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We read with great interest the article by Niv Ben-Shabat et al. in Arthritis Care and Research titled "Mortality in ankylosing spondylitis according to treatment: a nationwide retrospective cohort study of 5900 patients from Israel" (1). The study concludes that ankylosing spondylitis (AS) is associated with reduced life expectancy, but not amongst the small subgroup of AS patients treated with TNF-inhibitors. We have concerns regarding the study design and analyses that underpin these findings.

The axial spondyloarthritis (axSpA) disease concept has undergone substantial change from when the entity ankylosing spondylitis was defined by the modified New York criteria in 1984. Developments in imaging, therapy and genetics have all contributed to changing the concept of axSpA from one of erosions in the sacroiliac joints to a spectrum of disease with and without changes evident on plain radiographs. Changes to the previously held concept and construct of the disease have also necessitated new classification criteria. The use of MRI, primarily of the sacroiliac joints, has substantially altered the diagnosis and differential diagnosis of axSpA. Many in the axSpA community believe that the current classification criteria lack specificity, and the CLASSIC study is underway to examine this area. Although much about the evolving axSpA disease concept is universally agreed, there remains disagreement about operationalizing aspects of it, such as the requirement for the objective demonstration of axial inflammation for the classification of axSpA. New imaging technologies, biomarkers and genetics data will probably necessitate ongoing revision of axSpA classification criteria. Advances in our knowledge of the biology of axSpA will settle some differences in opinion as to how the disease concept is applied to the classification and diagnosis of patients.

Objective:Arterial stiffness may be a mechanism to explain the association between uric acid and cardiovascular disease. We aimed to analyse associations between serum uric acid and regional and local arterial stiffness, and assess potential differences related to sex and glucose metabolism status.Methods:A cross-sectional study was performed in 614 adults [52.6% men; mean age 58.7 +/- 8.5 years; 23.2% type 2 diabetes mellitus (by design)] from The Maastricht Study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), distensibility, and compliance coefficient of the carotid and femoral artery, and carotid artery Young's elastic modulus.Results:Higher uric acid (per SD of 74 mu mol/l) was associated with greater stiffness indicated by a significantly higher cfPWV [beta = 0.216 (95% confidence interval 0.061, 0.372); P = 0.006] and lower carotid distensibility coefficient [beta = -0.633 (95% confidence interval -1.099, -0.166); P = 0.008] after adjustment for sex, age, and glucose metabolism status. Associations lost significance after adjusting for mean arterial pressure, BMI, waist, smoking status, heart rate, total : high-density lipoprotein cholesterol ratio, triglycerides, estimated glomerular filtration rate, use of lipid-lowering, antihypertensive, and diabetes medication, and use of secondary uricosurics. No associations were found between uric acid and carotid compliance coefficient, carotid Young's elastic modulus, or stiffness of the femoral artery. A significant interaction (P Conclusion:Uric acid was not significantly associated with stiffness of the aorta, or the carotid or femoral artery among adults aged 40-75 years without and with type 2 diabetes mellitus.

Objective.To estimate costs of illness in a cross-sectional cohort of patients with gout attending an outpatient rheumatology clinic, and to evaluate which factors contribute to higher costs.Methods.Altogether, 126 patients with gout were clinically assessed. They completed a series of questionnaires. Health resource use was collected using a self-report questionnaire that was cross-checked with the electronic patient file. Productivity loss was assessed by the Work Productivity and Activity Impairment Questionnaire, addressing absenteeism and presenteeism. Resource use and productivity loss were valued by real costs, and annual costs per patient were calculated. Factors contributing to incurring costs above the median were explored using logistic univariable and multivariable regression analysis.Results.Mean (median) annual direct costs of gout were €5647 (€1148) per patient. Total costs increased to €6914 (€1279) or €10,894 (€1840) per patient per year when adding cost for absenteeism or both absenteeism and presenteeism, respectively. Factors independently associated with high direct and high indirect costs were a positive history of cardiovascular disease, functional limitations, and female sex. In addition, pain, gout concerns, and unmet gout treatment needs were associated with high direct costs.Conclusion.The direct and indirect costs-of-illness of gout are primarily associated with cardiovascular disease, functional limitations, and female sex.

Objective: Microvascular dysfunction has been suggested as a possible underlying mechanism for the association between uric acid and various diseases, such as hypertension, renal disease and cardiomyopathies. We therefore analysed the association between serum uric acid and skin microvascular function, a model of generalized microvascular function. Methods: A cross-sectional study was performed in 610 individuals [51.8% men; mean age 58.7 +/- 8.6 years; 23.6% with type 2 diabetes (by design)] from The Maastricht Study. We assessed skin capillary density (capillaries/mm(2)) by capillaroscopy at baseline, after 4 min of arterial occlusion, and after 2 min of venous congestion. Capillary recruitment after arterial occlusion and during venous congestion was expressed as the absolute change in capillary density after recruitment and as the percentage change in capillary density from baseline. Results: Crude linear regression analyses showed that serum uric acid [per +1 standard deviation (SD) of 74 mu mol/l] was not associated with baseline capillary density [beta = -0.21 (95% confidence interval, 95% CI -1.61 to 1.19) P = 0.765], while an inverse association was found between uric acid and absolute change in capillary density after arterial occlusion [beta = -1.15 (95% CI -2.36 to 0.06) P = 0.062] and during venous congestion [beta = -1.41 (95% CI -2.68 to -0.14) P = 0.029]. However, after adjustment for sex, age and glucose metabolism status, these associations were no longer statistically significant. In addition, we found no association between uric acid and percentage capillary recruitment after arterial occlusion [beta = -1.66 (95% CI -3.97 to 0.65) P = 0.159] or during venous congestion [beta = -2.02 (95% CI -4.46 to 0.42) P = 0.104] in unadjusted analyses; multivariable analyses gave similar results. Conclusion: These results do not support the hypothesis that generalized microvascular dysfunction (as estimated in skin microcirculation) is the underlying mechanism for the association between uric acid and cardiovascular and renal diseases. The possibility that uric acid is associated with microvascular dysfunction in specific end-organs, for example heart or kidney, needs further investigation.

BackgroundPhysical functioning can be assessed by different approaches that are characterized by increasing levels of individual appraisal. There is insufficient insight into which approach is the most informative in patients with ankylosing spondylitis (AS) compared with control subjects.ObjectiveThe objective of this study was to compare patients with AS and control subjects regarding 3 approaches of functioning: experienced ability to perform activities (Bath Ankylosing Spondylitis Functional Index [BASFI]), self-reported amount of physical activity (PA) (Baecke questionnaire), and the objectively measured amount of PA (triaxial accelerometer).MethodsThis case-control study included 24 AS patients and 24 control subjects (matched for age, gender, and body mass index). Subjects completed the BASFI and Baecke questionnaire and wore a triaxial accelerometer. Subjects also completed other self-reported measures on disease activity (Bath AS Disease Activity Index), fatigue (Multidimensional Fatigue Inventory), and overall health (EuroQol visual analog scale).ResultsBoth groups included 14 men (58%), and the mean age was 48 years. Patients scored significantly worse on the BASFI (3.9 vs 0.2) than their healthy peers, whereas PA assessed by Baecke and the accelerometer did not differ between groups. Correlations between approaches of physical functioning were low to moderate. Bath Ankylosing Spondylitis Functional Index was associated with disease activity (r = 0.49) and physical fatigue (0.73) and Baecke with physical and activity related fatigue (r = 0.54 and r = 0.54), but total PA assessed by accelerometer was not associated with any of these experience-based health outcomes.ConclusionsDifferent approaches of the concept physical functioning in patients with AS provide different information. Compared with matched control subjects, patients with AS report more difficulties but report and objectively perform the same amount of PA.

Objectives. The aims of this study were to investigate (i) associations between uric acid and prevalent cardiovascular disease (CVD), ankle-arm blood pressure index (AAIx) and carotid intima-media thickness (CIMT) in the total population and in predefined subgroups according to glucose metabolism status and (ii) the extent to which these associations are explained by low-grade inflammation.Methods. Cross-sectional analyses were conducted among 530 individuals [60.6% men, mean age 58.9 years (S. D. 6.9), 52.6% normal glucose metabolism (NGM)] at increased risk of CVD from the Cohort of Diabetes and Atherosclerosis Maastricht study. A low-grade inflammation score was computed by averaging the z-scores of eight inflammation markers [CRP, TNF-alpha, IL-6, IL-8, serum amyloid A, intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin].Results. After adjustment for traditional CVD risk factors, plasma uric acid (per S. D. of 81 mu mol/l) was associated with CVD in individuals with NGM [odds ratio (OR) = 1.66, 95% CI 1.06, 2.58] but not with disturbed glucose metabolism (DGM) (OR = 0.81, 95% CI 0.55, 1.19, P interaction = 0.165). Uric acid was associated with CIMT in the total population (beta = 0.024, 95% CI 0.007, 0.042) and slightly more strongly in individuals with NGM (beta = 0.030, 95% CI 0.006, 0.054) than DGM (beta = 0.018, 95% CI -0.009, 0.044, P interaction = 0.443). There was no association between uric acid and AAIx in any group (P interaction = 0.058). Uric acid was associated with low-grade inflammation in the total population (beta = 0.074, 95% CI 0.013, 0.134, P interaction = 0.737). Adding low-grade inflammation to the models did not attenuate any of the associations.Conclusion. The associations for uric acid with CIMT, and with CVD in NGM only, were not explained by low-grade inflammation. A difference in the strength of the associations between individuals with NGM and DGM was suggested.

Objective.To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS).Methods.A 96-week open-label extension study, which followed a 12-week double-blind placebo-controlled trial, was designed to provide longterm efficacy and safety data, including radiographic outcomes, for patients treated with etanercept 25 mg twice weekly (NCT00421980). In all, 81 patients were enrolled (96% of the participants from the double-blind study). Key efficacy measures included improvement using the Assessment in Ankylosing Spondylitis 20% (ASAS20) criteria, the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) method. Paired t tests were used to test within-group changes from baseline.Results.The percentage of responders, by ASAS20 criteria, remained relatively constant in patients who received etanercept during the 12-week double-blind study (60% at Week 0 and 83% at Week 96 of the open-label extension); more patients from the placebo group became responders after being switched to etanercept (23% and 74%, respectively). A similar trend was also observed using the ASAS40 and ASAS5/6 criteria, the BASFI, and the BASDAI. Most patients had no change from baseline in mSASSS values. Etanercept was well tolerated; the most frequent adverse events were injection site reactions (n = 30; 37.0%) and headache (n = 18; 22.2%), and the most frequent infections were upper respiratory tract infections (n = 43; 53.1%) and flu syndrome (n = 22; 27.2%).Conclusion.For 2 years, etanercept was clinically effective and well tolerated, with no unexpected safety findings.

The primary aim of the management of ankylosing spondylitis (AS) is symptomatic relief and prevention of structural changes and functional decline by both pharmaceutical and non-pharmaceutical interventions. NSAIDs are frequently used, but often have adverse effects or may not be effective enough to alleviate complaints. NSAIDs and Coxibs provide comparable symptomatic relief. It has now become clear, however, that these drugs are also associated with increased cardiovascular risk, probably due to imbalance between Cox-1- and Cox-2-inhibition. Limited evidence suggests that continuous use of NSAIDs may retard progression of axial structural changes as compared to 'on-demand' usage of these drugs. A critical appraisal of a recent paper on this topic indicates that more evidence is needed before continuous use of NSAIDs or Coxibs can be recommended taking also into consideration the increase cardiovascular risks of these drugs.

Aim: Ankylosing spondylitis (AS) is a chronic systemic inflammatory rheumatic disorder that primarily affects the axial skeleton. To date there is no satisfactory biomarker for diagnosis or prognosis of AS. This study is focused on detection of potential biomarkers for the diagnosis of AS using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with the ultimate goal of developing a progression biomarker for AS. Materials & methods: Protein profiles of sera of 38 AS patients and 38 healthy controls were obtained using ProteinChip arrays. Different arrays and conditions were compared with find out which condition resulted in the optimal discrimination of both groups. Results: Optimal discrimination was reached using weak cation exchange (CM10) and immobilized metal affinity capture coupled with copper (IMAC-Cu2+) arrays. Using a multimarker approach on protein profiles obtained with CM10 arrays resulted in a sensitivity of 66% and a specificity of 74%. Using a multimarker approach on protein profiles obtained with IMAC-Cu2+ arrays resulted in a sensitivity and specificity of 70%. Conclusions: This is the first study that shows that protein profiling in serum using SELDI-TOF-MS can be used as a diagnostic tool for AS. The biomarkers will be validated to confirm if they can be used as progression biomarkers.

Contains fulltext : 170857.pdf (Publisher’s version ) (Open Access) The objective of the present study is to explore knowledge, illness perceptions and stated practice behaviour in relation to gout in primary care. This is a mixed methods study among 32 general practitioners (GPs). The quantitative assessment included the Gout Knowledge Questionnaire (GKQ; range 0-10; better) and Brief Illness Perceptions Questionnaire (BIPQ; nine items, range 0-10; stronger). Structured individual interviews obtained further qualitative insight into knowledge and perceptions, in the context of daily practice. Among 32 GPs, 18 (56.3 %) were male, mean age 44.4 years (SD 9.6) and mean working experience 17.1 years (SD 9.7). Median score [interquartile ranges (IQR)] on the GKQ was 7.8 [6.7-8.9] and 9.0 [8.0-10.0], when presented as open or multiple-choice questions, respectively. The BIPQ (median; [IQR]) revealed that gout was seen as a chronic disease (8.0; [7.0-9.0]), affecting life and emotions moderately (6.5; [5.0-7.0]), having many severe symptoms (8.0; [7.0-9.0]) and in which treatment could be very helpful (8.0; [7.0-9.0]). Further interviews revealed large variation in specific aspects of knowledge and about gaps concerning indications for uric acid-lowering therapy (UALT), duration of UALT, target serum uric acid (sUA) level or duration of prophylactic treatment. Finally, patients' adherence was not checked systematically. Specific knowledge gaps and discrepancies between perceptions and stated practice behaviour were identified, which might hamper effective management of this well-treatable disease. Improving evidence on the rationale and effectiveness of treatment targets and adherence interventions, tailoring guidelines to general practice and intensification of implementation of guidelines in primary health care seem to be needed.

Classification criteria should facilitate selection of similar patients for clinical and epidemiologic studies, therapeutic trials, and research on etiopathogenesis to enable comparison of results across studies from different centers. We critically appraise the validity and performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). It is still debatable whether all patients fulfilling these criteria should be considered as having true axSpA. Patients with radiographically evident disease by the ASAS criteria are not necessarily identical with ankylosing spondylitis (AS) as classified by the modified New York criteria. The complex multi-arm selection design of the ASAS criteria induces considerable heterogeneity among patients so classified, and applying them in settings with a low prevalence of axial spondyloarthritis (SpA) greatly increases the proportion of subjects falsely classified as suffering from axial SpA. One of the unmet needs in non-radiographic form of axial SpA is to have reliable markers that can identify individuals at risk for progression to AS and thereby facilitate early intervention trials designed to prevent such progression. We suggest needed improvements of the ASAS criteria for axSpA, as all criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances.

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, time2 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 time2 −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.

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 Reumatoide 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 (β = 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 (

The longer you can look back, the better you can look forward—Sir Winston ChurchillObjectives: 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.

To investigate differences between HLA-B27(-) and HLA-B27(+) patients with ankylosing spondylitis (AS).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(-).The average age at disease onset was 27.7 years in B27(-) and 24.8 years in B27(+) AS (P0.01). 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 (age16 years) disease onset did not differ significantly (7.6% vs. 6.2%, respectively), whereas the percentage of late onset (age40 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.

Epidemiological studies on the spondyloarthritides have been hindered in the past by the lack of adequate classification criteria for the whole group of these diseases. Using the Amor and the European Spondyloathropathy Study Group (ESSG) criteria the total prevalence of such diseases has been found to be higher than estimated in the past. The prevalence of ankylosing spondylitis varies across populations, but closely parallels the frequency of HLA B27-associated subtypes. The lack of well established criteria for reactive arthritis and the varying expression of its clinical manifestations are the principal reasons for the under-reporting of the true prevalence and incidence of this type of spondyloarthritis. Few data exist on the prevalence and incidence of psoriatic arthritis. A recent European study on an inception cohort of patients having inflammatory bowel disease has evaluated the prevalence of spondyloarthritis using the ESSG criteria. Of the patients studied, 18% met these criteria. Undifferentiated spondyloarthritis is one of the most frequent spondyloarthritides. It also includes a number of different subtypes.

Objective The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA. Methods This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumatoide Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers). Results In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score ≥4, n = 49) and absence (Sharp score

Objective To evaluate the cost effectiveness and cost utility of a 3-week course of combined spa therapy and exercise therapy in addition to standard treatment consisting of antiinflammatory drugs and weekly group physical therapy in ankylosing spondylitis (AS) patients. Methods A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 was treated in a spa resort in Bad Hofgastein, Austria; group 2 in a spa resort in Arcen, The Netherlands. The control group stayed at home and continued their usual activities and standard treatment during the intervention weeks. After the intervention, all patients followed weekly group physical therapy. The total study period was 40 weeks. Effectiveness of the intervention was assessed by functional ability using the Bath Ankylosing Spondylitis Function Index (BASFI). Utilities were measured with the EuroQoL (EQ-5Dutility). A time-integrated summary score defined the clinical effects (BASFI-area under the curve [AUC]) and utilities (EQ-5Dutility-AUC) over time. Both direct (health care and non-health care) and indirect costs were included. Resource utilization and absence from work were registered weekly by the patients in a diary. All costs were calculated from a societal perspective. Results A total of 111 patients completed the diary. The between-group difference for the BASFI-AUC was 1.0 (95% confidence interval [95% CI] 0.4–1.6; P = 0.001) for group 1 versus controls, and 0.6 (95% CI 0.1–1.1; P = 0.020) for group 2 versus controls. The between-group difference for EQ-5Dutility-AUC was 0.17 (95% CI 0.09–0.25; P < 0.001) for group 1 versus controls, and 0.08 (95% CI 0.00–0.15; P = 0.04) for group 2 versus controls. The mean total costs per patient (including costs for spa therapy) in Euros (€) during the study period were €3,023 for group 1, €3,240 for group 2, and €1,754 for the control group. The incremental cost-effectiveness ratio per unit effect gained in functional ability (0–10 scale) was €1,269 (95% CI 497–3,316) for group 1, and €2,477 (95% CI 601–12,098) for group 2. The costs per quality-adjusted life year gained were €7,465 (95% CI 3,294–14,686) for group 1, and €18,575 (95% CI 3,678–114,257) for group 2. Conclusion Combined spa–exercise therapy besides standard treatment with drugs and weekly group physical therapy is more effective and shows favorable cost-effectiveness and cost-utility ratios compared with standard treatment alone in patients with AS.

Background The reproducibility of authentic assessment methods has been investigated for objective structured clinical examinations (OSCEs) and video assessment in general practice, but not for assessment with incognito standardized patients. Purpose To investigate the reproducibility of assessment with incognito standardized patients. Methods A total of 27 Dutch rheumatologists in 16 hospitals were each visited by 8 incognito standardized patients presenting with different rheumatological disorders. After each visit, the standardized patient completed a case-specific checklist containing items on medical history, physical examination and management. Over a 20-month period, 254 incognito visits took place, of which 201 were first visits. The standardized patient was detected by the rheumatologist in 2 cases only. These encounters were not included in the analysis. Generalizability theory was used to investigate the reproducibility of the assessment. Results One fifth of the variance can be attributed to variation between rheumatologists. The largest variance is due to the variation in difficulty among cases. A reproducible assessment requires 3 hours of testing time (6 cases) if it is obtained through a normreferenced interpretation of scores and 7 hours of testing time (14 cases) if it is obtained through an absolute interpretation of scores. Conclusion The reproducibility of performance assessment in clinical practice by incognito standardized patients is similar to that of other authentic measurements for the assessment of clinical competence and performance.

Objective: To determine whether the Bath Ankylosing Spondylitis Functional Index (BASFI) is applicable in older patients with ankylosing spondylitis and whether it shows major differences between younger and older patients with ankylosing spondylitis. Design: BASFI total scores and every BASFI item of 202 patients with ankylosing spondylitis aged ≥60 yr (group A) and 267 patients with ankylosing spondylitis aged ≤40 yr (group B) were calculated. The results were compared with the results of the Health Assessment Questionnaire for the Spondyloarthropathies. Results: The BASFI scores had a median of 4.2 in group A and 2.6 in group B. Marked differences between the age groups were found for every item of the BASFI. Internal consistency was high in both groups. The Spearman correlation coefficient between BASFI and the Health Assessment Questionnaire for the Spondyloarthropathies was r s(A) = 0.83 in group A and r s(B) = 0.78 in group B. Conclusion: The data suggest that the BASFI is also applicable to older patients experiencing AS. There is a significant difference in the BASFI score between younger and older patients with ankylosing spondylitis.

Objective To assess the minimal clinically important difference (MCID) in joint damage on hand and foot radiographs of patients with early rheumatoid arthritis (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to study how the smallest detectable difference (SDD) relates to the MCID for each method. Methods The judgments of an international panel of experts on the clinical relevance of progression of joint damage as seen on sets of radiographs obtained at 1-year intervals in 4 clinical settings (early versus late RA and mild versus high disease activity) were used as the external criterion, which was compared with the progression scores as determined by the 2 scoring methods. Progression scores with the highest combined sensitivity and specificity for detecting clinically relevant progression represented the MCID. Subsequently, the sensitivity and specificity of the scoring methods were determined when using the SDD as the threshold for relevant progression, and these were compared with the sensitivity and specificity of the MCID. Results The panel judged changes in joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method as minimal clinically important, resulting in satisfactory sensitivity (mean 79%) and specificity (mean 84%) for detecting clinically important progression in the 4 clinical settings when using the SDD as the threshold value. The MCID (mean 2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the sensitivity for detecting clinically important progression by applying the SDD as threshold was consequently low (mean 51%), accompanied by high specificity (mean 99%). Conclusion This study suggests that the SDD of the Sharp/van der Heijde method can be used as the MCID, i.e., as the threshold level for individual response criteria. The SDD of the Larsen/Scott method, however, turned out to be too insensitive to use as the threshold for individual clinically relevant change.

Objective The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome. Methods All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline). Results At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4–5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28. Conclusion An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.

Objectives. To investigate whether the single-item fatigue question of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Multidimensional Fatigue Inventory (MFI) are appropriate instruments to measure fatigue in ankylosing spondylitis (AS); to identify factors that influence fatigue in AS; and to assess how fatigue in all its aspects is associated with quality of life in AS. Methods. A total of 812 patients with AS were included. Patients completed questionnaires on disease activity (BASDAI), functional ability (Bath Ankylosing Spondylitis Functional Index [BASFI]), global well-being (Bath Ankylosing Spondylitis Global Score [BAS-G]), overall perceived health (EuroQoL visual analog scale), and quality of life (Ankylosing Spondylitis Quality of Life questionnaire, and Short Form 36 [SF-36]). Patients were dichotomized into a F+ group (fatigue = major symptom) if the BASDAI fatigue score was > 5.0 and a F- group (fatigue = minor symptom) if the fatigue score was < 5.0. Reproducibility was assessed with intraclass correlation coefficients, and responsiveness was calculated according to 3 different methods. Logistic regression analysis was used to determine which factors were associated with fatigue. Multiple regression analysis was used to investigate whether fatigue contributes in explaining quality of life. Results. Fifty-three percent of the patients were assigned to the F+ group. They scored significantly worse compared with the F- group with respect to each dimension of the MFI and to all other questionnaires studied (all P < 0.001). The BASDAI fatigue question, as well as each separate dimension of the MFI, showed moderate to good reproducibility (0.57-0.75) and responsiveness (0.23-0.96). Fatigue was, in the opinion of the patients, highly associated with pain (70% of patients) and stiffness (54% of patients). Logistic regression analysis showed that scores on BASDAI, BASFI, BAS-G, and mental health status (SF-36) were independently associated with fatigue (R2 = 0.52). Multiple regression analysis showed that scores on the BASDAI fatigue question were significantly associated with quality of life. With the 5 MFI dimensions as explanatory variables, different aspects of fatigue were associated with different domains of quality of life. Conclusion. Fatigue as a major symptom of AS can effectively be measured with either a single-item question on the intensity of fatigue or with the MFI. The MFI, however, provides more insight into specific dimensions of fatigue. Fatigue appears to be associated with the level of disease activity, functional ability, global well-being, and mental health status. In addition, fatigue negatively influences different aspects of quality of life.

Objective Several factors predict joint damage in early rheumatoid arthritis (RA). In the context of a trial in early RA, we studied the relationship between clinical signs in individual joints and their propensity to develop progressive damage. Methods The COBRA (Combinatietherapie Bij Reumatoide Artritis) multicenter trial compared the efficacy of prednisolone, methotrexate, and sulfasalazine against sulfasalazine alone in 155 patients with early RA. Two blinded observers interpreted radiographs in sequence (using the Sharp/Van der Heijde scoring system); in each center, one blinded observer performed clinical assessments every 3 months. The current analysis is based on clinical and radiologic data of the individual metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 135 patients. Conditional stepwise logistic regression analyzed the relationship between damage (progression) and clinical signs at baseline and followup for each of these joints individually in each patient. Results Combination therapy strongly retarded the progression of damage. Progression was stronger in patients with rheumatoid factor, HLA–DR4, and high levels of disease activity at baseline. At baseline, 6% of the MCP and PIP joints showed damage; after 1 year, disease had progressed in 10% of these joints. Baseline damage, swelling, or pain in a joint independently and strongly predicted the progression of damage in that joint (P < 0.001). Each additional point in the swelling score (range 0–2) tripled the risk for subsequent progression. Each additional point on the Sharp scale (range 0–8 per joint) and each additional point on the pain scale (range 0–3) doubled the risk. The mean pain and swelling scores over the year were even stronger predictors of damage. Conclusion Local expression of early RA disease activity, both at baseline and at 1-year followup, is strongly related to progression of damage in the individual joint.

Objective Change in a patient's condition is expressed as a percentage of the baseline value for a core set of measures in the American College of Rheumatology (ACR) improvement criteria for rheumatoid arthritis (RA), and this is used as the basis to decide whether a patient has improved. The result is dependent on whether the underlying measure has a score that increases or decreases on improvement. We examined the importance of this effect in the application of the ACR improvement criteria. Methods Data were obtained from the COBRA trial, in which 155 patients with early active RA had been randomized to receive either combination treatment with step-down prednisolone, methotrexate, and sulfasalazine or sulfasalazine alone. Patient and physician global assessments were recoded to reflect decreasing scores on improvement. The effects of this difference in scoring systems were compared among 3 response criteria levels (20%, 50%, and 70%) that are currently being used to assess improvement in RA clinical trials. Results Analyses showed that the effects of a decreasing, versus increasing, score on the designation of improvement cannot be ignored, especially at higher percentages of improvement (e.g., 50%, 70%). Conclusion We recommend that percentage improvement in RA be calculated only on scores that decrease on improvement. When necessary, raw data should be recoded before the ACR improvement criteria are applied.

To review the literature on the methods used in writing case-specific checklists for studies of internal medicine physicians' performances that were assessed by standardized patients.The authors searched Medline, Embase, Psychlit, and ERIC for articles in English published between 1966 and February 1998. The following search string was used: "[(standardi(*) or simulat(*) or programm(*)) near (patient(*) or client(*) or consultati(*))] and internal medicine." The authors then searched the reference lists of papers retrieved from the database searches, as well as those from seven proceedings of the International Ottawa Conference on Medical Education and Assessment.The procedure yielded 29 relevant articles: database searches yielded 14 published reports dealing with case-specific checklists, 11 articles were culled from the reference lists of these papers, and the Ottawa Conference proceedings yielded four articles. Only 12 articles reported specifically on the development of checklists. In general, there were three sources used for developing checklists: panels of experts, the investigators themselves, and responses from expert physicians to written protocols. No article indicated that researchers had relied exclusively on data from the literature to compose their checklists. Only three articles indicated that literature sources had informed their checklist development. All articles except one relied on explicit criteria for the inclusion of items on the checklists. In 21 of the 29 articles, the checklists had been scored by SPs, but the scoring of specific items on the checklists varied according to the purpose of the SP-physician encounter. Only four of the articles made the checklists available or indicated that the checklists could be obtained from the authors.The development of case-specific checklists for SP examinations of physicians' performance has received little attention. To judge the validity of studies of physicians' performances that use SPs, the development processes for the checklists need to be more fully described to enable readers to evaluate the validity and reliability of the studies.

Economic evaluation is attracting increasing attention to inform policy makers, insurers and other payers of the value of existing and new treatment modalities. Hence, it is desirable to assess not only the medical but also the economic consequences the new treatments produce. The available literature on economic evaluation revealed an urgent need for sound economic evaluation studies in the field of chronic musculoskeletal pain. Due to the generally weak methodology, the intended purpose of economic evaluation to help set funding priorities has often been bypassed. Although in general therapists have no direct responsibility for allocating scarce resources in the field of musculoskeletal pain, they are confronted with the results of these decisions in their everyday work. A clear understanding of the main principles of economic evaluation studies might therefore be advantageous. This paper addresses important methodological issues in economic evaluation research, such as the techniques for economic evaluation studies and the analytic perspective. In addition, the paper pays attention to the inclusion of costs and outcomes in economic evaluation research, sensitivity analysis, discounting, incremental analysis and ratios, and collecting of data. Further emphasis is placed on the transparent reporting of methods and study results. A clear reporting may help therapists and other researchers interpret the results of published studies and apply them to their own studies, and it may help decision makers generalize results from one setting to another.

The association between ankylosing spondylitis and human leukocyte antigen (HLA) B27 was reported for the first time in 1973. 34 This finding has stimulated quite a lot of research in many aspects of ankylosing spondylitis. However, the cause of the disease is still largely unknown. It has been postulated that an infectious agent ( possibly Klebsiella), in some way interacting with HLA-B27, may trigger the disease. 17 This theory is analogous to the situation in reactive arthritis or Reiter's syndrome where bowel infection owing to certain Shigella, Salmonella, Yersinia, or Campylobacter strains may cause disease. Also, the association between ankylosing spondylitis and chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis) has stimulated the idea that the causative agent in ankylosing spondylitis might belong to the (ubiquitous) bowel flora. This article briefly reviews the state of the art one quarter of a century later. It focuses on those topics that are most relevant from the clinical point of view.

Studies on the occurrence of gout show a large range in estimates. However, a clear insight into the factors responsible for this variation in estimates is lacking. Therefore, our aim was to review the literature on the prevalence and incidence of gout systematically and to obtain insight into the degree of and factors contributing to the heterogeneity. We searched MEDLINE, EMBASE, and Web of Science (January 1962 to July 2012) to identify primary studies on the prevalence and incidence of gout in the general population. Data were extracted by two persons on sources of clinical heterogeneity, methodological heterogeneity, and variation in outcome reporting. Meta-analysis and meta-regression analysis were performed for the prevalence of gout. Of 1,466 articles screened, 77 articles were included, of which 71 reported the prevalence and 12 the incidence of gout. The pooled prevalence (67 studies; N = 12,226,425) based on a random effects model was 0.6 % (95 % CI 0.4; 0.7), however there was a high level of heterogeneity (I2 = 99.9 %). Results from a mixed-effects meta-regression model indicated that age (p = 0.019), sex (p < 0.001), continent (p < 0.001), response rate (p = 0.016), consistency in data collection (p = 0.002), and case definition (p < 0.001) were significantly associated with gout prevalence and jointly accounted for 88.7 % of the heterogeneity. The incidence in the total population ranged from 0.06 to 2.68 per 1,000 person-years. In conclusion, gout is a common disease and the large variation in the prevalence data on gout is explained by sex, continent on which the study was performed, and the case definition of gout.

Objectives: The goals of this study were to determine the effects of an exercise program on physical fitness and perceived benefits among fibromyalgia syndrome [FMS] patients.Methods: Patients were randomly assigned [ratio 2:1, anticipating dropout] to a fitness intervention [FI, N = 58] group or a nonintervention [NI, N = 27] group. In both groups, physical fitness [maximal power output, muscular strength/endurance, flexibility, coordination] and body composition were measured before and after the six-month observation period. The Fl-group underwent a fitness program two times per week for six months while the NI-group continued their usual activity undirected. Benefits perceived by the Fl-group were assessed six months after finishing the study.Results: The dropout rate among the FI group was lower than expected [45 of 58 completed], while 27 of 29 in the NI-group completed. Despite randomization, completing Fl-group subjects were older than the NI-group [mean ages 47 ± 8 versus 42 ± 8 years]. The NI-gr...

Objectives. The Gout Assessment Questionnaire 2.0 (GAQ2.0) is a disease-specific patient-reported outcome measure for gout that distinguishes five different subscales and comprises overall 31 questions. The aims of this study were to translate the GAQ2.0 into Dutch and to test clinimetric properties. Methods. Recommendations for translation and cross-cultural adaptation were followed and no cultural adaptations were needed. The resulting Dutch GAQ2.0 was administered to patients registered at the rheumatology outpatient clinic diagnosed with gout. Internal consistency was tested using Cronbach’s a, reliability using intraclass correlation coefficient (ICC), content validity by linkage to the International Classification of Functioning, Disability and Health (ICF) and construct validity by correlating the subscales of the GAQ2.0 with the HAQ disability index (HAQ-DI) and 36-item Short Form Health Survey (SF-36). Results. A total of 126 patients [106 (84%) male, mean age 66.6 years (S.D. 10.4), mean disease duration 11.2 years (S.D. 10.6)] completed a number of questionnaires, including the GAQ2.0, HAQ-DI and SF-36, and underwent a clinical examination. Internal consistency was sufficient (Cronbach’s a = 0.830.94), except for the subscale gout medication side effects (Cronbach’s a = 0.51). Testretest reliability was good (ICCs 0.730.86) for all subscales, but moderate for the subscale unmet gout treatment need (ICC 0.56). Gout impact (GI) subscale scores showed only weak to moderate correlations with HAQ-DI and SF-36, but stronger emphasis on the emotional consequences of gout. Also, it correlated better with gout-specific outcomes such as the number of gout flares and pain. Conclusion. The Dutch GAQ2.0 shows sufficient evidence of validity to assess disease-specific functioning and health in patients with gout and seems to capture different aspects than those represented in the HAQ and SF-36.

This article explores various methodological issues of patient utility measurement in two randomized controlled clinical trials involving 85 patients with fibromyalgia and 144 with ankylosing spondylitis. In both trials one baseline and two follow-up measurements of the patients' preferences for their own health state and several hypothetical states were performed using the rating scale and the standard gamble methods. It was confirmed that standard gamble scores are consistently higher than rating scale scores for both the experienced and the hypothetical states. The 3-month test-retest reliability for hypothetical states measured by intraclass correlation coefficients ranged from 0.24 to 0.33 for the rating scale and from 0.43 to 0.70 for the standard gamble. Although the reproducibility is not high, the group mean scores are fairly stable over time. Mean standard gamble scores tend to differ depending on the way the measurements are undertaken. Utilities elicited with chained gambles were significantly higher than utilities elicited with basic reference gambles. At the individual level some inconsistent responses occurred. However, more than 70% of these fell within the bounds of the measurement error, which ranged from 0.11 to 0.13 on the standard gamble (0-1 scale) and from 8 to 10 on the rating scale (0-100 scale). The large number of negative utilities for the severe hypothetical state, which was used as an anchor point in the chained gambles, and the magnitude of these negative utilities (down to -19) calls for intensified research efforts to handle these responses in utility calculations

Objective. To assess the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of spondyl-arthropathy. Methods. We conducted a 6-month randomized, placebo-controlled, double-blind, multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs. Patients were treated with SSZ (3 gm/day) or placebo. The primary efficacy variables were the physician's and patient's overall assessments, pain, and morning stiffness. End points were analyzed in the intent-to-treat and completer patient populations; the time course of effect was analyzed in the completer patient population. Results. Of the 351 patients enrolled, 263 (75%) completed the 6-month treatment period. The withdrawal rates were 35 (20%) and 53 (30%) in the placebo and SSZ groups, respectively. In the intent-to-treat analysis of end point efficacy, the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables, the patient's overall assessment of disease activity, for which 60% of the patients taking SSZ improved by at least 1 point on a 5-point scale, in contrast to 44% of the patients taking placebo. Laboratory markers of inflammation also showed statistically significant change in favor of SSZ. In subgroup analysis, the most impressive effects were seen in patients with psoriatic arthritis, both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints. Adverse events were more frequent in the SSZ group than the placebo group, but all were transient or reversible after cessation of treatment. Conclusion. The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy, notably in patients with psoriatic arthritis.

Classification of ankylosing spondylitis and spondylarthropathies is now satisfactory, but assessment of ankylosing spondylitis and related disorders could be improved. Currently, we do not completely encompass the spectrum of relevant outcomes. Functional status and toxicity assessment are frequently lacking. Although a considerable amount of progress has been made over the past decade in the development of patient status measures, this has mainly been achieved in rheumatic diseases that are characterized by predominant involvement of peripheral joints. This achievement is less prominent in ankylosing spondylitis. It may be relatively easy to define activity of extra-articular manifestations such as uveitis, but it is more difficult to define activity, severity, progress and outcome of a disease like ankylosing spondylitis with predominant spinal involvement.

Objectives: To characterize the fitness status of female fibromyalgia syndrome [FS] patients through comparison of performances in fitness testing between FS patients and matched performances in fitness testing between FS patients and matched healthy controls [HC]; examination of the reproducibility of fitness testing in FS patients; and analysis of the effect of [former] sports participation on fitness testing in FS patients. Methods: Eighty-seven FS patients [mean: 44.5 years of age, 12.5 yrs of disease duration] and 52 matched HCs from clerical personnel [44 years of age] participated in the study. Twelve fitness tests were selected to evaluate cardiorespiratory endurance, muscular strength and endurance, flexibility, coordination [skills] and body composition. Results: The peak workload achieved in incremental bicycle ergometer test was significantly lower [30 W, 19%] in FS patients than in HCs. The peak heart rate was also significantly lower [15 b/min, 11%] in FS patients, but the perceived exertion...

Purpose. Group physical therapy in patients with ankylosing spondylitis was studied to determine whether beneficial effects persisted after cessation of the intervention. Methods. After a 9-month period of supervised group physical therapy, 68 patients were randomized for another 9 months to unsupervised daily exercises at home (discontinuation group) or continuation of weekly sessions of supervised group physical therapy (continuation group). Endpoints were spinal mobility (thoracolumbar flexion and extension, chest expansion, cervical rotation), fitness (maximum work capacity), functioning (Sickness Impact Profile (SIP), Health Assessment Questionnaire for the Spondylarthropathies (HAQ-Sl, Functional Index [FI]), and patient's global health assessment on a visual analogue scale. Results. Time for exercises at home was significantly higher in the continuation than in the discontinuation group (mean duration 1.9 versus 1.2 hr per week, P < 0.05). The continuation group improved in global health (mean improvement 1.6; 32%) and in SIP score. Scores for thoraco-lumbar mobility and HAQ-S did not change very much, whereas chest expansion, cervical rotation, fitness, and FI deteriorated. The average attendance for group therapy sessions was 62%. The discontinuation group improved only marginally (0.2; 4%) in global health, whereas all other endpoints decreased. Only for global health and HAQ-S were the differences statistically significant in favor of the continuation group. Conclusions. Global health and functioning are sustained or even improved further if group physical therapy is continued. Spinal mobility decreased slightly in both groups.

To review recent data, in the context of what is already known, about an increased risk of vertebral fractures in ankylosing spondylitis patients.Osteoporosis and fractures of the vertebral body and its dorsal arch are now well recognized features in patients with ankylosing spondylitis, but their diagnosis is still often a challenge. The risk factors and clinical consequences for fractures in ankylosing spondylitis are increasingly understood in the context of osteoimmunology and of spinal biomechanical changes in material and structural components in the spine that result in bone failure.Diagnosing fractures of the vertebral body and its dorsal arch remains a challenge in studies and in clinical practice. Prospective studies are needed to evaluate to what degree such fractures can be prevented in 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.

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.

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