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Sjef van der Linden

Publications and source records attributed to Sjef van der Linden.

At least 19 recordsLinked to original sources

How do the EQ-5D, SF-6D and the well-being rating scale compare in patients with ankylosing spondylitis?

PURPOSE: To compare aspects of validity of EuroQol-5 Dimensions (EQ-5D) and Short-Form-6 Dimensions (SF-6D), two indirect utility instruments, and the well-being rating scale (RS) in ankylosing spondylitis (AS). METHODS: EQ-5D, SF-6D and RS were available for 254 patients fulfilling modified New York criteria. 134 patients were part of an observational cohort and 120 were part of a randomised controlled trial (RCT). Aspects of validity assessed were truth (agreement and correlation with external health measures) and discrimination (differentiation between health states, repeatability and detection of treatment effect). RESULTS: Median (range) values were 0.69 (-0.08-1.00) for the EQ-5D, 0.65 (0.35-0.95) for the SF-6D and 0.65 (0.14-1.00) for the RS. Agreement (intraclass correlation coefficient) was moderate (0.46-0.55). Instruments correlated equally with disease activity, functioning and quality of life. The SF-6D showed smaller average differences in utility between patients with better and worse disease compared with the EQ-5D and the RS. The smallest detectable difference (SDD) (in the control group of RCT) was 0.36, 0.17 and 0.33 for EQ-5D, SF-6D and RS, respectively. The ability to detect treatment effect (in the intervention trial) showed standardised effect sizes that were moderate for EQ-5D and SF-6D (0.63 and 0.64) and low for the RS (0.23). CONCLUSION: In patients with AS, EQ-5D, SF-6D and the RS correlate equally well with external measures of health, but have different psychometric properties. The SDD is most favourable for the SF-6D, but it discriminates less well between patients with different disease severities. The RS has a poorer ability to detect treatment effects. It is difficult to recommend one of the instruments.

Adult↗

Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy.

The main objectives of medical therapy in ankylosing spondylitis (AS) are to relieve pain, stiffness and fatigue and to prevent structural damage. The Assessment in Ankylosing Spondylitis Working Group has proposed different domains with specific instruments to assess the efficacy of therapeutic agents classified as symptom-modifying and disease-controlling antirheumatic drugs. Non-steroidal antiinflammatory drugs (NSAIDs) are still the first-line treatment in the management of AS, and they are effective in controlling symptoms such as pain and stiffness and maintaining mobility in many patients. A recent randomized trial suggested that the progression of radiological damage occurs less on continuous use of celecoxib compared with on-demand use. If such findings were confirmed by other studies, the therapeutic value of NSAIDs in AS may extend beyond symptom control. However, for each individual patient, the expected advantages of treatment with NSAIDs should be weighted against any possible gastrointestinal and cardiovascular disadvantages. Disease-modifying antirheumatic drugs (DMARDs) are widely used for second-line therapy in AS, but the evidence for their efficacy is poor. The term 'DMARD' has been borrowed from rheumatoid arthritis, and none of the DMARDs have been shown to prevent or significantly decrease the rate of progression of structural damage which is required to be qualified as a disease-controlling antirheumatic drug for AS. Sulphasalazine is the most extensively studied DMARD and studies suggest some degree of clinical benefit confined to peripheral joint involvement, but no evidence of benefit in axial disease. Methotrexate, which is the gold standard DMARD in rheumatoid arthritis, does not seem to have a substantial therapeutic effect in AS on axial or peripheral joint involvement. Leflunomide appears to exert little beneficial effect, if any, even on peripheral joint involvement. There is also good evidence that local therapy with corticosteroids is effective and may be used in selected patients. Oral corticosteroids may be somewhat effective in relieving the symptoms of AS, but this has not been formally studied. Small studies have reported favourable results with intravenous methylprednisolone pulse therapy, but the effect is temporary. Pamidronate and thalidomide have been used in some preliminary trials but need further studies to assess their potential role in treating AS patients resistant or intolerant to other forms of treatment. Treatment with tumour necrosis factor blockers is not discussed in this review.

Anti-Inflammatory Agents, Non-Steroidal↗

Magnetic resonance imaging changes of sacroiliac joints in patients with recent-onset inflammatory back pain: inter-reader reliability and prevalence of abnormalities.

To study the inter-reader reliability of detecting abnormalities of sacroiliac (SI) joints in patients with recent-onset inflammatory back pain by magnetic resonance imaging (MRI), and to study the prevalence of inflammation and structural changes at various sites of the SI joints. Sixty-eight patients with inflammatory back pain (at least four of the five following criteria: symptom onset before age 40, insidious onset, morning stiffness, duration >3 months, improvement with exercise--or three out of five of these plus night pain) were included (38% male; mean age, 34.9 years [standard deviation 10.3]; 46% HLA-B27-positive; mean symptom duration, 18 months), with symptom duration <2 years. A MRI scan of the SI joints was made in the coronal plane with the following sequences: T1-weighted spin echo, short-tau inversion recovery, T2-weighted fast-spin echo with fat saturation, and T1-spin echo with fat saturation after the administration of gadolinium. Both SI joints were scored for inflammation (separately for subchondral bone and bone marrow, joint space, joint capsule, ligaments) as well as for structural changes (erosions, sclerosis, ankylosis), by two observers independently. Agreement between the two readers was analysed by concordance and discordance rates and by kappa statistics. Inflammation was present in 32 SI joints of 22 patients, most frequently located in bone marrow and/or subchondral bone (29 joints in 21 patients). Readers agreed on the presence of inflammation in 85% of the cases in the right SI joint and in 78% of the cases in the left SI joint. Structural changes on MRI were present in 11 patients. Ten of these 11 patients also showed signs of inflammation. Agreement on the presence or absence of inflammation and structural changes of SI joints by MRI was acceptable, and was sufficiently high to be useful in ascertaining inflammatory and structural changes due to sacroiliitis. About one-third of patients with recent-onset inflammatory back pain show inflammation, and about one-sixth show structural changes in at least one SI joint.

Adult↗

Prevalence and annual incidence of vertebral fractures in patients with ankylosing spondylitis.

OBJECTIVES: To evaluate the prevalence and annual incidence of clinically-manifest vertebral fractures among patients with ankylosing spondylitis (AS). METHOD: Coordinated by the Ankylosing Spondylitis International Federation, a self-administered general questionnaire which included some questions on gender, age, age at onset of disease, and a history of vertebral fracture was inserted in one issue of the membership journals of the AS patient organizations in Germany and Austria. RESULTS: Among the 1,071 patients responding who all had indicated that the diagnosis of AS had been established or confirmed by a physician, 61 (5.7%) indicated a history of vertebral fracture, 15 of them (1.4%) without an accident. The prevalence of vertebral fractures was 6.2% among male AS patients and 4.6% among females (NS), and 4.8% among HLA-B27+ patients and 9.9% among HLA-B27(-) patients (p<0.05). Spinal fractures occurred more often among AS patients with peripheral arthritis (7.1%) than among patients with axial involvement only (3.1%, p<0.01). The average delay between disease onset and diagnosis of AS was 10.5 years for patients with a vertebral fracture, compared to 8.7 years for patients without any such event (p<0.05). Among patients with a disease duration >or=42 years, the prevalence of vertebral fractures was 14%. The annual incidence of vertebral fractures which occurred without an accident had a maximum of 0.1% per annum at a disease duration of 20-35 years, whereas the incidence of vertebral fractures caused by an accident increased continuously with increasing disease duration, amounting to 1.3% per annum after a disease duration of 45 years. CONCLUSION: A considerable proportion of AS patients will experience a vertebral fracture during the course of the disease, in particular if peripheral joints are also involved.

Adult↗

Markers for type II collagen breakdown predict the effect of disease-modifying treatment on long-term radiographic progression in patients with rheumatoid arthritis.

OBJECTIVE: To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in patients with rheumatoid arthritis (RA). METHODS: Patients had participated in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) trial comparing aggressive step-down combination therapy (the COBRA regimen, including temporary high-dose prednisolone, temporary low-dose methotrexate, and sulfasalazine [SSZ]) and mild monotherapy (SSZ). Urinary CTX-I and CTX-II levels were measured at baseline and 3, 6, 9, and 12 months after initiation of treatment. Radiographs were scored according to the modified Sharp/van der Heijde method (mean of 2 independent readers who were aware of the sequence). Individual long-term radiographic progression was estimated, using baseline radiographs and all radiographs obtained during the followup period, by simple linear regression analysis (curve fitting). RESULTS: Both COBRA therapy and SSZ monotherapy produced a significant decrease in urinary CTX-I and CTX-II levels at 3 months, and this decrease was amplified at 6 months. COBRA therapy suppressed CTX-II (change from baseline levels -36% and -43% at 3 and 6 months, respectively), but not CTX-I, significantly better than did SSZ (-17% and -21% at 3 and 6 months, respectively) at 3 and 6 months. The magnitude of the decrease in urinary CTX-II levels at 3 months significantly predicted long-term (5-year) radiographic progression (beta = 0.48 [95% confidence interval (95% CI) 0.13, 0.83]). This effect was independent of the change in disease activity and inflammation indices at 3 months. Patients whose CTX-II levels were normalized (<150 ng/mmoles of urinary creatinine) at 3 months had a significantly higher chance of radiographic stability (no progression over 5 years) than did patients whose CTX-II levels were increased both at baseline and at 3 months (odds ratio 4.5 [95% CI 1.5, 13]). CONCLUSION: The individual CTX-II response measured after 3 months of therapy in patients with active RA who had increased CTX-II levels at baseline independently predicts long-term radiographic progression. Urinary CTX-II levels may be used as early markers of treatment efficacy in patients with RA.

Adult↗

The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis.

OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. METHODS: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients.

Adult↗

What is the most appropriate radiologic scoring method for ankylosing spondylitis? A comparison of the available methods based on the Outcome Measures in Rheumatology Clinical Trials filter.

OBJECTIVE: To select the most appropriate radiologic scoring method for the evaluation of radiographic progression in ankylosing spondylitis (AS) in clinical trials. METHODS: The validity of the currently available methods, the Bath Ankylosing Spondylitis Radiology Index (BASRI), the Stoke Ankylosing Spondylitis Spine Score (SASSS), and the modified SASSS (M-SASSS), was tested according to the aspects of the Outcome Measures in Rheumatology Clinical Trials filter: truth, discrimination (reliability and sensitivity to change), and feasibility, using radiographs of 133 patients at 4 different time points (baseline, 1 year, 2 years, and 4 years). One observer scored these sets in chronological order. To assess interobserver reliability, a second observer scored radiographs of 20 patients at the 4 different time points. RESULTS: After 4 years, 9% and 8% of patients showed changes >0 in the sacroiliac (SI) joints and hips, respectively. Independent of the method chosen, approximately 40% of patients showed changes in both the lumbar and cervical spine. Therefore, it was concluded that, for the assessment of progression, SI joints and hips are of minor importance. The intraclass correlation coefficient (ICC) varied from 0.87 to 0.98 and ICCs for intraobserver scores varied from 0.96 to 0.99. Concerning progression scores, only the ICC for the M-SASSS measured after 2 years remained acceptable (0.82). The intraobserver scores for progression after 2 years of followup were an ICC of 0.93 for the BASRI, an ICC of 0.79 for the SASSS, and an ICC of 0.95 for the M-SASSS. Concerning sensitivity to change, it was found that the M-SASSS classified the highest percentage of patients with a change >0. CONCLUSION: The M-SASSS is the most appropriate method by which to score the radiographic progression in AS patients in clinical trials.

Follow-Up Studies↗

The Sharp/van der Heijde method out-performed the Larsen/Scott method on the individual patient level in assessing radiographs in early rheumatoid arthritis.

OBJECTIVE: To test the reliability of two radiologic scoring methods in rheumatoid arthritis (RA)--the Sharp/van der Heijde (SvH) and the Larsen/Scott (LS)--with generalizability analyses. STUDY DESIGN AND SETTING: Films of 51 patients representing the spectrum of early RA were read by two raters for each method. The discriminative ability and responsiveness were expressed as: intraclass correlation coefficients (ICCs), two types of smallest detectable difference (SDD), and two types of smallest detectable change (SDC); reflecting measurement error when discriminating between or detecting changes within (1) individuals or (2) groups. They were calculated for (average) scores of one to three raters. RESULTS: The discriminative capacity (0.85-0.97) and responsiveness (0.91-0.97) were good when expressed by ICC. On the group level the SDDs and SDCs ranged between 0.6-3.3% of the max. obtainable score. On the individual level, the scores showed better reliability measured with the SvH (SDDs 2.0-3.4%) than with the LS (SDDs 5.3-9.2%). The SvH also assessed changes in scores in individuals with less measurement error (SDCs 1.3-2.2%) than the LS (SDCs 2.3-3.9%). CONCLUSION: For early RA patients, the SvH seems preferable if analyses on individual level are included.

Analysis of Variance↗

A tale of two cities: hospitalization costs in 1897 and 1997.

OBJECTIVES: To compare the hospitalization day price, and the hospitalization costs 100 years ago with the present situation. METHODS: Municipal and hospital archives of two cities, Maastricht in The Netherlands and Tongeren in Belgium, were studied systematically for reports of costs. These were compared with the present accounts. RESULTS: Starting from the second part of the nineteenth century, an official day price was calculated each year by averaging the total hospital expenditures by the total number of hospitalization days. Of all expenditures, nutrition accounted for nearly 50% of expenses. Differences with the current situation are striking. Nowadays, the day price is a negotiated tariff. Management and salaries make up more than 70% of the present expenditures. CONCLUSIONS: Hospitalization day prices have been used for approximately 150 years to determine hospitalization costs. Since then, the total hospital expenditures and the relative cost components have changed considerably. Compared with the spending power of people, the cost of one day in the hospital increased substantially.

Belgium↗

ICF Core Sets for low back pain.

OBJECTIVE: To report on the results of the consensus process integrating evidence from preliminary studies to develop the first version of a Comprehensive ICF Core Set and a Brief ICF Core Set for low back pain. METHODS: A formal decision-making and consensus process integrating evidence gathered from preliminary studies was followed. Preliminary studies included a Delphi exercise, a systematic review and an empirical data collection. After training in the ICF and based on these preliminary studies, relevant ICF categories were identified in a formal consensus process by international experts from different backgrounds. RESULTS: The preliminary studies identified a set of 503 ICF categories at the second, third and fourth ICF levels with 211 categories on body functions, 47 on body structures, 190 on activities and participation and 55 on environmental factors. Eighteen experts from 15 different countries attended the consensus conference on low back pain. Altogether 78 second-level categories were included in the Comprehensive ICF Core Set with 19 categories from the component body functions, 5 from body structures, 29 from activities and participation and 25 from environmental factors. The Brief ICF Core Set included a total of 35 second-level categories with 10 on body functions, 3 on body structures, 12 on activities and participation and 10 on environmental factors. CONCLUSION: A formal consensus process integrating evidence and expert opinion based on the ICF framework and classification led to the definition of ICF Core Sets for low back pain. Both the Comprehensive ICF Core Set and the Brief ICF Core Set were defined.

Activities of Daily Living↗

Radiological scoring methods in ankylosing spondylitis. Reliability and change over 1 and 2 years.

OBJECTIVE: To compare reliability and change over time of radiological scoring methods in ankylosing spondylitis (AS). METHODS: Two trained observers scored 217 sets of radiographs from baseline and from one and 2 years' followup. Sacroiliac (SI) joints were grade 0-4 by the New York method and Stoke Ankylosing Spondylitis Spine Score (SASSS). Hips and cervical and lumbar spine were graded 0-4 by Bath Ankylosing Spondylitis Radiology Index (BASRI). BASRI spinal scores and New York SI are combined into BASRI-spine (score 2-12) and with the addition of BASRI-hips into BASRI-total (2-16). Cervical and lumbar spine were also scored in detail (SASSS, 0-36 each) and were combined into SASSS-total or "modified" SASSS (both range 0-72). To assess change a smallest detectable difference (SDD) was estimated for data on a quasi-interval scale. RESULTS: The SI scoring methods showed intra and interobserver kappa between 0.36 and 0.70. The BASRI-hip reached kappa between 0.59 and 0.84. Combined SASSS scores were most reliable, with intra and interobserver intraclass correlation coefficients (ICC) between 0.90 and 0.96. The ICC of the combined BASRI scores were also very good, ranging from 0.85 to 0.95. For SI New York, SI SASSS, and BASRI-hip, 0.3-1.2% of patients deteriorated 1 grade; 7.5% deteriorated 1 grade (6.3% of maximum score) in BASRI-spine and BASRI-total, and observers agreed in up to 48% of the cases that no change occurred. The SDD was lowest (7.5; 10% of maximum score) for "modified" SASSS. Only 0.8% of patients deteriorated more than the SDD and observers agreed in up to 92% of the cases that no change occurred. CONCLUSION: Radiological scoring methods for AS are moderately to excellently reliable. Under the selected scoring conditions (concealed time order, average of 2 observers, SDD based on interobserver data, unselected patient population) there was too little change over 2 years to be detected reliably by the scoring methods.

Adolescent↗

Measurement of spinal mobility in ankylosing spondylitis: comparison of occiput-to-wall and tragus-to-wall distance.

OBJECTIVE: To investigate if the tragus-to-wall distance (TWD) is more reliable compared to the occiput-to-wall distance (OWD) as a measurement for thoracic spine extension in patients with ankylosing spondylitis (AS). METHODS: Data from the OASIS cohort, an international longitudinal observational study on outcome in AS, were used. Measurements of OWD and TWD were performed at baseline and at 6, 12, 18, and 24 months. Paired data of Tx and Tx+6 months were used to perform test-retest measurements (intraclass correlations, limits of agreement, and interperiod correlation matrix). Bland and Altman plots were constructed to investigate the agreement between both observations, assuming that there was no true change between 0 and 6 months. To investigate whether a change in disease activity would have influenced the results, limits of agreement were calculated in a subgroup of patients with a stable Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; defined as a maximum BASDAI change of +/- 1) between T0 and T6 and compared with the results of the whole group. Limits of agreement were also calculated for kyphosed patients only. RESULTS: The test-retest intraclass correlations were between 0.94 and 0.96 for OWD and between 0.93 and 0.95 for TWD. The direct measurement-remeasurement correlation calculated by extrapolation of the interperiod correlation regression line was 0.92 for OWD and 0.90 for TWD. OWD and TWD showed comparable reliability on the entire value of scores. The lower 95% limit of agreement was between -3.4 cm and -2.5 cm for OWD and between -3.4 cm and -3.1 cm for TWD. The upper limit of agreement was between 3.1 cm and 4.2 cm for OWD and between 2.9 cm and 3.9 cm for TWD. In all patients as well as in kyphosed patients only, limits of agreement were comparable between OWD and TWD. The patterns of the scatterplots according to Bland and Altman were similar for OWD and TWD. Measurement error was more pronounced in kyphosed patients compared to patients with a normal thoracic extension. However, over the entire range of kyphosis, measurement error was similar. CONCLUSION: OWD and TWD are equally reliable in assessing thoracic spine extension. Although the TWD is in general easier to perform in AS patients compared to OWD, we recommend the OWD measurement over TWD: in OWD measurement a value of zero easily distinguishes patients with normal thoracic spine extension from kyphosed patients.

Adult↗

Clinical vertebral fractures in patients with ankylosing spondylitis.

OBJECTIVE: To evaluate the prevalence and characteristics of clinically confirmed vertebral fractures (CVF) in patients with ankylosing spondylitis (AS). METHODS: Coordinated by the Ankylosing Spondylitis International Federation in Germany and in Denmark, a self-administered questionnaire was sent to all their members about age, diagnosis, disease duration, HLA-B27 status, and history of CVF. Patients who were aware of having had a CVF were asked to return the questionnaire with additional specification of the location of CVF, associated trauma, neurological complications, therapy for these complications, and recovery. We also reviewed available radiographs. RESULTS: Out of 15,097 questionnaires, 59 patients (0.4%) reporting 66 CVF returned the complete questionnaire (46 men, 13 women). Mean age at fracture was 50 +/- 9 years, after a mean duration of symptoms of 26 +/- 11 years. CVF with wedging or crush or transverse fracture were reported in the cervical (n = 21, 36%), thoracic (n = 21, 36%), and lumbar spine (n = 16, 27%), with one unspecified. In 37 fractures (56%), patients reported no/low or medium trauma in relation to the fracture. In 31 fractures (47%), patients reported neurological complications, occurring mostly without trauma (n = 11, 35%) or after minimal trauma (n = 7, 23%). Twenty (65%) of these patients did not have full neurological recovery. CONCLUSION: We found that 0.4% of patients with AS reported CVF at a mean age of 50 years, occurring after 2 decades of disease, mainly without trauma or after minimal trauma, with frequent neurological complications mostly followed by incomplete neurological recovery.

Adult↗

Patient compliance in rheumatoid arthritis, polymyalgia rheumatica, and gout.

OBJECTIVE: (1) To explore patient compliance with prescribed drug regimens in the setting of usual care for outpatients with rheumatoid arthritis (RA), gout, and polymyalgia rheumatica (PMR) by utilizing electronic medication event monitors (MEMS(R)) to register openings of the medication package. (2) To examine the influence of disease, frequency of intake of the drug, and class of drug on compliance. (3) To explore the influence of demographic factors, quality of life measures, coping, health status, and functional ability as potential predictors of patient compliance. METHODS: A total of 127 consenting consecutive patients were enrolled: 81 patients with RA, 33 taking nonsteroidal antiinflammatory drugs (13 diclofenac TID and 20 naproxen BID) and 48 taking disease modifying antirheumatic drugs [25 sulfasalazine (SSZ) BID and 23 methotrexate (MTX) once weekly]; 17 patients with PMR starting with prednisolone QD; and 29 patients with gout starting with colchicine (12, QD) or starting with uric acid lowering agents (17, QD). All patients received first prescriptions and were instructed to take the medication as prescribed. Followup was 6 months (gout 12 mo). All patients were aware of the monitoring capability of the package. At baseline a series of questionnaires was completed. We summarized the dosing histories as "taking compliance" (percentage of total prescribed doses taken), "correct dosing" (percentage of doses taken as prescribed), and "timing compliance" (percentage of doses taken within +/- 25% of prescribed interdose intervals). RESULTS: A total of 26,685 days (> 73 patient-years) were monitored. Compliance expressed as "taking compliance," mean (95% CI), "correct dosing," mean (95% CI), and "timing compliance," mean (95% CI) are: naproxen: 82% (75-90), 68% (57-80), 48% (34-61); diclofenac: 77% (61-93), 67% (47-87), 39% (21-57); MTX: 107% (98-117), 81% (75-87), 83% (76-90); SSZ: 72% (60-84), 55% (44-67), 25% (18-33); prednisolone: 96% (89-102), 88% (83-92), 82% (74-89); colchicine: 65% (48-81), 44% (26-62), 32% (18-46); and uric acid lowering agents: 84% (76-92), 74% (63-85), 65% (52-79). Missed doses occurred more frequently than taking of extra doses: in RA, on 10% of all monitored days there was no evidence of dosing, while on 3% of all monitored days extra doses were taken. In PMR and gout these data are 10% and 4%, and 15% and 7%, respectively. We observed a decline of compliance over time in all study medication groups. Multiple regression analyses showed that the class of medication (symptom modifying or disease controlling), the dosing frequency, the patient's sex, coping pattern (avoidance, passive reaction pattern, and expression of emotions), and the overall health (total Nottingham Health Profile score) together explained 67% of the variance in taking compliance (adjusted R2) (p = 0.002). CONCLUSION: Studying patient compliance with prescribed drug regimens utilizing electronic medication event monitors in RA, gout, and PMR showed that large differences exist in compliance between the various medication groups. Compliance declines over time. A regression model shows that it is possible to relate differences in patient compliance to a number of medication and patient related factors.

Activities of Daily Living↗

Factors associated with body function and disability in patients with ankylosing spondylitis: a cross-sectional study.

OBJECTIVE: To determine for patients with ankylosing spondylitis (AS) which factors are associated with disability and restricted body function. METHODS: In 1538 patients with AS, occiput-to-wall distance, chest expansion, cervical rotation, finger-floor distance, and modified Schober test were measured cross-sectionally, and for each measure the patient's respective percentile was calculated. The mean of the 5 percentiles was summarized in the mobility restriction score (MRS). In addition, patients answered questions on disease progression and completed the Bath AS Functional Index (BASFI) questionnaire. All data were coded into 40 variables, used as independent variables in multiple regression analyses to identify factors associated with BASFI and MRS. RESULTS: Finger-to-floor distance (beta positive, +), cervical rotation (-), time since first AS symptoms (-), age (+), height loss (+), maximum height (-), delay in diagnosis (+), hip replacement (+), regular practice of sports (-), chest expansion (-), sex (worse BASFI in females), exposure to cold and dampness (+), and regular participation in AS group physical exercises (+) were significantly associated with worse BASFI. Significantly associated factors for worse MRS were height loss (+), sex (higher MRS in males), active inflammation of the cervical region (+), age (+), maximum height (-), active inflammation of the hip region (+), involvement of shoulders (+), time since first AS symptoms (+), urethritis (-), regular practice of sports (-), involvement of feet (-), and hip replacement (+). The models explain 47% of the variance observed for both the BASFI and MRS. CONCLUSION: The amount of variance explained for both BASFI and MRS is rather high. The results apply primarily to groups of patients, but are insufficient to guide clinical decisions in individual patients. These findings contribute to our understanding of factors influencing disability and restriction in body function in AS.

Adolescent↗

The compliance-questionnaire-rheumatology compared with electronic medication event monitoring: a validation study.

OBJECTIVE: To validate the 19-item Compliance-Questionnaire-Rheumatology (CQR) against the "gold standard" in compliance measurement, electronic medication event monitoring. METHODS: Among 127 consenting patients, 81 with rheumatoid arthritis taking nonsteroidal antiinflammatory drugs (13 diclofenac, 20 naproxen) or disease modifying antirheumatic drugs (25 sulfasalazine, 23 methotrexate), 17 patients with polymyalgia rheumatica taking prednisone, and 29 patients with gout taking daily prophylactic colchicine (n = 12) or the uric acid lowering drugs allopurinol (10) or benzbromaron (7), 104 used their medication from a regular medication bottle fitted with a special cap containing microelectronics capable of recording time and date of opening and closing, defined as a medication event. Data were processed for the following: (1) the percentage of prescribed medication events during the study period (taking compliance) and (2) the percentage of days with the prescribed number of medication events (i.e., correct dosing). Satisfactory compliance was defined as taking compliance or correct dosing > 80%, while unsatisfactory compliance was defined as taking compliance or correct dosing < or = 80%. All patients were informed about the monitoring, and were followed for 6 months (gout: 1 year). At baseline 85 patients completed a set of questionnaires including the 19-item CQR. RESULTS: A total of 85 patients who had complete questionnaire and electronic monitoring data were analyzed. Multiple linear regression analyses showed that the total, weighted CQR score significantly and adequately predicts taking compliance (p = 0.001, r2 = 0.46) and correct dosing (p = 0.004, r2 = 0.42). Discriminant analyses showed that specificity and sensitivity to detect good taking compliance were 95% and 62%, respectively, with a prevalence of good compliance of 52%. The predictive value to detect unsatisfactory taking compliance was 86%, and to detect good taking compliance was 83%. The likelihood ratio of the CQR-19 to detect low taking compliance was 11.6. Four items were especially predictive: fear of forgetting to take the drug, being able to function well, routines in daily life, and side effects (combined r2 = 0.35). CONCLUSION: These results support the validity of the Compliance Questionnaire Rheumatology.

Aged↗

Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis.

OBJECTIVE: To investigate differences between HLA-B27(-) and HLA-B27(+) patients with ankylosing spondylitis (AS). METHODS: A total of 1080 patients with AS responded to a questionnaire containing 30 questions; 945 (87.5%) knew their HLA-B27 status, 10% of them being B27(-). RESULTS: The average age at disease onset was 27.7 years in B27(-) and 24.8 years in B27(+) AS (P < 0.01). The average age at diagnosis was 39.1 and 33.2 years and the average diagnosis delay 11.4 and 8.5 years, respectively. The distribution in age at disease onset was significantly wider in B27(-) (standard deviation 10.0 years) than in B27(+) AS (8.3 years). The percentages with childhood (age < 16 years) disease onset did not differ significantly (7.6% vs. 6.2%, respectively), whereas the percentage of late onset (age > 40 years) was significantly greater among B27(-) (13%) than among B27(+) (5%) patients with AS. There is a difference in average age at disease onset between male (25.7 years) and female (24.2 years) AS patients, and no difference between patients with primary AS and AS associated with psoriasis, inflammatory bowel disease, or reactive arthritis. Acute anterior uveitis was significantly less frequent in B27(-) (26%) than in B27(+) (41%) patients with AS. CONCLUSIONS. This study of a much larger number of B27(-) AS patients than have been studied previously confirms earlier reports indicating a significantly older average age at disease onset and a less frequent prevalence of acute anterior uveitis in B27(-) than in B27(+) AS. The frequency of late disease onset (after 40 years of age) is significantly higher in B27(-) AS. We provide the first report on significant differences in the distribution curves for the age at disease onset and for the age at diagnosis between B27(-)and B27(+) patients with AS. The average delay between the first spondyloarthritic symptoms and the diagnosis is significantly longer in B27(-) than in B27(+) AS. The frequency of juvenile disease onset (before age 16 years) is nearly the same, irrespective of the B27 status.

Acute Disease↗