January 2004 and 1 May 2022.

Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial.

Background: Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept.

Methods: The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands.

Stakeholder perceptions of preventive approaches to rheumatoid arthritis: qualitative study of healthcare professionals' perspectives on predictive and preventive strategies.

Background: There is increasing research interest in the development of preventive treatment for individuals at risk of rheumatoid arthritis (RA). Previous studies have explored the perceptions of at-risk groups and patients about predictive and preventive strategies for RA, but little is known about health care professionals' (HCPs) perspectives.

Methods: One-to-one semi-structured qualitative interviews were conducted (face-to-face or by telephone) with HCPs.

The student patient alliance: development and formative evaluation of an initiative to support collaborations between patient and public involvement partners and doctoral students.

Background: While the integration of patient and public involvement (PPI) in clinical research is now widespread and recommended as standard practice, meaningful PPI in pre-clinical, discovery science research is more difficult to achieve. One potential way to address this is by integrating PPI into the training programmes of discovery science postgraduate doctoral students. This paper describes the development and formative evaluation of the Student Patient Alliance (SPA), a programme developed at the University of Birmingham that connects PPI partners with doctoral students.

Maximum Acceptable Risk Estimation Based on a Discrete Choice Experiment and a Probabilistic Threshold Technique.

Objective: We aimed to empirically compare maximum acceptable risk results estimated using both a discrete choice experiment (DCE) and a probabilistic threshold technique (PTT).

Methods: Members of the UK general public (n = 982) completed an online survey including a DCE and a PTT (in random order) measuring their preferences for preventative treatment for rheumatoid arthritis. For the DCE, a Bayesian D-efficient design consisting of four blocks of 15 choice tasks was constructed including six attributes with varying levels.

Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes.

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause.

Differential effect of lactate on synovial fibroblast and macrophage effector functions.

Introduction: The synovial membrane is the main site of inflammation in rheumatoid arthritis (RA). Here several subsets of fibroblasts and macrophages, with distinct effector functions, have been recently identified. The RA synovium is hypoxic and acidic, with increased levels of lactate as a result of inflammation.

Number of days required to measure sedentary time and physical activity using accelerometery in rheumatoid arthritis: a reliability study.

This study aimed to determine the minimum number of days required to reliably estimate free-living sedentary time, light-intensity physical activity (LPA) and moderate-intensity physical activity (MPA) using accelerometer data in people with Rheumatoid Arthritis (RA), according to Disease Activity Score-28-C-reactive protein (DAS-28-CRP). Secondary analysis of two existing RA cohorts with controlled (cohort 1) and active (cohort 2) disease was undertaken. People with RA were classified as being in remission (DAS-28-CRP < 2.

Is symptom duration before DMARD therapy a determinant of direct and indirect costs in DMARD-naïve RA patients? A systematic review.

Objective: Early treatment of RA improves clinical outcomes; however, the impact on health economic outcomes is unclear. This review sought to investigate the relationship between symptom/disease duration and resource utilization/costs and the responsiveness of costs following RA diagnosis.

Methods: A systematic search was performed on Pubmed, EMBASE, CINAHL and Medline.

Predictors of the likelihood that patients with rheumatoid arthritis will communicate information about rheumatoid arthritis risk to relatives: A quantitative assessment.

First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) are increasingly recruited to prediction and prevention studies. Access to FDRs is usually via their proband with RA. Quantitative data on predictors of family risk communication are lacking.

Fibroblast heterogeneity: Keystone of tissue homeostasis and pathology in inflammation and ageing.

Fibroblasts, derived from the embryonic mesenchyme, are a diverse array of cells with roles in development, homeostasis, repair, and disease across tissues. In doing so, fibroblasts maintain micro-environmental homeostasis and create tissue niches by producing a complex extracellular matrix (ECM) including various structural proteins. Although long considered phenotypically homogenous and functionally identical, the emergence of novel technologies such as single cell transcriptomics has allowed the identification of different phenotypic and cellular states to be attributed to fibroblasts, highlighting their role in tissue regulation and inflammation.

Acceptable risks of treatments to prevent rheumatoid arthritis among first-degree relatives: demographic and psychological predictors of risk tolerance.

Objectives: To quantify tolerance to risks of preventive treatments among first-degree relatives (FDRs) of patients with rheumatoid arthritis (RA).

Methods: Preventive treatments for RA are under investigation. In a preference survey, adult FDRs assumed a 60% chance of developing RA within 2 years and made choices between no treatment and hypothetical preventive treatment options with a fixed level of benefit (reduction in chance of developing RA from 60% to 20%) and varying levels of risks.

Outcomes of periodontal therapy in rheumatoid arthritis: The OPERA feasibility randomized trial.

Aim: Periodontitis is independently associated with rheumatoid arthritis (RA); however, there is limited data on whether periodontal treatment improves overall RA disease activity. We conducted a pilot feasibility randomized controlled clinical trial to test whether intensive periodontal therapy reduces RA disease activity in patients with active RA and periodontitis.

Materials And Methods: The following inclusion criteria were applied: patients with RA and periodontitis, aged 18+, stable on treatment with disease-modifying anti-rheumatic drugs for ≥3 months, disease activity score (DAS28) ≥3.

Patient and public involvement in an international rheumatology translational research project: an evaluation.

Background: Rheuma Tolerance for Cure (RTCure) is a five-year international collaboration between academia, industry and patients/members of the public. It focuses on developing approaches to predict the onset of rheumatoid arthritis (RA) and designing clinical trials to reduce the risk of disease development through immune-tolerising and other treatments. We conducted a mid-term evaluation of patient and public involvement (PPI) within the project.

Comorbidity phenotypes and risk of mortality in patients with osteoarthritis in the UK: a latent class analysis.

Background: Osteoarthritis (OA) is a common chronic condition but its association with other chronic conditions and mortality is largely unknown. This study aimed to use latent class analysis (LCA) of 30 comorbidities in patients with OA and matched controls without OA to identify clusters of comorbidities and examine the associations between the clusters, opioid use, and mortality.

Methods: A matched cohort analysis of patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 2000 and 2019.

Early onset of immune-mediated diseases in minority ethnic groups in the UK.

Background: The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis.

Methods: This was a population-based retrospective primary care study.

Acceptability of predictive testing for ischemic heart disease in those with a family history and the impact of results on behavioural intention and behaviour change: a systematic review.

Background: Tests to predict the development of chronic diseases in those with a family history of the disease are becoming increasingly available and can identify those who may benefit most from preventive interventions. It is important to understand the acceptability of these predictive approaches to inform the development of tools to support decision making. Whilst data are lacking for many diseases, data are available for ischemic heart disease (IHD).

Preferences for preventive treatments for rheumatoid arthritis: discrete choice survey in the UK, Germany and Romania.

Objective: To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries.

Methods: A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments.