Rheumatoid Arthritis: Kirwan JR

Kirwan JR. · No affiliation provided · Scand J Rheumatol. · Pubmed #17657667 No free full text.

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Kirwan JR. · No affiliation provided · Arthritis Rheum. · Pubmed #14730593 links to  free full text

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Riemsma RP, Taal E, Kirwan JR, Rasker JJ. · No affiliation provided · BMJ. · Pubmed #12228119 links to  free full text

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Kirwan JR, Bálint G, Szebenyi B. · No affiliation provided · Rheumatology (Oxford). · Pubmed #10342620 links to  free full text

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Hewlett S, Hehir M, Kirwan JR. · University of the West of England, Bristol, UK. · Arthritis Rheum. · Pubmed #17394228 links to  free full text

Abstract: OBJECTIVE: Fatigue is an important outcome for patients with rheumatoid arthritis (RA). The purpose of this study was to identify the scales being used to measure RA fatigue, and to systematically examine the evidence for their validation. METHODS: Articles measuring fatigue in RA were sought using the terms RA and fatigue, and RA and tiredness, plus scale, questionnaire, inventory, and checklist. Index articles reporting identifiable RA fatigue data were examined for the fatigue scale used. Index and validation articles for each scale were reviewed for evidence supporting scale validation to measure RA fatigue using a standardized checklist of content, face, criterion, and construct validity, reliability, and sensitivity to change. RESULTS: A total of 61 index articles used 23 different fatigue scales to measure RA fatigue on 71 occasions. Seventeen scales had either no data on validation in RA or limited evidence. Reasonable evidence of validation was identified for 6 scales, each also having some evidence of sensitivity to change: ordinal scales, the Short Form 36 vitality subscale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, visual analog scales (VAS), the Profile of Mood States, and the RA-specific Multidimensional Assessment of Fatigue scale (MAF). However, the 4 generic scales would benefit from further validation in patients with RA, the VAS requires standardization, and the MAF would benefit from further sensitivity data. CONCLUSION: It was possible to identify evidence of reasonable validation for 6 of 23 scales being used to measure RA fatigue. Researchers and clinicians should select scales to measure RA fatigue carefully.

Kirwan JR, Bijlsma JW, Boers M, Shea BJ. · Liverpool Women's Hospital, Crown Street, Liverpool, UK, L8 7SS. · Cochrane Database Syst Rev. · Pubmed #17253590 No free full text.

Abstract: BACKGROUND: Glucocorticoid use in rheumatoid arthritis (RA) is widespread. Two Cochrane Reviews have been published examining the short term clinical benefit of low dose glucocorticoids compared to non-steroidal anti-inflammatory drugs and demonstrate good short term and medium term clinical benefits. The possibility that glucocorticoids may have a fundamental 'disease modifying' effect in RA, which would be seen by a reduction in the rate of radiological progression, has been raised by several authors. OBJECTIVES: To perform a systematic review of studies evaluating glucocorticoid efficacy in inhibiting the progression of radiological damage in rheumatoid arthritis. SEARCH STRATEGY: A search of MEDLINE (from 1966 to 22 February 2005) and the Cochrane Controlled Trials Register was undertaken, using the terms 'corticosteroids' and 'rheumatoid arthritis' expanded according to the Cochrane Collaboration recommendations. Identified abstracts were reviewed and appropriate reports obtained in full. Additional reports were identified from the reference lists and from expert knowledge. SELECTION CRITERIA: Randomized controlled or cross-over trials in adults with a diagnosis of rheumatoid arthritis in which prednisone or a similar glucocorticoid preparation was compared to either placebo controls or active controls (i.e. comparative studies) and where there was evaluation of radiographs of hands, or hands and feet, or feet by any standardised technique. Eligible studies had at least one treatment arm with glucocorticoids and one without glucocorticoids. DATA COLLECTION AND ANALYSIS: Standardised data extraction obtain the mean and standard deviation (SD) of change in erosion scores over 1 year or 2 years. (Where SD for change was not given a conservative estimate was taken from baseline data.) At least two authors selected the studies and extracted the data. Radiographic erosion scores were expressed as a percentage of the maximum possible score for the method used. The results were pooled after weighting in a random effects model to provide a standardised mean difference (SMD). MAIN RESULTS: The initial search produced 217 citations, and 15 were added from experts, abstracts and review of reference lists. Authors of 4 trials being prepared for publication (and subsequently published) kindly shared their data. After application of eligibility criteria 15 studies and 1,414 patients were included. The majority of trials studied early RA (disease duration up to 2 yrs), and the mean cumulative dose of glucocorticoid was 2,300 mg prednisone equivalent (range 270 mg - 5,800 mg) over the first year. Glucocorticoids were mostly added to other disease modifying anti-rheumatoid drug (DMARD) treatment. The standardised mean difference in progression was 0.40 in favour of glucocorticoids (95% CI 0.27, 0.54). In studies lasting 2 years (806 patients included), the standardised mean difference in progression in favour of glucocorticoids at 1 year was 0.45 (0.24, 0.66) and at 2 years was 0.42 (0.30, 0.55). All studies except one showed a numerical treatment effect in favour of glucocorticoids. The beneficial effects of glucocorticoids were generally achieved when used in conjunction with other DMARD treatment. AUTHORS' CONCLUSIONS: Even in the most conservative estimate, the evidence that glucocorticoids given in addition to standard therapy can substantially reduce the rate of erosion progression in rheumatoid arthritis is convincing. There remains concern about potential long-term adverse reactions to glucocorticoid therapy, such as increased cardiovascular risk, and this issue requires further research.

Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Inês LB, de Koning EJ, Buttgereit F, Cutolo M, Capell H, Rau R, Bijlsma JW. · Reumatologia, Hospitais da Universidade, 3000-075 Coimbra, Portugal. · Ann Rheum Dis. · Pubmed #16107513 links to  free full text

Abstract: Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.

Riemsma RP, Taal E, Kirwan JR, Rasker JJ. · Centre for Reviews and Dissemination, University of York, York, United Kingdom. · Arthritis Rheum. · Pubmed #15593105 links to  free full text

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Riemsma RP, Kirwan JR, Taal E, Rasker JJ. · NHS Centre for Reviews and DIssemination, University of York, Heslington, York, UK, YO10 5DD. · Cochrane Database Syst Rev. · Pubmed #12804484 No free full text.

Abstract: BACKGROUND: Because of the unpredictability people with arthritis face on a daily basis, patient education programmes have become an effective complement to traditional medical treatment giving people with arthritis the strategies and the tools necessary to make daily decisions to cope with the disease. OBJECTIVES: To assess the effectiveness of patient education interventions on health status in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched MEDLINE, EMBASE and PsycINFO and the Cochrane Controlled Trials Register. A selection of review articles (see references) were examined to identify further relevant publications. There was no language restriction. SELECTION CRITERIA: Randomised controlled trials (RCT's) evaluating patient education interventions that included an instructional component and a non-intervention control group; pre- and post-test results available separately for RA, either in the publication or from the studies' authors; and study results presented in full, end-of-study report. MAIN RESULTS: Thirty-one studies with relevant data were included. We found significant effects of patient education at first follow-up for scores on disability, joint counts, patient global assessment, psychological status, and depression. A trend favouring patient education was found for scores on pain. Physician global assessment was not assessed in any of the included studies. The dimensions of anxiety and disease activity showed no significant effects. At final follow up no significant effects of patient education were found, although there was a trend favouring patient education for scores on disability. REVIEWER'S CONCLUSIONS: Patient education as provided in the studies reviewed here had small short-term effects on disability, joint counts, patient global assessment, psychological status and depression. There was no evidence of long-term benefits in adults with rheumatoid arthritis.

Riemsma RP, Kirwan JR, Taal E, Rasker JJ. · NHS Centre for Reviews and DIssemination, University of York, Heslington, York, UK, YO10 5DD. · Cochrane Database Syst Rev. · Pubmed #12137706 No free full text.

Abstract: BACKGROUND: Because of the unpredictability people with arthritis face on a daily basis, patient education programmes have become an effective complement to traditional medical treatment giving people with arthritis the strategies and the tools necessary to make daily decisions to cope with the disease. OBJECTIVES: To assess the effectiveness of patient education interventions on health status in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched MEDLINE, EMBASE and PsycINFO and the Cochrane Controlled Trials Register. A selection of review articles (see references) were examined to identify further relevant publications. There was no language restriction. SELECTION CRITERIA: Randomised controlled trials (RCT's) evaluating patient education interventions that included an instructional component and a non-intervention control group; pre- and post-test results available separately for RA, either in the publication or from the studies' authors; and study results presented in full, end-of-study report. MAIN RESULTS: Twenty-four studies with relevant data were included. We found significant effects of patient education at first follow-up for scores on disability, joint counts, patient global assessment and psychological status. Physician global assessment was not assessed in any of the included studies. The two separate dimensions of psychological status: anxiety and depression showed no significant effects, nor did the dimensions of pain and disease activity. At final follow up no significant effects of patient education were found. REVIEWER'S CONCLUSIONS: Patient education as provided in the studies reviewed here had moderate short-term effects on patient global assessment, and small short-term effects on disability, joint counts and psychological status. There were no long-term benefits.

Riemsma RP, Kirwan JR, Taal E, Rasker JJ. · NHS Centre for Reviews and DIssemination, University of York, Heslington, York, UK, YO10 5DD. · Cochrane Database Syst Rev. · Pubmed #12076505 No free full text.

Abstract: BACKGROUND: Because of the unpredictability people with arthritis face on a daily basis, patient education programmes have become an effective complement to traditional medical treatment giving people with arthritis the strategies and the tools necessary to make daily decisions to cope with the disease. OBJECTIVES: To assess the effectiveness of patient education interventions on health status in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched MEDLINE, EMBASE and PsycINFO and the Cochrane Controlled Trials Register. A selection of review articles (see references) were examined to identify further relevant publications. There was no language restriction. SELECTION CRITERIA: Randomised controlled trials (RCT's) evaluating patient education interventions that included an instructional component and a non-intervention control group; pre- and post-test results available separately for RA, either in the publication or from the studies' authors; and study results presented in full, end-of-study report. MAIN RESULTS: Twenty-four studies with relevant data were included. We found significant effects of patient education at first follow-up for scores on disability, joint counts, patient global assessment and psychological status. Physician global assessment was not assessed in any of the included studies. The two separate dimensions of psychological status: anxiety and depression showed no significant effects, nor did the dimensions of pain and disease activity. At final follow up no significant effects of patient education were found. REVIEWER'S CONCLUSIONS: Patient education as provided in the studies reviewed here had moderate short-term effects on patient global assessment, and small short-term effects on disability, joint counts and psychological status. There were no long-term benefits.

Kirwan JR. · Rheumatology Unit, University Division of Medicine, Bristol Royal Infirmary, Bristol, United Kingdom. · Rheum Dis Clin North Am. · Pubmed #11396099 No free full text.

Abstract: Glucocorticoids provide a large, immediate improvement in the symptoms of rheumatoid arthritis. At doses acceptable for long-term treatment, however, symptoms gradually re-emerge. Relatively low doses of glucocorticoids can, for several years, substantially retard the rate of joint destruction shown on radiographs. This differential effect implies the coexistence of two pathologic processes within diseased joints. Long term, low dose glucocorticoid therapy probably increases the risk of serious adverse effects, but an evidence-based case can be made for the limited use of low dose glucocorticoid treatment in early disease.

Kirwan JR. · University of Bristol, Division of Medicine, Bristol Royal Infirmary, UK. · J Rheumatol. · Pubmed #11327270 No free full text.

Abstract: The relationship between the development of radiographic joint destruction in rheumatoid arthritis and its longterm consequences for the patient is not well understood. Two objectives for further research have been identified: elucidating this relationship and relating pathological processes to the features visible on radiographs. Extrapolation from a proposed model suggests that if radiographic progression is suppressed early in the disease, it might take many years before the benefit can be clearly appreciated against a background of variation within individual patients. Two approaches have recently been brought to bear on this issue, including a detailed modeling of medium term observations from a single dataset and a review of a large number of published studies. There are a number of reservations about the notion of a minimum clinically important change, but one possibility for defining such a change for radiographs is in relation to longterm functional outcome.

Kirwan JR. · Rheumatology Unit, University of Bristol Division of Medicine, Bristol Royal Infirmary, Bristol BS2 8HW, UK. · Z Rheumatol. · Pubmed #11155811 No free full text.

Abstract: Radiographic erosions develop in about two thirds of patients with rheumatoid arthritis (RA). Glucocorticoids offer rapid and substantial control of the symptoms of inflammation in the short and medium term. Data are reviewed which suggest that this benefit may not last into the longer term (more than 1 year). However, recent studies provide unequivocal evidence that joint destruction can be halted in this disease. Also, by separating the short-term anti-inflammatory effect from a more prolonged suppression of joint destruction, these studies have shed light on the underlying pathological processes. The evidence from these therapeutic clinical trials strengthens the view that inflammation and joint destruction are parallel processes, loosely linked by the underlying cause of RA, but progressing to some extent independently. It is intriguing to speculate that different effects of glucocorticoids might relate to their different modes of action outlined elsewhere in this symposium.

Kirwan JR. · University Department of Medicine, Bristol Royal Infirmary, UK. · J Rheumatol. · Pubmed #10648052 No free full text.

Abstract: To describe the Larsen index and its strengths and weaknesses. I reviewed the original publication, a number of published modifications, tests of reproducibility, and some clinical studies that have used the index. The Larsen index is essentially a grading of erosion severity that has satisfactory reproducibility for use in groups of patients. The Larsen index can clearly distinguish different rates of erosive progression in groups of patients with different characteristics or treatments. Recent studies using the Larsen index have identified clear treatment effects. Difficulty in measuring the success of previous treatments designed to hold back the progression of erosions relates to the inefficacy of those treatments, not insensitivity of the Larsen index.

Kirwan JR. · Rheumatology Unit, University Division of Medicine, Bristol Royal Infirmary, UK. · J Rheumatol. · Pubmed #10090190 No free full text.

Abstract: Radiographic scoring systems for rheumatoid arthritis (RA) should be based on current understanding of disease pathology. Evidence suggests that there may be at least two intraarticular pathologies that may result in change in different radiographic features. There is therefore a strong argument for devising a radiographic score based on the observation of features rather than broad categorizations of the total radiographic change. Features may subsequently be amalgamated in relation to other criteria such as sensitivity, specificity, and responsiveness to change, and may be related to subsequent developments in understanding the biology of RA. A second challenge is in elucidating the relationship between radiographic change and the longterm consequences of RA for the patient. Current practice is predicated on the assumption that in the longterm radiographic change correlates well with functional loss and possibly noninflammatory, endstage joint pain. Although hand and feet radiographs broadly represent destructive change in all joints, in cross sectional studies they correlate only moderately with late stage functional loss. The issue may be resolved by longterm observational studies of radiographic change and functional loss. It is recommended that specific radiographic features relevant to joint pathophysiology be used to create a radiographic damage index for comparison with current scoring systems and that longterm observational studies specifically address the relationship between radiographic joint damage and functional outcome.

Haugeberg G, Strand A, Kvien TK, Kirwan JR. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Arch Intern Med. · Pubmed #15956010 links to  free full text

Abstract: BACKGROUND: Bone damage in rheumatoid arthritis presents as osteoporosis and joint erosions. Prednisolone has been shown to reduce the rate of hand joint destruction as seen on radiography but has not been shown to reduce the rate of hand bone loss. METHODS: In a double-blind study comparing oral prednisolone (7.5 mg/d for 2 years) with placebo, hand bone density assessed with digital x-ray radiogrammetry was examined in 95 patients with rheumatoid arthritis with disease duration of less than 2 years. RESULTS: The mean loss of hand bone density was less in prednisolone-treated patients compared with placebo-treated patients at the 1-year follow-up (-0.011 vs -0.022 g/cm(2)) (P = .005) and at the 2-year follow-up (-0.026 vs -0.039 g/cm(2)) (P = .03). The mean percentage group difference in loss of hand bone density was 2.8% (P = .004) at the 1-year follow-up and 3.5% (P = .01) at the 2-year follow-up. In the first year, C-reactive protein, a marker of inflammation, was strongly correlated with hand bone loss in placebo-treated patients but not in prednisolone-treated patients, suggesting that prednisolone breaks the link between bone loss and inflammation. CONCLUSIONS: To our knowledge, this is the first double-blind randomized study to show that disease-related loss of hand bone density in rheumatoid arthritis can be decelerated by prednisolone. This finding suggests that the deleterious effect of prednisolone on bone may be counteracted by its anti-inflammatory effect.

Kirwan JR, Hällgren R, Mielants H, Wollheim F, Bjorck E, Persson T, Book C, Bowman S, Byron M, Cox N, Field M, Kanerud L, Leirisalo-Repo M, Malaise M, Mohammad A, Palmer R, Petersson IF, Ringertz B, Sheldon P, Simonsson M, Snowden N, Van den Bosch F. · Academic Rheumatology Unit, University Division of Medicine, Bristol Royal Infirmary, Bristol BS2 8HW, UK. · Ann Rheum Dis. · Pubmed #15140776 links to  free full text

Abstract: OBJECTIVES: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. METHODS: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. RESULTS: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. CONCLUSIONS: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment.

Kirwan JR, Mitchell K, Hewlett S, Hehir M, Pollock J, Memel D, Bennett B. · Academic Rheumatology, University of Bristol Division of Medicine, Bristol Royal Infirmary, Bristol, UK. · Rheumatology (Oxford). · Pubmed #12626791 links to  free full text

Abstract: BACKGROUND: Patients with rheumatoid arthritis (RA) are traditionally seen regularly as out-patients, irrespective of whether it is appropriate or timely to see them. A randomized controlled trial has shown that over 2 yr, seeing patients only when they or their general practitioner (GP) request a review saves time and resources and is more convenient. This study aimed to assess clinical and psychological outcomes when the trial was extended to 4 yr. METHOD: A total of 209 patients were randomized into either 'routine review' (control) or 'no routine follow-up' but access to rapid review on request (direct access). Clinical and psychological status and patient satisfaction and confidence were reviewed after 24 and 48 months. RESULTS: Mean age at entry was 56 yr and mean disease duration 11 yr, and 134 patients remained in the study after 48 months. There were no differences between the groups, nor between those who completed the study and those who did not. There were no major differences in clinical or psychological status between the groups at 24 or 48 months. However, self-efficacy for function was stronger at 48 months for direct access patients (mean 64.0 vs 52.0, P=0.005), as was self-efficacy for other symptoms (mean 67.8 vs 59.3, P=0.009). Satisfaction at 48 months was increased in direct access compared with control (mean 8.7 vs 7.6, P=0.01) as was confidence in the system (8.9 vs 7.6, P<0.01). CONCLUSION: It is effective for patients with rheumatoid arthritis to have no regular follow-up, provided they have access to rapid review when they or their GP request it. Patients using a self-referral system of care had higher self-efficacy and greater satisfaction and confidence than those using the traditional system.

Hewlett S, Mitchell K, Haynes J, Paine T, Korendowych E, Kirwan JR. · Rheumatology Unit, University of Bristol Division of Medicine, Bristol Royal Infirmary, UK. · Rheumatology (Oxford). · Pubmed #10986304 links to  free full text

Abstract: OBJECTIVES: To evaluate the clinical efficacy, cost and acceptability of a shared care system of patient- or general practitioner (GP)-initiated hospital review in rheumatoid arthritis (RA). METHODS: A 2-yr randomized controlled trial of routine rheumatologist-initiated review was compared with a shared care system. Shared care patients had no routine follow-up but patients or GPs initiated access to rapid review by the multidisciplinary team via a nurse-run helpline. Control patients had a rheumatologist-initiated medical review at intervals of 3-6 months. Clinical and psychological status, resource use, and patient and GP satisfaction and confidence were assessed. Three-monthly clinical data were assessed (blind) for safety monitoring, with failure set at a 20% increase in pain, disability or disease activity. RESULTS: Two hundred and nine established RA patients participated, of whom 182 were evaluable. Safety-net failures were not different between groups. Shared care patients had less pain (24 months, 3.9 cm on a 10-cm visual analogue scale vs 4.8 cm for controls; P: < 0.05), a smaller increase in pain over 2 yr (+ 0.4 cm vs +1.6 cm for controls; P: < 0.01), greater self-efficacy (6, 15, 18, 21 months, P: < 0.05), used 33.5% less resources (208 ponds sterling per patient per year vs 313 pound sterling for controls; P: < 0.001) and were more confident in the system (6, 9, 12, 18, 21, 24 months, P: < 0.01 to P: < 0.001). CONCLUSIONS: A patient-initiated system for hospital review over 2 yr offers some clinical benefit compared with the traditional system, using fewer resources and attracting greater patient confidence. Longer-term assessment of the system would be appropriate.

Young PJ, Weeden S, Kirwan JR. · Department of Health Sciences, The University of York, Heslington, York, YO1 5DD, U.K. · Stat Med. · Pubmed #10407237 No free full text.

Abstract: In many long-term chronic diseases, patients pass through an observable sequence of ordered clinical states as their condition progressively worsens. Often the information on which disease state the patient is in is incompletely recorded, usually with information only available on the occasion of a clinic visit. This article describes a novel analysis of data from a clinical trial, in which several such outcome measures of disease state have been recorded simultaneously. The article is motivated by the analysis of a multi-centre double-blind placebo-controlled clinical study into the effect of continual low dose corticosteroid treatment on the progression of X-ray scores for patients with rheumatoid arthritis. Previous methods of analysis of such data have been based on an independence analysis, thus ignoring any correlation that may exist between the outcomes. This article shows that such an approach can lead to biased underestimates of the covariate effects if an independence model is used. Biased estimates of the covariate effects were found when the model was fitted to the trial data. The bivariate model was also shown to provide a significantly better fit to the data. However, the bivariate model did prove more difficult to fit, and both models demonstrated a highly significant treatment effect with comparable clinical effect.

Perry MG, Kirwan JR, Jessop DS, Hunt LP. · Academic Rheumatology Unit,University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK. · Ann Rheum Dis. · Pubmed #18375536 links to  free full text

Abstract: OBJECTIVE: To investigate overnight variations in absolute values and patterns of cytokines including interleukin 6 (IL6) and tumour necrosis factor alpha (TNFalpha) in rheumatoid arthritis (RA), and to relate any changes to those occurring in blood cortisol. METHODS: A total of 16 people (8 female) with active RA and who had received no recent glucocorticoids were admitted overnight. Blood samples were obtained at 13 time points between 21.00 and 10.00. RESULTS: The geometric mean IL6 concentration rose significantly from 35 pg/ml at 22:00 to 64 pg/ml at 07:15 (repeated measures analysis of variance (ANOVA), p<0.001). The geometric mean cortisol concentration rose significantly overnight from 57 ng/ml at 01:00 to 229 ng/ml at 07:15 (repeated measures ANOVA, p<0.001). Neither TNFalpha nor the other cytokines measured changed significantly. Using cubic regression modelling IL6 began to rise before cortisol (range 0.01 to 4.83 h) in eight participants and after cortisol (range 1.11 to 5.14 h) in three participants. In a random coefficient model including data from all participants, the estimated mean IL6 value began to rise 3.05 h before the estimated mean cortisol value, with the IL6 peak occurring 0.70 h before the cortisol peak. CONCLUSION: The mean IL6 and cortisol concentrations showed a significant overnight variation. Neither TNFalpha nor the other cytokines measured changed significantly. In a random coefficient model IL6 began to rise approximately 3 h, and reached a peak about 40 min, before cortisol. These studies confirm that there are abnormalities in plasma cortisol and IL6 concentrations and dynamics. The data also link the overnight rise in IL6 to the circadian variation in symptoms.

Wilson O, Kirwan JR. · University of Bristol Academic Rheumatology Unit, University Department of Clinical Science, Bristol Royal Infirmary, Bristol, UK. · Musculoskeletal Care. · Pubmed #17042013 No free full text.

Abstract: OBJECTIVES: (1) To determine the test-retest reliability of monofilaments pressed against the skin as a method of assessing sensation in the feet of patients with rheumatoid arthritis (RA) and in controls using two grades of monofilaments; (2) to determine the stability of findings over 6 weeks; and (3) to calculate initial estimates of frequency of loss of sensation and to investigate its association with disease status. METHOD: Clinical examination of the feet was undertaken in 51 patients with RA and 20 normal controls. Six sites on each foot were tested twice with both 10 g and 3 g research grade monofilaments and this was repeated after 6 weeks. Disease status was measured using the Disease Activity Score, the Health Assessment Questionnaire, visual analogue scales of pain, and the acute phase response using erythrocyte sedimentation rate and plasma viscosity. RESULTS: Reproducibility was high for 3 g (kappa=0.73) and 10 g (kappa=0.75) monofilaments. The best balance between sensitivity (58.8%) and specificity (87.5%) for distinguishing the feet of patients from the feet of controls was using the 3 g filament and defining reduced protective sensation as being sensitive to less than 11 of 12 applications. Using this definition, the prevalence of reduced protective sensation is 59% in the patient group and 12.5% in the feet of controls. There was some variation in sensation over 6 weeks in the patient group, but this was not related to measures of clinical status. CONCLUSION: The use of monofilaments in assessing sensation levels in the RA foot is repeatable and reproducible over a six-week period and requires only a short time to perform. The frequency of reduced sensation in the feet of patients with RA was greater than previously reported. Future studies should assess relationships with disease duration and inflammatory status.

Kirwan JR, Hewlett S, Cockshott Z, Barrett J. · Rheumatology Unit, University of Bristol Division of Medicine, Bristol, UK. · Musculoskeletal Care. · Pubmed #17041989 No free full text.

Abstract: OBJECTIVE: Evidence that patient education improves outcome in self-selected patients is often based on studies using patients with a mixture of diagnoses (primarily osteoarthritis) and where the education is delivered in a community setting. This study explored whether hospital outpatients with rheumatoid arthritis (RA) who were offered a self-management programme showed a similar response. METHODS: A randomized controlled trial was undertaken of either observation or observation plus an educational intervention of five sessions (12.5 hours) designed to enhance self-management. Pain and self-efficacy for pain were the primary outcome measures. These and other standardized assessments were made at 0, 4, 8 and 36 weeks for a variety of psychological and disease states. Knowledge of RA and its treatment was measured at 0 and 4 weeks using a multiple-choice questionnaire. RESULTS: Sixty-eight of 79 randomized patients provided adequate data. In those randomized to be offered education, knowledge of RA and its treatment increased by 18% compared to 9% in controls (p = 0.058). Self-efficacy for pain improved between weeks 0 and 4 by 10.3% (p = 0.015) in those offered education, and by 14.1% in those who were offered and accepted education (p = 0.001) but the difference from controls was not maintained after four weeks. There were no significant differences between groups in pain or in any of the remaining variables. Most patients reported that the education had been helpful. CONCLUSIONS: Patients offered education gained knowledge and reported personal benefit, but only improved in self-efficacy for pain and only for a short time. RA patients drawn from hospital outpatient clinics and allocated to an educational intervention may not gain changes in health status as measured by the instruments employed in this study.

Kirwan JR, Hickey SH, Hällgren R, Mielants H, Björck E, Persson T, Wollheim FA. · University of Bristol Academic Rheumatology Unit, Bristol Royal Infirmary, Bristol, UK. · Arthritis Rheum. · Pubmed #16645969 links to  free full text

Abstract: OBJECTIVE: To measure the effect of low-dose systemic glucocorticoid treatment on the adrenal response to adrenocorticotropic hormone (ACTH) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA who took part in a randomized double-blind placebo-controlled trial of budesonide (3 mg/day and 9 mg/day) and prednisolone (7.5 mg/day) underwent a short (60-minute) test with injection of ACTH (tetracosactide hexaacetate) at baseline and the day after completing the 3-month treatment program. Plasma cortisol measurements at baseline and 3 months were compared within and between the treatment groups. Individual patients were classified as normal responders to ACTH or as abnormal responders if changes were >2 SD below the pretreatment value in the entire group of study patients. RESULTS: Short tests with ACTH injection were performed on 139 patients before beginning the study medication and on 134 patients after cessation of the medication. There were no changes in the placebo group. Mean plasma cortisol levels following treatment were reduced in all active treatment groups. In addition, mean values were significantly reduced for the 30-minute and 60-minute responses to ACTH. The maximum reduction (35%) occurred in the prednisolone group at 60 minutes. Following treatment, 34% of patients taking budesonide 9 mg and 46% of those taking prednisolone 7.5 mg failed to reach the normal maximum cortisol response to ACTH. Four patients failed to achieve the normal percentage increase in cortisol levels, but only 1 patient failed to meet both criteria. CONCLUSION: Low doses of a glucocorticoid resulted in depression of baseline and ACTH-stimulated cortisol levels after 12 weeks of therapy. Although the responsiveness of the hypothalamic-pituitary-adrenal axis in individual patients generally remained within the normal range, these changes should be investigated further.