Implementation of recommendations in rheumatic and musculoskeletal diseases: considerations for development and uptake.

A clinical guideline is a document with the aim of guiding decisions based on evidence regarding diagnosis, management and treatment in specific areas of healthcare. Specific to rheumatic and musculoskeletal diseases (RMDs), adherence to clinical guidelines recommendations impacts the outcomes of people with these diseases. However, currently, the implementation of recommendations is less than optimal in rheumatology.The WHO has described the implementation of evidence-based recommendations as one of the greatest challenges facing the global health community and has identified the importance of scaling up these recommendations. But closing the evidence-to-practice gap is often complex, time-consuming and difficult. In this context, the implementation science offers a framework to overcome this scenario.This article describes the principles of implementation science to facilitate and optimise the implementation of clinical recommendations in RMDs. Embedding implementation science methods and techniques into recommendation development and daily practice can help maximise the likelihood that implementation is successful in improving the quality of healthcare and healthcare services.

Local adaptation of recommendation-based materials for shared decision-making and management of comorbidity in rheumatoid arthritis.

OBJECTIVES: To describe local adaptations of materials derived from evidence-based recommendations in a training programme in rheumatoid arthritis (RA). METHODS: The eRA (evolving the management of rheumatoid arthritis) programme generated shared decision-making practises and a checklist for managing comorbidity in RA, among others, at the international level. Unmet needs in RA management were first identified and prioritised. Then educational materials were designed and developed to address these gaps. These materials were evaluated in detailed and discussed in small regional groups by practicing rheumatologists. Voting, open discussions and recommendations were extracted from the meetings. RESULTS: Thirty-five Spanish rheumatologists discussed a comorbidity checklist and a shared decision-making tool. The results of the local meetings were synthesised as (1) a judicious commitment to check agreed comorbidities, and (2) a list of barriers and facilitators for the implementation of shared decision making in the local settings. With regards to ways to implement the agreed list and periodicity, two issues stand-out: (1) patient education and (2) the need of easy access to information and the use of local organisational systems in place. With respect to shared decision-making, issues raised included messages for self-awareness, challenges, and practical facilitators. CONCLUSIONS: Discussion, adaptation, and planning are needed before implementing any evidence-based recommendation and materials if we want to achieve a successful implementation. Further studies should demonstrate whether this initiative was successful in achieving the goals of improved patient care. Our experience could be used as a guidance or example for implementation elsewhere.

Prevalence of Metabolic Syndrome in Psoriatic Arthritis: Systematic Literature Review and Results From the CARMA Cohort.

OBJECTIVE: To analyze the prevalence of metabolic syndrome (MetS) in patients with psoriatic arthritis (PsA) in a systematic literature review (SLR) and in the Spanish CArdiovascular in RheuMAtology (CARMA) cohort. METHODS: A SLR and a subanalysis of the CARMA cohort were performed. In the SLR, PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov up to March 2019 were searched. Systematic literature reviews, clinical trials, and observational studies that analyzed the prevalence or frequency of MetS in PsA were analyzed. Two reviewers selected the articles, assessed the quality of the studies, and collected data, independently. In addition, data on sociodemographic characteristics and MetS in patients with PsA from the CARMA cohort were collected and analyzed. Comparative descriptive analysis was performed. RESULTS: The SLR included 18 articles, of moderate to high quality, with PsA patients of both sexes, with mean ages between 42 and 59 years. The rate of MetS varied from 23.5% to 62.9%. The most commonly used classification method was that of the National Cholesterol Education Program. Additionally, 724 PsA patients from the CARMA cohort were analyzed; 327 (45.4%) were women, 157 (21.8%) smokers, with a mean age of 51 years and a mean PsA disease duration of 9 years. Hypertension was the most common abnormal finding (66.8%), followed by hyperglycemia (42.6%) and hypertriglyceridemia (30.6%). Notably, 222 patients (30.6%) had MetS. CONCLUSIONS: The prevalence of MetS in PsA varies, depending on the definition. Whereas 23.5% to 62.9% of PsA patients have MetS, in the CARMA cohort almost a third of patients with PsA have MetS.

Management of particular clinical situations in psoriatic arthritis: an expert's recommendation document based on systematic literature review and extended Delphi process.

To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA. In a nominal group meeting, the results of the SLR were discussed and a set of recommendations were proposed for a Delphi process. A total of 65 rheumatologists were invited to participate in the Delphi. Agreement was defined if ≥ 70% of the participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grade of recommendation was established based on the Oxford Evidence-Based Medicine categorisation. Particular clinical situations included monoarthritis, axial disease, or non-musculoskeletal manifestations. The SLR finally comprised 131 articles. A total of 16 recommendations were generated, all but 1 reached consensus. According to them, it is crucial to carefully analyse the impact of individual manifestations on patients (disability, quality of life, etc.), but also to recognise the impact of each drug singularities on selected clinical phenotypes to adopt the most appropriate treatment strategy. Early diagnosis and treatment to target approach, along with a close risk management, is also necessary. These recommendations are intended to complement gaps in national and international guidelines by helping health professionals address and manage particular clinical situations in PsA.

Implementation of an assessment checklist for patients with spondyloarthritis in daily practice.

OBJECTIVES: To analyse the feasibility and changes in the collection of clinical measures after the implementation in daily practice of a checklist designed for an optimal evaluation and monitoring of patients with spondyloarthritis (SpA). METHODS: An observational prospective study was performed. The feasibility of the assessment checklist (paper/on-line format) for patients with SpA was tested (time to complete the checklist, simplicity, amenity clarity, usefulness). Through a medical files review, changes in the number of the checklist variables collected were analysed previous to the implementation of the checklist and 6 months later. A descriptive and bivariate analysis was performed. RESULTS: A total 6 hospitals and 11 rheumatologists participated. The median time to checklist completion was 15 (12-20) minutes, and the mean scores for the rest of variables of the feasibility test were in general positives. A total of 83 and 68 medical files pre-implementation and post-implementation were reviewed respectively. We observed a significant increase in the collection of many of the checklist variables after the implementation. The record of BASDAI increased from 46.2% to 73.1% (p=0.001), physical activity from 48.2% to 88.2% (p<0.0001), physician global (VAS) from 28.0% to 73.5% (p<0.0001), patient global (VAS) from 48.8% to 85.3% (p<0.0001), morning stiffness from 62.8% to 84.8% (p=0.003), ASDAS from 12.2% to 32.8% (p=0.002), BASFI from 43.7% to 65.7% (p=0.008), or DAS28 from 24.7% to 46.3% (p=0.006). These changes were observed irrespectively of SpA classification. CONCLUSIONS: The implementation of an assessment checklist in daily practice is feasible and improves the assessment of SpA patients.

"There is something you must see": breaking down the remission concept in rheumatoid arthritis from a rheumatologist's perspective.

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and the implications of the existing definitions when applied to clinical practice among rheumatologists with different profiles. METHODS: A qualitative study through focus groups was conducted. Three focus groups were organised from February to March 2016. Each group was composed of rheumatologists with extensive clinical experience with different profiles; experts in basic research (RBR), experts in imaging techniques research (RIR), and experts in clinical research (RCR). The data was collected with audio recording. Verbatim transcriptions of the audio files were made, and a subsequent reflexive thematic analysis assisted by ATLAS.ti (GmbH, Berlin, v. 7) software was performed. RESULTS: From the reflexive thematic analysis, three main themes were generated: (1) remission limitations, (2) instruments or measures to assess remission, and (3) a new definition of remission. Rheumatologists mentioned frequently that the following variables should be considered when developing a new remission definition: inflammatory activity, calprotectin, psychological variables, sex, disease stage, and sociocultural factors. Contrary to what could be expected, all groups acknowledged that their research field could contribute with domains for a gold standard remission instrument, but not in a hierarchical arrangement of importance. The dissonance existing in the entire remission evaluation process was outlined: remission in clinical practice versus remission in clinical trials, remission following the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean versus Musculoskeletal Ultrasound (US) remission, and remission from the rheumatologist's point of view versus the patient's point of view. CONCLUSIONS: Currently, rheumatologists would not accept a domain as more important than others in remission. Our suggestion is, not to generate a universal definition of remission - one that could cover all aspects - but rather to develop definitions of remission for the different settings that could be pondered by the patient's perspective.

Efficacy and safety of biological therapy compared to synthetic immunomodulatory drugs or placebo in the treatment of Behçet's disease associated uveitis: a systematic review.

The aim of this study is to compare the efficacy and safety of biological therapy with cyclosporin A (CsA), azathioprine (AZA), or placebo in uveitis flares and other ocular outcomes in patients with Behçet disease. A comprehensive and sensitive search in MEDLINE, EMBASE, and the Cochrane Library was performed. We selected articles including: (1) adult patients with Behçet's and uveitis; (2) on biological therapies; (3) placebo or active control with CsA or AZA; (4) analyzing efficacy (number of uveitis flares, macular edema, etc.) and/or safety outcomes. Meta-analyses, systematic reviews, clinical trials, and observational studies with > 10 patients were included. The selection, data collection and quality assessment (Oxford scale) was carried out by 2 reviewers independently. Nine articles of moderate quality were included (6 randomized clinical trials and 3 retrospective studies) involving 378 patients. Most of them, apart from the study drugs received systemic corticosteroids and other immunosuppressant drugs. Infliximab was more effective than CsA in reducing short-term uveitis flares and severe complications of retinal vasculitis in the long term. Rituximab was similar to a combination of cytotoxic drugs in improving inflammatory activity. In patients with active uveitis adalimumab was associated with a lower risk of uveitic flare or visual impairment, and in patients with inactive uveitis to a significantly lowered the risk of flare upon corticosteroid withdrawal. Secukinumab and daclizumab were not superior to placebo in reducing uveitis flares, like interferonα compared to other drugs. Our results highlight the need for better designed comparative studies on Behçet's uveitis.

Gender differences in early systemic sclerosis patients: a report from the EULAR scleroderma trials and research group (EUSTAR) database.

OBJECTIVES: To describe differences in clinical presentation between men and women in a large group of patients with early (<3 years' duration) systemic sclerosis (SSc) according to disease subsets. METHODS: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research database (EUSTAR) was performed. Patients fulfilling preliminary ACR 1980 classification criteria for SSc, with less than 3 years from the first non-Raynaud's symptom at first entry, were selected. A group of patients with less than 3 years from the first SSc symptom, including Raynaud's phenomenon, was also analysed. SSc related variables, including antibodies, SSc subsets, disease activity and organ involvement were included. Descriptive and bivariate analyses were performed. RESULTS: A total of 1,027 patients were included, 90% Caucasian, 80% women, and 40% with diffuse cutaneous disease. In early stages of SSc, men showed more frequently than women active disease, diffuse cutaneous subset, anti-Scl-70 antibodies, elevated acute phase reactants, muscular and pulmonary involvement. Differences between men and women were confirmed in the limited, but not in the diffuse SSc subset. The results were similar when 650 patients with less than three years from the first SSc symptom, including Raynaud's phenomenon, were analysed. CONCLUSIONS: In early stages of SSc, men present signs and symptoms of more severe disease. In the limited disease subset, men might appear with clinical features and organ involvement similar to those of the diffuse subgroup. In clinical practice, the identification of such differences might help to select the appropriate management for each particular patient.

Expert recommendations on the psychological needs of patients with rheumatoid arthritis.

OBJECTIVE: To establish feasible and practical recommendations for the management of the psychological needs of patients with rheumatoid arthritis (RA) from the moment of diagnosis through the course of the disease. METHODS: A nominal group meeting was held with an RA expert team including rheumatologists and psychologists, at which a guided discussion addressed the most important psychological and emotional needs in RA. Based on the comments collected, and a literature review, a matrix document of recommendations for telematics discussion was prepared, as well as a Delphi survey to test agreement with these recommendations. Agreement was defined if at least 80% of participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grading of recommendations was established following the Oxford criteria, and the degree of agreement through the Delphi. RESULTS: Thirteen recommendations were established, addressing several key processes: (1) identification of psychological problems and needs in patients with RA, and a guideline for their management in daily practice; (2) communication with patients; (3) referral criteria to mental health professionals. CONCLUSIONS: These recommendations are intended to help health care professionals openly address the psychological aspects of patients in daily practice to follow and treat them properly.

Clinical determinants of elevated systolic pulmonary artery pressure measured by transthoracic Doppler echocardiography in early systemic sclerosis.

OBJECTIVES: To explore the prevalence and clinical associations of elevated systolic pulmonary artery pressure (sPAP), measured by Transthoracic Doppler-echocardiography (TTE) in patients with early systemic sclerosis (SSc). METHODS: A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research (EUSTAR) database was performed. SSc patients with <3 years from the first non-Raynaud's phenomenon (RP) symptom at baseline EUSTAR visit, were selected. Elevated sPAP was defined as sPAP>40 mmHg on baseline TTE. First visit SSc related variables, including disease subsets, antibodies and visceral involvement, were examined. RESULTS: From 1,188 patients, 81% were women. Mean (SD) age at first non-RP symptom was 50 (14) years, 55% had limited cutaneous SSc (lcSSc) and 42% active disease. Elevated sPAP was found in 17% of patients, both lcSSc and diffuse cutaneous SSc (dcSSc). In lcSSc, older age at first non-RP symptom, ACA positivity, joint contractures, restrictive defect and lower DLCO, were independently associated with elevated sPAP. In dcSSc, older age at first non-RP symptom, longer time between RP onset and first non-RP symptom, digital ulcers, cardiac blocks, and proteinuria were associated with elevated sPAP. CONCLUSIONS: The prevalence of elevated sPAP on TTE in early SSc patients is considerable. Association with cardiac, lung and renal involvement suggests that, although some patients might have pulmonary arterial hypertension, others may present pulmonary hypertension secondary to lung or heart involvement. Our findings emphasize the need to consider right heart catheterisation in selected early SSc patients with PH suspicion, to clearly determine the cause of PH.

Exploring the remission concept in rheumatoid arthritis with patients and rheumatologists: time for a new approach?

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and to compare remission definitions and related concepts between rheumatologists and patients with the purpose of identifying similarities and disparities to comprehend the different perspectives of the disease. METHODS: This was a qualitative study of discourse and content analysis through focus groups, conducted from February to March 2016. Four focus groups were set up, each one with different interests: rheumatologists involved in basic research (BR), rheumatologists with high specialisation in imaging techniques (IR), clinical rheumatologists (CR), and patients (PA). RESULTS: There is no consensus in a remission definition in RA; differences exist between-groups, rheumatologists and patients value remission differently, and there are discrepancies within the group of rheumatologists. Rheumatologists highlight quantifiable objective parameters, in contrast, patients did not consider objective measures as the best instruments, and they prefer subjective measures of remission. The data confirmed the existence of two sources of knowledge of the disease, technical (physicians) and experiential (patients). These sources of knowledge should concur in order to establish new remission criteria well-adjusted to reality. CONCLUSIONS: The lack of consensus between key groups implicated in defining remission and remission criteria suggests a new strategy for its operational definition. Our group proposes that subjects with a balance between experiential and technical knowledge, should be the ones in charge of this assignment.

Anti-citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review.

Anti-citrullinated peptide antibodies (ACPAs) play an important pathogenic role both at the onset and during the disease course. These antibodies precede the clinical appearance of rheumatoid arthritis (RA) and are associated with a less favorable prognosis, both clinically and radiologically. The objective of this work was to conduct a comprehensive review of studies published through September 2015 of ACPAs' role as a predictor of the therapeutic response to the biological agents in RA patients. The review also includes summary of the biology and detection of ACPAs as well as ACPAs in relation to joint disease and CV disease and the possible role of seroconversion. The reviews of studies examining TNF inhibitors and tocilizumab yielded negative results. In the case of rituximab, the data indicated a greater probability of clinical benefit in ACPA(+) patients versus ACPA(-) patients, as has been previously described for rheumatoid factor. Nonetheless, the effect is discreet and heterogeneous. Another drug that may have greater effectiveness in ACPA(+) patients is abatacept. Some studies have suggested that the drug is more efficient in ACPA(+) patients and that those patients show greater drug retention. In a subanalysis of the AMPLE trial, patients with very high ACPA titers who were treated with abatacept had a statistically significant response compared to patients with lower titers. In summary, the available studies suggest that the presence of or high titers of ACPA may predict a better response to rituximab and/or abatacept. Evidence regarding TNFi and tocilizumab is lacking. However, there is a lack of studies with appropriate designs to demonstrate that some drugs are superior to others for ACPA(+) patients.

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.

Development of patient-centred standards of care for osteoarthritis in Europe: the eumusc.net-project.

OBJECTIVE: The eumusc.net project is an initiative founded by the European Community and the European League Against Rheumatism. One aim of the project was to facilitate equal standards for musculoskeletal health across Europe. The aim of this work-package was to develop patient-centred and consensus based standards of care (SOC) for osteoarthritis (OA), which should be available in a professional and a patient version. METHODS: A systematic review concerning guidelines dealing with OA was conducted. Furthermore, experts in musculoskeletal diseases were contacted to ensure that 'grey' literature was not excluded. Documents that fulfilled predefined inclusion/exclusion criteria were included and all interventions for OA were extracted and categorised. Based on this list of interventions, a three round Delphi exercise with an international and multidisciplinary expert panel, including patient research partners, was performed to achieve expert consensus. RESULTS: Six documents were included and used for further analysis. Out of them, 46 interventions have been extracted and 10 consensus based SOC were formulated. In addition, a patient version, written in a lay-understandable wording and in the format of checklist questions was developed. An example is SOC 5: "People with OA should achieve optimal pain control using pharmacological and non-pharmacological means." The matching patient-centred checklist question reads: "Do I know how to control pain associated with OA?" CONCLUSIONS: The SOC for OA will be available in the 23 languages of the European Union to enhance unified information to patients and professionals and to further harmonise the treatment/care of OA within Europe.

The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers.

OBJECTIVE: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers.

Adherence to biologic therapies and associated factors in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis: a systematic literature review.

OBJECTIVES: To analyse the evidence on adherence to biologic therapies in rheumatoid arthris (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of studies retrieved by a sensitive search strategy in MEDLINE database (1961 through March 2012). To be selected, studies had to include patients with RA, SpA, or PsA, treatment with intravenous or subcutaneous biologic therapies, and had to report on measures of adherence. By design, only randomised controlled trials (RCT) or high quality cohort studies with a control group were selected. RESULTS: A total of 24 studies were included, of which 12 reported results from national or local biologic registers, 9 were retrospective studies, 2 prospective studies, and only one was an RCT. Patients included were mostly women with diagnosis of RA or SpA and, less frequently, PsA. There was a great variability in the definition of adherence, measurement methods, and associated factors analysed. In general, adherence to etanercept was superior to that of other biologics, by the measures utilised. The main predictive factors - age, sex, comorbidity, baseline clinical condition, previous or concomitant use of DMARDs, anti-TNF in monotherapy or in combination with MTX - produced diverse, even divergent results across studies. CONCLUSIONS: There is a wide variability related to the adherence concept and its measurement, reflecting the complexity of the phenomenon. In order to draw more consistent conclusions about the relative value of predictive factors on adherence and persistence of biological therapy, larger controlled studies with better selection of variables and analysis of interactions are needed.

Safety of allopurinol compared with other urate-lowering drugs in patients with gout: a systematic review and meta-analysis.

UNLABELLED: Allopurinol is the most widely used urate-lowering drug (ULD). Together with efficacy and cost, safety is an aspect that helps taking clinical decisions. This systematic review analyzes allopurinol safety. The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library (January 2014). SELECTION CRITERIA: (a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis. PRIMARY OUTCOMES: rate of adverse events and death. The quality was assessed with the Jadad's scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40-240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6-85) and febuxostat (range 41.8-80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.

Efficacy of Raynaud's phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review.

To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed using Medline, EMBASE, and Cochrane Central Register of Controlled Trials (from 1961 to October 2011). We included meta-analyses, systematic reviews, clinical trials, and high-quality cohort studies published in English or Spanish. Patient populations had to include adults diagnosed with limited cutaneous or diffuse SSc who had associated RP and/or digital ulcers under pharmacological treatment. Efficacy of treatments was evaluated based on: number of RP episodes, RP severity, episode-free time, ulcer improvement/healing, and appearance of new ulcers. We used the Jadad scale of methodological quality to evaluate the quality of randomized clinical trials, and the 2009 Oxford Centre for Evidence-Based Medicine classification for other studies. Of a total of 1617 studies identified, only 27 fulfilled inclusion criteria. Drugs received the following grade recommendations: Grade A for nifedipine, nicardipine, quinapril, IV iloprost, bosentan, tadalafil, and MQx-503; Grade B for beraprost, cicaprost, DMSO, cyclofenil, and atorvastatin; and Grade C for misoprostol, prazosin, OPC-2826, enalapril, sildenafil, antioxidant, and stanazolol. Calcium channel blockers, prostanoids, tadalafil, and bosentan received the highest recommendation level for their effectiveness. However, most systematic reviews reviewed just a handful of studies with small sample sizes and short follow-ups. Our review shows that the existing evidence on the efficacy of RP treatment in SSc patients is inconclusive which calls for further research, especially in the form of prospective studies of high quality with long-term follow-ups.

Consensus statement on a framework for the management of comorbidity and extra-articular manifestations in rheumatoid arthritis.

The objective of the study was to develop evidence-based and practical recommendations for the detection and management of comorbidity in patients with rheumatoid arthritis (RA) in daily practice. We used a modified RAND/UCLA methodology and systematic review (SR). The process map and specific recommendations, based on the SR, were established in discussion groups. A two round Delphi survey permitted (1) to prioritize the recommendations, (2) to refine them, and (3) to evaluate their agreement by a large group of users. The recommendations cover: (1) which comorbidities should be investigated in clinical practice at the first and following visits (including treatments, risk factors and patient's features that might interfere with RA management); (2) how and when should comorbidities and risk factors be investigated; (3) how to manage specific comorbidities, related or non-related to RA, including major adverse events of RA treatment, and to promote health (general and musculoskeletal health); and (4) specific recommendations to assure an integral care approach for RA patients with any comorbidity, such as health care models for chronic inflammatory patients, early arthritis units, relationships with primary care, specialized nursing care, and self-management. These recommendations are intended to guide rheumatologists, patients, and other stakeholders, on the early diagnosis and management of comorbidity in RA, in order to improve disease outcomes.