David Coady

Factors influencing uptake of influenza vaccination in patients with rheumatoid arthritis

Recent British Society for Rheumatology (BSR) guidelines1 have advised that all patients with rheumatoid arthritis (RA) receiving methotrexate (MTX), cyclosporin A, or azathioprine should receive an annual influenza vaccination. Because there are relatively few data about immunisation rates in patients with RA, we undertook a study with the following aims: ( a ) to document the rate of uptake of influenza vaccine in patients with RA; ( b ) to assess the degree of conformity to the BSR guidelines; ( c ) to explore the factors that influence vaccine uptake. One hundred and twenty nine consecutive patients with RA were assessed between September 2001 and February 2002 during their routine hospital outpatient appointment. At the end of the consultation, the doctor inquired about vaccination status using standardised questionnaires. Information about whether the patient had been immunised during …

Health-related utility values of patients with primary Sjögren's syndrome and its predictors

Objectives EuroQoL-5 dimension (EQ-5D) is a standardised preference-based tool for measurement of health-related quality of life and EQ-5D utility values can be converted to quality-adjusted life years (QALYs) to aid cost-utility analysis. This study aimed to evaluate the EQ-5D utility values of 639 patients with primary Sjögrens syndrome (PSS) in the UK. Methods Prospective data collected using a standardised pro forma were compared with UK normative data. Relationships between utility values and the clinical and laboratory features of PSS were explored. Results The proportion of patients with PSS reporting any problem in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 42.2%, 16.7%, 56.6%, 80.6% and 49.4%, respectively, compared with 5.4%, 1.6%, 7.9%, 30.2% and 15.7% for the UK general population. The median EQ-5D utility value was 0.691 (IQR 0.587–0.796, range −0.239 to 1.000) with a bimodal distribution. Bivariate correlation analysis revealed significant correlations between EQ-5D utility values and many clinical features of PSS, but most strongly with pain, depression and fatigue (R values>0.5). After adjusting for age and sex differences, multiple regression analysis identified pain and depression as the two most important predictors of EQ-5D utility values, accounting for 48% of the variability. Anxiety, fatigue and body mass index were other statistically significant predictors, but they accounted for <5% in variability. Conclusions This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.

Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis

Objective A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. Methods Production of GM-CSF by peripheral blood (PB) and synovial fluid (SF) CD4+ T cells was assessed by ELISA and flow cytometry. In vitro CD4+ T-cell polarisation experiments were performed with T-cell activating CD2/CD3/CD28-coated beads in the absence or presence of pro-Th1 or pro-Th17 cytokines. CD1c+ DC and CD16+ macrophage subsets were flow-sorted and analysed morphologically and functionally (T-cell stimulatory/polarising capacity). Results RA-SF CD4+ T cells produced abundant GM-CSF upon stimulation and significantly more than RA-SF mononuclear cells depleted of CD4+ T cells. GM-CSF-producing T cells were significantly increased in RA-SF compared with non-RA inflammatory arthritis SF, active RA PB and healthy donor PB. GM-CSF-producing CD4+ T cells were expanded by Th1-promoting but not Th17-promoting conditions. Following coculture with RA-SF CD4+ T cells, but not healthy donor PB CD4+ T cells, a subpopulation of monocytes differentiated into CD1c+ infDC; a process dependent on GM-CSF. These infDC displayed potent alloproliferative capacity and enhanced GM-CSF, interleukin-17 and interferon-γ production by CD4+ T cells. InfDC with an identical phenotype to in vitro generated cells were significantly enriched in RA-SF compared with non-RA-SF/tissue/PB. Conclusions We demonstrate a therapeutically tractable feedback loop of GM-CSF secreted by RA synovial CD4+ T cells promoting the differentiation of infDC with potent capacity to induce GM-CSF-producing CD4+ T cells.

Validation of MSAT : an instrument to measure medical students' self-assessed confidence in musculoskeletal examination skills

Context  Self‐assessment promotes reflective practice, helps students identify gaps in their learning and is used in curricular evaluations. Currently, there is a dearth of validated self‐assessment tools in rheumatology. We present a new musculoskeletal self‐assessment tool (MSAT) that allows students to assess their confidence in their skills in and knowledge of knee and shoulder examination.

Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines.

Objectives This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögrens syndrome (pSS). Methods Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögrens Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels. Results 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines—interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)—were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy. Conclusions Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

The attitudes and beliefs of clinicians involved in teaching undergraduate musculoskeletal clinical examination skills

The aim of this study was to explore which regional musculoskeletal examination skills medical students should learn and be examined on. A qualitative research study was undertaken, and six focus groups were formed involving 36 consultants from four chosen specialties. The feeling was that greater emphasis should be placed on the functional assessment of a patient. Students should be able to discern through examination what the patient can and cannot do with his/her affected limb/joint. It was felt that many of the traditional eponymously named special tests (e.g.Thomas’ test, Trendelenburg’s test) should be dispensed with along with traditional descriptions such as varus, valgus, swan neck and Boutonniere deformities. It was felt these were often a cause of confusion for medical undergraduates. A broad view and diversity in opinions was detected with differences between specialties. The strongest theme to emerge by far was the desire to simplify and standardize the regional examination as much as possible.

Rheumatoid arthritis patients' experiences of night pain

Background:Night pain is a significant problem for many patients with rheumatoid arthritis (RA), but clinicians often overlook it. This study aimed to explore the issue of night pain among patients with RA both at home and in the hospital setting. Methods:This was a qualitative study involving in-depth interviews among 8 hospital inpatients with established RA. Each interview was recorded, transcribed, and underwent framework analysis. Results:The following themes were identified: Night pain in RA is a significant problem both at home and in hospital. All patients had established routines that they used in the home setting when disturbed by night pain. This often included getting out of bed and walking around, making hot drinks, and/or taking extra painkillers. These activities were often curtailed in the hospital setting for fear of disturbing other patients or the nurses. The effect of disturbed sleep and night pain on other people, be it partners or family members at home or patients and nurses in the hospital, was raised by all interviewees. Conclusion:Night pain in particular appears harder to control in the hospital setting than at home, and some of this may stem from lack of a tailored routine and fears of disturbing others. Information could be provided when patients are first admitted to the ward. This could describe or orient patients to the facilities available, which may be beneficial in the management of night pain. Further work on identifying influences upon night pain needs to be undertaken.

Regional musculoskeletal examination: what the students say.

Confusion exists over which musculoskeletal examination skills medical students should learn. This study aimed to explore the views of third-year medical students. This was a qualitative study to allow in-depth exploration of beliefs and attitudes. Twenty students were randomly assigned to 1 of 2 focus groups. Their attitudes towards musculoskeletal examination were explored and discussed. The groups’ discussions were recorded, transcribed, and framework analysis was undertaken with the aid of NUD*IST computer software. The following themes were identified: students dislike eponymous names for clinical tests; students felt there is a need for a more structured approach to musculoskeletal examination; students appeared unaware that many clinical tests were not based on evidence; students complained of a lack of confidence in the use of musculoskeletal clinical tests. Students confidence in their musculoskeletal examination skills may be improved by the development of an agreed set of so-called core examination skills.

Eligibility for clinical trials in primary Sjogren's syndrome: lessons from the UK Primary Sjogren's Syndrome Registry.

OBJECTIVE To identify numbers of participants in the UK Primary Sjögrens Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. METHODS We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. RESULTS In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögrens Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögrens syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögrens Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögrens Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögrens Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögrens Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögrens Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. CONCLUSION The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters.

Do the EULAR Sjögren’s syndrome outcome measures correlate with health status in primary Sjögren’s syndrome?

OBJECTIVE This study sets out to investigate the relationship between health status [EuroQol five-dimensions questionnaire (EQ-5D)] in primary SS and three of the European League Against Rheumatism (EULAR) SS outcome measures-the disease activity index (ESSDAI), the patient reported index (ESSPRI) and the sicca score. In particular, the goal was to establish whether there is a relationship between the EULAR outcome measures and quality of life. METHODS Health status was evaluated using a standardized measure developed by the EuroQol Group-the EQ5D. This permits calculation of two measures of health status: time trade-off (TTO) values and the EQ-5D visual analogue scale (VAS) scores. We used Spearmans rank correlation analysis to investigate the strength of association between health status and three EULAR measures of physician- and patient-reported disease activity in 639 patients from the UK primary SS registry (UKPSSR) cohort. RESULTS This study demonstrates that the EULAR SS disease-specific outcome measures are significantly correlated with health outcome values (P < 0.001). Higher scores on the ESSDAI, EULAR sicca score and ESSPRI are associated with poorer health states-i.e. lower TTO values and lower VAS scores. While all three are significantly correlated with TTO values and EQ-5D VAS scores, the effect is strongest for the ESSPRI. CONCLUSION This study provides further evidence supporting the use of ESSDAI, EULAR sicca score and ESSPRI measures in the clinic. We also discuss the need for disease-specific measures of health status and their comparison with standardized health outcome measures.