Iain Goff

Reliability and validity of ultrasound imaging of features of knee osteoarthritis in the community

BackgroundRadiographs are the main outcome measure in epidemiological studies of osteoarthritis (OA). Ultrasound imaging has unique advantages in that it involves no ionising radiation, is easy to use and visualises soft tissue structures. Our objective was to measure the inter-rater reliability and validity of ultrasound imaging in the detection of features of knee OA.MethodsEighteen participants from a community cohort, had both knees scanned by two trained musculoskeletal sonographers, up to six weeks apart. Inter-rater reliability for osteophytes, effusion size and cartilage thickness was calculated by estimating Kappa (κ) and Intraclass correlation coefficients (ICC), as appropriate. A measure of construct validity was determined by estimating κ between the two imaging modalities in the detection of osteophytes.ResultsReliability: κ for osteophyte presence was 0.77(right femur), 0.65(left femur) and 0.88 for both tibia. ICCs for effusion size were 0.70(right) and 0.85(left). Moderate to substantial agreement was found in cartilage thickness measurements. Validity: For osteophytes, κ was moderate to excellent at 0.52(right) and 0.75(left).ConclusionSubstantial to excellent agreement was found between ultrasound observers for the presence of osteophytes and measurement of effusion size; it was moderate to substantial for femoral cartilage thickness. Moderate to substantial agreement was observed between ultrasound and radiographs for osteophyte presence.

Cardiovascular risk in juvenile idiopathic arthritis

JIA is the most common chronic inflammatory arthritis in children and young people. More than one-third of individuals have persistent active disease into adulthood. In RA, there has been considerable interest in long-term cardiovascular outcomes. Increased cardiovascular mortality and morbidity have been observed and consensus guidelines recommend annual cardiovascular risk assessment for adults with RA. The increased risk is attributed to a higher prevalence of traditional cardiovascular risk factors and the role of systemic inflammation in the acceleration of atherosclerosis. The long-term risk of cardiovascular disease for individuals with JIA remains uncertain and guidance on risk assessment is not currently available. Given the potential for longer disease duration, it is possible that cardiovascular risk in this group surpasses that observed in adult-onset inflammatory arthritides. In this article, we consider the evidence for cardiovascular risk in JIA.

Poor sensitivity of musculoskeletal history in children

Objectives To demonstrate the sensitivity of musculoskeletal (MSK) history taking. Design Prospective study: consecutive children attending outpatient clinics. Setting and patients Paediatric rheumatology clinic (n=45; girls n=28; median age 12 years, range 3–18), acute general paediatric assessment unit (n=50; girls n=21; median age 8 years, range 3–16). Intervention Pro forma recording abnormal joint involvement from history taking and then following MSK examination completed by clinicians. Main outcome measures Sensitivity of MSK history taking compared with clinical examination. Results Paediatric rheumatology clinic: 135 abnormal joints identified in 34 children; 53/135 (39%) by history alone, 82/135 (61%) detected on examination resulting in MSK history sensitivity 53%, specificity 98%. Acute paediatric unit: 29 abnormal joints identified in 17 children; 18/29 identified on history (sensitivity 62%). Conclusions MSK history taking failed to identify a large number of abnormal joints which were detected on physical examination, emphasising the need for all joints to be examined as part of a screening examination as a minimum.

Paediatric musculoskeletal learning needs for general practice trainees: achieving an expert consensus.

What is already known in this area Medical trainees of all specialties have poor confidence and skills in dealing with children presenting with musculoskeletal problems. There has not previously been a curriculum to direct learners in this area. What this work adds This work proposes a curriculum for paediatric musculoskeletal medicine to be taught to trainees in general practice. suggestions for future work Evaluation of the impact of introducing a curriculum on the confidence and competence of GPs in dealing with paediatric musculoskeletal disorders.

MediLex: the medical jargon-busting game.

During their training, medical students are expected to acquire the ability to use thousands of new terms that make up the medical lexicon. Clear communication requires knowledge of this lexicon. We developed a simple word game, MediLex, to facilitate the development of these skills. This paper describes the intervention and evaluates students’ experiences.

Detecting joint disease in children—dispelling the myths

Children frequently present to primary care, emergency departments and paediatricians with musculoskeletal (MSK) problems, and hence all of these professionals should be competent to perform a MSK assessment.1 Many of these children will have self-limiting illness/injury, however some will be presenting with chronic or life-threatening disease.2–4 The challenge is to reassure those with self-limiting disease, while identifying those presenting for the first time with new inflammatory arthritis such as juvenile idiopathic arthritis (JIA), or other serious conditions which can present with MSK features, such as malignancies, infections and neuromuscular diseases. There is a growing acceptance that early diagnosis and aggressive management of JIA leads to improved functional outcomes,5–7 while early access to therapies for non-inflammatory MSK disease reduces recovery times and prevents progression to pain amplification syndromes.8–10 This evidence stands in stark contrast to the reality experienced by many children with MSK disease, who still suffer long delays between disease onset and referral to a specialist service.11 ,12 Part of this delay is undoubtedly due to the paucity of training about MSK disease delivered to UK trainees in frontline specialties.13–16 This paper aims to dispel some of the myths that have developed regarding the diagnosis of joint disease in children. Children with musculoskeletal disease present with joint pain Although pain is the most common MSK symptom encountered by frontline paediatric clinicians, it is unusual for this to be the principal presenting feature of serious MSK disease.17 The majority of children with JIA present with stiffness, joint swelling, limp or functional impairment, with pain either not apparent or not verbalised. More frequently, parents notice abnormalities in an uncomplaining child such as clumsiness, a change in mood or avoidance of activities or play that were previously enjoyed. There may …

Rheumatologists’ ultrasound confidence and technique are improved by a two day cadaveric sonoanatomy course

Background Correct interpretation of musculoskeletal ultrasound (MSUS) requires thorough knowledge of normal anatomy, but several authors report deficiencies in anatomy skills among rheumatologists. Cadaver-based anatomy review courses improve clinical and injection skills, but the value of such courses in MSUS training is unclear. During 2010-12 we delivered two cadaver based, MSUS anatomy courses for the British Society of Rheumatology (BSR), and measured confidence to perform key MSUS learning objectives before and after the course using a self-assessment questionnaire.

Rheumatologists' Ultrasound Confidence and Interpretation of Normal Anatomy Are Improved by a Cadaver Based Sonoanatomy Course

Background/Purpose: MicroRNAs (miRs) are a novel class of posttranscriptional regulators. A single miR can have profound effects on cell activation due to its ability to modulate multiple pathways at once. We have previously shown that miR-155 is upregulated in rheumatoid arthritis (RA) synovial macrophages and promotes the development of autoimmunity and joint inflammation. Pre-clinical arthritis may be associated with lung changes e.g. bronchial wall thickening, thus the aim of this study was to investigate the contribution of miR-155 regulated pathways to lung homeostasis. Methods: Normal human lung tissue was tested by in situ hybridisation with miR-155 and control probes. To model the fibrotic response, WT and miR-155 / mice were given bleomycin (0.06 unit/mouse) intranasally. Intervention included intraperitoneal injections of the Liver X Receptor (LXR) agonist (GW3965 daily; 40 mg/kg). End-points included bronchial lavage (BAL) cytology, lung tissue histology, evaluation of the expression of inflammatory and fibrotic genes by qPCR and concentrations of soluble mediators in serum and BAL fluid by multiplex assays. The validation of miR-155 binding to LXR, and the LXR response element in collagen gene promoters were performed with reporter assays. Results: In situ hybridisation showed an abundant expression of miR-155 in the normal human lung suggesting that this miR may contribute to normal lung homeostasis. miR-155 / mice developed more severe bleomycininduced lung fibrosis compared to WT mice, as seen by increased collagen 1a/3a mRNA expression and protein deposition in the lungs, as well as accumulation of macrophages and lymphocytes in BAL. Gene expression analysis of lung extracts revealed an increase in the M2 pro-fibrotic macrophage markers Arginase 2, IL-13R and Ym1. In addition, the levels of pro-fibrotic cytokines such as VEGF and bFGF were significantly higher in BAL and serum of miR-155 / mice. Primary lung fibroblast lines derived from miR-155 / mice showed higher proliferation rates and motility compared to WT cells in wound healing assays. Computational analysis followed by functional luciferase assays revealed that the transcription activator LXR alpha is a direct target of miR-155 in the lungs. Expression of LXR alpha was significantly upregulated in the lungs of naive miR-155 / mice and was further increased in mice given bleomycin compared to similarly treated WT controls. Injection of the LXR agonist to WT mice increased LXR expression and mirrored the same phenotypic response to bleomycin as the miR-155 deficient mice; shown by increased collagen deposition and M2 macrophage and fibroblast activation. Promoter analysis revealed that LXRs could directly induce collagen production by binding to col1a and col3a promoters. / Conclusion: miR-155 appears important for lung homeostasis, likely by fine tuning levels of LXR thereby protecting from excessive remodelling. Given this and the emerging contribution of miR-155 to development of autoimmunity, this miR may act as a master-switch determining the duration of inflammation and the initiation of remodelling, as well as the balance between the immune and auto-immune responses.Background/Purpose: High mobility group box 1 (HMGB1) is a non-histone DNA binding protein that is passively released by dying cells or actively secreted by immunocompetent cells and the receptor for advanced glycation end-products (RAGE) is one of its receptors. Higher levels of HMGB1 have been found in patients with granulomatosis with polyangiitis (GPA) with active disease whereas higher HMGB1 and lower soluble (sRAGE) levels have been found in patients with acute atherosclerotic events suggesting sRAGE acts as a decoy receptor. This study aims to evaluate HMGB1 levels in relation to subclinical carotid atherosclerosis in GPA, and the impact of therapy on HMGB1 levels. Methods: A cross-sectional study was performed on 23 GPA patients during a quiescent phase of the disease in comparison to 20 matched controls. All study participants underwent carotid ultrasound to assess atherosclerotic plaques and intima-media thickness (IMT) and were tested for traditional risk factors for atherosclerosis, serum HMGB1 levels (ELISA-Shino Test, Kanagawa, Japan), and sRAGE levels (ELISA RD P = 0.978), HDLcholesterol (1.41 ± 0.37 vs. 1.51±0.33 mmol/L; P = 0.359), LDLcholesterol (3.01±0.79 vs. 3.29±0.82 mmol/L; P = 0.267), and a similar frequency of smoking (8.7% vs. 5.0%; P = 0.635), family history of premature coronary artery disease (CAD) (39.1% vs. 40.0%; P = 0.954), and obesity (4.3% vs. 10.0%; P = 0.446). Hypertension was only found in GPA patients (39.1% vs. 0.0%; P = 0.002) while no study participants had diabetes. Overt cardiovascular disease was found only in 13.0% of GPA patients. Statins were prescribed for 21.7% of GPA patients and 5.0% of controls (P = 0.127). Among GPA patients, prednisolone was being used by 34.8% with a median daily dose of 5.0mg (2.5-15.0) and azathioprine by 34.8%. Only two GPA patients used statins and prednisolone concomitantly. Carotid plaques were found in 30.4% of GPA patients and in 15.0% of controls (P = 0.203) and the overall IMT was similar in GPA patients and in controls (0.833±0.256 vs. 0.765±0.133mm; P = 0.861). Median serum HMGB1 levels were similar between GPA patients and controls [2.13ng/mL (1.11-7.22) vs. 2.42ng/mL (0.38-6.75); P = 0.827] as well as mean sRAGE levels (1256.1±559.6 vs. 1483.3±399.8pg/mL; P = 0.155). No correlations were found between HMGB1 and sRAGE ( = 0.068; P = 0.681) and between HMGB1 and maximum IMT in carotid arteries ( = -0.067; P = 0.720). GPA patients on prednisolone (1.77±0.76 vs. 3.53±2.06ng/ mL; P = 0.017) and statins (1.39±0.28 vs. 3.34±1.94ng/mL; P = 0.001) presented significantly lower serum HMGB1 levels whereas no difference in mean HMGB1 levels was found regarding azathioprine use (2.89±2.28 vs. 2.93±1.75; P = 0.970). Conclusion: No association was found between subclinical atherosclerosis in carotid arteries and HMGB1 levels in GPA patients. Furthermore, the use of either prednisone or statins was associated with lower HMGB1 levels in GPA patients. These findings suggest that the anti-inflammatory properties of statins include effects on serum HMGB1 levels in GPA.