Rheumatoid Arthritis: Scott D

Thomas J, Scott D. · Norfolk and Norwich University Hospital, Norwich. · Practitioner. · Pubmed #16856503 No free full text.

This publication has no abstract.

Maddison P, Kiely P, Kirkham B, Lawson T, Moots R, Proudfoot D, Reece R, Scott D, Sword R, Taggart A, Thwaites C, Williams E. · Department of Rheumatology, Ysbyty Gwynedd Hospital, University of Wales, Bangor LL57 2PW, UK. · Rheumatology (Oxford). · Pubmed #15657072 links to  free full text

Abstract: OBJECTIVES: To determine, by consensus, the optimal use of leflunomide in rheumatoid arthritis (RA), using a multidisciplinary panel of experts and performing meta-analyses of available data. METHODS: A multidisciplinary panel of experts in RA was convened. Important questions, pertinent to the use of leflunomide in the treatment of RA, were defined by consensus at an initial meeting. Each question was allocated to subgroups of two or three members, who worked separately to prepare a balanced opinion, based on published literature, data from individual patients taking part in phase II and phase III clinical trials provided by Aventis, and data from a USA-based medical claims database (AETNA). The full group then reconvened to agree on an overall consensus statement. Recommendations concerning efficacy and tolerability versus comparator drugs and placebo were derived from two new meta-analyses. RESULTS: Leflunomide was at least as effective as sulphasalazine and methotrexate, and equally well tolerated on meta-analysis of trial data. Overall withdrawal rates for all adverse events were similar for all three drugs. Avoidance of the loading dose reduces 'nuisance' side-effects (e.g. nausea), but probably delays the onset of action. Adverse events could usually be managed by dose reduction and/or symptomatic therapy. CONCLUSIONS: On the basis of efficacy, safety and cost, leflunomide should be considered in patients with RA who have failed first-line DMARD drug therapy. In refractory cases, leflunomide may be used in combination with, for example, methotrexate before biological agents. Therapy should be initiated by a specialist, but repeat prescribing in general practice on a shared care basis is acceptable using agreed protocols. Clear mechanisms are required to monitor toxicity, with good communication between the patient and rheumatologist to manage nuisance side-effects and avoid unnecessary discontinuation of leflunomide.

Edmonds J, Saudan A, Lassere M, Scott D. · Department of Rheumatology, St. George Hospital, Sydney, Australia. · J Rheumatol. · Pubmed #10090193 No free full text.

Abstract: To examine its ability to evaluate progressive radiological damage, the Scott modification of the Larsen score was used for the hands, wrists, and feet (metatarsophalangeal joints) at time zero and at 12 months in 52 patients with early rheumatoid arthritis taking part in a therapeutic intervention study. The major practical difficulty was the technical discrepancy between initial and followup films in some patients. The metrological problems are discussed in the analysis, which compares the score on the same films using the Sharp score.

van der Heijde D, Kalden J, Scott D, Smolen J, Strand V. · Division of Internal Medicine, Department of Rheumatology, University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands. · Ann Rheum Dis. · Pubmed #15140783 links to  free full text

Abstract: OBJECTIVES: To assess the effect of long term (>2 years) leflunomide treatment on radiographic progression in patients with RA. METHODS: Patients treated with leflunomide for >2 years in one of three phase III trials and subsequent extensions, for whom paired, evaluable radiographs at baseline and study end point were available, were included. Radiographs of hands and feet were assessed according to the modified Sharp/van der Heijde scoring method, for erosion, joint space narrowing, and total score. Changes from baseline were assessed, and a predicted yearly progression rate estimated for each patient. RESULTS: 128 of the original 824 patients were included, with mean disease duration 5.1 years and mean leflunomide treatment duration 4.3 years until the final x ray examination. The mean change from baseline in total score was 8.6 with yearly adjusted rate 1.9, and the median change was 2 with yearly adjusted rate 0.5, compared with 7.9 and 4.9, respectively, before leflunomide treatment. After treatment, the rate improved in 92/128 (72%) patients and deteriorated in 21/128 (16%). In 42 (33%) patients who had a total score >0 at baseline, no radiographic progression occurred after leflunomide treatment. CONCLUSIONS: In a subset of patients who continued treatment long term, leflunomide treatment reduced the rate of radiographic damage.

Tibble JA, Sigthorsson G, Foster R, Scott D, Fagerhol MK, Roseth A, Bjarnason I. · Department of Medicine, Guys, King's, St Thomas's School of Medicine and Dentistry, London, UK. · Gut. · Pubmed #10446103 links to  free full text

Abstract: BACKGROUND: The diagnosis of non-steroidal anti-inflammatory drug (NSAID) induced enteropathy is difficult, requiring enteroscopy or the use of four day faecal excretion of (111)In labelled white cells. AIMS: To assess faecal calprotectin (a non-degraded neutrophil cytosolic protein) as a method for diagnosing NSAID enteropathy. METHODS: Single stool faecal calprotectin concentrations were compared with the four day faecal excretion of (111)In labelled white cells in 47 patients taking NSAIDs. The prevalence and severity of NSAID enteropathy was assessed using this method in 312 patients (192 with rheumatoid arthritis, 65 with osteoarthritis, 55 with other conditions) taking 18 different NSAIDs. RESULTS: The four day faecal excretion of (111)In white cells correlated significantly with faecal calprotectin concentrations. In the group of 312 patients on NSAIDs faecal calprotectin concentrations were significantly higher than in controls, the prevalence of NSAID enteropathy being 44%. The prevalence and severity of NSAID enteropathy was independent of the particular type or dose of NSAID being taken or other patient variables. CONCLUSIONS: Assay of faecal calprotectin provides a simple practical method for diagnosing NSAID enteropathy in man. Forty four per cent of patients receiving these drugs had NSAID induced enteropathy when assessed by this technique; 20% of these had comparable levels of inflammation to that previously reported in patients with inflammatory bowel disease.

Lempp H, Thornicroft G, Leese M, Fearns N, Graves H, Khoshaba B, Lasalvia A, Scott D, Tansella M. · Academic Department of Rheumatology/NIHR Guy's and St. Thomas' Foundation Trust Biomedical Research Centre, King's College London, London, UK. · Qual Life Res. · Pubmed #19430960 No free full text.

Abstract: PURPOSE: To investigate whether people with long term conditions, whatever their specific nature, need to be assessed and treated for the full range of mental, physical and social problems. Main question investigated: that rheumatoid arthritis and schizophrenia will be associated with significantly greater impairment across the subscores of the SF36 scale than in reference general population samples. Specific hypothesis tested: while rheumatoid arthritis and schizophrenia will impair both physical and mental functioning, when comparing the two groups there will be a greater difference between the physical component scores than there will be between the mental/emotional component scores of the short form health survey (SF-36). METHODS: Cross sectional comparison of SF-36 subscore profiles of cohorts of: (1) people with rheumatoid arthritis attending specialist Rheumatology outpatient clinics in five London hospitals (n = 446), and (2) people with schizophrenia treated by community psychiatric teams in four sites in Europe (n = 409). RESULTS: Both groups had greater impairments across the whole spectrum of mental and physical problems assessed by the SF-36 than age specific normative data for the general population. The results also support our hypothesis that, comparing the people with rheumatoid arthritis and schizophrenia, we did find that there is a greater discrepancy between the physical scales than there is between the mental/emotional scales of the SF-36. CONCLUSIONS: These findings show that whether the primary long-term condition is presenting as physical or as mental disorder, the practitioner should ensure that the full range of physical, mental and social problems is assessed and treated.

Lempp H, Scott D, Kingsley G. · Academic Department of Rheumatology, King's College London School of Medicine at Guy's, King's and St. Thomas' Hospitals, Weston Education Centre, Cutcombe Road, London SE5 9PJ, UK. · Chronic Illn. · Pubmed #17175654 No free full text.

Abstract: OBJECTIVE: To provide a detailed understanding of the direct personal experiences of living with rheumatoid arthritis (RA) and the impact of the illness upon patients' lives, to inform the improvement of clinical care and training. METHOD: A qualitative study was performed using data from semi-structured interviews with 26 patients who live with RA, recruited at two outpatient clinics in south-east England. RESULTS: In addition to the physical impact of RA on patients' lives, their accounts gave detailed descriptions of how their identity was affected in relation to: (1) their private lives (e.g., difficulties in their relationships, or caring for others); (2) their public roles and responsibilities (e.g., in their paid work and in experiences of stigmatization or discrimination); and (3) their private and public domains (e.g., perceived change of physical appearance, alteration of self-image, and change or loss of social roles). Young patients (25-45 years) did report some differences in their chronic illness experiences, but patients from black and ethnic minorities did not. DISCUSSION: The study highlights new findings which can facilitate more open communication between staff and patients on the personal impact of RA, on patients' coping strategies, and on the effects on their identity both in private and in public. This will allow multidisciplinary outpatient services to provide care more closely matched to the difficulties that are directly experienced by patients.

Symmons D, Turner G, Webb R, Asten P, Barrett E, Lunt M, Scott D, Silman A. · ARC Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. · Rheumatology (Oxford). · Pubmed #12096230 links to  free full text

Abstract: BACKGROUND: It is 40 yr since the last age- and sex-specific estimates of the prevalence of rheumatoid arthritis (RA) for the UK were published. Since then the classification criteria for RA have been revised and there has been evidence of a fall in the incidence of RA, especially in women. OBJECTIVES: To estimate the age- and sex-specific point prevalence of RA (defined as fulfilment of a modification of the 1987 ACR classification criteria for RA on the day of assessment). The estimate was made in the primary care setting in Norfolk, UK. METHODS: A stratified random sample was drawn from seven age and gender bands. The 7050 individuals selected were mailed a screening questionnaire. Positive responders were invited to attend for a clinical examination. The sample was matched against the names in the Norfolk Arthritis Register (NOAR), a register of incident cases of inflammatory polyarthritis which has been in existence since 1990. RESULTS: The overall response rate was 82%. Sixty-six cases of RA were identified. Extrapolated to the population of the UK, the overall minimum prevalence of RA is 1.16% in women and 0.44% in men. A number of incident cases of RA previously notified to NOAR were not identified as cases in the survey because they had entered into treatment-induced remission. In addition, some cases who failed to attend for examination had significant disability. These prevalence figures are therefore an underestimate. CONCLUSIONS: The prevalence of RA in women, but not in men, in the UK may have fallen since the 1950s.

Scott D. · Guy's, King's & St Thomas' School of Medicine, Dulwich Hospital, London. · Clin Med. · Pubmed #11706885 No free full text.

Abstract: More than ten years have passed since the first UK guidelines for the management of rheumatoid arthritis were published. Since then many different guidelines have been produced, including contributions from the American College of Rheumatology and the Scottish Intercollegiate Guidelines (SIGN) network. These give similar recommendations on management. For example, they all stress the need for starting disease-modifying drugs early. The North American guidelines codify the range of acceptable practice, rather than giving specific detailed recommendations. By contrast the SIGN guidelines are more prescriptive and delineate what the authors consider to be 'best clinical practice'. The next step is to introduce guidelines that focus on specific aspects of care, rather than defining the whole range of management options. This is already happening with the introduction of guidelines for high cost treatments such as immunotherapy directed at anti-tumour necrosis factor.

Carpenter GH, Proctor GB, Pankhurst CL, O'Donohue J, Scott D, Hunnable MP. · Department of Oral Pathology, GKT, King's College Hospital, London, UK. · J Oral Pathol Med. · Pubmed #11016688 No free full text.

Abstract: Sjögren's syndrome is an autoimmune condition affecting the lacrimal and salivary glands and can be associated with rheumatoid arthritis and primary biliary cirrhosis. Parotid salivas collected from patients and normal controls were analysed for lactoferrin, IgA and beta2-microglobulin (measured by ELISA), and cystatin (measured by a enzyme inhibition assay). Output data provided less variable means, whilst expressing results as a proportion of the total protein provided greater specificity as markers for Sjögren's syndrome. Levels of specificity for IgA, lactoferrin and beta2-microglobulin were all high (100, 95 and 100%, respectively). Sensitivity levels of these markers (but not cystatin) tended to be similar for Sjögren's syndrome secondary to primary biliary cirrhosis (IgA, 25%; lactoferrin, 63%; and beta2-microglobulin, 50%), compared to Sjögren's syndrome secondary to connective tissue diseases such as rheumatoid arthritis (IgA, 50%; lactoferrin, 86%; and beta2-microglobulin; 38%).

Coleman PJ, Scott D, Mason RM, Levick JR. · Department of Physiology, St George's Hospital Medical School, London SW17 0RE, UK. · J Physiol. · Pubmed #10896731 links to  free full text

Abstract: 1. Synovial fluid drains out of joints through an interstitial pathway. Hyaluronan, the major polysaccharide of synovial fluid, attenuates this fluid drainage; it creates a graded opposition to outflow that increases with pressure (outflow 'buffering'). This has been attributed to size-related molecular reflection at the interstitium-fluid interface. Chain length is reduced in inflammatory arthritis. We therefore investigated the dependence of outflow buffering on hyaluronan chain length. 2. Hyaluronan molecules of mean molecular mass approximately 2200, 530, 300 and 90 kDa and concentration 3.6 mg ml-1 were infused into the knees of anaesthetized rabbits, with Ringer solution as control in the contralateral joint. Trans-synovial drainage rate was recorded at known joint pressures. Pressure was raised in steps every 30-60 min (range 2-24 cmH2O). 3. With hyaluronan-90 and hyaluronan-300 the fluid drainage rate was reduced relative to Ringer solution (P < 0.001, ANOVA) but increased steeply with pressure. The opposition to outflow, defined as the pressure required to drive unit outflow, did not increase with pressure, i.e. there was no outflow buffering. 4. With hyaluronan-530 and hyaluronan-2000 the fluid drainage rate became relatively insensitive to pressure, causing a near plateau of flow. Opposition to outflow increased markedly with pressure, by up to 3.3 times over the explored pressures. 5. Hyaluronan concentration in the joint cavity increased over the drainage period, indicating partial reflection of hyaluronan by synovial interstitium. Reflected fractions were 0.12, 0.33, 0.25 and 0.79 for hyaluronan-90, -300, -530 and -2200, respectively. 6. Thus the flow-buffering effect of hyaluronan depended on chain length, and shortening the chains reduced the degree of molecular reflection. The latter should reduce the concentration polarization at the tissue interface, and hence the local osmotic pressure opposing fluid drainage. In rheumatoid arthritis the reduced chain length will facilitate the escape of hyaluronan and fluid.

Molenaar ET, Boers M, van der Heijde DM, Alarcón G, Bresnihan B, Cardiel M, Edmonds J, Felson D, Furst DE, Kirwan J, Lassere M, Paulus H, Rau R, van Riel PL, Scott D, Simon L, Strand V. · Department of Rheumatology, VU University Hospital, Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #10090196 No free full text.

Abstract: None of the current scoring methods for radiological damage in rheumatoid arthritis (RA) is ideal. The objective for RA imaging at OMERACT IV was to start discussion about the problems and applicability of the current scoring methods for radiological damage and to start discussion on the challenge of new imaging techniques. The RA imaging module comprised preconference reading material, plenary sessions, small group discussions, and a plenary report of the group sessions, combined with interactive voting. The OMERACT filter guided the discussions. Priorities for further research in imaging studies were: (1) pathologies versus features on radiographs; (2) relation with longterm outcome; and (3) definition of minimum clinically important difference.