Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages.

INTRODUCTION: The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. METHODS: Translation and cross-cultural adaptation has been carried out following the forward-backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. RESULTS: The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option 'not applicable' was added to two items of the ASAS HI to improve appropriateness. DISCUSSION: This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.

Cost savings with a new screening algorithm for pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is now standard care in this disease. The existing Australian Scleroderma Interest Group algorithm (ASIGSTANDARD ) is based on transthoracic echocardiography (TTE) and pulmonary function tests (PFT). Recently, ASIG has derived and validated a new screening algorithm (ASIGPROPOSED ) that incorporates N-terminal pro-B-type natriuretic peptide level together with PFT in order to decrease reliance on TTE, which has some limitations. Right heart catheterisation (RHC) remains the gold standard for the diagnosis of PAH in patients who screen 'positive'. AIM: To compare the cost of PAH screening in SSc with ASIGSTANDARD and ASIGPROPOSED algorithms. METHODS: We applied both ASIGSTANDARD and ASIGPROPOSED algorithms to 643 screen-naïve SSc patients from the Australian Scleroderma Cohort Study (ASCS), assuming a PAH prevalence of 10%. We compared the costs of screening, the number of TTE required and both the total number of RHC required and the number of RHC needed to diagnose one case of PAH, and costs, according to each algorithm. We then extrapolated the costs to the estimated total Australian SSc population. RESULTS: In screen-naïve patients from the ASCS, ASIGPROPOSED resulted in 64% fewer TTE and 10% fewer RHC compared with ASIGSTANDARD , with $1936 (15%) saved for each case of PAH diagnosed. When the costs were extrapolated to the entire Australian SSc population, there was an estimated screening cost saving of $946 000 per annum with ASIGPROPOSED , with a cost saving of $851 400 in each subsequent year of screening. CONCLUSIONS: ASIGPROPOSED substantially reduces the number of TTE and RHC required and results in substantial cost savings in SSc-PAH screening compared with ASIGSTANDARD .

Interpretation of an Extended Autoantibody Profile in a Well-Characterized Australian Systemic Sclerosis (Scleroderma) Cohort Using Principal Components Analysis.

OBJECTIVE: To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort. METHODS: Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data. RESULTS: A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures. CONCLUSION: Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.

The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis.

OBJECTIVES: To determine the prevalence and correlates of antiphospholipid antibodies (APLA) in systemic sclerosis (SSc). METHODS: Nine hundred and forty SSc patients were tested for APLA using an ELISA assay at recruitment. Clinical manifestations were defined as present, if ever present from SSc diagnosis. Logistic regression analysis was used to determine the associations of APLA. RESULTS: One or more types of APLA were present in 226 (24.0%) patients. Anticardiolipin (ACA) IgG (ACA-IgG) antibodies were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH), with higher titres corresponding with a higher likelihood of PAH (moderate titre (20-39 U/ml) ACA-IgG odds ratio [OR] 1.70, 95% CI: 1.01-2.93, p=0.047; high titre (>40 U/ml) ACA-IgG OR 4.60, 95% CI:1.02-20.8, p=0.047). Both ACA-IgM (OR 2.04, 95% CI: 1.4-3.0, p<0.0001) and ACA-IgG (OR 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). Increasing ACA-IgM and IgG titres were associated with increased likelihood of ILD. ACA-IgG was a marker of coexistent pulmonary hypertension and ILD (ILD-PH) (OR 2.10, 95% CI: 1.1-4.2, p=0.036). We also found an association between ACA-IgG and digital ulcers (OR 1.76, 95% CI: 1.16-2.67, p=0.008) and ACA-IgM and Raynaud's phenomenon (OR 2.39, 95% CI: 1.08-5.27, p=0.031). There was no association between APLA and SSc disease subtype, peak skin score, presence of other autoantibodies, mortality or other disease manifestations. CONCLUSIONS: The association of APLA with PAH, ILD, ILD-PH, Raynaud's phenomenon and digital ulcers suggests that endothelial abnormalities and small vessel thrombosis may be important in the pathogenesis of these disease features.

Should patients with systemic sclerosis-related pulmonary arterial hypertension be anticoagulated?

Pulmonary arterial hypertension (PAH) is a major cause of mortality in scleroderma and despite 'advanced' therapies confers a median survival of less than 5 years. Anticoagulation in systemic sclerosis-related PAH (SSc-PAH) is currently one of the most contentious issues in the management of patients with connective tissue disease. While some studies have shown a survival benefit with warfarin therapy in this disease, others have not. Accordingly, a state of clinical equipoise exists in relation to anticoagulation in SSc-PAH. With an over fivefold reduction in mortality demonstrated in some observational studies, the issue of anticoagulation in SSc-PAH demands resolution through a well-designed randomised controlled trial.

The accuracy of methods for urate crystal detection in synovial fluid and the effect of sample handling: a systematic review.

This study aims to compare different methods of monosodium urate crystal (MSU) detection in synovial fluid (SF) and the effect of sample storage and handling on crystal detection. A systematic literature search was performed in MEDLINE, EMBASE, the Cochrane Library and the American College of Rheumatology/European League Against Rheumatism conference abstracts of 2010 and 2011. Studies that compared a method for detecting MSU crystals in SF with polarised light microscopy (PLM) or compared various SF storage and handling factors with the detection of MSU crystals as an outcome were included. Twelve studies out of 247 identified references were included in the review. Seven studies compared different methods of MSU crystal detection in SF with PLM. Due to study heterogeneity, methodological limitations and risk of bias, no firm conclusions could be drawn from the available data. Five studies examining SF storage and handling factors were identified. A reduction in MSU crystal concentration was observed over time at room temperature that was not seen in refrigerated samples. The use of anticoagulation as a storage medium provided no benefit. Dried cytospin preparations appeared to be a suitable medium for long-term storage and delayed crystal analysis for at least 12 months. The existing data do not provide a compelling argument for the replacement of PLM as the current standard. SF sample storage and handling have an effect on MSU crystals and may impact on the reliability of analysis.

Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

Differences and similarities between ankylosing spondylitis and rheumatoid arthritis: epidemiology.

Ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are among the most common rheumatic diseases. The epidemiology of these diseases highlights both similarities and differences. Prevalence rates of approximately 0.2-1% have been reported for the diseases, but the rate for AS is increasing while RA is declining. Geographical variations exist in the incidence and prevalence of the diseases, although the majority of studies have been conducted in northern Europe and North America. AS is a predominantly a male disorder, whereas more females are affected by RA. Both diseases result in increased disability, reduced work productivity, and increased mortality rates. These similarities and differences may give us important clues as to the aetiology of both diseases.

Mortality in rheumatoid arthritis and ankylosing spondylitis.

The rheumatic diseases not only bring pain, disability and poorer quality of life, but also a premature mortality which is often overlooked. Alongside mortality due to the direct complications of disease comes an increase in deaths related to specific therapies and indirect causes such as cancer and cardiovascular mortality. By comparing mortality and its causes in two of the most common inflammatory arthritides, rheumatoid arthritis and ankylosing spondylitis, common threads emerge which give us insight into the impact of chronic inflammatory disease and new directions for patient management.

Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

Mortality in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease which causes pain along with loss of physical function and quality of life over many years. It has also been shown to increase mortality compared to the general population, independent of treatment modalities. Cardiovascular deaths are increased, and recent studies suggest both an abnormality of lipid regulation and microvascular changes. Increased rates of suicide, accidental death, and alcohol-related deaths have also been reported. This review examines rates and causes of increased mortality in AS and highlights a need to focus on cardiovascular risk factors and psychological health in addition to physical disability in patients with AS.

Use of NSAIDs and infection with Helicobacter pylori--what does the rheumatologist need to know?

OBJECTIVES: NSAID-induced gastroduodenal lesions are a frequent and potentially serious health problem in patients with rheumatic diseases. Helicobacter pylori (H. pylori) has also been recognized as a major risk factor for the development of ulcer disease. However, the role of H. pylori in the pathogenesis of NSAID-induced gastroduodenal lesions has remained controversial, and there is currently no clear consensus on the management of NSAID users who are infected with H. pylori. METHODS: To clarify this situation we have performed a systematic literature search to find randomized controlled trials comparing the efficacy of eradication in patients receiving NSAIDs to prevent ulcer development. RESULTS: Seven randomized controlled trials and one meta-analysis were identified. There were three papers on NSAID-naive patients. According to this data, NSAID-naive users benefit from testing for H. pylori infection and subsequent H. pylori eradication therapy prior to the initiation of NSAID. In contrast, H. pylori eradication alone does not protect chronic NSAID users with recent ulcer complications from further gastrointestinal (GI) events. To prevent recurrent ulcer bleeding long-term acid suppressive therapy is needed. CONCLUSIONS: In conclusion, ulcer risk reduction after H. pylori eradication therapy is clearly more marked in patients beginning NSAID therapy than in patients who were already receiving and tolerating NSAID therapy. Thus, the management of H. pylori infection and the prevention of GI complications in NSAID users need to be individualized on the basis of recently published data.

Quality indicators, guidelines and outcome measures in ankylosing spondylitis.

The challenge of managing knowledge is a difficult one, and it is no longer enough simply to conduct clinical trials. Quality of care requires the incorporation of research knowledge into clinical practice. As our knowledge of the chronic inflammatory rheumatic disease ankylosing spondylitis (AS) has grown, evidence-based recommendations for the early diagnosis and management of AS and scientifically-derived outcome measures have been developed to aid the clinician at the point of care. Some of these, including the ASAS/EULAR recommendations for the management of AS, are now being validated in national and international studies. This article discusses existing recommendations and the need for specific quality indicators in the field of AS.

[International classification of functioning, disability and health and its significance for rheumatology]. / Die Internationale Klassifikation für Funktionsfähigkeit, Behinderung und Gesundheit und ihre Bedeutung für die Rheumatologie.

The international classification of functioning, disability and health (ICF) has been developed by the World Health Organization (WHO) to describe health and handicaps in more detail in order to allow better classification and registration. The ICF comprises the disease, structure, functioning, activity and participation as well as corresponding factors related to the individual and the environment. By this means an integrated concept and assessment of biologic, individual and social aspects of health is attained. The ICF represents an essential addition to the international classification of diagnoses (ICD) and procedures (OPS). The ICF consists of two interelated parts. The first part that describes functioning and disability contains two components: one related to the body (functioning and structure) and one related to activity and participation. The second part describes the context factors (related to the environment and the individual). Body functions are the physical and mental functions of the organism. Body structures are the anatomically defined parts of the body. Activity describes how a task is solved or how an action can be performed and participation is the way in which an individual is involved in the environment and society. The ICF categories make the classification of all aspects of functioning and health in individuals easier and independent of diseases or specific assessment instruments. However, since there are more than 1,400 categories, the ICF cannot be used in daily practice in this form. Therefore, attempts are made to identify those parts of the ICF that are relevant for specific patients, situations and disease states or activities. These are the so-called ICF core sets. This article attempts to give an overview on the ICF, to provide an insight into recent work on the ICF related to musculoskeletal and rheumatic diseases and, finally, to describe how an ICF core set for patients with acute arthritis was made possible by means of a successful multicenter cooperative effort.

Identification of relevant functional issues for the care of patients with acute arthritis by health professionals, using the ICF framework and a multi-disciplinary focus group approach.

OBJECTIVE: To identify the most relevant problems to be addressed in the multi-disciplinary care of patients with acute arthritis using focus groups of health professionals followed by a Delphi process. METHODS: Focus group and Delphi methodology were applied. The focus groups were conducted at three specialist rheumatology hospital clinics in Germany, each group comprising rheumatologists, nurses, physiotherapists, occupational therapists, psychologists and social workers. The participants were asked to decide which categories of the International Classification of Functioning, Disability and Health (ICF) are relevant to the care of patients with acute inflammatory arthritis. The results from the focus groups were then followed by an anonymous Delphi process. RESULTS: Twenty-six health professionals participated in the 3 focus groups. 167 of the second-level ICF categories (63% of all second-level categories) were considered as relevant by the rheumatology health professionals. Items from all four components, Body Functions, Body Structures, Activities and Participation and Environmental Factors were represented. Agreement between focus groups and between different health professional groups was substantial for all components with the exception of Environmental Factors (Cohen's kappa 0.23). CONCLUSION: The involvement of experts from different health professions is a valuable tool to identify typical patient characteristics, expressed as distinct ICF categories, to aid in patient care in the acute rheumatology setting. Acute patient care cannot and should not be separated from ongoing long-term management.

International Classification of Functioning, Disability and Health (ICF) Core Set for patients with acute arthritis.

OBJECTIVE: The aim of this consensus process was to construct a preliminary version of the ICF Core Set for acute inflammatory arthritis. METHODS: The development of the ICF Core Set involved a formal decision-making and consensus process, integrating evidence gathered from preliminary studies including focus groups of health professionals, a systematic review of the literature, and empiric data collection from patients. RESULTS: Thirty-three experts selected a total of 79 second-level categories for the Comprehensive Core Set and 40 second-level categories for the Brief Core Set. The largest number of categories was selected from the ICF component Activities and Participation (28 categories or 35%). Eighteen (23%) of the categories were selected from the component Body Functions, 13 (16%) from the component Body Structures, and 20 (25%) from the component Environmental Factors. CONCLUSION: The ICF Core Set for acute arthritis is a clinical framework designed to comprehensively assess patients in acute care hospitals and early post-acute rehabilitation facilities. This preliminary version of the ICF Core Set will be further tested through empiric studies in German-speaking countries and internationally.

Rheumatic manifestations of lymphoproliferative disorders.

OBJECTIVE: The association between musculoskeletal features and lymphoproliferative disorders as well as the association of rheumatic diseases with an increased risk of malignancies is well-known. METHODS: This paper describes three patients with inflammatory joint diseases treated with disease modifying antirheumatic drugs who developed lymphoproliferative disorders either of an abnormal type or with unusual clinical features. RESULTS: The difficulty in differentiating the musculoskeletal symptoms of an underlying lymphoproliferative disease from the features of the rheumatic disease itself with special regard to treatment with disease-modifying antirheumatic drugs including biologics is emphasised on the example of patient 1. Patient 2 presented with a rare type of lymphoma and had been mistakenly diagnosed as having seronegative RA. The last patient with oligoarthritis represents an example of the sarcoidosis-lymphoma syndrome. CONCLUSION: This article addresses several of the problems rheumatologists may experience with the various rheumatologic manifestations of lymphoproliferative disorders. Until more definitive data are available, patients who develop unexpected arthritis should be considered for histologic biopsy to rule out coexistent neoplasia.

Remission in ankylosing spondylitis.

Remission is a major goal of medical therapy in chronic disease. Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that affects the axial skeleton and other body structures, causing pain, stiffness, functional loss, and disability. Until recently only symptomatic therapies were available, and control was poor in patients with severe disease. However, the TNF antagonists have now changed this substantially. The concept of disease remission in AS has not received much attention in the current literature. There exists one set of partial remission criteria formally developed by the ASsessments in Ankylosing Spondylitis (ASAS) working group on the basis of clinical trials with nonsteroidal anti-inflammatory drugs for use in clinical trials. Furthermore, a state of low disease activity has been defined empirically in studies of anti-tumour necrosis factor (anti-TNF) therapy to describe clinically relevant treatment efficacy. As more effective therapies become available for AS, disease remission is increasingly regarded as an appropriate therapeutic goal that may then be translated into modification of progressive structural damage. There is a need to further define and evaluate current proposals concerning remission in AS.

[Recommendations for the management of ankylosing spodylitis after ASAS/EULAR. Evaluation in the German language area]. / Empfehlungen für das Management der ankylosierenden Spondylitis gemäss ASAS/EULAR. Evaluation im deutschsprachigen Raum.

AIM: Our aim was to adapt and implement the evidence based recommendations for the management of ankylosing spodylitis (AS) of the "Assessments in AS" (ASAS) International Working Group together with the European League Against Rheumatism (EULAR) within the framework of a competence network (CN) in rheumatology in the German language area. METHODS: The ASAS/EULAR project calculated the effective size (ES), rate ratio, number of patients requiring treatment (number needed to treat, NNT) and the incremental cost-effectiveness ratio (ICER). The strength of the recommendations was determined through the evidence level found in the literature, the risk-benefit trade-off and the clinical experience of the experts. The recommendations were recently published in English. All of the centers taking part in the study area Spondyloarthritis (SpA) CN, as well as an additional 35 experts, were sent the English manuscript. All 35 participants were asked to evaluate the ten main management recommendations on a scale from 0 to 10. RESULTS: The recommendations encompass the use of drugs such as non-steroid anti-inflammatories (NSAR), which, along with conventional NSAR include coxibs and the parallel application of gastroprotectives, so called disease-modifying anti-rheumatic drugs, biologicals, simple analgesics, local and systematic glucocorticoids, non-drug therapies (such as patient training, medical training therapy and physiotherapy), in addition to surgical treatment methods. Moreover, three general recommendations were formulated and a therapy scheme created, taking into consideration the various clinical manifestations. The strength of the ASAS/EULAR recommendations was generally high. There was a marked consensus between the German speaking experts and the international proposal: a mean of 9.13 with relatively low variation between the recommendations. SUMMARY: Ten key recommendations for the treatment of AS were developed. These were strengthened by a systematic search of the literature and by expert consensus. The large group of German speaking experts were largely in agreement with the proposal. This can be seen as a starting point for the dissemination and implementation of the recommendations.