Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio

Sex differences in rheumatoid arthritis: more than meets the eye...

Sex differences in the prevalence of autoimmune diseases such as rheumatoid arthritis (RA) are well described, but the literature is not as clear about sex differences in RA disease course and prognosis. A recent study from a very large cross-sectional international cohort demonstrated slightly worse levels of disease activity and function in female patients with RA, compared with men. These findings are discussed in the context of our evolving knowledge of sex differences in the expression of this prototypic autoimmune disease, both in terms of the actual disease activity level, the effects that the disease has on physical function, and our ability accurately to measure these aspects

Disease activity level, remission and response in established rheumatoid arthritis: Performance of various criteria sets in an observational cohort, treated with anti-TNF agents

<p>Abstract</p> <p>Background</p> <p>Most composite indices of disease activity and response criteria in RA have been validated and compared in clinical trials rather than routine care. We therefore wanted to compare the performance of the DAS28, SDAI and CDAI activity indices, their activity states, their response criteria, and also compare with the ACR response criteria in an observational clinical setting.</p> <p>Methods</p> <p>Agreement between the criteria sets was investigated using κ statistics in a non-randomized cohort of 1789 RA patients from southern Sweden, starting their first course of anti-TNF-treatment. Mean disease duration was 12 years. Completer analysis was used.</p> <p>Results</p> <p>Agreement between high, moderate and low activity states was moderate or substantial, with κ = 0.5 or better for all criteria. Agreement between SDAI and CDAI disease states was > 90% in these categories with κ > 0.8. DAS28 original and modified cut point remission had good agreement (κ = 0.91). Agreement between responses was substantial at the overall/ACR20 level (about 95%, κ = 0.7 or better) for all criteria. By contrast, agreement was poor between moderate and high level responses.</p> <p>Conclusion</p> <p>Disease activity states according to the various indices perform similarly and show substantial agreement at all levels except remission. Agreement between SDAI and CDAI states is excellent. Response criteria, applied at the individual patient level, are hard to interpret and show poor agreement, except at the lowest level of response. Thus, they should not be applied uncritically in clinical practice.</p

The relationship between change in subjective outcome and change in disease: a potential paradox

Contains fulltext : 87756.pdf (publisher's version ) (Closed access)BACKGROUND: Response shift theory suggests that improvements in health lead patients to change their internal standards and re-assess former health states as worse than initially rated when using retrospective ratings via the then-test. The predictions of response shift theory can be illustrated using prospect theory, whereby a change in current health causes a change in reference frame. Therefore, if health deteriorates, the former health state will receive a better rating, whereas if it improves, the former health state will receive a worse rating. OBJECTIVE: To explore the predictions of response shift and prospect theory by relating subjective change to objective change. METHODS: Baseline and 3-month follow-up data from a cohort of rheumatoid arthritis patients (N = 197) starting on TNFalpha-blocking agents were used. Objective disease change was classified according to a disease-specific clinical outcome measure (DAS28). Visual analogue scales (VAS) for general health (GH) and pain were used as self-reported measures. Three months after starting on anti-TNFalpha, patients used the then-test to re-rate their baseline health with regard to general health and pain. Differences between then-test value and baseline values were calculated and tested between improved, non-improved and deteriorated patients by the Student t-test. RESULTS: At 3 months, 51 (25.9%) patients had good improvement in health, 83 (42.1%) had moderate improvement, and 63 (32.0%) had no improvement or deteriorated in health. All patients no matter whether they improved, did not improve, or even became worse rated their health as worse retrospectively. The difference between the then-test rating and the baseline value was similarly sized in all groups. CONCLUSION: More positive ratings of retrospective health are independent of disease change. This suggests that patients do not necessarily change their standards in line with their disease change, and therefore it is inappropriate to use the then-test to correct for such a change. If a then-test is used to correct for shifts in internal standards, it might lead to the paradoxical result that patients who do not improve or even deteriorate increase significantly on self-reported health and pain. An alternative explanation for differences in retrospective and prospective ratings of health is the implicit theory of change which is more successful in explaining our results than prospect theory.1 september 201

A model of impairment and functional limitation in rheumatoid arthritis

BACKGROUND: We have previously proposed a theoretical model for studying physical disability and other outcomes in rheumatoid arthritis (RA). The purpose of this paper is to test a model of impairment and functional limitation in (RA), using empirical data from a sample of RA patients. We based the model on the disablement process framework. METHODS: We posited two distinct types of impairment in RA: 1) Joint inflammation, measured by the tender, painful and swollen joint counts; and 2) Joint deformity, measured by the deformed joint count. We hypothesized direct paths from the two impairments to functional limitation, measured by the shirt-button speed, grip strength and walking velocity. We used structural equation modeling to test the hypothetical relationships, using empirical data from a sample of RA patients recruited from six rheumatology clinics. RESULTS: The RA sample was comprised of 779 RA patients. In the structural equation model, the joint inflammation impairment displayed a strong significant path toward the measured variables of joint pain, tenderness and swelling (standardized regression coefficients 0.758, 0.872 and 0.512, P ≤ 0.001 for each). The joint deformity impairment likewise displayed significant paths toward the measured upper limb, lower limb, and other deformed joint counts (standardized regression coefficients 0.849, 0.785, 0.308, P ≤ 0.001 for each). Both the joint inflammation and joint deformity impairments displayed strong direct paths toward functional limitation (standardized regression coefficients of -0.576 and -0.564, respectively, P ≤ 0.001 for each), and explained 65% of its variance. Model fit to data was fair to good, as evidenced by a comparative fit index of 0.975, and the root mean square error of approximation = 0.058. CONCLUSION: This evidence supports the occurrence of two distinct impairments in RA, joint inflammation and joint deformity, that together, contribute strongly to functional limitations in this disease. These findings may have implications for investigators aiming to measure outcome in RA

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background. Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis. Methods. A multicenter stratified randomized single-blind controlled trial is currently being performed in patients 18 years or older with recent-onset arthritis. Eight hundred ten patients are being stratified according to the likelihood of their developing persistent arthritis. In patients with a high probability of persistent arthritis, we will study combination Disease Modifying Antirheumatic Drug therapy compared to monotherapy methotrexate. In patients with an intermediate probability of persistent arthritis, we will study Disease Modifying Antirheumatic Drug of various intensities. In patients with a low probability, we will study non-steroidal anti-inflammatory drugs, hydroxychloroquine and a single dose of corticosteroids. If disease activity is not sufficiently reduced, treatment will be adjusted according to a step-up protocol. If remission is achieved for at least six months, medication will be tapered off. Patients will be followed up every three months over two years. Discussion. This is the first rheumatological study to base treatment in early arthritis on a prediction rule. Treatment will be stratified according to the probability of persistent arthritis, and different combinations of treatment per stratum will be evaluated. Treatment will be started early, and patients will not need to meet the ACR-criteria for rheumatoid arthritis. Trial registration. This trial has been registered in Current Controlled Trials with the ISRCTN26791028

Predictive modelling of a novel anti-adhesion therapy to combat bacterial colonisation of burn wounds

As the development of new classes of antibiotics slows, bacterial resistance to existing antibiotics is becoming an increasing problem. A potential solution is to develop treatment strategies with an alternative mode of action. We consider one such strategy: anti-adhesion therapy. Whereas antibiotics act directly upon bacteria, either killing them or inhibiting their growth, anti-adhesion therapy impedes the binding of bacteria to host cells. This prevents bacteria from deploying their arsenal of virulence mechanisms, while simultaneously rendering them more susceptible to natural and artificial clearance. In this paper, we consider a particular form of anti-adhesion therapy, involving biomimetic multivalent adhesion molecule 7 coupled polystyrene microbeads, which competitively inhibit the binding of bacteria to host cells. We develop a mathematical model, formulated as a system of ordinary differential equations, to describe inhibitor treatment of a Pseudomonas aeruginosa burn wound infection in the rat. Benchmarking our model against in vivo data from an ongoing experimental programme, we use the model to explain bacteria population dynamics and to predict the efficacy of a range of treatment strategies, with the aim of improving treatment outcome. The model consists of two physical compartments: the host cells and the exudate. It is found that, when effective in reducing the bacterial burden, inhibitor treatment operates both by preventing bacteria from binding to the host cells and by reducing the flux of daughter cells from the host cells into the exudate. Our model predicts that inhibitor treatment cannot eliminate the bacterial burden when used in isolation; however, when combined with regular or continuous debridement of the exudate, elimination is theoretically possible. Lastly, we present ways to improve therapeutic efficacy, as predicted by our mathematical model

Relationship between time-integrated disease activity estimated by DAS28-CRP and radiographic progression of anatomical damage in patients with early rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>The main aim of the study was to investigate the relationship between persistent disease activity and radiographic progression of joint damage in early rheumatoid arthritis (ERA).</p> <p>Methods</p> <p>Forty-eight patients with active ERA was assessed every 3 months for disease activity for 3 years. Radiographic damage was measured by the Sharp/van der Heijde method (SHS). The cumulative inflammatory burden was estimated by the time-integrated values (area under the curve-AUC) of Disease Activity Score 28 joint based on C-reactive protein (DAS28-CRP) in rapid progressors versus non-progressors. Bland and Altman's 95% limits of agreement method were used to estimate the smallest detectable difference (SDD) of radiographic progression. The relationship between clinical and laboratory predictors of radiographic progression and their interactions with time was analysed by logistic regression model.</p> <p>Results</p> <p>After 3-years of follow-up, radiographic progression was observed in 54.2% (95%CI: 39.8% to 67.5%) of patients and SDD was 9.5 for total SHS. The percentage of patients with erosive disease increased from 33.3% at baseline to 76% at 36 months. The total SHS of the progressors worsened from a median (interquartile range) of 18.5 (15-20) at baseline to 38.5 (34-42) after 3 years (p < 0.0001) whereas non-progressors worsened from a median of 14.5 (13-20) at baseline to 22.5 (20-30) after 3 years (p < 0.001). In the regression model, time-integrated values of DAS28-CRP and anti-CCP positivity have the highest positive predictive value for progression (both at level of p < 0.0001). Radiographic progression was also predicted by a positive IgM-RF (p0.0009), and a high baseline joint damage (p = 0.0044).</p> <p>Conclusions</p> <p>These data indicate that the level of disease activity, as measured by time-integrated DAS28-CRP, anti-CCP and IgM-RF positivity and a high baseline joint damage, affects subsequent progression of radiographic damage in ERA.</p