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41.
OBJECTIVE: To assess whether the American College of Rheumatology response criteria ACR20 should be replaced by another definition of response with enhanced discriminant validity. METHODS: We worked with statisticians to define over 100 different ways of defining response, including dichotomous definitions (e.g., ACR20; ACR50; ACR70; low disease activity), ordinal definitions (EULAR response; ACR20, ACR50, ACR70), disease activity indexes [Disease Activity Score (DAS); Disease Activity Index, SDAI], continuous definitions (mean percentage improvement in all core set measures; nACR, ACRn), and hybrid definitions (ACR20, ACR50, ACR70 defined for a patient as 0, 1, 2, 3 scale with continuous measures between intervals) along with variations on each of these approaches (e.g., percentage vs absolute change in DAS; e.g., measures requiring vs not requiring joint count improvement). To test clinical validity, we administered a survey using patients from a trial who had various levels of improvement and asked rheumatologists whether and by how much these patients improved. For Sn-to-Chge, we are collecting data from large disease modifying antirheumatic drug multicenter trials in rheumatoid arthritis and ranking candidate definitions of response on their average p values in distinguishing active treatment from placebo or combination compared to single comparator. RESULTS: We surveyed 52 rheumatologists about which trial patients had improved and by how much. Trial data were obtained and tested for sensitivity to change. CONCLUSION: A rigorous data-driven consensus process was used to reassess the ACR20. 相似文献
42.
Ronald F. van Vollenhoven Jos G. A. Houbiers Frank Buttgereit Joanna in 't Hout Maarten Boers Susanne Leij Tore K. Kvien Ben A. C. Dijkmans Leszek Szczepaski Istvan Szombati Stanislaw Sierakowski Andr M. M. Miltenburg 《Arthritis \u0026amp; Rheumatology》2010,62(2):351-358
Objective
Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor α (ERα) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity.Methods
A 10‐week, multicenter, randomized, double‐blind, placebo‐controlled, parallel group, dose‐finding, proof‐of‐concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28).Results
Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose‐related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial.Conclusion
The observed lack of clinical benefit in RA patients treated with an ERα agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ERα‐mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs.43.
44.
Johannes Berkhof Dirk L. Knol Frank Rijmen Jos W.R. Twisk Bernard J.M. Uitdehaag Maarten Boers 《Journal of clinical epidemiology》2009,62(10):1085-1094
ObjectiveTo compare statistical models for the analysis of two-state disease processes.Study Design and SettingA two-armed randomized trial of patients with early rheumatoid arthritis (RA) treated by either combination therapy (sulfasazaline, methotrextate, prednisolone) or monotherapy (sulfasazaline). Disease activity (remission or relapse) was analyzed with the logistic regression model, the proportional hazards regression model, and the continuous-time Markov process model for panel data. The dependence among the switching times was studied by (1) including correlated normal random patient effects for the relapse–remission and remission–relapse switching probabilities; (2) assuming the population to be a mixture of patients responsive and nonresponsive to therapy; (3) including separate parameters for the first and subsequent relapse–remission switch; and (4) combining (1) and (3). The four approaches were compared using parametric bootstrap checks.ResultsThe logistic regression model, the proportional hazards regression model, and the continuous-time Markov process model for panel data yielded similar combination therapy effects. The inclusion of random patient effects (approaches 1 and 4) gave the best fit to the observed disease activity pattern.ConclusionModels with correlated random effects can provide a satisfactory fit to two-state disease patterns. 相似文献
45.
Hoes JN Jacobs JW Boers M Boumpas D Buttgereit F Caeyers N Choy EH Cutolo M Da Silva JA Esselens G Guillevin L Hafstrom I Kirwan JR Rovensky J Russell A Saag KG Svensson B Westhovens R Zeidler H Bijlsma JW 《Annals of the rheumatic diseases》2007,66(12):1560-1567
Objective
To develop evidence‐based recommendations for the management of systemic glucocorticoid (GC) therapy in rheumatic diseases.Methods
The multidisciplinary guideline development group from 11 European countries, Canada and the USA consisted of 15 rheumatologists, 1 internist, 1 rheumatologist–epidemiologist, 1 health professional, 1 patient and 1 research fellow. The Delphi method was used to agree on 10 key propositions related to the safe use of GCs. A systematic literature search of PUBMED, EMBASE, CINAHL, and Cochrane Library was then used to identify the best available research evidence to support each of the 10 propositions. The strength of recommendation was given according to research evidence, clinical expertise and perceived patient preference.Results
The 10 propositions were generated through three Delphi rounds and included patient education, risk factors, adverse effects, concomitant therapy (ie, non‐steroidal anti‐inflammatory drugs, gastroprotection and cyclo‐oxygenase‐2 selective inhibitors, calcium and vitamin D, bisphosphonates) and special safety advice (ie, adrenal insufficiency, pregnancy, growth impairment).Conclusion
Ten key recommendations for the management of systemic GC‐therapy were formulated using a combination of systematically retrieved research evidence and expert consensus. There are areas of importance that have little evidence (ie, dosing and tapering strategies, timing, risk factors and monitoring for adverse effects, perioperative GC‐replacement) and need further research; therefore also a research agenda was composed.Since 1948, glucocorticoids (GCs) have been widely used in medicine.1 Although GCs soon became associated with the occurrence of adverse effects (AEs), they are still the most frequently used anti‐inflammatory and immune‐suppressive drugs in rheumatic diseases. Recent studies have demonstrated the disease‐modifying potential of low‐dose GCs in rheumatoid arthritis (RA) and this has renewed the debate on the risk–benefit ratio of this treatment.2 Current literature on the risk–benefit ratio of GCs is nevertheless inconsistent, and inappropriate use of GCs could lead to increased toxicity;3 this emphasises the need for clear statements on proper use of GCs. Hence, a EULAR task force on GCs, including a patient, was formed to develop evidence‐based recommendations, to provide a tool for the better use and management of GC‐therapy in rheumatic diseases. 相似文献46.
47.
48.
Minimal disease activity, remission, and the long-term outcomes of rheumatoid arthritis 总被引:2,自引:0,他引:2
OBJECTIVE: To determine the prevalence of minimal disease activity (MDA) and remission in patients with rheumatoid arthritis (RA), to assess the effect of anti-tumor necrosis factor (anti-TNF) therapy on MDA, and to determine the extent to which MDA status improves long-term outcomes. METHODS: Using the Patient Activity Scale (PAS) as a surrogate, we assessed the prevalence of MDA and remission in 18,062 patients with RA using the newly developed Outcome Measures in Rheumatology Clinical Trials (OMERACT) criteria for MDA. RESULTS: MDA was noted in 20.2% of 18,062 patients and persistent MDA, operationally defined as having MDA during >or=2 consecutive 6-month observation periods, occurred in 13.5% of 7,433 patients followed longitudinally. Disease activity at remission levels was noted in 7%. Among patients with MDA, 82% received disease-modifying antirheumatic drugs or biologic agents. Following anti-TNF initiation, the cumulative probability of achieving MDA at 2 and 6 years was 4.1% and 7.6%, respectively, and persistent MDA probabilities were 2.7% and 4.5%, respectively. Regardless of RA duration, patients with MDA had substantially better outcomes, including a 10-fold reduction in work disability and an approximately 2-fold reduction in total joint replacement and mortality. CONCLUSION: Remission remains uncommon in RA, and the prevalence of new remission in community practice is substantially lower than noted in published trials of biologic therapy. On average, persons with MDA appear to have persistently mild RA. This might be the effect of milder RA and/or more effective treatment in early RA. The PAS had satisfactory levels of agreement with the full MDA criteria and appears suitable for use in clinical and epidemiologic research. 相似文献
49.
50.
Neural-tube defects and derangement of homocysteine metabolism 总被引:16,自引:0,他引:16
R P Steegers-Theunissen G H Boers F J Trijbels T K Eskes 《The New England journal of medicine》1991,324(3):199-200