Pain sensitisation and joint inflammation in patients with active rheumatoid arthritis.

Introduction: Despite better therapies and strategies, many people with rheumatoid arthritis (RA) have persistent pain, often from abnormal pain processing, now termed nociplastic pain. However, RA patients with fibromyalgia (FM), a central nociplastic pain syndrome, also have power doppler ultrasound (PDUS+) joint inflammation. To understand the complex causes of pain, we performed clinical examination and patient-reported outcome measures (PROMs) plus comprehensive PDUS evaluation not previously combined.

Remote monitoring of patients with rheumatoid arthritis in a low disease activity state: a mixed methods evaluation across six hospitals in London, UK.

Objectives: This study evaluated the scale-up of a remote monitoring service, capturing monthly Rheumatoid Arthritis Impact of Disease scores and patient-generated text messages, for patients with rheumatoid arthritis (RA; in remission or with low disease activity) attending routine outpatient clinics across six hospitals. We explored patients and staff experiences and implementation outcomes.

Methods: A pragmatic, mixed methods approach was used, with active patient involvement throughout.

Correction to: Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) - a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) - a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial.

Background: Persistent physical symptoms (PPS), also known as medically unexplained symptoms (MUS), affect approximately 50% of patients in secondary care and are often associated with disability, psychological distress and increased health care costs. Cognitive behavioural therapy (CBT) has demonstrated both short- and long-term efficacy with small to medium effect sizes for PPS, with larger treatment effects for specific PPS syndromes, including non-cardiac chest pain, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS). Research indicates that PPS conditions share similar cognitive and behavioural responses to symptoms, such as avoidance and unhelpful beliefs.

Real world long-term impact of intensive treatment on disease activity, disability and health-related quality of life in rheumatoid arthritis.

Background: The emphasis on treating rheumatoid arthritis (RA) intensively reduces disease activity but its impact in routine care is uncertain. We evaluated temporal changes in disease activities and outcomes in a 10-year prospective observational cohort study of patients in routine care at one unit.

Methods: The Guy's and St Thomas' RA cohort was established in 2005.

The frequency of remission and low disease activity in patients with rheumatoid arthritis, and their ability to identify people with low disability and normal quality of life.

Objective: Treat-to-target in rheumatoid arthritis (RA) recommends targeting remission, with low disease activity (LDA) being an alternative goal. When deciding to target remission or LDA, important considerations are the likelihood of attaining them, and their impacts on function and health-related quality of life (HRQoL). We have addressed this by studying: (a) the frequency of remission and LDA/remission; (b) DAS28-ESR trends after remission; (c) ability of remission vs.

Flares in Rheumatoid Arthritis Patients with Low Disease Activity: Predictability and Association with Worse Clinical Outcomes.

Objective: To investigate predictors of flare in rheumatoid arthritis (RA) patients with low disease activity (LDA) and to evaluate the effect of flare on 12-month clinical outcomes.

Methods: Patients with RA who were taking disease-modifying antirheumatic drugs and had a stable 28-joint count Disease Activity Score (DAS28) < 3.2 were eligible for inclusion.

Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A Randomized Trial.

Background: Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments are sparse.

Objective: To determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment of hand osteoarthritis.

Design: Randomized, double-blind, placebo-controlled clinical trial with 12-month follow-up.

Rheumatoid arthritis patients with fibromyalgic clinical features have significantly less synovitis as defined by power Doppler ultrasound.

Background: In patients with rheumatoid arthritis (RA) clinical measures of disease activity may not reliably discriminate between patients with active inflammatory disease and those with concomitant fibromyalgia (FM). Recent work has shown RA patients with a 28 tender joint count (TJC) minus swollen joint count (SJC) of 7 or more (joint count criteria) are more likely to meet classification criteria for FM. This study aimed to determine whether RA patients meeting clinical criteria for FM had lower levels of joint inflammation as determined by ultrasound (US).

Safety and patient response as indicated by biomarker changes to binding immunoglobulin protein in the phase I/IIA RAGULA clinical trial in rheumatoid arthritis.

Objectives: Binding immunoglobulin protein (BiP) is a human endoplasmic reticulum-resident stress protein. In pre-clinical studies it has anti-inflammatory properties due to the induction of regulatory cells. This randomized placebo-controlled, dose ascending double blind phase I/IIA trial of BiP in patients with active RA, who had failed accepted therapies, had the primary objective of safety.

Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial.

Background: Osteoarthritis (OA) is the fastest growing cause of disability worldwide. Current treatments for OA are severely limited and a large proportion of people with OA live in constant, debilitating pain. There is therefore an urgent need for novel treatments to reduce pain.

Interleukin-17+CD8+ T cells are enriched in the joints of patients with psoriatic arthritis and correlate with disease activity and joint damage progression.

Objective: Psoriatic arthritis (PsA) is associated with HLA class I genes, in contrast to the association with HLA class II in rheumatoid arthritis (RA). Since IL-17+ cells are considered important mediators of synovial inflammation, we sought to determine whether IL-17-producing CD8+ T cells may be found in the joints of patients with PsA and whether these cells might contribute to the disease process.

Methods: Mononuclear cells from paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with PsA or patients with RA were stimulated ex vivo, and CD4- T cells were examined by flow cytometry for cytokine expression, cytotoxic markers, and frequencies of γ/δ or mucosal-associated invariant T cells.

Development of a novel recombinant biotherapeutic with applications in targeted therapy of human arthritis.

Objective: To isolate recombinant antibodies with specificity for human arthritic synovium and to develop targeting reagents with joint-specific delivery capacity for therapeutic and/or diagnostic applications.

Methods: In vivo single-chain Fv (scFv) antibody phage display screening using a human synovial xenograft model was used to isolate antibodies specific to the microvasculature of human arthritic synovium. Single-chain Fv antibody tissue-specific reactivity was assessed by immunostaining of synovial tissues from normal controls and from patients with rheumatoid arthritis and osteoarthritis, normal human tissue arrays, and tissues from other patients with inflammatory diseases displaying neovasculogenesis.

A structured course teaching junior doctors invasive medical procedures results in sustained improvements in self-reported confidence.

Pressure on working hours has led to a decrease in opportunities for training in invasive medical procedures for junior doctors. The effect of a structured course on immediate and medium-term changes in self-reported confidence was investigated. A one-day model-based practical course was run on two separate occasions teaching central venous line placement, lumbar puncture, Seldinger-technique chest drain insertion and knee joint aspiration.

Treating early rheumatoid arthritis intensively: current UK practice does not reflect guidelines.

Recent guidance published in the UK by the National Institute for Health and Clinical Excellence has recommended that patients with early rheumatoid arthritis (RA) are treated with combination disease-modifying anti-rheumatic drugs (DMARDs). It is unclear to what extent this reflects current UK practice. UK rheumatologists were asked to complete a web-based questionnaire asking about their treatment preferences in early RA and to indicate their attitudes to combination DMARD therapy.

A novel model for the pre-clinical imaging of inflamed human synovial vasculature.

Objective: The purpose of this study was to explore the development of a pre-clinical nuclear imaging model as a tool for testing novel radiopharmaceutical agents for imaging and/or delivery systems to human tissues. Here we report for the first time the imaging of human synovial tissue transplanted into SCID mice using a radiolabelled anti-E-selectin antibody and NanoSPECT/CT technology.

Methods: Human synovium was transplanted into SCID mice.

In vivo phage display selection in the human/SCID mouse chimera model for defining synovial specific determinants.

Phage display has represented a phenomenal technological advance of the last two decades. This technique is a very effective way of producing large numbers (up to 10(12)) of diverse peptides and proteins (including antibodies), presented as fusion proteins on the viral capsid, that can be used for isolating specific molecules for therapeutic targeting. The increasing realization of the importance of the vascular endothelium in chronic inflammation as well as in neoplastic growth/spreading has prompted the targeting of blood vessels using phage display.