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Biomedical subjects

J Fransen

Publications and source records attributed to J Fransen.

At least 19 recordsLinked to original sources
PubMed2006

Performance of response criteria for assessing peripheral arthritis in patients with psoriatic arthritis: analysis of data from randomised controlled trials of two tumour necrosis factor inhibitors.

BACKGROUND: In recent clinical trials in patients with psoriatic arthritis (PsA), the response criteria and disease activity measures that have been used were those developed for rheumatoid arthritis. However, these have not yet been validated in PsA. OBJECTIVE: To compare the responsiveness and discriminative capacity of the psoriatic arthritis response criteria (PsARC), American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the Disease Activity Score (DAS) and core-set measures in patients with PsA and peripheral arthritis, using the data from two randomised placebo-controlled trials of tumour necrosis factor inhibitors. METHODS: In an infliximab trial, 104 patients with active PsA were randomised to receive placebo or infliximab for 16 weeks. In an etanercept trial, 60 patients with active PsA were randomised to receive placebo or etanercept for 12 weeks. Data from baseline and the end of the intervention phase were used from each study. Responsiveness was assessed using the standardised response mean and effect size. Capacity to discriminate between the active drug and placebo was assessed using t values or a chi2 test. Measures were ranked in order of their t value or chi2 value. RESULTS: The EULAR criteria performed better in discriminating the active drug from placebo than the ACR20 improvement criteria, which in turn performed better than the PsARC. It was also found that the pooled indices (DAS and DAS28) were generally more responsive, and performed better in discriminating active drug from placebo, than the single core-set measures. CONCLUSION: Response criteria and pooled indices developed for rheumatoid arthritis are useful for the assessment of arthritis in PsA clinical trials.

Antibodies, Monoclonal↗
PubMed2005

Effectiveness of systematic monitoring of rheumatoid arthritis disease activity in daily practice: a multicentre, cluster randomised controlled trial.

OBJECTIVE: To test the efficacy of standardised monitoring using the disease activity index DAS28 versus usual care on disease modifying antirheumatic drug (DMARD) prescription and disease activity in rheumatoid arthritis. METHODS: A 24 week cluster randomised trial. Rheumatology outpatient centres were randomised to systematic monitoring of disease activity using the DAS28 (12 centres, 205 patients) or usual care (12 centres, 179 patients). The aim for the DAS group was to reach a DAS28 score of < or =3.2 by changes in DMARD treatment, at the discretion of the rheumatologist and the patient. RESULTS: At baseline, disease activity was the same in both groups, with an overall mean (SD) DAS28 of 4.5 (1.2); 13% of the patients had a DAS28 of < or =3.2. At 24 weeks, 31% of patients in the DAS group had a DAS28 < or =3.2, while in the usual care centres this was 16% (p = 0.028). DMARDs were changed on average in 18% of visits in the DAS centres; in the 12 usual care centres they were changed on 8% of the visits (p = 0.013). The doses of methotrexate, sulfasalazine, and corticosteroids appeared to be higher in the DAS centres than in the usual care centres, but the differences were not significant. CONCLUSIONS: In daily practice, systematic monitoring of disease activity in rheumatoid arthritis may lead to more changes in DMARD treatment, resulting in a larger number of patients with low disease activity.

Adrenal Cortex Hormones↗
PubMed2004

Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria.

OBJECTIVE: To determine which cut-off point in the RA disease activity score (DAS28) corresponds to fulfilment of the ARA criteria for clinical remission. METHODS: The disease activity of patients included in the Nijmegen RA inception cohort was systematically assessed every 3 months. For all visits, a modification of the ARA preliminary criteria for clinical remission was applied and the DAS28 was calculated. Receiver operating characteristic analysis was used to determine the cut-off point with maximum sensitivity and specificity in DAS28 corresponding with fulfilment of the modified ARA criteria. RESULTS: Three hundred and seventy-eight patients contributed 4378 visits. In 6.5% of the visits four of the five items and in 1.5% all five items of the modified ARA criteria were fulfilled. The optimal cut-off point for the DAS28 that corresponds to fulfilment of the modified ARA criteria was determined to be 2.66. CONCLUSION: DAS28 <2.6 corresponds to fulfilment of the preliminary ARA criteria for clinical remission in RA.

Antirheumatic Agents↗
PubMed2004

Influence of guideline adherence on outcome in a randomised controlled trial on the efficacy of methotrexate with folate supplementation in rheumatoid arthritis.

OBJECTIVE: To study the influence of rheumatologists' adherence to a methotrexate guideline on efficacy and toxicity in the treatment of rheumatoid arthritis. METHODS: In a 48 week randomised controlled trial of methotrexate, comparing folates with placebo, rheumatologists were advised on methotrexate dosage using a guideline reflecting daily practice. The influence of guideline non-adherence on outcome was analysed using generalised estimating equations and survival analysis. RESULTS: In 51% of the 411 study patients the guidelines were always followed. Non-adherence resulted in lower doses of methotrexate in 25% of cases, and higher doses in 24%. The reduction in the disease activity score was significantly greater (mean -0.4; p = 0.0085) in the adherent group than in the "low dose" group; the "high dose" group did not differ from the adherent group. Dropout caused by severe adverse events did not differ between the three groups. CONCLUSIONS: There is an indication that adherence to guidelines on methotrexate dosage may benefit patients with rheumatoid arthritis by improving disease activity without increasing toxicity. For definite proof, a randomised controlled trial comparing guideline supported dosing with usual care is needed.

Adult↗
PubMed2003

Rheumatologists' opinions on the feasibility of a measurement feedback system in rheumatoid arthritis and the influence of motivation.

OBJECTIVE: To assess rheumatologists' opinions about the feasibility of a measurement feedback system in rheumatoid arthritis (RA) and to analyse if motivational aspects play a role in assessing the value of the system and in determining the extent to which it is used. METHODS: A survey sample (n=105) was randomly selected from participants of a measurement feedback system. A survey questionnaire assessed opinions on system outcome, structures and processes, motivation and overall satisfaction. Survey results are given descriptively and groups differing in motivation are compared. RESULTS: The overall response rate was 62%. The system was generally perceived to fulfil its aims, but the effort required to use the system was rated less positive. Rheumatologists had as their motivation either 'science/obligation' or 'individual patient evaluation'. Rheumatologists with the latter motivation were more satisfied with the measurement feedback system, perceived its feasibility as better, and made more use of it. CONCLUSION: Motivation for participating in a measurement feedback system has a significant impact on overall satisfaction with the system and the use of the system. Influencing motivation and reduction of the amount of effort required to use the system might increase overall acceptance.

Arthritis, Rheumatoid↗
PubMed2003

Effectiveness of a measurement feedback system on outcome in rheumatoid arthritis: a controlled clinical trial.

BACKGROUND: With the help of a measurement feedback system, the treatment strategy for individual patients with rheumatoid arthritis (RA) can be adjusted to achieve optimal control of disease activity. OBJECTIVE: To study whether a measurement feedback system is effective in reducing disease activity in patients with RA. METHODS: Forty eight rheumatologists and 264 patients participated in a controlled clinical trial. A three month control period was followed by a 12 month period, where feedback on disease activity, disability, and damage was provided to the rheumatologist. The primary outcome measure was the rheumatoid arthritis disease activity index (RADAI). RESULTS: The feedback system was used for 142/228 (62%) patients. Disease modifying antirheumatic drug changes occurred in 69/169 (41%) patients. In patients with high disease activity and feedback use (n=70), the RADAI decreased in the feedback period by -0.27 points per 30 days (p<0.05), as compared with the control period. Patients for whom the feedback system was used had a better outcome than non-users. CONCLUSION: Much more training on the use of a feedback system and outcome measures, as well as the inclusion of explicit treatment guidelines will be necessary to increase the clinical use of measurement feedback and, possibly, to reduce disease activity for a larger number of patients with RA.

Acute Disease↗
PubMed2002

The ICIDH-2 as a framework for the assessment of functioning and disability in rheumatoid arthritis.

OBJECTIVE: To investigate by a cross sectional study in patients with rheumatoid arthritis (RA) the relationship between measures of impairment, activity limitation, and participation of the model of functioning and disability (ICIDH-2). METHODS: Inclusion data of patients with RA (n=803) from the Swiss Clinical Quality Management Group were used. Impairments were measured by the Short Form-36 (SF-36) bodily pain scale, rheumatoid arthritis disease activity index (RADAI), disease activity score (DAS28), and radiographic scoring (x ray). Activity limitation was measured with the Health Assessment Questionnaire (HAQ) and the SF-36 physical functioning scale. Participation was measured with the SF-36 role and social functioning scales. Spearman (partial) correlations were used for analysis. RESULTS: Impairment and activity limitation dimensions of the ICIDH-2 model are related; correlations with the HAQ were: SF-36 bodily pain (r(s)=-0.61), RADAI (r(s)=0.58), DAS28 (r(s)=0.49), and x ray (r(s)=0.35). Similar correlations were found for SF-36 physical functioning. Activity limitation and participation restriction dimensions are also related: the HAQ correlates well with SF-36 role-physical (r(s)=-0.53) and SF-36 social functioning (r(s)=-0.43); SF-36 physical functioning correlates similarly. For impairment and participation restriction dimensions only SF-36 bodily pain is substantially correlated (r(s)=0.47 and 0.48) with SF-36 role-physical, after correcting for the influence of the activity limitation dimension (HAQ and SF-36 physical functioning). CONCLUSIONS: In this cross sectional study of patients with RA, impairments are associated with activity limitations, and activity limitations are associated with participation restrictions. Pain is the only impairment directly associated with participation restrictions. Based on the results of this study, it is strongly recommended that the ICIDH-2 framework is used in clinical trials and observational studies including the assessment of disease consequences in RA.

Activities of Daily Living↗
PubMed2001

Responsiveness of the self-assessed rheumatoid arthritis disease activity index to a flare of disease activity.

OBJECTIVE: To assess the responsiveness of the Rheumatoid Arthritis Disease Activity Index (RADAI) to increases in disease activity, using the occurrence of a flare of disease activity as an external standard. METHODS: A post hoc analysis was performed on data from a randomized, double-blind, controlled trial of methotrexate versus type II collagen in 92 patients with rheumatoid arthritis (RA). Responsiveness was analyzed by 1) correlating change in the RADAI score with change in the Disease Activity Score (DAS28), 2) determining the RADAI's ability to detect a disease flare by plotting a receiver operating characteristic (ROC) curve, and 3) using a responsiveness statistic, the standardized effect size (SES). The contribution of the single RADAI items to the change in total RADAI score was analyzed by the item score change in absolute value, the item responsiveness by the standardized response mean, and the correlation of item score change with total RADAI score change by Cronbach's alpha. RESULTS: Changes in the RADAI score correlated strongly with changes in the DAS28 (R2 = 0.70, P < 0.0001). The area under the ROC curve for the RADAI was 0.88 (95% confidence interval 0.78-0.95), which was similar to that for the DAS28. The SES for the RADAI was 1.56, which was also similar to that for the DAS28. The RADAI items of past global disease activity and morning stiffness contributed least to the total score change. CONCLUSION: This study provides evidence that the RADAI is sensitive to relevant increases in disease activity in RA patients. The RADAI may complement clinical measures in clinical studies, or may be used as a proxy for disease activity in epidemiologic studies.

Arthritis, Rheumatoid↗
PubMed2001

Identification of case complexity and increased health care utilization in patients with rheumatoid arthritis.

OBJECTIVES: To document biopsychosocial profiles of patients with rheumatoid arthritis (RA) by means of the INTERMED and to correlate the results with conventional methods of disease assessment and health care utilization. METHODS: Patients with RA (n = 75) were evaluated with the INTERMED, an instrument for assessing case complexity and care needs. Based on their INTERMED scores, patients were compared with regard to severity of illness, functional status, and health care utilization. RESULTS: In cluster analysis, a 2-cluster solution emerged, with about half of the patients characterized as complex. Complex patients scoring especially high in the psychosocial domain of the INTERMED were disabled significantly more often and took more psychotropic drugs. Although the 2 patient groups did not differ in severity of illness and functional status, complex patients rated their illness as more severe on subjective measures and on most items of the Medical Outcomes Study Short Form 36. Complex patients showed increased health care utilization despite a similar biologic profile. CONCLUSIONS: The INTERMED identified complex patients with increased health care utilization, provided meaningful and comprehensive patient information, and proved to be easy to implement and advantageous compared with conventional methods of disease assessment. Intervention studies will have to demonstrate whether management strategies based on INTERMED profiles can improve treatment response and outcome of complex patients.

Adult↗
PubMed2001

[Clinical quality management in rheumatoid arthritis].

Clinical quality management in rheumatoid arthritis (RA) aims at reducing inflammatory activity and pain in the short term and damage and disability in the long term. In the "Swiss Clinical Quality Management in rheumatoid arthritis" (SCQM) project, which started in 1997, a measurement-improvement system with feedback reports allows the rheumatologists to follow their RA patients with the aim of improving the quality of outcome. Inflammatory activity is measured with the Disease Activity Score (DAS28) and the Rheumatoid Arthritis Disease Activity Index questionnaire (RADAI), damage with an X-ray score and disability with the Stanford Health Assessment Questionnaire (HAQ). The feedback is used by the individual rheumatologist to optimize the therapy of his/her RA patients. Beside the aim of improving the quality of treatment, the SCQM projects wants to build a Swiss cohort of RA patients, to improve the collaboration of rheumatologists in the clinic and in practice and to establish standards of treatment in RA. In this paper we describe the SCQM project in detail, we show two cases illustrating the usefulness of the SCQM in the management of individual RA patients, and we present the cross sectional analysis of the first 1223 RA patients included in the project.

Antirheumatic Agents↗
PubMed2000

Feasibility and validity of the RADAI, a self-administered rheumatoid arthritis disease activity index.

OBJECTIVE: The goal of the Rheumatoid Arthritis Disease Activity Index (RADAI) is to provide an easy to use assessment of disease activity. It is a self-administered questionnaire that combines five items into a single index: current and past global disease activity, pain, morning stiffness and a joint count. METHODS: A sample of 484 rheumatoid arthritis (RA) patients was used to assess the internal consistency and the convergent validity of the RADAI. This was achieved by calculating Cronbach's alpha and RADAI item and total score correlations with core set measures and DAS28. RESULTS: Cronbach's alpha was 0.87, supporting the summation of the items into a single index. The index correlated best with physicians' global assessment (r = 0.59; P < 0.0001), the Health Assessment Questionnaire (r = 0.55; P < 0.0001) and the number of tender joints (r = 0.55; P < 0.0001). Correlation with the erythrocyte sedimentation rate was low (r = 0.27; P < 0.0001). The RADAI and the DAS28 were correlated (r = 0.53; P < 0.0001), but there was low agreement. CONCLUSIONS: The RADAI is valid to assess disease activity in RA patients. However, the RADAI may not automatically replace other measures of disease activity, such as the DAS28.

Arthritis, Rheumatoid↗
PubMed2000

Clinical quality management in rheumatoid arthritis: putting theory into practice. Swiss Clinical Quality Management in Rheumatoid Arthritis.

Clinical quality management (CQM) in rheumatoid arthritis (RA) aims to reduce inflammatory activity and pain in the short term, and damage, and consequently disability, in the long term. Within CQM as used in Switzerland rheumatologists are provided with a measurement feedback system with which they can regularly follow their patients. Inflammatory activity is measured with the Disease Activity Score (DAS28) and the Rheumatoid Arthritis Disease Activity Index questionnaire (RADAI), damage with an X-ray score and disability with the Stanford Health Assessment Questionnaire (HAQ). Feedback is used to optimize therapy, which in the short term allows the activity of the inflammatory process to be adjusted or 'titrated'. In the long term, the therapy result for the individual patient is monitored by the course of disability and damage. In this paper we present a series of cases to illustrate the usefulness of the CQM system in the management of individual RA patients. CQM in RA may be helpful when making decisions about adjustment of treatment, and to document and communicate these decisions based on quantitative data.

Arthritis, Rheumatoid↗
PubMed2000

Transport and function of syntaxin 3 in human epithelial intestinal cells.

To follow the transport of human syntaxin (Syn) 3 to the apical surface of intestinal cells, we produced and expressed in Caco-2 cells a chimera made of the entire Syn3 coding sequence and the extracellular domain of the human transferrin receptor (TfR). This chimera (Syn3TfR) was localized to the apical membrane and was transported along the direct apical pathway, suggesting that this is also the case for endogenous Syn3. To test the potential role of Syn3 in apical transport, we overexpressed it in Caco-2 cells and measured the efficiency of apical and basolateral delivery of several endogenous markers. We observed a strong inhibition of apical delivery of sucrase-isomaltase (SI), an apical transmembrane protein, and of alpha-glucosidase, an apically secreted protein. No effect was observed on the basolateral delivery of Ag525, a basolateral antigen, strongly suggesting that Syn3 is necessary for efficient delivery of proteins to the apical surface of intestinal cells.

Antigens, Differentiation↗
PubMed1999

A FERM domain governs apical confinement of PTP-BL in epithelial cells.

PTP-BL is a cytosolic multidomain protein tyrosine phosphatase that shares homologies with several submembranous and tumor suppressor proteins. Here we show, by transient expression of modular protein domains of PTP-BL in epithelial MDCK cells, that the presence of a FERM domain in the protein is both necessary and sufficient for its targeting to the apical side of epithelial cells. Furthermore, immuno-electron microscopy on stable expressing MDCK pools, that were obtained using an EGFP-based cell sorting protocol, revealed that FERM domain containing fusion proteins are enriched in microvilli and have a typical submembranous location at about 10-15 nm from the plasma membrane. Immunofluorescence microscopy suggested colocalization of the FERM domain moiety with the membrane-cytoskeleton linker ezrin. However, at the electron microscopy level this colocalization cannot be confirmed nor can we detect a direct interaction by immunoprecipitation assays. Fluorescence recovery after photobleaching (FRAP) experiments show that PTP-BL confinement is based on a dynamic steady state and that complete redistribution of the protein may occur within 20 minutes. Our observations suggest that relocation is mediated via a cytosolic pool, rather than by lateral movement. Finally, we show that PTP-BL phosphatase domains are involved in homotypic interactions, as demonstrated by yeast two-hybrid assays. Both the highly restricted subcellular compartmentalization and its specific associative properties may provide the appropriate conditions for regulating substrate specificity and catalytic activity of this member of the PTP family.

Animals↗
PubMed1997

The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88.

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.

Amino Acid Sequence↗