Efficacy of a Web-Based Self-Management Enhancing Program for Patients with Rheumatoid Arthritis: Explorative Randomized Controlled Trial.

BACKGROUND: Web-based self-management enhancing programs have the potential to support patients with rheumatoid arthritis (RA) in their self-management; for example, improve their health status by increasing their self-efficacy or taking their prescribed medication. We developed a Web-based self-management enhancing program in collaboration with RA patients and professionals as co-designers on the basis of the intervention mapping framework. Although self-management programs are complex interventions, it is informative to perform an explorative randomized controlled trial (RCT) before embarking on a larger trial. OBJECTIVE: This study aimed to evaluate the efficacy of a Web-based self-management enhancing program for patients with RA and identify outcome measures most likely to capture potential benefits. METHODS: A multicenter exploratory RCT was performed with an intervention group and a control group. Both groups received care as usual. In addition, the intervention group received 12 months of access to a Web-based self-management program. Assessment occurred at baseline, 6 months, and 12 months. Outcome measures included self-management behavior (Patient Activation Measurement, Self-Management Ability Scale), self-efficacy (Rheumatoid Arthritis task-specific Self-Efficacy, Perceived Efficacy in Patient-Physician Interaction), general health status (RAND-36), focus on fatigue (Modified Pain Coping Inventory for Fatigue), and perceived pain and fatigue (Numeric Rating Scales). A linear mixed model for repeated measures, using the intention-to-treat principle, was applied to study differences between the patients in the intervention (n=78) and control (n=79) groups. A sensitivity analysis was performed in the intervention group to study the influence of patients with high (N=30) and low (N=40) use of the intervention. RESULTS: No positive effects were found regarding the outcome measurements. Effect sizes were low. CONCLUSIONS: Based on these results, it is not possible to conclude on the positive effects of the intervention or to select outcome measures to be regarded as the primary/main or secondary outcomes for a future trial. A process evaluation should be performed to provide more insight into the low compliance with and effectiveness of the intervention. This can determine for whom this sort of program will work and help to fine-tune the inclusion criteria. TRIAL REGISTRATION: Netherlands Trial Register NTR4871; https://www.trialregister.nl/trial/4726.

The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: validation in six countries.

Objective: To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. Methods: We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach's α and construct validity by Spearman's correlation. Results: A total of 1276 patients participated (76% female, 25% with a disease duration <5 years, median HAQ 1.0). The original BRAF-MDQ four-factor structure and RAID single-factor structure were confirmed in every country with ⩾66% of variation in items explained by each factor and all item factor loadings of 0.71-0.98. Internal consistency for the BRAF-MDQ total and subscales was a Cronbach's α of 0.75-0.96 and for RAID, 0.93-0.96. Fatigue construct validity was shown for the BRAF-MDQ and BRAF-NRS severity and effect scales, correlated internally with SF-36 vitality and with RAID fatigue (r = 0.63-0.93). Broader construct validity for the BRAFs and RAID was shown by correlation with each other, HAQ and SF-36 domains (r = 0.46-0.82), with similar patterns in individual countries. The revised BRAF-NRS V2 Coping item had stronger validity than the original in all analyses. The revised Spanish RAID coping item performed as well as the original. Conclusion: Across six European countries, the BRAF-MDQ identifies the same four aspects of fatigue, and along with the RAID, shows strong factor structure and internal consistency and moderate-good construct validity. The revised BRAF-NRS V2 shows improved construct validity and replaces the original.

Low disease activity (DAS28≤3.2) reduces the risk of first cardiovascular event in rheumatoid arthritis: a time-dependent Cox regression analysis in a large cohort study.

OBJECTIVE: Systemic inflammation appears to contribute to the excess risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objective of this study was to investigate the effect of different levels of disease activity over time, particularly low disease activity and remission, on CVD risk in patients with RA. METHODS: Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events within the first 10 years of follow-up. Cut points of the DAS28 for remission (<2.6) and low (≤3.2), moderate (3.2-5.1) and high (>5.1) disease activity were used. The effect of disease activity on CVD risk was analysed using Cox-proportional hazards regression with DAS28 as a time-dependent covariate and also conventionally with time-averaged DAS28 as the primary dependent variable. RESULTS: Low DAS28 (≤3.2) was significantly associated with a reduced risk of CVD (HR 0.65, 95% CI 0.43 to 0.99) compared with DAS28 >3.2, both when included as a time-dependent covariate and as time-averaged DAS28 ≤3.2 (HR 0.52, 95% CI 0.33 to 0.81). Remission had a modest, non-significant protective effect against CVD (HR 0.67, 95% CI 0.43 to 1.07). CONCLUSION: Results of this study suggest that low disease activity is sufficient to achieve a protective effect against CVD in RA. Apparently, remission defined as DAS28 <2.6 has no additional protective effect against CVD compared with low disease activity. Our results strengthen the use of tight control strategies in daily clinical practice to achieve low stable disease activity or remission in patients with RA as soon as possible.

Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial.

OBJECTIVE: Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year data from the DRESS study (Dose REduction Strategy of Subcutaneous TNF inhibitors study). METHODS: In the intervention phase (month 0-18) of the DRESS study (Dutch trial register, NTR 3216), patients were randomised to DR or usual care (UC). In the extension phase (month 18-36), treatment strategies in both groups converged to continuation of protocolised tight control and allowed dose optimisation. Intention-to-treat analyses were done on flare, disease activity (28 joint count-based disease activity score with C reactive protein (DAS28-CRP)), functioning (health assessment questionnaire-disability index (HAQ-DI)), quality of life (Euroqol 5 dimensions 5 levels questionnaire (EQ5D-5L)), medication use, radiographic progression (Sharp van der Heijde score (SvdH)) and AE. RESULTS: 172/180 patients included in the DRESS study were included in the extension phase. Cumulative incidences of major flare were 10% and 12% (-2%, 95% CI -8 to 15) in DR and UC groups in the extension phase, and 17% and 14% (3%, 95% CI -9 to 13) from 0 to 36 months. Cumulative incidences of short-lived flares were 43% (33 to 52%)%) and 35% (23 to 49%)%) in DR and UC groups in the extension phase, and 83% (75 to 90%)%) and 44% (31 to 58%)%) from 0 to 36 months. Mean DAS28-CRP, HAQ-DI, EQ5D-5L and SvdH remained stable and not significantly different between groups. TNFi use remained low in the DR group and decreased in the UC group. Cumulative incidences of AE were not significantly different between groups. CONCLUSIONS: Safety and efficacy of disease activity guided TNFi DR in RA are maintained up to 3 years, with a large reduction in TNFi use, but no other benefits. Implementation of DR would vastly improve the cost-effective use of TNFi.

Update of EULAR recommendations for the treatment of systemic sclerosis.

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.

Performance of the 2015 ACR-EULAR classification criteria for gout in a primary care population presenting with monoarthritis.

Objective: To test the performance of the 2015 ACR-EULAR gout classification criteria against presence of SF MSU crystals in a primary healthcare population. Methods: The criteria were applied to an existing dataset of consecutive patients with monoarthritis presenting to Dutch family physicians; all patients underwent microscopic SF analysis by design. The data had been prospectively collected to develop a diagnostic decision rule for gout in 2010. Diagnostic performance was assessed by calculating area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and constructing calibration plots for the full version of the criteria (including SF analysis results of all patients) and the clinical-only version (not including SF analysis results). Performance of both versions was compared with the 2010 diagnostic rule. Results: Of 381 patients enrolled into the study, 216 (57%) were MSU crystal-positive. The full and clinical-only versions of the criteria had satisfactory area under the receiver operating characteristic curve (0.96 and 0.87, respectively), high specificity (0.98 and 0.84), high PPV (0.98 and 0.84), but lower sensitivity (0.68 and 0.68) and NPV (0.70 and 0.67). Specificity and PPV of both versions were higher compared with 0.71 and 0.89 of the 2010 diagnostic decision rule. The decison rule had the highest sensitivity and NPV (0.99 and 0.97). Conclusion: This study presents the first external validation of the 2015 ACR-EULAR gout classification criteria in a primary healthcare setting. The criteria perform well in this setting in patients presenting with monoarthritis for the purpose of enrolling into gout clinical trials.

The effect of curriculum sample selection for medical school.

In the Netherlands, students are admitted to medical school through (1) selection, (2) direct access by high pre-university Grade Point Average (pu-GPA), (3) lottery after being rejected in the selection procedure, or (4) lottery. At Radboud University Medical Center, 2010 was the first year we selected applicants. We designed a procedure based on tasks mimicking the reality of early medical school. Applicants took an online course followed by an on-site exam, resembling courses and exams in early medical school. Based on the exam scores, applicants were selected or rejected. The aim of our study is to determine whether curriculum sample selection explains performance in medical school and is preferable compared to selection based on performance in secondary school. We gathered data on the performance of students of three consecutive cohorts (2010-2012, N = 954). We compared medical school performance (course credits and grade points) of selected students to the three groups admitted in other ways, especially lottery admissions. In regression analyses, we controlled for out of context cognitive performance by adjusting for pu-GPA. Selection-admitted students outperformed lottery-admitted students on most outcome measures, unadjusted as well as adjusted for pu-GPA (p ≤ 0.05). They had higher grade points than non-selected lottery students, both unadjusted and adjusted for pu-GPA (p ≤ 0.025). Adjusted for pu-GPA, selection-admitted students and high-pu-GPA students performed equally. We recommend this selection procedure as it adds to secondary school cognitive performance for the general population of students, is efficient for large numbers of applicants and not labour-intensive.

Performance of classification criteria for gout in early and established disease.

OBJECTIVES: To compare the sensitivity and specificity of different classification criteria for gout in early and established disease. METHODS: This was a cross-sectional study of consecutive rheumatology clinic patients with joint swelling in which gout was defined by presence or absence of monosodium urate crystals as observed by a certified examiner at presentation. Early disease was defined as patient-reported onset of symptoms of 2 years or less. RESULTS: Data from 983 patients were collected and gout was present in 509 (52%). Early disease was present in 144 gout cases and 228 non-cases. Sensitivity across criteria was better in established disease (95.3% vs 84.1%, p<0.001) and specificity was better in early disease (79.9% vs 52.5%, p<0.001). The overall best performing clinical criteria were the Rome criteria with sensitivity/specificity in early and established disease of 60.3%/84.4% and 86.4%/63.6%. Criteria not requiring synovial fluid analysis had sensitivity and specificity of less than 80% in early and established disease. CONCLUSIONS: Existing classification criteria for gout have sensitivity of over 80% in early and established disease but currently available criteria that do not require synovial fluid analysis have inadequate specificity especially later in the disease. Classification criteria for gout with better specificity are required, although the findings should be cautiously applied to non-rheumatology clinic populations.

The influence of patient perceptions of disease on medication intensification in daily practice.

OBJECTIVE: The objectives of this study were twofold: to assess if there are independent effects of variables representing patients' perceptions of disease on intensification of drug therapy in patients with RA seen in daily practice; and to test the hypothesis that effects of patients' perceptions of disease are mediated through patient self-reported willingness to alter therapy. METHODS: Before being seen by a physician, consecutive patients with RA, attending the Radboudumc outpatient rheumatology clinic, were asked to fill out a short questionnaire regarding the following four items: perceived health change, satisfaction with current health, willingness to change therapy and expected health change until the next visit. Independent associations between these measures, registered clinical measures and synthetic DMARD/biologic DMARD (including CSs) intensification were studied with logistic regression. Mediation analysis was performed focusing on the strongest predictor and self-reported willingness as a mediator. RESULTS: Out of 453 patients with RA, 65% female, 67% RF positive, medication was intensified for 82 patients (18%). All patient perception measures exhibited significant associations, independent of clinical measures, of which patient satisfaction with current health state was the strongest [odds ratio (OR) 0.21, 95% CI: 0.10, 0.44]. Significant mediation of the effect of patient satisfaction through willingness to alter therapy on actual registered medication intensification was found. CONCLUSION: Treat to Target interventions should address patients' perceptions of their disease, and the related health goals patients aim to achieve, in addition to the attained level of disease activity.

An easy prediction rule for diffuse cutaneous systemic sclerosis using only the timing and type of first symptoms and auto-antibodies: derivation and validation.

OBJECTIVE: DcSSc is associated with high morbidity related to widespread skin disease and poor prognosis due to earlier and more severe organ involvement. The objective of this study is to derive and validate a simple prediction rule for identifying patients at the time of initial diagnosis of SSc who are likely to progress to dcSSc. METHODS: The Nijmegen cohort consists of 619 SSc patients. Logistic regression was used for predictive modelling. A prediction rule was created by rounding regression coefficients. Patients were stratified as being at low risk (<1) or high risk (⩾1) of progression to dcSSc. Performance was analysed in 445 SSc patients from Madrid. RESULTS: One hundred and seventy-four out of 535 patients were classified as dcSSc. The final model consisted of gender, time between RP and non-RP, sclerodactyly (first non-Raynaud symptom) and SSc-specific auto-antibodies. The model performed well in the derivation cohort [area under the curve = 0.78 (95% CI: 0.74, 0.82)] and validation cohort [area under the curve = 0.78 (95% CI: 0.74, 0.83)]. At the optimal cut point (1) for the prediction rule, sensitivity was 87% and specificity 61% in the derivation cohort, compared with 78% and 65% in the validation cohort. Upon application of the prediction rule to 392 lcSSc patients at initial diagnosis, 32 out of 34 patients were correctly classified as dcSSc. CONCLUSION: A simple prediction rule was designed to attribute a low/high risk category for development of dcSSc.This method is suited for assigning intensified screening at the time of initial diagnosis of SSc to patients most at risk for dcSSc. It provides the opportunity for early identification of potential dcSSc patients for enrolment into clinical trials.

Survival and organ involvement in patients with limited cutaneous systemic sclerosis and anti-topoisomerase-I antibodies: determined by skin subtype or auto-antibody subtype? A long-term follow-up study.

OBJECTIVE: LcSSc is associated with ACAs and a mild course, whereas dcSSc is associated with anti-topoisomerase antibodies (ATAs) and a more severe course. However, ATAs are also present in lcSSc. Little is known about survival and organ involvement in this subgroup. The aim of this study is to determine whether survival and organ involvement of lcSSc ATA-positive patients differs from lcSSc ATA-negative or dcSSc ATA-positive patients. Furthermore, transition from lcSSc to dcSSc was evaluated. METHODS: Data from The Nijmegen Systemic Sclerosis cohort were used, with up to 15 years of follow-up. Kaplan-Meier analysis was performed for survival and organ involvement, including interstitial lung disease, pulmonary arterial hypertension, cardiac involvement and Scleroderma Renal Crises. Cox proportional hazard modelling was performed to adjust for confounders. RESULTS: A total of 460 patients were included: 58 (13%) lcSSc ATA-positive patients, 237 (52%) lcSSc ATA-negative patients and 78 (17%) dcSSc ATA-positive patients. Cumulative survival in lcSSc ATA-positive patients was 75%, in lcSSc ATA-negative patients 58% and in dcSSc ATA-positive patients 53%. Interstitial lung disease was more prevalent in lcSSc ATA-positive patients (49%) than in lcSSc ATA-negative patients (25%), but less than in dcSSc ATA-positive patients (60%). Forty-eight patients developed dcSSc: 24 ATA-negative and 24 ATA-positive (P < 0.001). CONCLUSION: LcSSc ATA-positive patients differ from lcSSc ATA-negative patients and dcSSc ATA-positive patients concerning survival and organ involvement. LcSSc patients who are ATA-positive are more likely to develop dcSSc than lcSSc patients who are ATA negative.

A multidimensional 'path analysis' model of factors explaining fatigue in rheumatoid arthritis.

OBJECTIVES: Fatigue is one of the most commonly reported symptoms in rheumatoid arthritis (RA). Many factors may play a causal role on fatigue in RA patients, but their contribution and interplay is barely understood. The objective was to develop a multidimensional model of factors that explain fatigue severity in RA. METHODS: A cross-sectional study (n=228) of consecutive patients with RA was performed. Fatigue, disease characteristics and psychosocial and behavioural outcomes were collected. Baseline differences between non severely fatigued patients (CIS-fatigue <35) and severely fatigued patients (CIS-fatigue ≥35) were tested. Structural equation modeling was used to test a hypothesised model for fatigue. RESULTS: The final model includes pain, physical functioning, mood, sense of control, sleep quality and fatigue, with good fit (CFI=0.976) explaining 74% of the variance in RA fatigue. Accordingly, poor sleep quality (ß=0.42, p<0.001) and less physical functioning (ß=0.65, p<0.001) are directly related to a higher level of fatigue. Less sense of control is related to more mood disturbance (ß=0.64, p<0.001), more pain (ß=0.389, p<0.001) and less physical functioning (ß=-0.24, p<0.001). More mood disturbance is related to poor sleep quality (ß=0.78, p<0.001) and higher pain level is related to less physical functioning (ß=0.75, p<0.001). CONCLUSIONS: RA fatigue is directly influenced by poor sleep quality and physical functioning, and indirectly by sense of control, mood and pain. Treatment of these factors by psychological interventions and physical exercise could help to improve fatigue in patients with RA.

The effect of disease duration and disease activity on the risk of cardiovascular disease in rheumatoid arthritis patients.

OBJECTIVE: Disease duration and disease activity may be associated with an increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objectives of this study were to investigate (1) the relationship between duration of inflammation and the development of CVD in RA patients and (2) the relationship between RA disease activity over time and CVD in patients with RA. METHODS: RA patients with a follow-up of ≥6 months in the Nijmegen early RA cohort without prior CVD were included. Disease activity over time was calculated using the time-averaged  28 joint disease activity score (DAS28) for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were used for the analyses. RESULTS: During follow-up of the 855 patients that were included, 154 CV events occurred. The course of hazards over time did not indicate a change in the risk of CVD over the course of RA (disease duration), which is also reflected by the absence of a deflection in the survival curves. The survival distributions did not differ between patients with a disease duration of <10 years or >10 years (Log-rank test: p=0.82). Time-averaged DAS28 was significantly associated with CVD (p=0.002) after correction for confounders. CONCLUSIONS: Disease duration does not appear to independently affect the risk of CVD. The risk of CVD in RA patients was not increased after 10 years of disease duration compared with the first 10 years. Disease activity over time may contribute to the risk of CVD.

Imaging modalities for the classification of gout: systematic literature review and meta-analysis.

BACKGROUND: Although there has been major progress in gout imaging, no gout classification criteria currently include advanced imaging techniques. OBJECTIVE: To examine the usefulness of imaging modalities in the classification of gout when compared to monosodium urate (MSU) crystal confirmation as the gold standard, in order to inform development of new gout classification criteria. METHODS: We systematically reviewed the published literature concerning the diagnostic performance of plain film radiography, MRI, ultrasound (US), conventional CT and dual energy CT (DECT). Only studies with MSU crystal confirmation as the gold standard were included. When more than one study examined the same imaging feature, the data were pooled and summary test characteristics were calculated. RESULTS: 11 studies (9 manuscripts and 2 meeting abstracts) satisfied the inclusion criteria. All were set in secondary care, with mean gout disease duration of at least 7 years. Three features were examined in more than one study: the double contour sign (DCS) on US, tophus on US, and MSU crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus, were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively. CONCLUSIONS: US and DECT show promise for gout classification but the few studies to date have mostly been in patients with longstanding, established disease. The contribution of imaging over clinical features for gout classification criteria requires further examination.

2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSIONS: The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

The validation of a diagnostic rule for gout without joint fluid analysis: a prospective study.

OBJECTIVE: The gold standard for diagnosing gout is the identification of MSU crystals in joint fluid. In secondary care, the facilities or expertise to analyse joint fluid are not always available and gout is diagnosed clinically. To improve the predictive value of the clinical diagnosis of gout in secondary care, a diagnostic rule developed in primary care could be helpful. The aim of this study was to validate this diagnostic rule in a secondary care population with the gold standard as reference test. METHODS: Three hundred and ninety patients with monoarthritis were included. The variables of the diagnostic rule (male sex, previous arthritis attack, onset <1 day, joint redness, involvement of the first MTP joint, hypertension or one or more cardiovascular disease, and serum uric acid >5.88 mg/dl) were collected and scored. The affected joint was aspirated and joint fluid was analysed for the presence of MSU crystals. RESULTS: In 219 patients (56%) MSU crystals were found. The positive predictive value of a score of ≥8 points was 0.87, the negative predictive value of a score of ≤4 points was 0.95. The area under the receiver operating characteristic curve for the diagnostic rule was 0.86 (95% CI 0.82, 0.89). The Hosmer-Lemeshow goodness-of-fit test showed that the difference between the expected and the observed probability was non-significant (P = 0.64), indicating good agreement. CONCLUSION: An easy-to-use diagnostic rule for gout developed in primary care shows good performance in secondary care and improves the predictive value of the clinical diagnosis of gout when joint fluid analysis is not available.

Individual patient monitoring in daily clinical practice: a critical evaluation of minimal important change.

PURPOSE: In daily practice, physicians translate knowledge from clinical trials to practice, to improve health in individual patients. To help interpret meaningful change on disease outcome measures, the concept of minimal important change (MIC) was conceived. The objective of this study was to investigate whether MIC values are suited for individual patient monitoring. METHODS: Three main elements of the MIC concept were evaluated: (1) MIC values for improvement and deterioration were determined, and the amount of misclassification present in quantifying minimal change was analyzed. (2) Discordance between change categories (improved, unchanged, deteriorated), defined by the MIC values, and patients' satisfaction with their health was inspected. (3) Discordance between change categories, defined by MIC values, and patients' willingness to alter therapy was inspected. RESULTS: MIC value analysis was based on 469 patients with RA seen in daily practice. The chance of falsely classifying health change of an individual patient was high (false-positive range 19-30 % and false-negative range 43-72 %). Of patients classified as improved, 24 % were not satisfied with their health and 69 % were not willing to change therapy. Of patients classified as deteriorated, 54 % were satisfied with their health and 57 % were not willing to change therapy. CONCLUSIONS: The misclassification in the quantification of change and high proportions of discordance between change categories defined by MIC cutoff values and patients' satisfaction and willingness to alter therapy indicate that MIC values as such are not suited for individual patient monitoring.

Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis.

OBJECTIVES: The EULAR (European League Against Rheumatism) Scleroderma Trials and Research Group (EUSTAR) has identified preliminary criteria for very early diagnosis of systemic sclerosis (SSc). Our aim was to assess the prevalence of each proposed diagnostic item in a large observational patient cohort with Raynaud's phenomenon (RP). METHODS: Baseline data of 469 RP patients enrolled into the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) cohort are presented. RESULTS: 68% of all RP patients were antinuclear antibody (ANA) positive. ANA+ RP patients more frequently had previous or current puffy fingers (PuFi) (38.5% and 23.3%, p<0.01) and an SSc pattern on nailfold capillaroscopy (NC) (53.6% and 13.4%, p<0.001) than ANA- patients. Telangiectasia, current digital ulcers and digital pitting scars were also commoner in ANA+ RP patients. 38% of ANA+ patients presented with all three features, which should raise suspicion of very early SSc (ANA+RP+PuFi constitutes a 'red flag'). These patients more frequently exhibited an NC SSc pattern, sclerodactyly and telangiectases compared to ANA+ patients without PuFi. Almost 90% of patients with 'red flags' had anti-centromere or anti-topoisomerase I antibodies and/or an NC SSc pattern, and fulfilled the EUSTAR criteria for very early SSc. Previous or current PuFi were present in 23.3% of ANA- RP patients, eight of whom also had an NC SSc pattern. CONCLUSIONS: In addition to well-characterised predictive factors, PuFi is an important sign raising suspicion for underlying very early SSc in patients with RP. The relevance of PuFi in ANA- RP patients should be clarified.

2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative.

OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

Difference in the risk of serious infections in patients with rheumatoid arthritis treated with adalimumab, infliximab and etanercept: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry.

BACKGROUND: Tumour necrosis factor (TNF)-inhibiting therapy increases the risk of serious infections in rheumatoid arthritis (RA). However, it is not clear whether this risk differs between TNF inhibitors. OBJECTIVE: To analyse whether the risk of serious infections in patients with RA treated with an anti-TNF inhibitor is different for adalimumab, infliximab and etanercept. METHODS: Data from the Dutch RA monitoring registry were used. Incidence rates were calculated from the observed number of first serious infections and follow-up time up to 5 years. A Cox proportional hazards model with time-to-first-serious infection was used to estimate risk differences among the anti-TNF treatment groups, with correction for confounders. RESULTS: The unadjusted incidence rate of a first serious infection in patients with RA per 100 patient-years was 2.61 (95% CI 2.21 to 3.00) for adalimumab, 3.86 (95% CI 3.33 to 4.40) for infliximab and 1.66 (95% CI 1.09 to 2.23) for etanercept. Age, year of starting anti-TNF therapy, comorbidities at baseline and disease activity score 28 over time were included as confounders. No difference in risk for serious infections was found between adalimumab and infliximab with an adjusted HR (adjHR) of 0.90 (95% CI 0.55 to 1.48). The risk of serious infections was significantly lower in etanercept than in both infliximab (adjHR=0.49 (95% CI 0.29 to 0.83)) and adalimumab (adjHR=0.55 (95% CI 0.44 to 0.67)). CONCLUSIONS: The risk of serious infections in patients with RA treated with adalimumab or infliximab was similar, while the risk of serious infections in patients with RA treated with etanercept was lower than with both adalimumab and infliximab.