Ricardo J. O. Ferreira

The accuracy of osteoporotic fracture risk prediction tools: a systematic review and meta-analysis

Objectives To identify and synthesise the best available evidence on the accuracy of the currently available tools for predicting fracture risk. Methods We systematically searched PubMed MEDLINE, Embase and Cochrane databases to 2014. Two reviewers independently selected articles, collected data from studies, and carried out a hand search of the references of the included studies. The Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS) checklist was used, and the primary outcome was the area under the curve (AUC) and 95% CIs, obtained from receiver operating characteristic (ROC) analyses. We excluded tools if they had not been externally validated or were designed for specific disease populations. Random effects meta-analyses were performed with the selected tools. Results Forty-five studies met inclusion criteria, corresponding to 13 different tools. Only three tools had been tested more than once in a population-based setting: FRAX (26 studies in 9 countries), GARVAN (6 studies in 3 countries) and QFracture (3 studies in the UK, 1 also including Irish participants). Twenty studies with these three tools were included in a total of 17 meta-analyses (for hip or major osteoporotic fractures; men or women; with or without bone mineral density). Conclusions Most of the 13 tools are feasible in clinical practice. FRAX has the largest number of externally validated and independent studies. The overall accuracy of the different tools is satisfactory (>0.70), with QFracture reaching 0.89 (95% CI 0.88 to 0.89). Significant methodological limitations were observed in many studies, suggesting caution when comparing tools based solely on the AUC.

Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative

In chronic inflammatory rheumatic diseases, comorbidities such as cardiovascular diseases and infections are suboptimally prevented, screened for and managed. The objective of this European League Against Rheumatism (EULAR) initiative was to propose points to consider to collect comorbidities in patients with chronic inflammatory rheumatic diseases. We also aimed to develop a pragmatic reporting form to foster the implementation of the points to consider. In accordance with the EULAR Standardised Operating Procedures, the process comprised (1) a systematic literature review of existing recommendations on reporting, screening for or preventing six selected comorbidities: ischaemic cardiovascular diseases, malignancies, infections, gastrointestinal diseases, osteoporosis and depression and (2) a consensus process involving 21 experts (ie, rheumatologists, patients, health professionals). Recommendations on how to treat the comorbidities were not included in the document as they vary across countries. The literature review retrieved 42 articles, most of which were recommendations for reporting or screening for comorbidities in the general population. The consensus process led to three overarching principles and 15 points to consider, related to the six comorbidities, with three sections: (1) reporting (ie, occurrence of the comorbidity and current treatments); (2) screening for disease (eg, mammography) or for risk factors (eg, smoking) and (3) prevention (eg, vaccination). A reporting form (93 questions) corresponding to a practical application of the points to consider was developed. Using an evidence-based approach followed by expert consensus, this EULAR initiative aims to improve the reporting and prevention of comorbidities in chronic inflammatory rheumatic diseases. Next steps include dissemination and implementation.

Drivers of patient global assessment in patients with rheumatoid arthritis who are close to remission: an analysis of 1588 patients

Objectives ACR/EULAR Boolean remission in RA is frequently not obtained solely due to a patient global assessment (PGA) >1/10 (a condition often designated as near-remission). This study aimed to assess which domains of impact could explain an elevated PGA in near-remission patients. Methods We performed an ancillary analysis of data from three cross-sectional studies in patients with established RA. Three disease activity states were defined: remission (tender and swollen joint counts, CRP and PGA all ⩽1), near-remission (tender and swollen joint counts, and CRP are all ≤1 but PGA >1) and non-remission. Physical and psychological domains were assessed using the RA Impact of Disease 0-10 (numeric rating scale) as explanatory factors of PGA. Univariable and multivariable linear regression analyses were performed to explain PGA. Results A total of 1588 patients (79.1% females) were analysed. The mean disease duration was 13.0 years (s.d. 9.8) and the 28-joint DAS with four variables was 3.2 (s.d. 1.4). Near-remission [mean PGA 3.6 (s.d. 1.9)] was more frequent (19.1%) than remission (12.3%). Scores of RA Impact of Disease domains were similar in near-remission and non-remission patients. In near-remission, PGA was explained (R2adjusted = 0.55) by pain (β = 0.29), function (β = 0.23), physical well-being (β = 0.19) and fatigue (β = 0.15). Conclusion Near-remission was more frequent than remission. These patients, despite having no signs of significant inflammation, report an impact of disease similar to the non-remission patients. PGA in near-remission seems to be driven by physical rather than psychological domains. Selecting the best therapy for these patients requires a better understanding of the meaning of PGA, both globally and in individual patients.

Determinants of happiness and quality of life in patients with rheumatoid arthritis: a structural equation modelling approach

Objectives Besides increasing longevity, the ultimate goal of medical care is to improve patients’ enjoyment of life, a concept akin to happiness. This study examined the determinants of happiness and quality of life (QoL) in patients with rheumatoid arthritis (RA). Methods In this observational, cross-sectional study, patients were assessed on disease activity, disease impact, personality, QoL and happiness. Structural equation modelling estimation was used to analyse the associations between these dimensions, pursuing three hypotheses: H1—disease activity and perceived impact of disease are negatively associated with overall QoL and happiness in patients with RA; H2—‘positive’ personality traits are related to happiness both directly and indirectly through perceived disease impact; H3—happiness has a mediating effect in the relation between impact of disease and QoL. Results Data from 213 patients were analysed. Results supported all driving hypotheses. Happiness was positively related to ‘positive’ personality and, to a lesser extent, negatively related to impact of disease. Impact of disease, in turn, was positively related to disease activity and mitigated by ‘positive’ personality traits. Impact of disease had a much stronger relation with QoL than with happiness. Happiness mitigated the negative effect of disease impact on QoL. Conclusion Optimisation of QoL and happiness of people with RA requires effective control of the disease process and also improvement of the disease impact domains. Personality seems to play a pivotal mediating role in these relations.

Outcome Measures in Polymyalgia Rheumatica. A Systematic Review

Objective. To identify the instruments used to assess polymyalgia rheumatica (PMR) in published studies. Methods. A systematic literature review of clinical trials and longitudinal observational studies related to PMR, published from 1970 to 2014, was carried out. All outcome and assessment instruments were extracted and categorized according to core areas and domains, as defined by the OMERACT (Outcome Measures in Rheumatology) Filter 2.0. Results. Thirty-five articles (3221 patients) were included: 12 randomized controlled trials (RCT); 3 nonrandomized trials; and 20 observational studies. More than 20 domains were identified, measured by 29 different instruments. The most frequently used measures were pain, morning stiffness, patient global assessment and physician global assessment, erythrocyte sedimentation rate, and C-reactive protein. The definition of outcomes varied considerably between studies. Conclusion. The outcome measures and instruments used in PMR are numerous and diversely defined. The establishment of a core set of validated and standardized outcome measurements is needed.

The Portuguese Rheumatoid Arthritis Impact of Disease (RAID) score and its measurement equivalence in three countries: validation study using Rasch Models

PurposeThe Rheumatoid Arthritis Impact of Disease (RAID) score assesses seven impact domains of interest for people with RA. This study aimed to test patients’ understanding of the Portuguese RAID and evaluate its cross-cultural validity for use in Portugal.MethodsThis was a mixed methods study comprising two phases: (i) cognitive debriefing to determine patient’s comprehension of the Portuguese RAID and (ii) cross-cultural validation using Rasch analysis. Construct validity was determined by fit to the model, invariance culture (compared with France and UK datasets) and evidence of convergent and divergent validity.ResultsPatients’ input (n = 38) led to minor changes in the phrasing of two items to ensure conceptual equivalence between the Portuguese and the original RAID. In Rasch analysis (n = 288), two items ‘Sleep’ and ‘Physical well-being’ in the Portuguese dataset did not adequately fit the model specifications, suggesting multidimensionality (sleep—not necessarily associated with RA) and redundancy (physical well-being overlapping with functional disability). Despite the imperfections, the scale had high internal consistency, evidence of convergent and divergent validity and invariance to culture (compared to France n = 195 and UK n = 205 datasets). The scale was well targeted for patients with different levels of disease impact.ConclusionsThe RAID has been successfully adapted into Portuguese and it can be used with confidence in clinical practice. Further research will be required to ensure it captures the full range of sleep problems in RA. Meanwhile, data across the three countries (Portugal, France and the UK) are comparable except for the two items (sleep and physical well-being).

The controversy of using PGA to define remission in RA

We read with interest the commentary by van Tuyl and Boers (van Tuyl, L. H. D. & Boers, M. Remission — keeping the patient experi‐ ence front and centre. Nat. Rev. Rheumatol. 13, 573–574 (2017))1 referring to our paper on the role of patient global assessment (PGA) in the definition of remission in rheumatoid arthritis (RA)2. However, we cannot agree with their interpretation that by suggesting to remove the PGA from the ACR/EULAR remission definition we are “calling for a para‐ digm change that limits the responsibility of the rheumatologist to prescribing immuno‐ suppressive therapy,” or that our proposal is “taking away the incentive to improve RA care by removing the patient’s perspective from the remission criteria.”1 Nothing could be further from the inter‐ pretation we made of our own data and from our proposals. What we actually proposed is that the management of RA should be guided by two separate targets: a measure of inflam‐ matory activity (physician’s perspective) and a measure of disease impact (patient’s perspective). We advocate that 3v‐remission (defined as swollen and tender 28‐joint counts and C‐reactive protein in mg/dl all ≤1) is the most appropriate target for immunosuppressive therapy given that PGA has been shown to have no more than a weak correlation with disease activity, and is at least as much linked to personality and emotional aspects, which are not amenable to change by immunosuppres‐ sive therapy. Achieving 3v‐remission is a decisive step towards achieving good patient outcomes but does not guarantee the total abrogation of dis‐ ease impact. In fact, the percentage of patients with RA who are missing remission solely because of a high PGA score is greater than the percentage who achieve full remission2,3. To further assist such patients, physicians ought to consider adjuvant interventions instead of reinforced immunosuppression. For these reasons, a measure of disease impact should be part of the recommended treatment targets in RA management. This measure should be examined separately from inflammatory activity and include more ana‐ lytical measures than PGA, in order to guide efforts to alleviate impact beyond what is achieved through control of inflammation. We suggest that the Rheumatoid Arthritis Impact of Disease (RAID) score, using its seven domains as separate items, is ideally suited for this purpose. The RAID score was developed in close cooperation with patients from various countries4. Our views were summarized in the abstract: “PGA mainly reflects fatigue, pain, function, and psychological domains, which are inadequate to define the target for immuno suppressive therapy. This considera‐ tion suggests that clinical practice should be guided by two separate remission targets: inflammation (3v‐remission) and disease impact.”2 In summary, we do not propose to “limit the responsibility of the rheuma‐ tologist to prescribing immunosuppressive therapy”1, but rather we want to highlight the rheumatologist ́s and multidisciplinary team’s responsibility to assess and manage disease impact. The appropriateness of these proposals will be further scrutinized by clari‐ fying whether high PGA in patients otherwise in remission is associated with subclinical inflammation and whether full remission is a better predictor than 3v‐remission (with‐ out PGA) of a long‐term good radiological outcome5. Both investigations are underway. Ricardo J. O. Ferreira1,2*, Cátia Duarte1,3, Mwidimi Ndosi4, Maarten de Wit5,6, Laure Gossec7,8 and J. A. P. da Silva1,3

Como Realizar e Interpretar uma Meta-Análise em Rede para Comparações Indiretas e Mistas: Estratégias Metodológicas Fundamentais

Background : Meta-analysis techniques were traditionally used to assess the effectiveness and safety of a treatment through direct comparison with a single...