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Biomedical subjects

S van der Linden

Publications and source records attributed to S van der Linden.

At least 19 recordsLinked to original sources

Selection of instruments in the core set for DC-ART, SMARD, physical therapy, and clinical record keeping in ankylosing spondylitis. Progress report of the ASAS Working Group. Assessments in Ankylosing Spondylitis.

To select specific instruments for each domain of the core set for endpoints in ankylosing spondylitis (AS), we gathered all instruments described in the literature to assess the domains chosen as endpoints in AS and sent them to 43 members of the Assessments in Ankylosing Spondylitis (ASAS) Working Group. The following domains were taken into account: function, pain, spinal mobility, patient global assessment, morning stiffness, peripheral joints and entheses, acute phase reactants, x-ray spine, x-ray hips, fatigue. For each instrument the members were asked to judge if the instrument was feasible and relevant. If an instrument was judged to be not feasible or not relevant by more than 50% of the respondents the instrument was deleted from the list. These data were presented during an ASAS workshop and the final decisions were about which instruments to include in the core set. This process was repeated separately for the settings disease controlling antirheumatic therapy (DC-ART), symptom modifying antirheumatic drugs (SMARD) and physical therapy, and clinical record keeping. The response rate to the questionnaire was 72%. For each domain one or more instruments were selected, except for Entheses and Fatigue. The chosen instruments were similar for the 3 above settings. Core sets of specific instruments were selected for the OMERACT filter test for relevance and feasibility. For all these instruments the remaining aspects of the OMERACT filter (truth and discrimination) should be assessed by literature review and if needed by additional research. It is recommended to use these instruments in all research projects in AS.

Antirheumatic Agents

A comparative study of the usefulness of the Bath Ankylosing Spondylitis Functional Index and the Dougados Functional Index in the assessment of ankylosing spondylitis.

To determine whether the Bath Ankylosing Spondylitis Functional Index (BASFI, score 0-10) or Dougados Functional Index (DFI, score 0-40) is superior in measuring physical function in ankylosing spondylitis (AS) we studied 191 consecutive outpatients with AS in the Netherlands, France, and Belgium. The participating centers are secondary and tertiary referral centers. The external criterion for disease activity (DA) was: both patient and physician assessment of disease activity on a visual analog scale (VAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The external criterion for damage was 2 radiological scores of the spine; BASRI-s (Bath Ankylosing Spondylitis Radiology Index-spine) and a modified SASSS (Stoke Ankylosing Spondylitis Spine Score). Median scores for BASFI and DFI were 2.5 (range 0-10) and 8.5 (range 0-35), respectively. Spearman correlation coefficient between both indexes was 0.89. The average correlation with disease activity variables was 0.42 for BASFI and 0.41 for DFI. For both BASFI and DFI the correlation with BASRI-s was 0.42 and with SASSS 0.36. When distinguishing between patients with high and low disease activity, sensitivity for both indexes was between 76 and 94%, while specificity was between 66 and 87% for all 3 DA measures. Average misclassification between BASFI, DFI and DA was 23 and 27%, respectively. Both BASFI and DFI correlate equally well with disease activity and damage.

Adolescent

Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis.

Our aim was to determine whether C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) is more appropriate in measuring disease activity in ankylosing spondylitis (AS). We studied 191 consecutive outpatients with AS in The Netherlands, France, and Belgium. Patients were attending secondary and tertiary referral centers. The external criterion for disease activity was: physician and patient assessment of disease activity on a visual analog scale (VAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). In each measure we defined 3 levels of disease activity: no activity, ambiguous activity, and definite disease activity. The patients with AS (modified New York criteria) were divided into 2 groups: those with spinal involvement only (n=149) and those who also had peripheral arthritis and/or inflammatory bowel disease (IBD) (n=42). For each criterion of disease activity, the patients with no activity and with definite activity were included in receiver operator curves and used to determine cutoff values with the highest sensitivity and specificity. We also calculated Spearman correlations. The median CRP and ESR were 16 mg/l and 13 mm/h, respectively, in the spinal group and 25 mg/l and 21 mm/h, respectively, in the peripheral/IBD group. In both groups the Spearman correlation coefficients between CRP and ESR were around 0.50. There was moderate to poor correlation between CRP, ESR, and the 3 disease activity variables (0.06-0.48). Sensitivity for both ESR and CRP was 100% for physician assessment and between 44 and 78% for patient assessment of disease activity and the BASDAI, while specificity was between 44 and 84% for all disease activity measures. The positive predictive values of CRP and ESR in our setting were low (0.15-0.69). We conclude that neither CRP nor ESR is superior to assess disease activity.

Adult

Radiological scoring methods in ankylosing spondylitis: reliability and sensitivity to change over one year.

Our aim was to compare reliability and sensitivity to change of different radiological scoring methods in ankylosing spondylitis (AS). Two trained observers scored 30 AS radiographs twice with an interval of 4 weeks. The same two observers scored 187 AS radiographs in pairs, at baseline and after one year followup, to measure change and agreement on change. The sacroiliac (SI) joints were scored in 5 grades by the New York method and the SASSS (Stoke Ankylosing Spondylitis Spine Score). Hips were graded 0-5 (according to Larsen). Cervical and lumbar spine were graded (0-4, Bath Ankylosing Spondylitis Radiological Index, BASRI), and scored in detail (0-72, SASSS). SASSS of the cervical and lumbar spine scored on the anterior sites of the vertebrae proved most reliable, with both intra and interobserver intraclass correlation coefficients (ICC) between 0.87 and 0.97. BASRI was only moderately reliable, with Cohen's kappa ranging between 0.50 and 0.82 for intra, and 0.38-0.64 for interobserver reliability. Similarly, SI joint scores (New York, SASSS) showed intraobserver kappa between 0.56 and 0.84, and interobserver reliability with kappa between 0.37 and 0.47. Larsen hip scores proved unreliable: moderate intraobserver kappa of 0.47-0.58 and low interobserver kappa of 0.29. After retraining, interobserver kappa did not improve (0.45 and 0.17). In retrospect, a one year period was too short to measure sensitivity to change. Observers agreed that no change occurred in up to 89% of cases. A measurable change of deterioration or improvement occurred rarely. We conclude that in AS, only the SASSS method for the spine and the BASRI reached good reliability. Other methods for spine, SI joints, and hips were moderately reliable at best. There was moderate to good agreement on no change between the observers. No method showed change over a period of one year in a considerable number of patients.

Arthrography

Chronicity of back problems during working life.

STUDY DESIGN: A follow-up study of a cohort of 444 patients aged 16 to 59 years who consulted with their general practitioners (GPs) in 1987-1988 for an incident episode of back pain. OBJECTIVES: To determine the proportion of patients with back pain in whom chronic back problems develop after a follow-up of 7 years, to compare health outcomes and labor force participation of patients with and without chronic back problems and to identify determinants of chronicity. SUMMARY OF BACKGROUND DATA: The incidence and prevalence of back pain are very high. A large proportion of the costs related to medical consumption, absence from work, and disability are probably caused by chronic back problems. It is unknown what proportion of back problems become chronic, especially after a long follow-up period, and which factors can predict chronicity. METHODS: Data on the course of the symptoms and medical consumption from the period between 1987-1988 and 1991 were gathered retrospectively. Data on several health outcomes, including LFP, and data on some work characteristics were collected prospectively in 1991. A more extensive data set on health outcomes including psychologic status and working situation was collected in 1994. RESULTS: Chronic back problems developed in 28% of the patients. These patients reported more pain, higher levels of medical resource consumption, worse health outcomes, and lower labor force participation. Episodes of back pain before 1987-1988, severe pain in 1991, and disability score in 1991 were positively associated with chronicity in 1994, difficulties with job performance in 1991, and frequent stooping in the subgroup of patients who held a paying job in the follow-up period. CONCLUSIONS: Even after a follow-up of 7 years, the proportion of people with chronic back problems was high. The consequences for quality of life, labor force participation, and consumption of medical resources are clear. Further research is necessary to examine determinants and ways to prevent chronicity.

Adolescent

Ankylosing spondylitis. Clinical features.

The clinical spectrum of ankylosing spondylitis (AS) is wider than just symptomatic sacroiliitis. The disease may be atypical or may occur as forme fruste. Atypical cases are encompassed in classification criteria for the whole family of spondyloarthropathies. AS may result primarily from additive genetic variability. Nonsteroidal anti-inflammatory drugs and physical exercise remain the cornerstone in the treatment of AS. Core sets for the assessment of the disease now exist for different treatment settings.

HLA-B27 Antigen

Measures of outcome in ankylosing spondylitis and other spondyloarthritides.

This chapter describes core sets that can be used in the assessment of ankylosing spondylitis and other spondyloarthritides. Various core sets are described for the evaluation of disease-controlling antirheumatic therapy, symptom-modifying antirheumatic drugs and physical therapy, or for use in clinical record keeping. These core sets describe domains and also give advice on specific instruments. The value of spinal mobility and acute-phase reactants in the assessment of ankylosing spondylitis in AS are described in more detail. The available radiological scoring methods are discussed.

Acute-Phase Proteins

Comparison of the electrophysiology and morphology of layers III and II neurons of the rat medial entorhinal cortex in vitro.

The basic membrane characteristics of neurons in layers II and III of the medial entorhinal cortex (MEA) were recorded using the intracellular current clamp technique in in vitro slices of the rat brain. Two types of cells were distinguished according to the presence of a time-dependent inward rectification (SAG current) with hyperpolarizing current pulses. The cells in which this inward rectification was not observed (No-SAG cells) had a larger input resistance, a more negative resting membrane potential and a more depolarized firing threshold. They more often displayed a strongly adapting firing pattern, and their action potentials had a slower decay rate and lacked a depolarizing afterpotential, compared with the SAG cells. SAG cells typically had a prominent rebound depolarization at the end of a hyperpolarizing current and membrane potential oscillations (7 Hz) upon subthreshold depolarizations. Cs+ blocked the time-dependent inward rectification. The rebound depolarization persisted, even in the presence of tetrodotoxin. Biocytin labelling showed that layer III consisted mainly of pyramidal-shaped cells. Most layer III cells were of the No-SAG type. All cells in layer II, stellate and pyramidal cells, were classified as SAG cells. We conclude that the cells in MEA layers II and III display different electroresponsiveness, but that this appears to be more related to the layer where they are located than to a specific morphology. As layer III consisted mainly of cells of the No-SAG type, we suggest that layer III cells are less excitable than the SAG type layer II cells.

Animals

Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: randomized comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone. COBRA Trial Group. Combinatietherapie Bij Reumatoïde Artritis.

OBJECTIVE: Assessment of the cost-effectiveness and cost-utility of early intervention in rheumatoid arthritis (RA) patients, with combined step-down prednisolone, methotrexate and sulphasalazine, compared to sulphasalazine alone. METHODS: Multicentre 56 week randomized double-blind trial with full economic analysis of direct costs and utility analysis with rating scale and standard gamble measurement techniques. RESULTS: The combined-treatment group included 76 patients and the sulphasalazine group 78 patients. The mean total costs per patient in the first 56 weeks of follow-up were $5519 for combined treatment and $6511 for treatment with sulphasalazine alone (P = 0.37). Out-patient care, in-patient care and non-health care each contributed about one-third to the total costs. The combined-treatment group appeared to generate savings in the length of hospital stay for RA, non-protocol drugs and costs of home help, but comparisons were not statistically significant. Protocol drugs and monitoring were slightly more expensive in the combined-treatment group. Clinical, radiographic and functional outcomes significantly favoured combined treatment at week 28 (radiography also at week 56). Utility scores also favoured combined treatment. CONCLUSION: Combined treatment is cost-effective due to enhanced efficacy at lower or equal direct costs.

Adult

[Combination therapy in early rheumatoid arthritis: the COBRA study].

The scheme 'Combination therapy in rheumatoid arthritis' (COBRA) in early rheumatoid arthritis (RA) involves administration of not only sulfasalazine but also prednisolone and methotrexate during the first six months. The trial showed that the COBRA scheme over a period of 1.5 years was superior to sulfasalazine alone: less disease activity in the major part of the year of treatment, less articular damage on radiographs, fewer side effects and equal or reduced costs. An 'aggressive' treatment in patients with early RA is indicated, with (re)assessment of the use of corticosteroids.

Anti-Inflammatory Agents

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis.

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.

Adult

Facilitated analysis of data on drug regimen compliance.

Drug actions depend on dose and intervals between doses, in ways that are drug-specific and sometimes complex, complicating the use of drug dosing histories as an explanatory variable in the analysis of clinical trials. We describe a spread-sheet method for conveniently displaying patients' drug dosing histories, to facilitate identification of dosing correlates of clinically important events.

Anti-Inflammatory Agents, Non-Steroidal

Preliminary core sets for endpoints in ankylosing spondylitis. Assessments in Ankylosing Spondylitis Working Group.

An international working group was formed to select core sets to be used as endpoints in clinical trials in ankylosing spondylitis (AS). The results of the first steps of the selection of these core sets are described. The definition of the settings for which the core set will be intended are defined. The methods used to select the core sets were a combination of literature search, nominal group discussions, and plenary discussions. The following settings were defined: disease controlling antirheumatic therapy (DC-ART), symptom modifying antirheumatic drugs (SMARD)/physical therapy, and clinical record keeping. Over 110 variables used as endpoints in AS were found in the literature. The preliminary core set for DC-ART consists of physical function, pain, spinal mobility, patient global assessment, peripheral joints/entheses, x-ray spine. The selected core set for SMARD/physical therapy includes physical function, pain, spinal mobility, spinal stiffness, and patient global assessment. The core set for clinical record keeping includes all measures of the SMARD/physical therapy core set completed by peripheral joints/entheses, and acute phase reactants. Three preliminary core sets for AS have been defined. Further research will be performed to select specific measures for all domains.

Antirheumatic Agents